S-4
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As filed with the Securities and Exchange Commission on November 10, 2022

Registration No. 333-            

 

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM S-4

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

 

 

Imara Inc.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   2834   81-1523849
(State or jurisdiction   (Primary Standard Industrial   (I.R.S. Employer
of incorporation)   Classification Code Number)   Identification Number)

1309 Beacon Street, Suite 300, Office 341

Brookline, Massachusetts 02446

(617) 206-2020

(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)

 

 

Rahul D. Ballal

President and Chief Executive Officer

1309 Beacon Street, Suite 300, Office 341

Brookline, MA 02446

(617) 206-2020

(Name, address, including zip code, and telephone number, including area code, of agent for service)

 

 

Copies to:

 

Cynthia T. Mazareas, Esq.   Stephen M. Migausky, Esq.   Tony Jeffries, Esq.
Joseph B. Conahan, Esq.   Senior VP, Legal and General Counsel   Robert Ishii, Esq.
Mark Nylen, Esq.  

1309 Beacon Street, Suite 300, Office 341

  Jennifer Knapp, Esq.
Stephanie L. Leopold, Esq.  

Brookline, MA 02446

  Rich Mullen, Esq.
WilmerHale   (617) 206-2020   Wilson Sonsini Goodrich & Rosati
60 State Street South     1881 9th Street, Suite 110
Boston, MA 02109     Boulder, CO 80302
(617) 526 6000     (303) 256-5900

 

 

Approximate date of commencement of proposed sale to the public: As soon as practicable after the effective date of this registration statement and the satisfaction or waiver of all other conditions under the Merger Agreement described herein.

If the securities being registered on this Form are being offered in connection with the formation of a holding company and there is compliance with General Instruction G, check the following box:  ☐

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ☐

If this Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

 

Large accelerated filer      Accelerated filer  
Non-accelerated filer      Smaller reporting company  
     Emerging growth company  

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act.  ☐

If applicable, place an X in the box to designate the appropriate rule provision relied upon in conducting this transaction:

Exchange Act Rule 13e-4(i) (Cross-Border Issuer Tender Offer)  ☐

Exchange Act Rule 14d-1(d) (Cross-Border Third-Party Tender Offer)  ☐

 

 

The Registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the Registrant shall file a further amendment which specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933, as amended, or until the registration statement shall become effective on such date as the Securities and Exchange Commission, acting pursuant to said Section 8(a), may determine.

 

 

 


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The information in this proxy statement/prospectus is not complete and may be changed. These securities may not be sold until the registration statement filed with the Securities and Exchange Commission is effective. This proxy statement/prospectus is not an offer to sell and it is not soliciting an offer to buy these securities in any jurisdiction where the offer or sale is not permitted.

 

SUBJECT TO COMPLETION, DATED NOVEMBER 10, 2022

PROPOSED MERGER

YOUR VOTE IS VERY IMPORTANT

 

 

To the Stockholders of Imara Inc. and Enliven Therapeutics, Inc.,

Imara Inc., a Delaware corporation, or Imara, and Enliven Therapeutics, Inc., a Delaware corporation, or Enliven, entered into an Agreement and Plan of Merger, or the Merger Agreement, on October 13, 2022, pursuant to which, subject to the terms and conditions thereof, a wholly owned subsidiary of Imara, Iguana Merger Sub, Inc., or Merger Sub, will merge with and into Enliven, with Enliven surviving as a wholly owned subsidiary of Imara, and the surviving corporation of the merger, which transaction is referred to herein as the Merger. The combined company following the Merger is referred to herein as the combined company.

Immediately prior to the effective time of the Merger, each share of Enliven’s preferred stock will be converted into shares of Enliven’s common stock and at the effective time of the Merger, each share of Enliven’s common stock, including those shares of Enliven common stock issued upon conversion of Enliven’s preferred stock and those shares of Enliven common stock issued in the Enliven pre-closing financing, defined below (but excluding shares to be canceled pursuant to the Merger Agreement and excluding dissenting shares), will be converted into the right to receive a number of shares of Imara common stock equal to the exchange ratio described in more detail in the section titled “The Merger—Exchange Ratio” beginning on page 190 of the accompanying proxy statement/prospectus. Based on Imara’s and Enliven’s capitalization as of October 13, 2022, the date the Merger Agreement was executed, the exchange ratio is estimated to be equal to approximately 1.1580 shares of Imara common stock for each share of Enliven capital stock, which exchange ratio does not give effect to the expected reverse stock split of Imara common stock. The final exchange ratio is subject to adjustment prior to closing of the Merger based upon Imara’s net cash at closing and the aggregate proceeds from the sale of Enliven common stock in the Enliven pre-closing financing.

In connection with the Merger, each stock option granted under Enliven’s 2019 Equity Incentive Plan, or the Enliven 2019 Plan, that is outstanding immediately prior to the effective time of the Merger will be assumed by Imara and will become an option to acquire, on the same terms and conditions as were applicable to such Enliven stock option immediately prior to the effective time of the Merger, a number of shares of Imara common stock equal to the number of shares of Enliven common stock subject to the unexercised portion of the Enliven stock option immediately prior to the effective time of the Merger, multiplied by the exchange ratio (rounded down to the nearest whole share number), with an exercise price per share for the options equal to the exercise price per share of such Enliven stock option immediately prior to the effective time of the Merger divided by the exchange ratio (rounded up to the nearest whole cent). Such assumed options will continue to be governed by the terms and conditions of the Enliven 2019 Plan.

Prior to the closing of the Merger, Imara will conduct a reverse stock split of the Imara common stock, at a ratio of not less than 1-for-                 and not more than 1-for-                , and thereafter, each share of Imara common stock and option to purchase Imara common stock that is issued and outstanding at the effective time of the Merger will remain issued and outstanding and such shares will be unaffected by the Merger. Immediately after the Merger, Imara securityholders as of immediately prior to the Merger are currently estimated to own approximately 15.9% of the outstanding shares of the combined company on a fully-diluted basis and former Enliven securityholders, including those purchasing shares in the Enliven pre-closing financing described in the accompanying proxy statement/prospectus, are currently estimated to own approximately 84.1% of the outstanding shares of the combined company on a fully-diluted basis, subject to certain assumptions, including, but not limited to, (a) Imara’s net cash as of the closing being approximately $82 million, (b) Enliven raising approximately $164.5 million in the Enliven pre-closing financing described in the accompanying proxy statement/prospectus, (c) a valuation for Imara equal to its net cash as of the business day immediately prior to the closing date of the Merger, plus $10 million and (d) a valuation for Enliven equal to $324.6 million, plus the gross proceeds of the Enliven pre-closing financing, in each case as further described in the Merger Agreement.

Shares of Imara common stock are currently listed on The Nasdaq Global Select Market under the symbol “IMRA.” Enliven has filed a listing application for the combined company with The Nasdaq Stock Market Inc., or Nasdaq. After completion of the Merger, the combined company will be renamed “Enliven Therapeutics,


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Inc.” and it is expected that the common stock of the combined company will trade on The Nasdaq Stock Market under the symbol “ELVN.” On                     , the last trading day before the date of the accompanying proxy statement/prospectus, the closing sale price of Imara common stock was $                     per share.

Certain investors have agreed to purchase shares of Enliven common stock at a purchase price of $3.84098 per share, for an aggregate purchase price of approximately $164.5 million, referred to as the Enliven pre-closing financing, which is expected to close immediately prior to the closing of the Merger. The closing of the Enliven pre-closing financing is conditioned upon the satisfaction or waiver of the conditions to the closing of the Merger as well as certain other conditions. The shares of Enliven common stock that are issued in the Enliven pre-closing financing will be converted into the right to receive a number of shares of Imara common stock equal to the exchange ratio described in more detail in the section titled “The Merger—Exchange Ratio” beginning on page 190 of the accompanying proxy statement/prospectus.

Imara stockholders are cordially invited to attend the special meeting of Imara stockholders. Imara is holding its special meeting of stockholders, or the Imara special meeting, on             ,             , at                     , unless postponed or adjourned to a later date, in order to obtain the stockholder approvals necessary to complete the Merger and related matters. The Imara special meeting will be held entirely online. Imara stockholders will be able to attend and participate in the Imara special meeting online by visiting www.                 .com, where they will be able to listen to the meeting live, submit questions and vote. At the Imara special meeting, Imara will ask its stockholders:

 

  1.

To approve the issuance of shares of common stock of Imara pursuant to the terms of the Merger Agreement (as it may be amended from time to time), a copy of which is attached as Annex A to the accompanying proxy statement/prospectus, for purposes of Nasdaq Listing Rules 5635(a), (b) and (d);

 

  2.

To adopt and approve an amendment to the restated certificate of incorporation of Imara to increase the number of authorized shares of Imara common stock from 200,000,000 shares to 400,000,000 shares.

 

  3.

To adopt and approve an amendment to the restated certificate of incorporation of Imara to effect a reverse stock split of Imara common stock, by a ratio of not less than 1-for-                 and not more than 1-for-                , and a proportionate reduction in the number of authorized shares of Imara common stock, such ratio and the implementation and timing of the reverse stock split to be determined in the discretion of Imara’s board of directors;

 

  4.

To approve the adoption of the Imara Inc. Amended and Restated 2020 Equity Incentive Plan;

 

  5.

To approve an amendment to the Imara Inc. 2020 Employee Stock Purchase Plan, or the Imara 2020 ESPP, to increase the number of shares of common stock reserved for issuance under the Imara 2020 ESPP to 1,628,535 shares; and

 

  6.

To consider and vote upon an adjournment of the Imara special meeting, if necessary, to solicit additional proxies if there are not sufficient votes in favor of Proposal Nos. 1, 2, 3, 4 and 5.

As described in the accompanying proxy statement/prospectus, certain Imara stockholders who in the aggregate owned approximately 33% of the outstanding shares of Imara as of October 13, 2022, and certain Enliven stockholders who in the aggregate owned approximately 88.2% of the outstanding shares of Enliven capital stock as of October 13, 2022, are parties to stockholder support agreements with Imara and Enliven, respectively, whereby such stockholders have agreed to vote in favor of the approval of the transactions contemplated therein, including, with respect to Enliven stockholders, adoption of the Merger Agreement and approval of the Merger and, with respect to such Imara stockholders, the issuance of Imara common stock in the Merger pursuant to the Merger Agreement, subject to the terms of the support agreements. Following the effectiveness of the registration statement on Form S-4 of which the accompanying proxy statement/prospectus is a part and pursuant to the Merger Agreement, Enliven stockholders holding a sufficient number of shares of Enliven capital stock to adopt the Merger Agreement and approve the Merger and related transactions will be asked to execute written consents providing for such adoption and approval.

After careful consideration, each of the Imara and Enliven boards of directors has approved the Merger Agreement and has determined that it is advisable to consummate the Merger and the other transactions contemplated by the Merger Agreement. Imara’s board of directors has approved the proposals described in the accompanying proxy statement/prospectus and recommends that its stockholders vote “FOR” the proposals described in the accompanying proxy statement/prospectus.

 

 

 


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More information about Imara, Enliven, the Merger Agreement and transactions contemplated thereby and the foregoing proposals is contained in the accompanying proxy statement/prospectus. Imara urges you to read the accompanying proxy statement/prospectus carefully and in its entirety. IN PARTICULAR, YOU SHOULD CAREFULLY CONSIDER THE MATTERS DISCUSSED UNDER “RISK FACTORS” BEGINNING ON PAGE 26 OF THE ACCOMPANYING PROXY STATEMENT/PROSPECTUS.

Imara and Enliven are excited about the opportunities the Merger brings to Imara’s and Enliven’s stockholders and thank you for your consideration and continued support. Sincerely,

 

Rahul Ballal, Ph.D.    Sam Kintz
President and Chief Executive Officer    President and Chief Executive Officer
Imara Inc.    Enliven Therapeutics, Inc.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or passed upon the adequacy or accuracy of the accompanying proxy statement/prospectus. Any representation to the contrary is a criminal offense.

 

 

The accompanying proxy statement/prospectus is dated             ,             and is first being mailed to Imara stockholders on or about             ,             .


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IMARA INC.

1309 Beacon Street, Suite 300, Office 341

Brookline, Massachusetts 02446

(617) 206-2020

NOTICE OF SPECIAL MEETING OF STOCKHOLDERS

To the stockholders of Imara Inc.:

NOTICE IS HEREBY GIVEN that a virtual special meeting of stockholders, or the Imara special meeting, will be held on                     , at                     Eastern Time, unless postponed or adjourned to a later date. The Imara special meeting will be held entirely online. You will be able to attend and participate in the Imara special meeting online by visiting http://www.                .com, where you will be able to listen to the meeting live, submit questions and vote.

The Imara special meeting will be held for the following purposes:

 

  1.

To approve the issuance of shares of common stock of Imara Inc., or Imara, pursuant to the terms of the Agreement and Plan of Merger, dated as of October 13, 2022 (as it may be amended from time to time), or the Merger Agreement, a copy of which is attached as Annex A to this proxy statement/prospectus, for purposes of Nasdaq Listing Rules 5635(a), (b) and (d);

 

  2.

To adopt and approve an amendment to the restated certificate of incorporation of Imara to increase the number of authorized shares of Imara common stock from 200,000,000 shares to 400,000,000 shares.

 

  3.

To adopt and approve an amendment to the restated certificate of incorporation of Imara to effect a reverse stock split of Imara common stock, by a ratio of not less than 1-for-                 and not more than 1-for-                , and a proportionate reduction in the number of authorized shares of Imara common stock, such ratio and the implementation and timing of the reverse stock split to be determined in the discretion of Imara’s board of directors;

 

  4.

To approve the adoption of the Imara Inc. Amended and Restated 2020 Equity Incentive Plan;

 

  5.

To approve an amendment to the Imara Inc. 2020 Employee Stock Purchase Plan, or the Imara 2020 ESPP, to increase the number of shares of common stock reserved for issuance under the Imara 2020 ESPP to 1,628,535 shares; and

 

  6.

To consider and vote upon an adjournment of the Imara special meeting, if necessary, to solicit additional proxies if there are not sufficient votes in favor of Proposal Nos. 1, 2, 3, 4 and 5.

 

Record Date:    Imara’s board of directors has fixed the close of business on                 as the record date for the determination of stockholders entitled to notice of, and to vote at, the Imara special meeting and any adjournment or postponement thereof. Only holders of record of shares of Imara common stock at the close of business on the record date are entitled to notice of, and to vote at, the Imara special meeting. At the close of business on the record date, Imara had                shares of common stock outstanding and entitled to vote.

Your vote is important. Assuming a quorum is present (i) the affirmative vote of the holders of a majority in voting power of the votes cast by the holders of all of the shares of Imara common stock present or represented at the meeting and voting affirmatively or negatively on such matter is required for approval of Proposal Nos. 1, 4, 5 and 6, and (ii) the affirmative vote of the holders of a majority of the outstanding shares of Imara common stock entitled to vote thereon is required for approval of Proposal Nos. 2 and 3. Approval of Proposal No. 1 is a condition to the completion of the Merger. Therefore, the Merger cannot be consummated without the approval of Proposal No. 1.

Even if you plan to virtually attend the Imara special meeting, Imara requests that you sign and return the enclosed proxy or submit a proxy to vote by mail or online to ensure that your shares will be represented at the Imara special meeting if you are unable to virtually attend. You may change or revoke your proxy at any time before it is voted at the Imara special meeting.


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IMARA’S BOARD OF DIRECTORS HAS DETERMINED AND BELIEVES THAT EACH OF THE PROPOSALS OUTLINED ABOVE IS FAIR TO, IN THE BEST INTERESTS OF, AND ADVISABLE TO IMARA AND ITS STOCKHOLDERS AND HAS APPROVED EACH SUCH PROPOSAL. IMARA’S BOARD OF DIRECTORS RECOMMENDS THAT IMARA STOCKHOLDERS VOTE “FOR” EACH SUCH PROPOSAL.

 

Important Notice Regarding the Availability of Proxy Materials for the Stockholders’ Meeting to             Be Held on                         at                         Eastern Time via the internet

 

The proxy statement/prospectus and annual report to stockholders are available at http://www.                 .com

 

By Order of Imara’s Board of Directors,

Rahul D. Ballal, Ph.D.

President and Chief Executive Officer

Boston, Massachusetts

                    , 2022


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REFERENCES TO ADDITIONAL INFORMATION

This proxy statement/prospectus incorporates important business and financial information about Imara that is not included in or delivered with this document. You may obtain this information without charge through the Securities and Exchange Commission website (www.sec.gov) or upon your written or oral request by contacting the Corporate Secretary of Imara Inc., 1309 Beacon Street, Suite 300, Office 341, Brookline, Massachusetts 02446, by calling (617) 206-2020 or via email to IR@imaratx.com.

To ensure timely delivery of these documents, any request should be made no later than                     to                     receive them before the Imara special meeting.

For additional details about where you can find information about Imara, please see the section titled “Where You Can Find More Information” beginning on page 425 of this proxy statement/prospectus.


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TABLE OF CONTENTS

 

QUESTIONS AND ANSWERS ABOUT THE MERGER

     1  

PROSPECTUS SUMMARY

     9  

The Companies

     9  

The Merger

     11  

Imara Reasons for the Merger

     13  

Enliven Reasons for the Merger

     13  

Recommendation of Imara Board of Directors

     14  

Opinion of Imara’s Financial Advisor

     14  

Overview of the Merger Agreement and Agreements Related to the Merger Agreement

     15  

Management Following the Merger

     19  

Interests of Certain Directors, Officers and Affiliates of Imara and Enliven

     19  

Material U.S. Federal Income Tax Consequences of the Merger

     21  

Material U.S. Federal Income Tax Consequences of Receipt of CVRs

     21  

Material U.S. Federal Income Tax Consequences of the Reverse Stock Split

     21  

Risk Factor Summary

     22  

Regulatory Approvals

     23  

Nasdaq Stock Market Listing

     23  

Anticipated Accounting Treatment

     24  

Appraisal Rights and Dissenters’ Rights

     24  

Comparison of Stockholder Rights

     24  

Market Price and Dividend Information

     25  

RISK FACTORS

     26  

Risks Related to the Strategic Transactions

     26  

Risks Related to Imara

     33  

Risks Related to Enliven

     82  

Risks Related to the Combined Company

     147  

CAUTIONARY STATEMENT CONCERNING FORWARD-LOOKING STATEMENTS AND MARKET AND INDUSTRY DATA

     157  

THE SPECIAL MEETING OF IMARA STOCKHOLDERS

     161  

Date, Time and Place

     161  

Purposes of the Imara Special Meeting

     161  

Recommendation of Imara’s Board of Directors

     161  

Record Date and Voting Power

     162  

Voting and Revocation of Proxies

     162  

Required Vote

     163  

Solicitation of Proxies

     164  

Other Matters

     164  

THE MERGER

     165  

Background of the Merger

     165  

Imara Reasons for the Merger

     172  

Enliven Reasons for the Merger

     175  

Opinion of Imara’s Financial Advisor

     177  

Interests of Imara Directors and Executive Officers in the Merger

     185  

Interests of Enliven Directors and Executive Officers in the Merger

     188  

Limitations of Liability and Indemnification

     189  

Form of the Merger

     190  

Merger Consideration

     190  

Fractional Shares

     190  

Exchange Ratio

     190  

Calculation of Imara’s Final Net Cash

     191  

Procedures for Exchanging Enliven Stock Certificates

     193  

Effective Time of the Merger

     193  


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Regulatory Approvals

     193  

Material U.S. Federal Income Tax Consequences of the Merger

     194  

Anticipated Accounting Treatment

     197  

Nasdaq Stock Market Listing

     197  

Appraisal Rights and Dissenters’ Rights

     198  

THE MERGER AGREEMENT

     202  

Structure

     202  

Completion and Effectiveness of the Merger

     202  

Treatment of Enliven Options

     202  

Treatment of Imara Common Stock and Imara Options

     203  

Directors and Officers of Imara Following the Merger

     203  

Amendment of the Restated Certificate of Incorporation of Imara

     203  

Representations and Warranties

     203  

Covenants; Conduct of Business Pending the Merger

     204  

Contingent Value Rights

     207  

Non-Solicitation

     208  

Board Recommendation Change

     209  

Meeting of Imara’s Stockholders and Written Consent of Enliven’s Stockholders

     210  

Indemnification and Insurance for Directors and Officers

     211  

Imara Financial Statements

     211  

Additional Agreements

     211  

Conditions to the Completion of the Merger

     212  

Termination and Termination Fees

     216  

Amendment

     218  

Fees and Expenses

     218  

AGREEMENTS RELATED TO THE MERGER

     219  

Support Agreements

     219  

Lock-Up Agreements

     220  

Enliven Common Stock Purchase Agreement

     220  

CVR Agreement

     222  

IMARA EXECUTIVE AND DIRECTOR COMPENSATION

     228  

Executive Compensation

     228  

Executive and Director Compensation Processes

     228  

Summary Compensation Table

     228  

Narrative to Summary Compensation Table

     229  

Outstanding Equity Awards at Fiscal Year-End

     230  

401(k) Plan

     232  

Limitation of Liability and Indemnification

     232  

Rule 10b5-1 Plans

     233  

Director Compensation

     233  

ENLIVEN EXECUTIVE COMPENSATION

     235  

Overview

     235  

2021 Compensation and Named Executive Officers

     235  

Summary Compensation Table

     236  

Outstanding Equity Awards at Fiscal 2021 Year-End

     236  

Additional Narrative Disclosure

     237  

401(k) Plan

     237  

Equity Compensation Plans

     237  

Director Compensation

     240  

MATTERS BEING SUBMITTED TO A VOTE OF IMARA STOCKHOLDERS

     242  

PROPOSAL NO. 1: APPROVAL OF THE ISSUANCE OF SHARES OF IMARA COMMON STOCK PURSUANT TO THE TERMS OF THE MERGER AGREEMENT FOR PURPOSES OF NASDAQ LISTING RULES 5635(a), (b) AND (d).

     242  


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PROPOSAL NO. 2: ADOPTION AND APPROVAL OF AN AMENDMENT TO THE RESTATED CERTIFICATE OF INCORPORATION OF IMARA TO INCREASE THE NUMBER OF AUTHORIZED SHARES OF IMARA COMMON STOCK

     244  

PROPOSAL NO. 3: ADOPTION AND APPROVAL OF AN AMENDMENT TO IMARA’S RESTATED CERTIFICATE OF INCORPORATION TO EFFECT A REVERSE STOCK SPLIT OF IMARA COMMON STOCK BY A RATIO OF NOT LESS THAN 1-FOR-                 AND NOT MORE THAN 1-FOR-                , AND A PROPORTIONATE REDUCTION IN THE NUMBER OF AUTHORIZED SHARES OF COMMON STOCK, SUCH RATIO AND THE IMPLEMENTATION AND TIMING OF THE REVERSE STOCK SPLIT TO BE DETERMINED IN THE DISCRETION OF IMARA’S BOARD OF DIRECTORS

     246  

PROPOSAL NO. 4: APPROVAL OF THE ADOPTION OF THE IMARA INC. AMENDED AND RESTATED2020 EQUITY INCENTIVE PLAN

     254  

PROPOSAL NO. 5: APPROVAL OF AN AMENDMENT TO THE IMARA INC. 2020 EMPLOYEE STOCK PURCHASE PLAN, OR THE IMARA 2020 ESPP, TO INCREASE THE NUMBER OF SHARES OF COMMON STOCK RESERVED FOR ISSUANCE UNDER THE IMARA 2020 ESPP TO 1,628,535 SHARES

     269  

PROPOSAL NO. 6: APPROVAL OF A POSSIBLE ADJOURNMENT OF THE SPECIAL MEETING

     274  

IMARA’S BUSINESS

     275  

Summary

     275  

Exploration of Strategic Options

     275  

Historical Business and Programs

     275  

Sales and Marketing

     276  

Research and Development

     277  

Intellectual Property

     277  

Government Regulation and Product Approvals

     279  

ENLIVEN’S BUSINESS

     280  

Overview

     280  

Our Pipeline

     282  

Our Strategy

     284  

Our Team and Investors

     286  

Our Development Approach

     287  

Background on Cancer and Targeted Therapies

     289  

Our Programs

     291  

BCR-ABL Program: ELVN-001

     291  

Our Solution—ELVN-001

     299  

HER2 Program

     306  

Additional Programs

     320  

Competition

     320  

Manufacturing

     322  

Intellectual Property

     322  

Government Regulations

     324  

Employees and Human Capital

     336  

Facilities

     336  

Legal Proceedings

     336  

IMARA MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

     337  

Business Overview

     337  

Asset Purchase Agreement

     338  

Merger Agreement

     338  

Financial Overview

     338  

Impact of COVID-19 Pandemic

     339  

Financial Operations Overview

     340  

Results of Operations

     342  

Liquidity and Capital Resources

     345  


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Critical Accounting Policies and Estimates

     349  

Recent Accounting Pronouncements

     350  

Emerging Growth Company Status

     350  

ENLIVEN MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

     351  

Overview

     351  

Recent Developments

     353  

Results of Operations

     354  

Results of Operations

     356  

Liquidity and Capital Resources

     358  

Off-Balance Sheet Arrangements

     362  

Critical Accounting Policies and Significant Judgments and Estimates

     362  

Recently Issued Accounting Pronouncements

     365  

Quantitative and Qualitative Disclosures About Market Risks

     366  

MANAGEMENT FOLLOWING THE MERGER

     367  

Executive Officers and Directors of the Combined Company Following the Merger

     367  

Election of Officers

     371  

Board of Directors of the Combined Company Following the Merger

     371  

Non-Employee Director Compensation

     373  

CERTAIN RELATIONSHIPS AND RELATED PARTY TRANSACTIONS OF THE COMBINED COMPANY

     375  

Enliven Transactions

     375  

Imara Transactions

     378  

SELECTED HISTORICAL AND UNAUDITED PRO FORMA CONDENSED COMBINED FINANCIAL INFORMATION

     383  

Selected Historical Consolidated Financial Data Of Imara

     383  

Selected Historical Condensed Financial Data of Enliven

     384  

Selected Unaudited Pro Forma Condensed Combined Financial Data of Imara and Enliven

     384  

Unaudited Pro Forma Combined Financial Information

     386  

NOTES TO UNAUDITED PRO FORMA CONDENSED COMBINED FINANCIAL INFORMATION

     392  

DESCRIPTION OF IMARA CAPITAL STOCK

     399  

General

     399  

Common Stock

     399  

Preferred Stock

     399  

Anti-Takeover Effects of Delaware Law and Imara’s Charter and Amended and Restated Bylaws

     399  

Authorized but Unissued Shares

     400  

COMPARISON OF RIGHTS OF HOLDERS OF IMARA CAPITAL STOCK AND ENLIVEN CAPITAL STOCK

     402  

PRINCIPAL STOCKHOLDERS OF IMARA

     415  

PRINCIPAL STOCKHOLDERS OF ENLIVEN

     418  

PRINCIPAL STOCKHOLDERS OF THE COMBINED COMPANY

     421  

LEGAL MATTERS

     424  

EXPERTS

     424  

WHERE YOU CAN FIND MORE INFORMATION

     425  

TRADEMARK NOTICE

     427  

OTHER MATTERS

     427  

FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA INDEX TO FINANCIAL STATEMENTS

     F-1  

Annex A—Agreement and Plan of Merger

     A-1  

Annex B—Opinion of Imara’s Financial Advisor

     B-1  

Annex C—Form of Contingent Value Rights Agreement

     C-1  

Annex D—Form of Imara Inc. Support Agreement

     D-1  

Annex E—Form of Enliven Therapeutics, Inc. Support Agreement

     E-1  

Annex F—Form of Lock-Up Agreement

     F-1  


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Annex G—Form of Certificate of Amendment for the Authorized Share Increase

     G-1  

Annex H—Form of Certificate of Amendment for the Reverse Stock Split

     H-1  

Annex I—Amended and Restated 2020 Equity Incentive Plan

     I-1  

Annex J—Amendment to 2020 Employee Stock Purchase Plan

     J-1  

PART II INFORMATION NOT REQUIRED IN PROXY STATEMENT/PROSPECTUS

     II-1  

Item 20. Indemnification of Directors and Officers

     II-1  

Item 21. Exhibits and Financial Statement Schedules

     II-3  

Item 22. Undertakings

     II-3  

EXHIBIT INDEX

     II-5  


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QUESTIONS AND ANSWERS ABOUT THE MERGER

Except where specifically noted, the following information and all other information contained in this proxy statement/prospectus does not give effect to the proposed reverse stock split described in Proposal No. 3 of this proxy statement/prospectus.

The following section provides answers to frequently asked questions about the Merger. This section, however, provides only summary information. For a more complete response to these questions and for additional information, please refer to the cross-referenced sections.

Q: What is the Merger?

A: Imara Inc., or Imara, and Enliven Therapeutics, Inc., or Enliven, have entered into an Agreement and Plan of Merger, as it may be amended from time to time, or the Merger Agreement, dated as of October 13, 2022, a copy of which is attached as Annex A to this proxy statement/prospectus. The Merger Agreement contains the terms and conditions of the proposed business combination of Imara and Enliven. Pursuant to the Merger Agreement, Iguana Merger Sub, Inc., or Merger Sub, a direct, wholly owned subsidiary of Imara, will merge with and into Enliven, with Enliven surviving as a wholly owned subsidiary of Imara. This transaction is referred to in this proxy statement/prospectus as the Merger. After the completion of the Merger, Imara will change its corporate name to “Enliven Therapeutics, Inc.” The combined company following the Merger is referred to herein as the combined company.

Immediately prior to the effective time of the Merger, each share of Enliven preferred stock will be converted into shares of Enliven common stock, and at the effective time of the Merger, each share of Enliven’s common stock will be converted into the right to receive a number of shares of Imara common stock equal to the exchange ratio described in more detail in the section titled “The Merger —Exchange Ratio” beginning on page 190 this proxy statement/prospectus.

In connection with the Merger, each stock option granted under Enliven’s 2019 Equity Incentive Plan, or the Enliven 2019 Plan, that is outstanding immediately prior to the effective time of the Merger will be assumed by Imara and will become an option to acquire, on the same terms and conditions as were applicable to such Enliven stock option immediately prior to the effective time of the Merger, a number of shares of Imara common stock equal to the number of shares of Enliven common stock subject to the unexercised portion of the Enliven stock option immediately prior to the effective time of the Merger, multiplied by the exchange ratio (rounded down to the nearest whole share number), with an exercise price per share for the options equal to the exercise price per share of such Enliven stock option immediately prior to the effective time of the Merger divided by the exchange ratio (rounded up to the nearest whole cent). Such assumed options will continue to be governed by the terms and conditions of the Enliven 2019 Plan.

Each share of Imara common stock and option to purchase Imara common stock that is issued and outstanding at the effective time of the Merger will remain issued and outstanding and such shares and options will be unaffected by the Merger. Immediately after the Merger, Imara securityholders as of immediately prior to the Merger are currently estimated to own approximately 15.9% of the outstanding shares of the combined company on a fully-diluted basis and former Enliven securityholders, including those purchasing shares in the Enliven pre-closing financing, are currently estimated to own approximately 84.1% of the outstanding shares of the combined company on a fully-diluted basis, subject to certain assumptions, including, but not limited to, (a) Imara’s net cash as of the closing being approximately $82 million, (b) Enliven raising approximately $164.5 million in the Enliven pre-closing financing described in the accompanying proxy statement/prospectus, (c) a valuation for Imara equal to its net cash as of the business day immediately prior to the closing date of the Merger, plus $10 million and (d) a valuation for Enliven equal to $324.6 million, plus the gross proceeds of the Enliven pre-closing financing, in each case as further described in the Merger Agreement.

 

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Q: Why are the two companies proposing to merge?

A: Imara and Enliven’s management believe that combining the two companies will result in a company with a robust pipeline, strong leadership team and substantial capital resources, positioning it to potentially become a leading company researching, developing and commercializing therapies for cancer. For a more complete description of the reasons for the Merger, please see the sections titled “The Merger—Imara Reasons for the Merger” and “The Merger—Enliven Reasons for the Merger” beginning on pages 172 and 175, respectively, of this proxy statement/prospectus.

Q: Why am I receiving this proxy statement/prospectus?

A: You are receiving this proxy statement/prospectus because you have been identified as a stockholder of Imara as of the record date, and you are entitled to vote at the Imara special meeting to approve the matters set forth herein. This document serves as:

 

   

a proxy statement of Imara used to solicit proxies for the Imara special meeting to vote on the matters set forth herein; and

 

   

a prospectus of Imara used to offer shares of Imara common stock in exchange for shares of Enliven common stock, including those shares of Enliven common stock to be issued upon conversion of Enliven’s preferred stock and the shares of Enliven common stock to be issued in the Enliven pre-closing financing immediately prior to the effective time of the Merger.

Q: What is the Enliven pre-closing financing?

A: On October 13, 2022, immediately prior to the execution and delivery of the Merger Agreement, Enliven entered into a common stock purchase agreement with certain investors, pursuant to which the investors agreed to purchase shares of Enliven’s common stock for a per share purchase price of $3.84098 and an aggregate purchase price of approximately $164.5 million. The closing of the Enliven pre-closing financing is conditioned upon the satisfaction or waiver of the conditions to the closing of the Merger as well as certain other conditions.

Q: What proposals will be voted on at the Imara special meeting the approval of which are conditions to the closing of the Merger?

A: Pursuant to the terms of the Merger Agreement, the following proposal must be approved by the requisite stockholder vote at the I

mara special meeting in order for the Merger to close:

 

   

Proposal No. 1, to approve the issuance of shares of common stock of Imara pursuant to the terms of the Merger Agreement (as it may be amended from time to time), a copy of which is attached as Annex A to the accompanying proxy statement/prospectus, for purposes of Nasdaq Listing Rules 5635(a), (b) and (d).

Approval of Proposal No. 1 is a condition to the completion of the Merger. Therefore, the Merger cannot be consummated without the approval of Proposal No. 1.

In addition to the requirement of obtaining Imara stockholder approval, each of the other closing conditions set forth in the Merger Agreement must be satisfied or waived. For a more complete description of the closing conditions under the Merger Agreement, please see the section titled “The Merger Agreement—Conditions to the Completion of the Merger” beginning on page 212 of this proxy statement/prospectus.

Q: What proposals are to be voted on at the Imara special meeting, other than Proposal No. 1?

A: At the Imara special meeting, the holders of Imara common stock will also be asked to consider the following proposals:

 

   

Proposal No. 2, to adopt and approve an amendment to the restated certificate of incorporation of Imara to increase the number of authorized shares of Imara common stock from 200,000,000 shares to 400,000,000 shares.

 

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Proposal No. 3, to adopt and approve an amendment to the restated certificate of incorporation of Imara to effect a reverse stock split of Imara common stock, by a ratio of not less than 1-for-                 and not more than 1-for-                , and a proportionate reduction in the number of authorized shares of Imara common stock, such ratio and the implementation and timing of the reverse stock split to be determined in the discretion of Imara’s board of directors;

 

   

Proposal No. 4, to approve the adoption of the Imara Inc. Amended and Restated 2020 Equity Incentive Plan;

 

   

Proposal No. 5, to approve an amendment to the Imara Inc. 2020 Employee Stock Purchase Plan, or the Imara 2020 ESPP, to increase the number of shares of common stock reserved for issuance under the Imara 2020 ESPP to 1,628,535 shares; and

 

   

Proposal No. 6, to consider and vote upon an adjournment of the Imara special meeting, if necessary, to solicit additional proxies if there are not sufficient votes in favor of Proposal Nos. 1, 2, 3, 4 and 5.

The approval of Proposal Nos. 2, 3, 4, 5 and 6 are not a condition to the Merger. Such proposals, together with Proposal No. 1, are referred to collectively in this proxy statement/prospectus as the proposals.

The presence, by attending online or being represented by proxy, at the Imara special meeting of the holders of a majority in voting power of the shares of Imara common stock outstanding and entitled to vote at the Imara special meeting is necessary to constitute a quorum at the meeting for the purpose of approving the proposals.

Q: What stockholder votes are required to approve the proposals at the Imara special meeting?

A: Assuming a quorum is present, the affirmative vote of the holders of a majority in voting power of the votes cast by the holders of all of the shares of Imara common stock present or represented at the meeting and voting affirmatively or negatively on such matter is required for approval of Proposal Nos. 1, 4, 5 and 6. Abstentions and broker non-votes, if any, will have no effect on Proposal Nos. 1, 4, 5 and 6.

Assuming a quorum is present, the affirmative vote of the holders of a majority of the outstanding shares of Imara common stock entitled to vote at the Imara special meeting is required for approval of Proposal Nos. 2 and 3. Abstentions and broker non-votes, if any, will have the same effect as “AGAINST” votes on Proposal Nos. 2 and 3.

As of October 13, 2022, the directors and certain executive officers of Imara owned or controlled approximately 35.1% of the outstanding shares of Imara common stock entitled to vote at the Imara special meeting. As of October 13, 2022, the Imara stockholders that are party to support agreements, including the directors and certain executive officers of Imara, owned an aggregate of 8,256,404 shares of Imara common stock representing approximately 33% of the outstanding shares of Imara common stock. Pursuant to the support agreements, these stockholders, including the directors and certain executive officers of Imara, have agreed to vote all shares of Imara common stock owned by them as of the record date in favor of Proposal Nos. 1, 3, 4 and 5.

Q: What will Enliven stockholders and option holders receive in the Merger?

A: Enliven stockholders will receive shares of Imara common stock, and Enliven option holders will receive options to purchase Imara common stock. Applying the exchange ratio, the former Enliven securityholders immediately before the Merger, including those purchasing shares in the Enliven pre-closing financing, are currently estimated to own approximately 84.1% of the aggregate number of shares of the combined company’s common stock following the Merger on a fully-diluted basis and Imara securityholders as of immediately prior to the Merger are currently estimated to own approximately 15.9% of the aggregate number of shares of the combined company common stock following the Merger on a fully-diluted basis, in each case subject to certain assumptions, including, but not limited to, (a) Imara’s net cash as of the closing being approximately $82 million, (b) Enliven raising approximately $164.5 million in the Enliven pre-closing financing described in this proxy statement/prospectus, (c) a valuation for Imara equal to its net cash as of the business day immediately prior to

 

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the closing date of the Merger, plus $10 million and (d) a valuation for Enliven equal to $324.6 million, plus the gross proceeds of the Enliven pre-closing financing, in each case as further described in the Merger Agreement.

In connection with the Merger, each stock option granted under the Enliven 2019 Plan that is outstanding immediately prior to the effective time of the Merger will be assumed by Imara and will become an option to acquire, on the same terms and conditions as were applicable to such Enliven stock option immediately prior to the effective time of the Merger, a number of shares of Imara common stock equal to the number of shares of Enliven common stock subject to the unexercised portion of the Enliven stock option immediately prior to the effective time of the Merger, multiplied by the exchange ratio (rounded down to the nearest whole share number), with an exercise price per share for the options equal to the exercise price per share of such Enliven stock option immediately prior to the effective time of the Merger divided by the exchange ratio (rounded up to the nearest whole cent). Such assumed options will continue to be governed by the terms and conditions of the Enliven 2019 Plan.

For a more complete description of what Enliven stockholders and option holders will receive in the Merger, please see the sections titled “The Merger—Merger Consideration” and “The Merger—Exchange Ratio” beginning on page 190, respectively, of this proxy statement/prospectus. For a description of the effect of the Enliven pre-closing financing on Imara’s and Enliven’s current securityholders, please see the section titled “Agreements Related to the Merger—Enliven Common Stock Purchase Agreement” beginning on page 220 of this proxy statement/prospectus.

Q: Will the common stock of the combined company trade on an exchange?

A: Shares of Imara common stock are currently listed on The Nasdaq Global Select Market under the symbol “IMRA.” Enliven has filed a listing application for the combined company with Nasdaq. After completion of the Merger, the combined company will be renamed “Enliven Therapeutics, Inc.” and it is expected that the common stock of the combined company will trade on The Nasdaq Stock Market under the symbol “ELVN.” On             ,2022, the last trading day before the date of this proxy statement/prospectus, the closing sale price of Imara common stock was $             per share.

Q: Who will be the directors of the combined company following the Merger?

A: Immediately following the Merger, the combined company’s board of directors will be composed of nine (9) members, consisting of (i) one director appointed by Imara, namely Rahul Ballal, and (ii) eight directors appointed by Enliven, namely Sam Kintz (who is Enliven’s President and Chief Executive Officer and will serve as President and Chief Executive Officer of the combined company), Andrew Phillips, Joseph Lyssikatos (who is Enliven’s Chief Scientific Officer and will serve as Chief Scientific Officer of the combined company), Rishi Gupta, Andrew Schwab, Mika Derynck, Jake Bauer, and Richard Heyman.

Q: Who will be the executive officers of the combined company immediately following the Merger?

A: Immediately following the Merger, the executive management team of the combined company is expected to consist of members of the Enliven executive management team prior to the Merger, including:

 

    Name    Title
               Sam Kintz, M.B.A.    President, Chief Executive Officer and Director
  Helen Collins, M.D.    Chief Medical Officer
  Benjamin Hohl    Chief Financial Officer
 

Joseph Lyssikatos, Ph.D.

Anish Patel, Pharm.D.

  

Chief Scientific Officer and Director

Chief Operating Officer

 

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Q: As an Imara stockholder, how does Imara’s board of directors recommend that I vote?

A: After careful consideration, Imara’s board of directors recommends that Imara stockholders vote “FOR” all of the proposals.

Q: What risks should I consider in deciding whether to vote in favor of the Merger?

A: You should carefully review the section titled “Risk Factors” beginning on page 26 of this proxy statement/prospectus and the annexes attached hereto and documents incorporated by reference herein, which set forth certain risks and uncertainties related to the Merger, risks and uncertainties to which the combined company’s business will be subject, and risks and uncertainties to which each of Imara and Enliven, as independent companies, are subject.

Q: When do you expect the Merger to be consummated?

A: The Merger is anticipated to close promptly after the Imara special meeting scheduled to be held on                     , but the exact timing cannot be predicted. For more information, please see the section titled “The Merger Agreement—Conditions to the Completion of the Merger” beginning on page 212 of this proxy statement/prospectus.

Q: What do I need to do now?

A: Imara urges you to read this proxy statement/prospectus carefully, including the annexes attached hereto and the documents incorporated by reference, and to consider how the Merger affects you.

If you are an Imara stockholder of record, you may vote or provide your proxy instructions in one of four different ways:

 

   

You can attend the Imara special meeting online and vote online during the special meeting.

 

   

You can mail your signed proxy card in the enclosed return envelope.

 

   

You can provide your proxy instructions via telephone by following the instructions on your proxy card.

 

   

You can provide your proxy instructions via the internet by following the instructions on your proxy card.

Your signed proxy card, telephonic proxy instructions, or internet proxy instructions must be received by                     to be counted.

If you hold your shares in “street name” (as described below), you may provide your proxy instructions via telephone or the internet by following the instructions on your vote instruction form. Please provide your proxy instructions only once, unless you are revoking a previously delivered proxy instruction, and as soon as possible so that your shares can be voted at the Imara special meeting.

Q: What happens if I do not return a proxy card or otherwise vote or provide proxy instructions, as applicable?

A: If you are an Imara stockholder, the failure to return your proxy card or otherwise vote or provide proxy instructions will reduce the aggregate number of votes required to approve Proposal Nos. 1, 4, 5 and 6. Also, your shares will not be counted for purposes of determining whether a quorum is present at the Imara special meeting unless your broker has, and exercises, discretionary authority to vote on certain matters.

 

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Q: May I attend the Imara special meeting and vote in person?

A: The Imara special meeting will be held entirely online. Stockholders of record as of the close of business on         will be able to attend and participate in the Imara special meeting online by accessing www.                     .com. To join the Imara special meeting, you will need to have your 16-digit control number which is included on your Notice of Internet Availability of Proxy Materials and your proxy card. If your shares are held in “street name,” you should contact your bank, broker or other nominee to obtain your 16-digit control number or otherwise vote through your bank, broker or other nominee.

Q: Who counts the votes?

A: Mediant Communications Inc., or Mediant, will be engaged as Imara’s independent agent to tabulate stockholder votes, which Imara refers to as the inspector of election. If you are a stockholder of record, your executed proxy card is returned directly to Mediant for tabulation.

Q: If my Imara shares are held in “street name” by my broker, will my broker vote my shares for me?

A: Unless your broker has discretionary authority to vote on certain matters, your broker will not be able to vote your shares of Imara common stock on matters requiring discretionary authority without instructions from you. If you do not give instructions to your broker, your broker can vote your Imara shares with respect to “discretionary,” routine items but not with respect to “non-discretionary,” non-routine items. Discretionary items are proposals considered routine under Rule 452 of the New York Stock Exchange on which your broker may vote shares held in “street name” in the absence of your voting instructions. With respect to non-routine items for which you do not give your broker instructions, your Imara shares will be treated as broker non-votes. Proposal Nos. 1, 4 and 5 at the Imara special meeting will be non-routine. It is anticipated that Proposal Nos. 2, 3 and 6 will be routine. To make sure that your vote is counted, you should instruct your broker to vote your shares, following the procedures provided by your broker.

Q: What are broker non-votes and do they count for determining a quorum?

A: Generally, broker non-votes occur when there is at least one discretionary and one non-discretionary proposal to be voted on at the meeting and shares held by a broker in “street name” for a beneficial owner are voted on at least one “routine” proposal but not voted with respect to a particular proposal because the broker (i) has not received voting instructions from the beneficial owner for that proposal or (ii) lacks discretionary voting power to vote those shares for that proposal. A broker is entitled to vote shares held for a beneficial owner on routine matters without instructions from the beneficial owner of those shares. On the other hand, absent instructions from the beneficial owner of such shares, a broker is not entitled to vote shares held for a beneficial owner on non-routine matters.

Broker non-votes, if any, will be treated as shares present for the purpose of determining the presence of a quorum for the transaction of business at the Imara special meeting. Broker non-votes will not be treated as votes cast for or against a proposal and accordingly will not have any effect with respect to the outcome of Proposal Nos. 1, 4, 5 and 6, and will have the same effect as “AGAINST” votes for Proposal Nos. 2 and 3.

Q: May I change my vote after I have submitted a proxy or provided proxy instructions?

A: Imara stockholders of record, unless such stockholder’s vote is subject to a support agreement, may change their vote at any time before their proxy is voted at the Imara special meeting in one of four ways:

 

   

You may submit another properly completed proxy with a later date by mail or via the internet.

 

   

You can provide your proxy instructions via telephone at a later date.

 

   

You may send a written notice that you are revoking your proxy to Imara’s Corporate Secretary at info@imaratx.com.

 

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You may attend the Imara special meeting online and vote by following the instructions at www.                    .com. Simply attending the Imara special meeting will not, by itself, revoke your proxy.

Your signed proxy card, telephonic proxy instructions, internet proxy instructions, or written notice must be received by                     to be counted.

If an Imara stockholder who owns Imara shares in “street name” has instructed a broker to vote its shares of Imara common stock, the stockholder must follow directions received from its broker to change those instructions.

Q: Who is paying for this proxy solicitation?

A: Imara and Enliven will share equally the cost of printing and filing of this proxy statement/prospectus and the proxy card. Arrangements will also be made with brokerage firms and other custodians, nominees and fiduciaries who are record holders of Imara common stock for the forwarding of solicitation materials to the beneficial owners of Imara common stock. Imara will reimburse these brokers, custodians, nominees and fiduciaries for the reasonable out-of-pocket expenses they incur in connection with the forwarding of solicitation materials. Imara will retain Morrow Soldali to assist it in soliciting proxies using the means referred to above. Imara will pay the fees of Morrow Soldali, which Imara expects to be approximately $13,500, plus reimbursement of out-of-pocket expenses.

Q: What are the material U.S. federal income tax consequences of the Merger to Imara stockholders?

A: Imara stockholders will not sell, exchange or dispose of any shares of Imara common stock in the Merger. Thus, there will be no material U.S. federal income tax consequences to Imara stockholders upon consummation of the Merger.

Q: What are the material U.S. federal income tax consequences of the Merger to Enliven U.S. holders?

A: Imara and Enliven intend the Merger to qualify as a “reorganization” within the meaning of Section 368(a) of the Internal Revenue Code of 1986, as amended, or the Code, and in the event that former Enliven stockholders, including stockholders that participate in the Enliven pre-closing financing, are in “control” of Imara immediately after the effective time of the Merger (within the meaning of Section 368(c) of the Code), Imara and Enliven also intend the Merger to qualify as a non-taxable exchange of shares of Enliven common stock for shares of Imara common stock within the meaning of Section 351(a) of the Code. Assuming the Merger qualifies for the intended tax treatment, subject to the limitations and qualifications described in the section titled “The Merger—Material U.S. Federal Income Tax Consequences of the Merger,” an Enliven U.S. holder (as defined on page 195) will not recognize gain or loss for U.S. federal income tax purposes upon the receipt of shares of Imara common stock in exchange for shares of Enliven common stock in the Merger, except with respect to cash received in lieu of a fractional share of Imara common stock. For a more detailed discussion of the material U.S. federal income tax consequences of the Merger, see “The Merger—Material U.S. Federal Income Tax Consequences of the Merger” beginning on page 194 of this proxy statement/prospectus.

Q: What are the material U.S. federal income tax consequences of the receipt of contingent value rights, or CVRs, to Imara stockholders?

A: The U.S. federal income tax treatment of Imara stockholders’ receipt of the contingent value rights, or CVRs, is unclear. Imara will report the issuance of the CVRs to Imara stockholders as a distribution of property with respect to Imara common stock. Assuming such treatment, each Imara stockholder will be treated as receiving a distribution in an amount equal to the fair market value of the CVRs issued to such Imara stockholder on the date of the issuance. This distribution should be treated first as a taxable dividend to the extent of the Imara stockholder’s pro rata share of Imara’s current or accumulated earnings and profits for the year of issuance (as determined for U.S. federal income tax purposes), then as a non-taxable return of capital to the extent of the

 

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Imara stockholder’s basis in its Imara common stock, and finally as capital gain from the sale or exchange of Imara common stock with respect to any remaining value. Imara has no accumulated earnings and profits and expects to have no current earnings and profits for the relevant taxable year. Thus, Imara expects this distribution to be treated as a non-dividend distribution for U.S. federal income tax purposes. See the section titled “Agreements Related to the Merger—CVR Agreement—Material U.S. Federal Income Tax Consequences of the Receipt of CVRs” beginning on page 223 of this proxy statement/prospectus for a more complete description of the material U.S. federal income tax consequences of the receipt of CVRs to Imara stockholders, including possible alternative treatments.

Q: What are the material U.S. federal income tax consequences of the proposed reverse stock split to Imara U.S. holders?

A: Imara intends the proposed reverse stock split to qualify as a “recapitalization” within the meaning of Section 368(a)(1)(E) of the Code. Assuming such treatment, an Imara U.S. holder (as defined on page 224) should not recognize gain or loss upon the proposed reverse stock split, except to the extent an Imara U.S. holder receives cash in lieu of a fractional share of Imara common stock. See the section titled “Proposal No. 3 — Material U.S. Federal Income Tax Consequences of the Reverse Stock Split” beginning on page 251 of this proxy statement/prospectus for a more complete description of the material U.S. federal income tax consequences of the proposed reverse stock split to Imara U.S. holders.

Q: Who can help answer my questions?

A: If you are an Imara stockholder and would like additional copies of this proxy statement/prospectus without charge or if you have questions about the Merger, including the procedures for voting your shares, you should contact:

Morrow Sodali

509 Madison Avenue, Suite 1206

New York, NY 10022

Email: IMRA@info.morrowsodali.com

 

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PROSPECTUS SUMMARY

This summary highlights selected information from this proxy statement/prospectus and may not contain all of the information that is important to you. To better understand the Merger and the proposals being considered at the Imara special meeting, you should read this entire proxy statement/prospectus carefully, including the Merger Agreement and the other annexes to which you are referred in this proxy statement/prospectus and the documents incorporated by reference herein. For more information, please see the section titled Where You Can Find More Information beginning on page 425 of this proxy statement/prospectus. Except where specifically noted, the following information and all other information contained in this proxy statement/prospectus does not give effect to the proposed reverse stock split of Imara’s common stock described in Proposal No. 3 of this proxy statement/prospectus.

The Companies

Imara Inc.

1309 Beacon Street, Suite 300, Office 341

Brookline, Massachusetts, 02446

Telephone: (617) 206-2020

Imara is a biopharmaceutical company that has been dedicated to developing and commercializing novel therapeutics to treat patients suffering from serious diseases.

On April 5, 2022, Imara announced the results from interim analyses of its Ardent Phase 2b clinical trial of tovinontrine (IMR-687) in patients with sickle cell disease, SCD, and Forte Phase 2b clinical trial of tovinontrine in patients with ß-thalassemia. Based on the data generated by these interim analyses, Imara decided to discontinue the Ardent and Forte trials as well as the further development of tovinontrine in SCD and ß-thalassemia. Imara also decided to discontinue development of tovinontrine in heart failure with preserved ejection fraction, as well as its development plans with respect to IMR-261. In connection with these events, Imara’s board of directors approved a reduction of Imara’s workforce by approximately 83% across all areas of Imara, to a total of six remaining full-time employees. The workforce reduction was designed to substantially reduce Imara’s operating expenses while Imara undertook a comprehensive assessment of its strategic options to maximize stockholder value.

Following an extensive process of evaluating strategic alternatives, including identifying and reviewing potential candidates for a strategic acquisition or other transaction, Imara entered into an Asset Purchase Agreement, dated as of September 6, 2022, or the Asset Purchase Agreement, with Cardurion Pharmaceuticals, Inc., or Cardurion, providing for the sale of tovinontrine (IMR-687) and all other assets of Imara’s related to its PDE9 program, or the Asset Sale. On October 13, 2022, Imara, Merger Sub and Enliven entered into the Merger Agreement, pursuant to which, among other things, and subject to the satisfaction or waiver of the conditions set forth in the Merger Agreement, Merger Sub will merge with and into Enliven, with Enliven continuing as our wholly owned subsidiary and the surviving corporation of the Merger. If the Merger is completed, the business of Enliven will continue as the business of the combined company.

Enliven Therapeutics, Inc.

6200 Lookout Road

Boulder, CO 80301

Telephone: (720) 647-8519

 

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Enliven is a clinical-stage biopharmaceutical company focused on the discovery and development of small molecule inhibitors to help patients with cancer live not only longer, but better. Enliven aims to address existing and emerging unmet needs with a precision oncology approach that improves survival and enhances overall patient well-being. Enliven’s discovery process combines deep insights from clinically validated biological targets and differentiated chemistry with the goal of designing best-in-class or first-in-class therapies. By combining clinically validated targets and specific target product profiles, or TPPs, with disciplined clinical trial design and regulatory strategy, Enliven aims to develop drugs with an increased probability of clinical and commercial success. Clinically validated targets refers to biological targets that have demonstrated statistical significance on efficacy endpoints in published third-party clinical trials which Enliven believes supports the development of its product candidates by increasing its probability of success. Enliven has assembled a team of seasoned drug hunters with significant expertise in discovery and development of small molecule kinase inhibitors. Enliven’s team includes leading chemists who have been the primary or co-inventor of over 20 product candidates that have been advanced to clinical trials, including four FDA-approved products: Koselugo (selumetinib), Mektovi (binimetinib), Tukysa (tucatinib), and Retevmo (selpercatinib). Enliven is currently advancing two parallel lead product candidates, ELVN-001 and ELVN-002, as well as pursuing several additional research stage opportunities that align with its development approach.

Enliven’s first product candidate, ELVN-001, is a potent, highly selective, small molecule kinase inhibitor designed to specifically target the BCR-ABL gene fusion, the oncogenic driver for patients with Chronic Myeloid Leukemia (CML). Although the approval of BCR-ABL TKIs has improved the life expectancy of patients with CML significantly, tolerability, safety, resistance and patient convenience concerns have become more prominent as patients can now expect to live on therapy for decades. Achieving this survival benefit requires continuous daily therapy, and all available TKIs have off-target activity resulting in treatment related adverse events and drug discontinuation due to intolerance or resistance. These issues can result in the loss of molecular response and disease progression for many patients and drive approximately 20% of patients to switch therapy within the first year and approximately 40% to switch in the first 5 years. These factors, prolonged treatment course, off-target toxicities, and acquired resistance, explain why the global market for CML supports multiple blockbuster products, exceeding $6.0 billion of sales in 2021, and why there remains significant unmet need for an effective and more tolerable treatment. In Enliven’s preclinical studies, ELVN-001 has demonstrated improved kinome selectivity, tolerability and robust tumor growth inhibition when compared to certain leading and investigational therapies. In addition, ELVN-001 was highly active against the T315I mutation, which confers resistance to nearly all approved TKIs. Given ELVN-001’s mechanism of action, it potentially represents a complementary option to allosteric BCRABL inhibitors, which may play an increasingly important role in the standard of care for CML. Importantly, ELVN-001 was designed to be a more attractive option for patients with comorbidities, on concomitant medications or desiring more freedom from stringent administration requirements. ELVN-001 is currently being evaluated in a Phase 1 clinical trial in adults with CML and Enliven plans to present early clinical data by the end of 2023.

Enliven’s second product candidate, ELVN-002, is a potent, selective and irreversible HER2 inhibitor with activity against various HER2 mutations, including Exon 20 insertion mutations (E20IMs) in non-small cell lung cancer (NSCLC). While up to 3% of patients with NSCLC harbor HER2 E20IMs, currently there are no FDA-approved small molecules that specifically address these mutations. The current investigational TKIs targeting this population that have reported clinical data are all dual EGFR and HER2 inhibitors, and are dose limited by EGFR-related toxicities. ELVN-002 is designed to inhibit HER2 and key mutations of HER2, while sparing wild-type EGFR and avoiding EGFR-related toxicities. Enliven believes that if ELVN-002 achieves this profile, it will be able to achieve an improved therapeutic index compared to current approved and investigational TKIs as well as provide a meaningful therapeutic option to patients with brain metastases, a key mechanism of resistance to current therapies in patients with NSCLC and other HER2 driven diseases. While the initial focus for this program is for HER2 mutant NSCLC, Enliven intends to expand the opportunity to patients with other HER2 mutations as well as HER2 amplified or overexpressing tumors including breast, colorectal, and gastric

 

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cancers. ELVN-002 has demonstrated robust activity in preclinical models, including an intracranial model, at well-tolerated doses. Enliven filed an IND with the FDA for ELVN-002 in the fourth quarter of 2022, and, subject to IND clearance, it plans to initiate a Phase 1 clinical trial thereafter.

Over the last several years, it has become increasingly clear that cancers developing in various sites throughout the body often share the same genomic alterations. More specifically, research and clinical data suggest that some tumors are primarily or exclusively dependent on aberrantly activated enzymes, including kinases for their proliferation and survival. Kinases are cellular enzymes that regulate the biological activity of proteins through a process known as phosphorylation and represent one of the largest classes of oncogenic drivers when aberrantly mutated or expressed in the cell. Kinase inhibition is a proven approach to fighting cancer and for nearly two decades has effectively addressed an increasing number of oncology indications, which translated into $69 billion of worldwide sales in 2021 and is estimated to grow to more than $107 billion by 2028. However, despite the advancement of precision medicine in oncology, a significant unmet need remains for the majority of cancer patients for whom no targeted therapies exist or whose cancer has developed resistance to currently available targeted treatments.

Enliven believes that the fundamental change in the development of targeted kinase inhibitor therapies in unison with its development approach, rooted in validated biology and differentiated chemistry, represents a unique opportunity to provide cancer patients with medicines offering improved therapeutic profiles. To capitalize on this opportunity, Enliven is currently pursuing several additional research stage programs. Enliven is in the process of screening and optimizing the chemistry for multiple programs and expects to make a product candidate nomination for its third program by the first half of 2023.

Enliven’s Pipeline

Enliven is focused on the discovery and development of potentially best-in-class or first-in-class precision oncology therapies. Enliven aims to do this by addressing issues such as tolerability and combinability, resistance, and disease escape through brain metastases. Enliven is currently advancing two parallel lead product candidates, ELVN-001 and ELVN-002.

 

LOGO

Iguana Merger Sub, Inc.

c/o Imara Inc.

1309 Beacon Street, Suite 300, Office 341

Brookline, Massachusetts 02446

Telephone: (617) 206-2020

Merger Sub is a direct, wholly owned subsidiary of Imara and was formed solely for the purpose of carrying out the Merger.

The Merger (see page 165)

If the Merger is completed Merger Sub will merge with and into Enliven, with Enliven surviving the Merger as a wholly owned subsidiary of Imara.

 

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Subject to the terms and conditions of the Merger Agreement, at the closing of the Merger, each then outstanding share of Enliven common stock (including shares of Enliven common stock to be issued upon conversion of Enliven preferred stock and shares of Enliven common stock to be issued in the Enliven pre-closing financing transaction described below) will be converted into the right to receive a number of shares of Imara common stock (subject to the payment of cash in lieu of fractional shares and after giving effect to a reverse stock split of Imara common stock described below) calculated in accordance with the exchange ratio set forth in the Merger Agreement. Based on Imara’s and Enliven’s capitalization as of October 13, 2022, the date the Merger Agreement was executed, the exchange ratio is estimated to be equal to approximately 1.1580 shares of Imara common stock for each share of Enliven capital stock, which exchange ratio does not give effect to the expected reverse stock split of Imara common stock. The final exchange ratio is subject to adjustment prior to closing of the Merger based upon Imara’s net cash at closing and the aggregate proceeds from the sale of Enliven common stock in the Enliven pre-closing financing.

Additionally, subject to the terms and conditions of the Merger Agreement, at the effective time of the Merger, each stock option granted under the Enliven 2019 Plan that is outstanding immediately prior to the effective time of the Merger will be assumed by Imara and will become an option to acquire, on the same terms and conditions as were applicable to such Enliven stock option immediately prior to the effective time of the Merger, a number of shares of Imara common stock equal to the number of shares of Enliven common stock subject to the unexercised portion of the Enliven stock option immediately prior to the effective time of the Merger, multiplied by the exchange ratio (rounded down to the nearest whole share number), with an exercise price per share for the options equal to the exercise price per share of such Enliven stock option immediately prior to the effective time of the Merger divided by the exchange ratio (rounded up to the nearest whole cent). Such assumed options will continue to be governed by the terms and conditions of the Enliven 2019 Plan.

Under the exchange ratio formula in the Merger Agreement, upon the closing of the Merger, on a pro forma basis and based upon the number of shares of Imara common stock expected to be issued in the Merger, Imara securityholders as of immediately prior to the Merger are currently estimated to own approximately 15.9% of the combined company on a fully-diluted basis and former Enliven stockholders, including those purchasing shares in the Enliven pre-closing financing) are currently estimated own approximately 84.1% of the combined company on a fully-diluted basis, in each case subject to certain assumptions, including, but not limited to, (a) Imara’s net cash as of the closing being approximately $82 million, (b) Enliven raising approximately $164.5 million in the Enliven pre-closing financing described in this proxy statement/prospectus, (c) a valuation for Imara equal to its net cash as of the business day immediately prior to the closing date of the Merger, plus $10 million and (d) a valuation for Enliven equal to $324.6 million, plus the gross proceeds of the Enliven pre-closing financing, in each case as further described in the Merger Agreement. For purposes of calculating the exchange ratio, shares of Imara common stock underlying Imara stock options outstanding as of immediately prior to the closing of the Merger with an exercise price of less than $10.00 per share will be deemed to be outstanding and all shares of Enliven common stock underlying outstanding Enliven stock options and other derivative securities will be deemed to be outstanding. The provisions for calculating the exchange ratio assume a valuation for Enliven equal to $324.6 million, plus the gross proceeds of the Enliven pre-closing financing, and a valuation for Imara equal to its net cash as of the business day immediately prior to the closing date of the Merger, plus $10 million, in each case as further described in the Merger Agreement.

Each share of Imara common stock issued and outstanding at the time of the Merger will remain issued and outstanding and such shares will be appropriately adjusted to reflect the proposed reverse stock split. In addition, each option to purchase shares of Imara common stock that is outstanding immediately prior to the effective time of the Merger, whether vested or unvested, will survive the closing and remain outstanding in accordance with its terms. The number of shares of Imara common stock underlying such options, and the exercise prices for such stock options will be appropriately adjusted to reflect the proposed reverse stock split.

For a more complete description of the Merger and the exchange ratio please see the section titled “The Merger” beginning on page 165 in this proxy statement/prospectus.

 

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The Merger will be completed as promptly as practicable after all of the conditions to completion of the Merger are satisfied or waived, including the adoption of the Merger Agreement by the Enliven stockholders and the approval by the Imara stockholders of the issuance of Imara common stock pursuant to the terms of the Merger Agreement. Imara and Enliven are working to complete the Merger as quickly as practicable. The Merger is anticipated to close promptly after the Imara special meeting scheduled to be held on                     . However, Imara and Enliven cannot predict the exact timing of the completion of the Merger because it is subject to the satisfaction of various conditions. After completion of the Merger, assuming that Imara receives the required stockholder approval, Imara will be renamed “Enliven Therapeutics, Inc.”

Imara Reasons for the Merger (see page 172)

During the course of its evaluation of the Merger Agreement and the transactions contemplated by the Merger Agreement, Imara’s board of directors held numerous meetings, consulted with Imara’s senior management, legal counsel and financial advisor, and reviewed and assessed a significant amount of information. In reaching its decision to approve the Merger Agreement and the transactions contemplated by the Merger Agreement, Imara’s board of directors considered a number of factors that it viewed as supporting its decision to approve the Merger Agreement. Several factors considered by the Imara board of directors included:

 

   

the financial condition and prospects of Imara and the risks associated with continuing to operate Imara on a stand-alone basis, particularly in light of Imara’s April 2022 decision to not proceed with development of tovinontrine in HFpEF and reduce its workforce;

 

   

that Imara’s board of directors and its financial advisor undertook a comprehensive and thorough process of reviewing and analyzing potential strategic alternatives and merger partner candidates to identify the opportunity that would, in the view of Imara’s board of directors, create the most value for Imara stockholders; and

 

   

Imara’s board of directors’ belief, after a thorough review of strategic alternatives and discussions with Imara’s senior management, financial advisors and legal counsel, that the Merger is more favorable to Imara stockholders than the potential value that might have resulted from other strategic alternatives available to Imara, including continuing to operate Imara on a stand-alone basis or conducting a dissolution and liquidation of Imara and distributing any available cash to its stockholders.

For additional information, please see the section titled “The Merger—Imara Reasons for the Merger” beginning on page 172 of this proxy statement/prospectus.

Enliven Reasons for the Merger (see page 175)

The Enliven board of directors has unanimously approved the Merger Agreement, the Merger and the transactions contemplated thereby. The Enliven board of directors reviewed several factors in reaching its decision and believes that the Merger Agreement, the Merger and the transactions contemplated thereby are advisable and fair to, and in the best interests of Enliven and its stockholders. Several factors considered by the Enliven board of directors included:

 

   

the Merger will provide Enliven’s current stockholders with greater liquidity by owning publicly-traded stock, and expanding both the access to capital for Enliven and the range of investors potentially available as a public company, compared to the investors Enliven could otherwise gain access to if it continued to operate as a privately-held company;

 

   

the belief of the Enliven board of directors that this transaction provides a viable alternate public listing strategy, and addresses the risk of the lack of an available market for an initial public offering at a later date; and

 

   

the expected cash resources of the combined company (including the ability to support the combined company’s current and planned clinical trials and operations).

 

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For additional information, please see the section titled “The Merger—Enliven Reasons for the Merger” beginning on page 175 of this proxy statement/prospectus.

Recommendation of Imara’s Board of Directors (see page 161)

 

   

Imara’s board of directors has determined and believes that it is fair to, in the best interests of, and advisable to, Imara and its stockholders to approve the issuance of shares of common stock of Imara pursuant to the terms of the Merger Agreement (as it may be amended from time to time) for purposes of Nasdaq Listing Rules 5635(a), (b) and (d), as described in this proxy statement/prospectus. Imara’s board of directors recommends that Imara stockholders vote “FOR” Proposal No. 1.

 

   

Imara’s board of directors has determined and believes that it is fair to, in the best interests of, and advisable to, Imara and its stockholders to adopt and approve an amendment to the restated certificate of incorporation of Imara to increase the number of authorized shares of Imara common stock from 200,000,000 shares to 400,000,000 shares. Imara’s board of directors recommends that Imara stockholders vote “FOR” Proposal No. 2.

 

   

Imara’s board of directors has determined and believes that it is fair to, in the best interests of, and advisable to, Imara and its stockholders to adopt and approve an amendment to the restated certificate of incorporation of Imara to effect a reverse stock split of Imara common stock and a proportionate reduction in the number of authorized shares of Imara common stock, such ratio and the implementation and timing of the reverse stock split to be determined in the discretion of Imara’s board of directors, as described in this proxy statement/prospectus. Imara’s board of directors recommends that Imara stockholders vote “FOR” Proposal No. 3.

 

   

Imara’s board of directors has determined and believes that it is fair to, in the best interests of, and advisable to, Imara and its stockholders to approve the adoption of the Imara Inc. Amended and Restated 2020 Equity Incentive Plan, as described in this proxy statement/prospectus. Imara’s board of directors recommends that Imara stockholders vote “FOR” Proposal No. 4.

 

   

Imara’s board of directors has determined and believes that it is fair to, in the best interests of, and advisable to, Imara and its stockholders to approve an amendment to the Imara 2020 ESPP to increase the number of shares of common stock reserved for issuance under the Imara 2020 ESPP to 1,628,535 shares, as described in this proxy statement/prospectus. Imara’s board of directors recommends that Imara stockholders vote “FOR” Proposal No. 5.

 

   

Imara’s board of directors has determined and believes that it is fair to, in the best interests of, and advisable to, Imara and its stockholders to approve the adjournment of the Imara special meeting, if necessary, to solicit additional proxies if there are not sufficient votes in favor of Proposal Nos. 1, 2, 3, 4 and 5. Imara’s board of directors recommends that Imara stockholders vote “FOR” Proposal No. 6.

Opinion of Imara’s Financial Advisor (see page 177)

Imara retained SVB Securities LLC, or SVB Securities, as its financial advisor in connection with the Merger and the other transactions contemplated by the Merger Agreement. Imara’s board of directors selected SVB Securities to act as Imara’s financial advisor based on SVB Securities’ qualifications, reputation, experience and expertise in the biopharmaceuticals industry, its knowledge of and involvement in recent transactions in the biopharmaceutical industry, and its relationship and familiarity with Imara and its business. SVB Securities is an internationally recognized investment banking firm that has substantial experience in transactions similar to this transaction.

In connection with this engagement, Imara requested that SVB Securities evaluate the fairness, from a financial point of view, to Imara of the exchange ratio to be paid by Imara pursuant to the terms of the Merger Agreement. On October 13, 2022, at a meeting of Imara’s board of directors, SVB Securities rendered to Imara’s board of

 

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directors its oral opinion, which was subsequently confirmed by delivery of a written opinion dated October 13, 2022, that, as of such date and based upon and subject to the various assumptions made, and the qualifications and limitations upon the review undertaken by SVB Securities in preparing its opinion, the exchange ratio to be paid by Imara pursuant to the terms of the Merger Agreement was fair, from a financial point of view, to Imara.

The full text of SVB Securities’ written opinion, which describes the assumptions made, and the qualifications and limitations upon the review undertaken by SVB Securities in preparing its opinion, is attached to this proxy statement/prospectus as Annex B and is incorporated by reference in its entirety to this proxy statement/prospectus.

SVB Securities’ financial advisory services and opinion were provided for the information and assistance of the members of Imara’s board of directors (in their capacity as directors and not in any other capacity) in connection with and for purposes of Imara’s board of directors’ consideration of the Merger and the other transactions contemplated by the Merger Agreement and SVB Securities’ opinion addressed only the fairness, from a financial point of view, as of the date thereof, to Imara of the exchange ratio to be paid by Imara pursuant to the terms of the Merger Agreement. SVB Securities’ opinion did not address any other term or aspect of the Merger Agreement or the transactions contemplated thereby and does not constitute a recommendation to any stockholder of Imara as to whether or how such holder should vote with respect to the Merger or otherwise act with respect to the Merger or the other transactions contemplated by the Merger Agreement or any other matter.

The full text of SVB Securities’ written opinion should be read carefully in its entirety for a description of the assumptions made and the qualifications and limitations upon the review undertaken by SVB Securities in preparing its opinion.

Overview of the Merger Agreement and Agreements Related to the Merger Agreement (see page 202)

Merger Consideration (see page 190)

At the effective time of the Merger, upon the terms and subject to the conditions set forth in the Merger Agreement each outstanding share of Enliven common stock (after giving effect to the conversion of all shares of Enliven preferred stock and including the shares of Enliven common stock to be issued in the Enliven pre-closing financing, but excluding shares to be canceled pursuant to the Merger Agreement and excluding dissenting shares) will be automatically converted solely into the right to receive a number of shares of Imara common stock equal to the exchange ratio described in more detail below.

Immediately after the Merger, Imara securityholders as of immediately prior to the Merger are currently estimated to own approximately 15.9% of the outstanding shares of common stock of the combined company on a fully-diluted basis, subject to certain assumptions, including, but not limited to, (a) Imara’s net cash as of the closing being approximately $82 million, (b) Enliven raising approximately $164.5 million in the Enliven pre-closing financing described in this proxy statement/prospectus, (c) a valuation for Imara equal to its net cash as of the business day immediately prior to the closing date of the Merger, plus $10 million and (d) a valuation for Enliven equal to $324.6 million, plus the gross proceeds of the Enliven pre-closing financing, in each case as further described in the Merger Agreement. For information on the impact of the Enliven pre-closing financing, please see the section titled “Agreements Related to the Merger—Enliven Common Stock Purchase Agreement” beginning on page 220 of this proxy statement/prospectus.

Treatment of Enliven Options (see page 202)

Under the terms of the Merger Agreement, each stock option granted under the Enliven 2019 Plan that is outstanding immediately prior to the effective time of the Merger will be assumed by Imara and will become an option to acquire, on the same terms and conditions as were applicable to such Enliven stock option immediately prior to the effective time of the Merger, a number of shares of Imara common stock equal to the number of

 

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shares of Enliven common stock subject to the unexercised portion of the Enliven stock option immediately prior to the effective time of the Merger, multiplied by the exchange ratio (rounded down to the nearest whole share number), with an exercise price per share for the options equal to the exercise price per share of such Enliven stock option immediately prior to the effective time of the Merger divided by the exchange ratio (rounded up to the nearest whole cent). Such assumed options will continue to be governed by the terms and conditions of the Enliven 2019 Plan, including the adjustment and change in control provisions contained therein.

Treatment of Imara Common Stock and Imara Options (see page 203)

Each share of Imara common stock issued and outstanding at the time of the Merger will remain issued and outstanding and such shares will be appropriately adjusted to reflect the proposed reverse stock split. In addition, each option to purchase shares of Imara common stock and restricted stock unit covering shares of Imara common stock, to the extent unvested, will be vested in connection with the Merger. Each option will survive the closing and remain outstanding in accordance with its terms. The number of shares of Imara common stock underlying such options, and the exercise prices for such stock options, will be appropriately adjusted to reflect the proposed reverse stock split.

Conditions to the Completion of the Merger (see page 212)

To complete the Merger, Imara stockholders must approve Proposal No. 1 and Enliven stockholders must adopt the Merger Agreement. Additionally, each of the other closing conditions set forth in the Merger Agreement must be satisfied or waived (including the closing of the transactions contemplated by the funding agreements).

Non-Solicitation (see page 208)

The Merger Agreement contains “non-solicitation” provisions, pursuant to which, subject to specified exceptions, each of Imara and Enliven has agreed that neither it nor its subsidiaries will, and each of Imara and Enliven will use reasonable best efforts to cause its respective directors, officers, employees, attorneys, and financial advisors not to, directly or indirectly:

 

   

solicit, seek or initiate or knowingly take any action to facilitate or encourage any offers, inquiries or the making of any proposal or offer that constitutes, or would reasonably be expected to lead to, any Acquisition Proposal (as defined in the section of this proxy statement/prospectus titled “The Merger Agreement—Non-Solicitation”);

 

   

enter into, continue or otherwise participate or engage in any discussions or negotiations regarding any Acquisition Proposal, or furnish to any person any non-public information or afford any person other than Imara or Enliven, as applicable, access to such party’s property, books or records (except pursuant to a request by a governmental entity) in connection with any offers, inquiries or the making of any proposal or offer that constitutes, or would reasonably be expected to lead to, any Acquisition Proposal;

 

   

take any action to make the provisions of any takeover statute inapplicable to any transactions contemplated by an Acquisition Proposal; or

 

   

publicly propose to do any of the foregoing.

Board Recommendation Change (see page 209)

Subject to specified exceptions described in the Merger Agreement, Imara has agreed that its board of directors (and any committee thereof) may not take any of the following actions, each of which are referred to in this proxy statement/prospectus as an Imara board recommendation change:

 

   

fail to include its recommendation to Imara’s stockholders to solicit their approval of the share issuance at the special meeting of Imara’s stockholders in this proxy statement/prospectus or shall have withdrawn or modified such recommendation in a manner adverse to Enliven;

 

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withhold, withdraw or modify (or publicly propose to withhold, withdraw or modify) the approval or recommendation of the Imara board of directors with respect to the share issuance;

 

   

after the receipt by Imara of an Acquisition Proposal and Enliven’s subsequent request in writing that the Imara board of directors reconfirm its recommendation to Imara’s stockholders to solicit their approval of the required Imara voting proposal at the special meeting of Imara’s stockholders, fail to reconfirm its recommendation within ten business days after its receipt of Enliven’s request;

 

   

fail to recommend against acceptance of a tender offer within ten business days after commencement; or

 

   

publicly propose to adopt, approve or recommend, or have approved, adopted, or recommended any Acquisition Proposal.

Subject to specified exceptions described in the Merger Agreement, Enliven agreed that its board of directors may not take any of the following actions, each of which are referred to in this proxy statement/prospectus as an Enliven board recommendation change:

 

   

withhold, withdraw or modify (or publicly propose to withhold, withdraw or modify) the approval or recommendation of the Enliven board of directors with respect to the Merger;

 

   

fail to recommend against acceptance of a tender offer within ten business days after commencement; or

 

   

publicly propose to adopt, approve or recommend any Acquisition Proposal.

Termination of the Merger Agreement (see page 216)

Either Imara or Enliven may terminate the Merger Agreement under certain circumstances, which would prevent the Merger from being consummated.

Termination Fee (see page 218)

If the Merger Agreement is terminated under specified circumstances, Imara will be required to pay Enliven a termination fee of $3.0 million. If the Merger Agreement is terminated under certain specified circumstances, Enliven will be required to pay Imara a termination fee of $9.75 million or, in certain other circumstances, $3.0 million, as determined by the specified circumstances.

Support Agreements (see page 219)

In order to induce Imara to enter into the Merger Agreement, certain Enliven stockholders have entered into support agreements with Imara pursuant to which, among other things, each such stockholder has agreed, solely in his, her or its capacity as a Enliven stockholder, to vote all of his, her or its shares of Enliven capital stock in favor of the adoption of the Merger Agreement. These Enliven stockholders also agreed to vote against any competing Acquisition Proposal with respect to Enliven.

As of October 13, 2022, the Enliven stockholders that are party to a support agreement with Imara owned an aggregate of 65,069,168 shares of Enliven capital stock, representing approximately 88.2% of the outstanding shares of Enliven capital stock on an as converted to common stock basis. These stockholders include executive officers and directors of Enliven, as well as certain other stockholders owning a significant portion of the outstanding shares of Enliven capital stock. Following the effectiveness of the registration statement on Form S-4 of which this proxy statement/prospectus is a part and pursuant to the Merger Agreement, Enliven stockholders holding a sufficient number of shares of Enliven capital stock to adopt the Merger Agreement and approve the Merger and related transactions will be asked to execute written consents providing for such adoption and approval.

 

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In addition, in order to induce Enliven to enter into the Merger Agreement, certain Imara stockholders have entered into support agreements with Enliven pursuant to which, among other things, each such stockholder has agreed to vote all shares of Imara common stock owned by him or her as of the record date in favor of Proposals Nos. 1, 3, 4 and 5, and against any competing Acquisition Proposal. These Imara stockholders also agreed to vote against any competing Acquisition Proposal with respect to Imara.

As October 13, 2022, the Imara stockholders that are party to a support agreement owned an aggregate of 8,256,404 shares of Imara common stock representing approximately 33% of the outstanding shares of Imara common stock. These stockholders include certain executive officers and directors of Imara and certain other Imara stockholders holding a significant portion of the outstanding shares of Imara common stock.

Lock-Up Agreements (see page 220)

Certain of Enliven’s and Imara’s executive officers, directors and stockholders have entered into lock-up agreements, pursuant to which such parties have agreed not to, except in limited circumstances, offer, pledge, sell, contract to sell, sell any option to purchase, purchase any option or contract to sell, grant any option, right or warrant to purchase, or otherwise transfer or dispose of, any shares of Imara’s common stock (other than the shares obtained as merger consideration in respect of the Enliven shares issued in the Enliven pre-closing financing), until 180 days after the effective time of the Merger.

The Enliven stockholders who have executed lock-up agreements as of October 13, 2022 owned, in the aggregate, approximately 83.3% of the shares of Enliven’s outstanding capital stock. The Imara stockholders who have executed lock-up agreements as of October 13, 2022 owned, in the aggregate, approximately 33% of the shares of Imara’s outstanding common stock.

Common Stock Purchase Agreement (see page 220)

Immediately prior to the execution and delivery of the Merger Agreement, certain investors entered into a Common Stock Purchase Agreement with Enliven, or the Common Stock Purchase Agreement, pursuant to which such investors have agreed to purchase from Enliven shares of Enliven common stock for a per share purchase price of $3.84098 (representing an aggregate commitment of approximately $164.5 million) in the Enliven pre-closing financing, which is expected to be consummated immediately prior to the closing of the Merger. The closing of the Enliven pre-closing financing is conditioned upon the satisfaction or waiver of the conditions to the closing of the Merger as well as certain other conditions. Enliven’s obligations to consummate the Merger are conditioned upon the closing of the Enliven pre-closing financing such that Enliven receives gross proceeds of at least $131.6 million. Imara’s obligations to consummate the Merger is conditioned upon the closing of the Enliven pre-closing financing such that Enliven receives gross proceeds of at least $75 million. The shares of Enliven common stock that are issued in the Enliven pre-closing financing will be converted into shares of Imara common stock in the Merger. Accordingly, by approving Proposal No. 1, Imara stockholders will also be approving the issuance of shares of Imara common stock in exchange for all shares of Enliven common stock that are sold in the Enliven pre-closing financing.

The consummation of the Enliven pre-closing financing is subject to certain conditions, including the satisfaction or waiver of each of the conditions precedent to the consummation of the Merger set forth in the Merger Agreement (other than those conditions which, by their nature, are to be satisfied at the closing of the Merger pursuant to the Merger Agreement, and the condition regarding the Enliven pre-closing financing).

 

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Management Following the Merger (see page 367)

Effective as of the closing of the Merger, the combined company’s executive officers are expected to be members of the Enliven executive management team prior to the Merger, including:

 

    Name    Title
               Sam Kintz, M.B.A.    President, Chief Executive Officer and Director
  Helen Collins, M.D.    Chief Medical Officer
  Benjamin Hohl    Chief Financial Officer
  Joseph P. Lyssikatos, Ph.D.    Chief Scientific Officer and Director
  Anish Patel, Pharm.D.    Chief Operating Officer

Interests of Certain Directors, Officers and Affiliates of Imara and Enliven (see page 185)

Interests of Imara

In considering the recommendation of Imara’s board of directors with respect to issuing shares of Imara’s common stock in the Merger and the other matters to be acted upon by the Imara stockholders at the Imara special meeting, Imara’s stockholders should be aware that Imara’s directors and executive officers may have interests in the Merger that are different from, or in addition to, the interests of Imara’s stockholders generally. Interests of the directors and executive officers may be different from or in addition to the interests of the stockholders for the following reasons, among others:

 

   

One of Imara’s existing directors, who is expected to be Rahul Ballal, Imara’s President and Chief Executive Offer, will continue as a director of the combined company after the effective time of the Merger, and, following the closing of the Merger, will be eligible to be compensated as a non-employee director of Imara pursuant to the Imara non-employee director compensation policy that is expected to remain in place following the effective time of the Merger.

 

   

Under the Merger Agreement, Imara’s directors and executive officers are entitled to continued indemnification, expense advancement and insurance coverage.

 

   

Pursuant to the terms of the applicable retention agreements, upon closing of the Asset Sale on November 10, 2022, Dr. Ballal and Michael Gray, Imara’s Chief Financial Officer, became entitled to the remaining fifty percent of the retention payment provided for in their retention agreement. In addition, if Dr. Ballal and Mr. Gray remain employed by Imara on the date of the closing of the Merger, the exercise period for the outstanding stock options held by Dr. Ballal and Mr. Gray with an exercise price of less than $5.00 per share shall be extended until the date that is the earlier of (a) eighteen months following his respective cessation of employment from Imara and (b) the final exercise date for each such applicable stock option. In the case of Dr. Ballal, who is expected to continue as a director of the combined company, the applicable exercise period will be the later of 18 months following his cessation of employment from Imara or the exercise period that would otherwise apply following his termination of service as a director (but in either case not beyond the final exercise date for each such applicable stock option). In addition, pursuant to the terms of letter agreements with Dr. Ballal and Mr. Gray, Dr. Ballal and Mr. Gray will be entitled to full acceleration of all outstanding stock options and restricted stock units as of the date of a qualifying termination of employment.

 

   

The board of directors of Imara considered that David Bonita, M.D., a director of Imara, is a member of OrbiMed Advisors LLC, which is referred to collectively, together with its affiliates and affiliated investment entities (including OrbiMed Private Investments VII, L.P., OrbiMed Genesis Master Fund, L.P. and The Biotech Growth Trust PLC) as OrbiMed, and that OrbiMed is a stockholder of both Enliven and Imara, and that (i) OrbiMed Private Investments VII, L.P. and OrbiMed Genesis Master Fund, L.P. will receive proceeds as a result of the Merger akin to other stockholders of Enliven, (ii) Dr. Bonita serves as a representative of OrbiMed on Imara’s board of directors, (iii) OrbiMed

 

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participated in the Enliven pre-closing financing, which is expected to close immediately prior to the closing of the Merger and (iv) Rishi Gupta, a director of Enliven who is affiliated with OrbiMed, will be appointed to Imara’s board of directors in connection with the Merger.

These interests are discussed in more detail in the sections titled “The Merger—Interests of Imara Directors and Executive Officers in the Merger,” “The Merger Agreement—Indemnification and Insurance for Directors and Officers” and “Imara Executive and Director Compensation” beginning on pages 185, 211 and 228, respectively, of this proxy statement/prospectus. The members of Imara’s board of directors were aware of and considered these potential interests, among other things, in evaluating and negotiating the Merger Agreement and the Merger, and in recommending to the stockholders the proposals being submitted to Imara’s stockholders at the special meeting be approved.

Certain of Imara’s directors and executive officers have also entered into a support agreement and a lock-up agreement in connection with the Merger. For a more detailed discussion of the support agreements and lock-up agreements, please see the sections titled “Agreements Related to the Merger—Support Agreements” and “Agreements Related to the Merger—Lock-Up Agreements” beginning on page 219 and page 220, respectively, of this proxy statement/prospectus.

Interests of Enliven

In considering the recommendation of the Enliven board of directors with respect to approving the Merger, stockholders should be aware that Enliven’s directors and executive officers may have interests in the Merger that are different from, or in addition to, the interests of Enliven stockholders generally. Interests of the directors and executive officers may be different from or in addition to the interests of the stockholders for the following reasons, among others:

 

   

The board of directors of Enliven considered that Rishi Gupta, a director of Enliven, is affiliated with OrbiMed Private Investments VII, L.P., OrbiMed Genesis Master Fund, L.P. and The Biotech Growth Trust PLC, which is referred to collectively, together with its affiliates and affiliated investment entities, as OrbiMed, each of which and that OrbiMed is a stockholder of Enliven, and Imara or both Enliven and Imara, and that (i) OrbiMed Private Investments VII, L.P. and OrbiMed Genesis Master Fund, L.P. will receive proceeds as a result of the Merger akin to other stockholders of Enliven, (ii) OrbiMed has a representative serving on Imara’s board of directors, (iii) OrbiMed participated in the Enliven pre-closing financing and (iv) Mr. Gupta will be appointed to Imara’s board of directors in connection with the Merger.

 

   

As of October 15, 2022, Enliven’s current non-employee directors and executive officers beneficially owned, in the aggregate, approximately 69.2% of the shares of Enliven capital stock, which for purposes of this subsection excludes any Enliven shares issuable upon exercise or settlement of Enliven stock options held by such individual.

These interests are discussed in more detail in the sections titled “The Merger—Interests of Enliven Directors and Executive Officers in the Merger,” “The Merger Agreement—Indemnification and Insurance for Directors and Officers” and “Enliven Executive Compensation” beginning on pages 188, 211 and 235, respectively, of this proxy statement/prospectus. The members of Enliven’s board of directors were aware of and considered these interests, among other things, in evaluating and negotiating the Merger Agreement and the Merger, and in recommending to the stockholders the proposals being submitted to Enliven’s stockholders at the special meeting be approved.

Certain of Enliven’s directors and executive officers have also entered into a support agreement and a lock-up agreement in connection with the Merger. For a more detailed discussion of the support agreements and lock-up agreements, please see the sections titled “Agreements Related to the Merger—Support Agreements” and “Agreements Related to the Merger—Lock-Up Agreements” beginning on page 219 and page 220, respectively, of this proxy statement/prospectus.

 

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Material U.S. Federal Income Tax Consequences of the Merger (see page 194)

Imara and Enliven intend the Merger to qualify as a “reorganization” within the meaning of Section 368(a) of the Code, and in the event that former Enliven stockholders, including stockholders that participate in the Enliven pre-closing financing, are in “control” of Imara immediately after the effective time of the Merger (within the meaning of Section 368(c) of the Code), Imara and Enliven also intend the Merger to qualify as a non-taxable exchange of shares of Enliven common stock for shares of Imara common stock within the meaning of Section 351(a) of the Code. Assuming the Merger qualifies for the intended tax treatment, subject to the qualifications and limitations set forth in the section titled “The Merger—Material U.S. Federal Income Tax Consequences of the Merger,” an Enliven U.S. holder will not recognize gain or loss for U.S. federal income tax purposes upon the receipt of shares of Imara common stock in exchange for shares of Enliven common stock in the Merger, except with respect to cash received in lieu of a fractional share of Imara common stock.

If the Merger does not qualify for the intended tax treatment, then each Enliven U.S. holder would recognize gain or loss upon the exchange of shares of Enliven common stock for Imara common stock in the Merger equal to the difference between the fair market value of the shares of Imara common stock received in exchange for the shares of Enliven common stock (plus any cash received in lieu of a fractional share) and such Enliven U.S. holder’s adjusted tax basis in the shares of Enliven common stock surrendered.

Because the Imara stockholders will not sell, exchange or dispose of any shares of Imara common stock in the Merger, there will be no material U.S. federal income tax consequences to Imara stockholders upon consummation of the Merger.

See the section titled “The Merger — Material U.S. Federal Income Tax Consequences of the Merger” beginning on page 194 of this proxy statement/prospectus for a more complete description of the material U.S. federal income tax consequences of the Merger to Enliven U.S. holders.

Material U.S. Federal Income Tax Consequences of Receipt of CVRs (see page 223)

The U.S. federal income tax treatment of the Imara stockholders’ receipt of the CVRs is unclear. Imara will report the issuance of the CVRs to Imara stockholders as a distribution of property with respect to Imara common stock. Assuming such treatment, each Imara stockholder will be treated as receiving a distribution in an amount equal to the fair market value of the CVRs issued to such Imara stockholder on the date of the issuance. This distribution should be treated first as a taxable dividend to the extent of the Imara stockholder’s pro rata share of Imara’s current or accumulated earnings and profits (as determined for U.S. federal income tax purposes), then as a non-taxable return of capital to the extent of the Imara stockholder’s basis in its Imara common stock, and finally as capital gain from the sale or exchange of Imara common stock with respect to any remaining value. Imara has no accumulated earnings and profits and expects to have no current earnings and profits for the relevant taxable year. Thus, Imara expects this distribution to be treated as a non-dividend distribution for U.S. federal income tax purposes. See the section titled “Agreements Related to the Merger—CVR Agreement—Material U.S. Federal Income Tax Consequences of the Receipt of CVRs” beginning on page 223 of this proxy statement/prospectus for a more complete description of the material U.S. federal income tax consequences of the receipt of CVRs to Imara stockholders, including possible alternative treatments.

Material U.S. Federal Income Tax Consequences of the Reverse Stock Split (see pages 251)

Imara intends the proposed reverse stock split to qualify as a “recapitalization” within the meaning of Section 368(a)(1)(E) of the Code. Assuming such treatment, an Imara U.S. holder should not recognize gain or loss upon the proposed reverse stock split, except to the extent an Imara U.S. holder receives cash in lieu of a fractional share of Imara common stock. See the section titled “Proposal No. 3—Material U.S. Federal Income Tax Consequences of the Reverse Stock Split” beginning on page 251 of this proxy statement/prospectus for a more complete description of the material U.S. federal income tax consequences of the proposed reverse stock split to Imara U.S. holders.

 

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Risk Factor Summary

Both Imara and Enliven are subject to various risks associated with their businesses and their industries. In addition, the Merger, including the possibility that the Merger may not be completed, poses a number of risks to each company and its respective securityholders, including the following risks:

Risks Related to the Merger

 

   

The exchange ratio will not be adjusted based on the market price of Imara’s common stock, so the merger consideration at the closing may have a greater or lesser value than at the time the Merger Agreement was signed.

 

   

Failure to complete the Merger may result in either Imara or Enliven paying a termination fee to the other party, which could harm the common stock price of Imara and future business and operations of each company.

 

   

If the conditions to the Merger are not satisfied or waived, the Merger may not occur.

Risks Related to the Proposed Reverse Stock Split

 

   

The reverse stock split may not increase the combined company’s stock price over the long-term.

Risks Related to Imara

 

   

Imara has incurred significant losses since its inception. Imara expects to incur operating losses for the foreseeable future and may never achieve or maintain profitability.

 

   

If the Merger is not completed, Imara will reconsider its strategic alternatives, including dissolving and liquidating its assets, pursuing another strategic transaction, or operating its business. Imara’s future capital requirements depend on many factors, and adequate additional financing may not be available to it on acceptable terms, or at all.

Risks Related to Enliven

 

   

Enliven is early in its development efforts, with a limited operating history, and it has no products approved for commercial sale, which may make it difficult for you to evaluate its current business and likelihood of success and future viability.

 

   

Enliven has incurred significant net losses in each period since its inception, and it expects to continue to incur significant net losses for the foreseeable future.

 

   

Enliven has never generated revenue from product sales and may never achieve or maintain profitability.

 

   

Enliven is substantially dependent on ELVN-001 and ELVN-002. If Enliven is unable to advance ELVN-001 or ELVN-002 through clinical development, obtain regulatory approval and ultimately commercialize such product candidates, or experiences significant delays in doing so, Enliven’s business will be materially harmed.

 

   

The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and the results of Enliven’s clinical trials may not satisfy the requirements of the FDA, EMA or other comparable foreign regulatory authorities.

 

 

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Enliven has limited resources and is currently focusing its efforts on ELVN-001 and ELVN-002 for development in particular indications and advancing its other research programs. As a result, Enliven may fail to capitalize on programs, product candidates or indications that may be more profitable or for which there is a greater likelihood of success.

 

   

Enliven’s prospects depend in large part upon developing and commercializing ELVN-001 and ELVN-002 and discovering, developing and commercializing product candidates from its other research programs, and failure to successfully identify, develop and commercialize additional product candidates could impair Enliven’s ability to grow.

 

   

If clinical trials of Enliven’s product candidates fail to demonstrate safety and efficacy to the satisfaction of regulatory authorities or do not otherwise produce positive results, Enliven would incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of its product candidates.

 

   

The regulatory approval processes of the FDA, EMA and other comparable foreign regulatory authorities are lengthy, time consuming and inherently unpredictable. If Enliven is ultimately unable to obtain regulatory approval of its product candidates, Enliven will be unable to generate product revenue and its business will be substantially harmed.

 

   

Enliven’s success depends on its ability to protect its intellectual property and its proprietary technologies.

Risks Related to the Combined Company

 

   

The market price of the combined company’s common stock following the completion of the Merger is expected to be volatile, and the market price of the common stock may drop following the Merger.

 

   

Following the Merger, the combined company may be unable to integrate successfully and realize the anticipated benefits of the Merger.

 

   

The combined company will need substantial additional funding before it can complete the development of its product candidates. If the combined company is unable to obtain such additional capital on favorable terms, on a timely basis or at all, it would be forced to delay, reduce or eliminate its product development and clinical programs and may not have the capital required to otherwise operate its business.

 

   

The combined company will incur additional costs and increased demands upon management as a result of complying with the laws and regulations affecting public companies.

These risks and other risks are discussed in greater detail under the section titled “Risk Factors” beginning on page 26 of this proxy statement/prospectus. Imara and Enliven both encourage you to read and consider all of these risks carefully.

Regulatory Approvals (see page 193)

Under the Merger Agreement, the Merger cannot be completed until the waiting period (and any extensions thereof), if any, applicable to the Merger under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, or the HSR Act, has expired or otherwise been terminated. The initial waiting period under the HSR Act is set to expire at 11:59 p.m., Eastern Time, on Monday, November 28, 2022.

Nasdaq Stock Market Listing (see page 197)

Enliven has filed a listing application for the combined company’s common stock with Nasdaq following completion of the Merger. If such application is accepted, Imara and Enliven anticipate that the common stock of

 

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the combined company, which will be renamed to Enliven Therapeutics, Inc., will be listed on The Nasdaq Stock Market following the closing of the Merger under the trading symbol “ELVN.”

Anticipated Accounting Treatment (see page 197)

The Merger will be accounted for as a reverse recapitalization in accordance with U.S. generally accepted accounting principles, or GAAP. Under this method of accounting, Enliven will be deemed to be the accounting acquirer for financial reporting purposes. For accounting purposes, the Merger will be treated as the equivalent of Enliven issuing stock to acquire the net assets of Imara. As a result of the Merger, the net assets of Imara will be recorded at their acquisition-date fair value in the financial statements of Enliven and the reported operating results prior to the Merger will be those of Enliven. See the section titled “Selected Historical and Unaudited Pro Forma Condensed Combined Financial Information” beginning on page 383 of this proxy statement/prospectus for additional information.

Appraisal Rights and Dissenters’ Rights (see page 198)

Holders of Imara common stock are not entitled to appraisal rights in connection with the Merger under Delaware law. Holders of Enliven capital stock are entitled to appraisal rights in connection with the Merger under Delaware law. See the section titled “Appraisal Rights and Dissenters’ Rights” on page 198 of this proxy statement/prospectus for additional information.

Comparison of Stockholder Rights (see page 402)

Both Imara and Enliven are incorporated under the laws of the State of Delaware and, accordingly, the rights of the stockholders of each are currently, and will continue to be, governed by the Delaware General Corporation Law, or the DGCL. If the Merger is completed, Enliven stockholders will become Imara stockholders, and their rights will be governed by the DGCL, the amended and restated bylaws of Imara and the restated certificate of incorporation of Imara, as may be further amended by Proposal Nos. 2 and 3 if approved by the Imara stockholders at the Imara special meeting. The rights of Imara stockholders contained in the restated certificate of incorporation and amended and restated bylaws of Imara differ from the rights of Enliven stockholders under the amended and restated certificate of incorporation and amended and restated bylaws of Enliven, as more fully described under the section titled “Comparison of Rights of Holders of Imara Capital Stock and Enliven Capital Stock” beginning on page 402 of this proxy statement/prospectus.

 

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MARKET PRICE AND DIVIDEND INFORMATION

Market Price Information

Imara common stock is currently listed on The Nasdaq Global Select Market under the symbol “IMRA.”

The closing price of Imara’s common stock on October 13, 2022, the last trading day prior to the public announcement of the Merger, was $2.58 per share and the closing price of Imara’s common stock on November 7, 2022 was $4.46 per share, in each case as reported on The Nasdaq Global Select Market.

Because the market price of Imara common stock is subject to fluctuation, the market value of the shares of Imara common stock that Enliven stockholders will be entitled to receive in the Merger may increase or decrease.

Enliven is a private company and its shares of common stock and preferred stock are not publicly traded.

Assuming approval of Proposal No. 1 and successful application for initial listing with The Nasdaq Stock Market, Imara and Enliven anticipate that the common stock of the combined company, which will be renamed to Enliven Therapeutics, Inc., will be listed on The Nasdaq Stock Market following the closing of the Merger under the trading symbol “ELVN.”

As of                     , 2022, the Record Date for the Special Meeting, there were approximately                      holders of record of the Imara common stock. As of                     , 2022, Enliven had                      holders of record of Enliven common stock and                      holders of record of Enliven Preferred Stock. For detailed information regarding the beneficial ownership of certain Imara stockholders, see the sections titled “Principal Stockholders of Imara” and “Principal Stockholders of Enliven” on pages 415 and 418, respectively, of this proxy statement/prospectus.

Dividends

Imara has never declared or paid cash dividends on its capital stock and does not anticipate paying any cash dividends in the foreseeable future. Enliven has never paid or declared any cash dividends on its capital stock. Enliven intends to retain all available funds and any future earnings for use in the operation of its business and does not anticipate paying any cash dividends on its capital stock in the foreseeable future. Notwithstanding the foregoing, any determination to pay cash dividends subsequent to the Merger will be at the discretion of the combined company’s board of directors and will depend upon a number of factors, including the combined company’s results of operations, financial condition, future prospects, contractual restrictions, restrictions imposed by applicable law and other factors the combined company’s board of directors deems relevant.

 

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RISK FACTORS

The combined company will be faced with a market environment that cannot be predicted and that involves significant risks, many of which will be beyond its control. In addition to the other information contained or incorporated by reference in this proxy statement/prospectus, you should carefully consider the material risks described below before deciding how to vote your shares of Imara common stock. You should also read and consider the other information in this proxy statement/prospectus and additional information about Imara set forth in its Annual Report on Form 10-K for the fiscal year ended December 31, 2021, which is filed with the Securities and Exchange Commission, or the SEC, as such risks may be updated or supplemented in its subsequent Quarterly Reports on Form 10-Q or Current Reports on Form 8-K, each of which is incorporated by reference into this proxy statement/prospectus. Please see the section titled “Where You Can Find More Information” beginning on page 425 of this proxy statement/prospectus for further information regarding the documents incorporated by reference into this proxy statement/prospectus.

Risks Related to the Strategic Transactions

Risks Related to the Merger

The exchange ratio will not be adjusted based on the market price of Imara’s common stock, so the merger consideration at the closing may have a greater or lesser value than at the time the Merger Agreement was signed.

At the effective time of the Merger, outstanding shares of Enliven capital stock will be converted into shares of Imara common stock. Applying the exchange ratio, the former Enliven securityholders immediately before the Merger, including those purchasing shares in the Enliven pre-closing financing, are currently estimated to own approximately 84.1% of the aggregate number of shares of Imara common stock following the Merger on a fully-diluted basis, and Imara securityholders immediately before the Merger are currently estimated to own approximately 15.9% of the aggregate number of shares of Imara common stock following the Merger on a fully-diluted basis, subject to certain assumptions, including, but not limited to, (a) Imara’s net cash as of the closing being approximately $82 million, (b) Enliven raising approximately $164.5 million in the Enliven pre-closing financing described in this proxy statement/prospectus, (c) a valuation for Imara equal to its net cash as of the business day immediately prior to the closing date of the Merger, plus $10 million and (d) a valuation for Enliven equal to $324.6 million, plus the gross proceeds of the Enliven pre-closing financing, in each case as further described in the Merger Agreement.

Any changes in the market price of Imara stock before the completion of the Merger will not affect the number of shares Enliven stockholders will be entitled to receive pursuant to the Merger Agreement. Therefore, if before the completion of the Merger, the market price of Imara common stock increases from the market price on the date of the Merger Agreement, then Enliven stockholders could receive merger consideration with substantially more value for their shares of Enliven capital stock than the parties had negotiated when they established the exchange ratio. Similarly, if before the completion of the Merger the market price of Imara common stock declines from the market price on the date of the Merger Agreement, then Enliven stockholders could receive merger consideration with substantially lower value. The Merger Agreement does not include a price-based termination right.

Failure to complete the Merger may result in either Imara or Enliven paying a termination fee to the other party, which could harm the common stock price of Imara and future business and operations of each company.

If the Merger is not completed, Imara and Enliven are subject to the following risks:

 

   

if the Merger Agreement is terminated under certain specified circumstances, Imara will be required to pay Enliven a termination fee of $3.0 million;

 

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if the Merger Agreement is terminated under certain other specified circumstances, Enliven will be required to pay Imara a termination fee of $9.75 million or, in certain other circumstances, $3.0 million;

 

   

the price of Imara common stock may decline and could fluctuate significantly; and

 

   

costs related to the Merger, such as financial advisor, legal and accounting fees, which Imara estimates will total approximately $2.0 million, $2.5 million, and $0.4 million, respectively, a majority of which must be paid even if the Merger is not completed.

If the Merger Agreement is terminated and the board of directors of Imara or Enliven determines to seek another business combination, there can be no assurance that either Imara or Enliven will be able to find a partner with whom a business combination would yield greater benefits than the benefits to be provided under the Merger Agreement.

If the conditions to the Merger are not satisfied or waived, the Merger may not occur.

Even if the Merger Agreement is adopted by the stockholders of Enliven and the Merger and the issuance of Imara’s common stock pursuant thereto are approved by the stockholders of Imara, specified conditions must be satisfied or waived to complete the Merger. These conditions are set forth in the Merger Agreement and described in the section titled “The Merger Agreement—Conditions to the Completion of the Merger” beginning on page 212 of this proxy statement/prospectus. Imara and Enliven cannot assure you that all of the conditions to the consummation of the Merger will be satisfied or waived. If the conditions are not satisfied or waived, the Merger may not occur or the closing may be delayed, and Imara and Enliven each may lose some or all of the intended benefits of the Merger.

The Merger may be completed even though a material adverse effect may result from the announcement of the Merger, industry-wide changes or other causes.

In general, neither Imara nor Enliven is obligated to complete the Merger if there is a material adverse effect affecting the other party between October 13, 2022, the date of the Merger Agreement, and the closing of the Merger. However, certain types of changes are excluded from the concept of a “material adverse effect.” Such exclusions include but are not limited to changes in general economic or market conditions, industry wide changes, changes in GAAP, changes in laws, rules or regulations of general applicability or interpretations thereof, natural disasters, epidemics, pandemics or other disease outbreaks (including the COVID-19 pandemic), outbreaks of major hostilities or acts of terrorism, changes resulting from the announcement or pendency of the Merger, and failures to meet internal guidance, budgets, plans or forecasts. Therefore, if any of these events were to occur impacting Imara or Enliven, the other party would still be obliged to consummate the closing of the Merger. If any such adverse changes occur and Imara and Enliven consummate the closing of the Merger, the stock price of the combined company may suffer. This in turn may reduce the value of the Merger to the stockholders of Imara, Enliven or both. For a more complete discussion of what constitutes a material adverse effect on Imara or Enliven, see the section titled “The Merger Agreement—Conditions to Completion of the Merger” beginning on page 212 of this proxy statement/prospectus.

If Imara and Enliven complete the Merger, the combined company will need to raise additional capital by issuing equity securities or additional debt or through licensing arrangements, which may cause significant dilution to the combined company’s stockholders or restrict the combined company’s operations.

On October 13, 2022, Enliven entered into the Common Stock Purchase Agreement with certain investors, including existing investors of Enliven, pursuant to which the investors agreed to purchase, in the aggregate, approximately $164.5 million in shares of common stock of Enliven immediately prior to the closing of the Merger, referred to as the Enliven pre-closing financing. The closing of the Enliven pre-closing financing is conditioned upon the satisfaction or waiver of the conditions to the closing of the Merger as well as certain other

 

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conditions. The Enliven pre-closing financing is more fully described under the section titled “Agreements Related to the Merger—Enliven Common Stock Purchase Agreement” beginning on page 220 of this proxy statement/prospectus.

Additional financing may not be available to the combined company when it is needed or may not be available on favorable terms. To the extent that the combined company raises additional capital by issuing equity securities, such financing will cause additional dilution to all securityholders of the combined company, including Imara’s pre-Merger securityholders and Enliven’s former securityholders. It is also possible that the terms of any new equity securities may have preferences over the combined company’s common stock. Any debt financing the combined company enters into may involve covenants that restrict its operations. These restrictive covenants may include limitations on additional borrowing and specific restrictions on the use of the combined company’s assets, as well as prohibitions on its ability to create liens, pay dividends, redeem its stock or make investments. In addition, if the combined company raises additional funds through licensing arrangements, it may be necessary to grant licenses on terms that are not favorable to the combined company.

Some Imara and Enliven directors and executive officers may have interests in the Merger that are different from yours and that may influence them to support or approve the Merger without regard to your interests.

Directors and executive officers of Imara and Enliven may have interests in the Merger that are different from, or in addition to, the interests of other Imara stockholders generally. These interests with respect to Imara’s directors and executive officers may include, among others, that certain of Imara’s executives are entitled to, in connection with a qualifying termination of employment, accelerated vesting of options and restricted stock units with respect to Imara common stock and the payment of severance, that certain of Imara’s executives are entitled to the extension of the applicable executive’s post-termination exercise period with respect to their options in the event of the executive’s continued employment through the closing of the Merger, and that all of Imara’s directors and executive officers are entitled to certain indemnification and liability insurance coverage pursuant to the terms of the Merger Agreement. In addition, a current member of the Imara board of directors, who is expected to be Rahul Ballal, is expected to continue as a director of the combined company after the effective time of the Merger, and, following the closing of the Merger, will be eligible to be compensated as a non-employee director of the combined company pursuant to the Imara non-employee director compensation policy that is expected to remain in place following the effective time of the Merger. These interests with respect to Enliven’s directors and executive officers may include, among others, that certain of Enliven’s directors and executive officers have options, subject to vesting, to purchase shares of Enliven common stock which, after the effective time of the Merger, will be converted into and become options to purchase shares of the common stock of the combined company; Enliven’s executive officers are expected to continue as executive officers of the combined company after the effective time of the Merger; and all of Enliven’s directors and executive officers are entitled to certain indemnification and liability insurance coverage pursuant to the terms of the Merger Agreement. Further, all of the current members of Enliven’s board of directors are expected to continue as directors of the combined company after the effective time of the Merger, and, following the closing of the Merger, will be eligible to be compensated as non-employee directors of the combined company pursuant to the Imara non-employee director compensation policy that is expected to remain in place following the effective time of the Merger. The directors and executive officers own options to purchase the shares of and, in the case of executive officers of Imara, restricted stock units with respect to, their respective companies.

The board of directors of Imara also considered that David Bonita, M.D., a director of Imara, is a member of OrbiMed Advisors LLC, which is affiliated with OrbiMed Private Investments VII, L.P., OrbiMed Genesis Master Fund, L.P. and The Biotech Growth Trust PLC (referred to collectively with its affiliates and affiliated investment entities as OrbiMed) and the board of directors of Enliven considered that Rishi Gupta, a director of Enliven, is also affiliated with OrbiMed. Both the Imara and Enliven boards of directors considered, among other things, that (i) OrbiMed is a stockholder of Enliven and Imara, (ii) OrbiMed Private Investments VII, L.P. and OrbiMed Genesis Master Fund, L.P. will receive proceeds as a result of the Merger akin to other stockholder of Enliven, (iii) OrbiMed participated in the Enliven pre-closing financing and (iv) Mr. Gupta will be appointed to Imara’s board of directors in connection with the Merger.

 

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The Imara and Enliven boards of directors were aware of and considered those interests, among other things, in reaching their decisions to approve and adopt the Merger Agreement, approve the Merger, and recommend the approval of the Merger Agreement and certain related matters to Imara and Enliven stockholders. These interests, among other factors, may have influenced the directors and executive officers of Imara and Enliven to support or approve the Merger.

For more information regarding the interests of Imara and Enliven directors and executive officers in the Merger, please see the sections titled “The Merger—Interests of Imara Directors and Executive Officers in the Merger” beginning on page 185 and “The Merger—Interests of Enliven Directors and Executive Officers in the Merger” beginning on page 188 of this proxy statement/prospectus.

Imara’s stockholders may potentially not receive any payment on the CVRs and the CVRs may otherwise expire valueless.

The Merger Agreement contemplates that, at or prior to the effective time of the Merger, Imara will enter into a Contingent Value Rights Agreement, or the CVR Agreement, with a rights agent pursuant to which each of Imara’s stockholders of record immediately prior to the Merger will receive one CVR for each outstanding share of Imara’s common stock held by such stockholder on such date. Each CVR will represent the contractual right to receive payments upon the occurrence of certain events related to the Asset Sale or a potential sale or license involving IMR-261, in each case as set forth in, and subject to the permitted deductions set forth in, and in accordance with the terms and conditions of, the CVR Agreement. The right of Imara’s stockholders to derive any value from the CVRs will be contingent solely upon the disposition of such assets within the time periods specified in the CVR Agreement.

Imara may not be able to achieve successful results from the disposition of such assets as described above. If this is not achieved for any reason within the time periods specified in the CVR Agreement, or the permitted deductions set forth in the CVR Agreement are greater than any gross proceeds, no payments will be made under the CVRs, and the CVRs will expire valueless.

Imara stockholders may not realize a benefit from the Merger commensurate with the ownership dilution they will experience in connection with the Merger, including as a result of the conversion of Enliven common stock issued in the Enliven pre-closing financing.

If the combined company is unable to realize the full strategic and financial benefits currently anticipated from the Merger, Imara stockholders will have experienced substantial dilution of their ownership interests without receiving any commensurate benefit, or only receiving part of the commensurate benefit to the extent the combined company is able to realize only part of the strategic and financial benefits currently anticipated from the Merger.

If the Merger is not completed, Imara’s stock price may fluctuate significantly.

The market price of Imara’s common stock is subject to significant fluctuations. During the 12-month period ended November 1, 2022, the closing sales price of Imara’s common stock on The Nasdaq Global Select Market ranged from a high of $4.97 on November 1, 2022 to a low of $0.99 on April 12, 2022. Market prices for securities of pharmaceutical, biotechnology and other life science companies have historically been particularly volatile. In addition, the market price of Imara common stock will likely be volatile based on whether stockholders and other investors believe that Imara can complete the Merger or otherwise raise additional capital to support Imara’s operations if the Merger is not consummated and another strategic transaction cannot be identified, negotiated and consummated in a timely manner, if at all. The volatility of the market price of Imara common stock is exacerbated by low trading volume. Additional factors that may cause the market price of Imara common stock to fluctuate include:

 

   

the initiation of, material developments in, or conclusion of litigation to enforce or defend its intellectual property rights or defend against claims involving the intellectual property rights of others;

 

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the entry into, or termination of, key agreements, including commercial partner agreements;

 

   

announcements by commercial partners or competitors of new commercial products, clinical progress or lack thereof, significant contracts, commercial relationships or capital commitments;

 

   

the introduction of technological innovations or new therapies that compete with its future products;

 

   

the loss of key employees;

 

   

future sales of its common stock;

 

   

general and industry-specific economic conditions that may affect its research and development expenditures;

 

   

the failure to meet industry analyst expectations; and

 

   

period-to-period fluctuations in financial results.

Moreover, the stock markets in general have experienced substantial volatility that has often been unrelated to the operating performance of individual companies. These broad market fluctuations may also adversely affect the trading price of Imara common stock. In the past, following periods of volatility in the market price of a company’s securities, stockholders have often instituted class action securities litigation against such companies.

Imara and Enliven securityholders will have a reduced ownership and voting interest in, and will exercise less influence over the management of, the combined company following the completion of the Merger as compared to their current ownership and voting interests in the respective companies.

After the completion of the Merger, the current stockholders of Imara and Enliven will own a smaller percentage of the combined company than their ownership of their respective companies prior to the Merger. Immediately after the Merger, Imara securityholders as of immediately prior to the Merger are currently estimated to own approximately 15.9% of the outstanding shares of the combined company on a fully-diluted basis and former Enliven securityholders, including those purchasing shares in the Enliven pre-closing financing, are currently estimated to own approximately 84.1% of the outstanding shares of the combined company on a fully-diluted basis, subject to certain assumptions, including, but not limited to, (a) Imara’s net cash as of the closing being approximately $82 million, (b) Enliven raising approximately $164.5 million in the Enliven pre-closing financing described in this proxy statement/prospectus, (c) a valuation for Imara equal to its net cash as of the business day immediately prior to the closing date of the Merger, plus $10 million and (d) a valuation for Enliven equal to $324.6 million, plus the gross proceeds of the Enliven pre-closing financing, in each case as further described in the Merger Agreement. The Co-founder and Chief Executive Officer of Enliven will serve as the Chief Executive Officer of the combined company following the completion of the Merger.

During the pendency of the Merger, Imara and Enliven may not be able to enter into a business combination with another party on more favorable terms because of restrictions in the Merger Agreement, which could adversely affect their respective business prospects.

Covenants in the Merger Agreement impede the ability of Imara and Enliven to make acquisitions during the pendency of the Merger, subject to specified exceptions. As a result, if the Merger is not completed, the parties may be at a disadvantage to their competitors during that period. In addition, while the Merger Agreement is in effect, each party is generally prohibited from soliciting, proposing, seeking or knowingly encouraging, facilitating or supporting any inquiries, indications of interest, proposals or offers that constitute or may reasonably be expected to lead to certain transactions involving a third party, including a merger, sale of assets or other business combination, subject to specified exceptions. Any such transactions could be favorable to such party’s stockholders, but the parties may be unable to pursue them. For more information, see the section titled “The Merger Agreement—Non- Solicitation” beginning on page 208 of this proxy statement/prospectus.

 

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Certain provisions of the Merger Agreement may discourage third parties from submitting competing proposals, including proposals that may be superior to the transactions contemplated by the Merger Agreement.

The terms of the Merger Agreement prohibit each of Imara and Enliven from soliciting competing proposals or cooperating with persons making unsolicited takeover proposals, except in limited circumstances as described in further detail in the section titled “The Merger Agreement—Non-Solicitation.” In addition, if the Merger Agreement is terminated under specified circumstances, Imara would be required to pay Enliven a termination fee of $3.0 million. This termination fee may discourage third parties from submitting competing proposals to Imara or its stockholders, and may cause the Imara board of directors to be less inclined to recommend a competing proposal.

Because the lack of a public market for Enliven’s capital stock makes it difficult to evaluate the fair market value of Enliven’s capital stock, Imara may pay more than the fair market value of Enliven’s capital stock and/or the stockholders of Enliven may receive consideration in the Merger that is less than the fair market value of Enliven’s capital stock.

The outstanding capital stock of Enliven is privately held and is not traded in any public market. The lack of a public market makes it difficult to determine the fair market value of Enliven’s capital stock. Because the percentage of Imara equity to be issued to Enliven stockholders was determined based on negotiations between the parties, it is possible that the value of the Imara common stock to be received by Enliven stockholders will be less than the fair market value of Enliven’s capital stock, or Imara may pay more than the aggregate fair market value for Enliven’s capital stock.

The Merger may not qualify as either a “reorganization” within the meaning of Section 368(a) of the Code or a non-taxable exchange within the meaning of Section 351(a) of the Code for U.S. federal income tax purposes, resulting in recognition of taxable gain or loss by Enliven stockholders in respect of their Enliven common stock.

As described in the section titled “The Merger—Material U.S. Federal Income Tax Consequences of the Merger” in this proxy statement/prospectus, Imara and Enliven intend for the Merger to qualify as a “reorganization” within the meaning of Section 368(a) of the Code, and in the event that former Enliven stockholders, including stockholders that participate in the Enliven pre-closing financing, are in “control” of Imara immediately after the effective time of the Merger (within the meaning of Section 368(c) of the Code), Imara and Enliven also intend the Merger to qualify as a non-taxable exchange of shares of Enliven common stock for shares of Imara common stock within the meaning of Section 351(a) of the Code. However, Enliven has not sought and does not intend to seek any opinions of counsel or rulings from the U.S. Internal Revenue Service, or IRS, regarding the intended tax treatment of the Merger and, even if opinions of counsel were sought and obtained by Enliven, such opinions would not be binding upon the IRS or a court. Consequently, there can be no assurance that the IRS will not challenge the intended tax treatment of the Merger and, if challenged, that a court would not sustain the IRS’ position. In the event that the Merger does not qualify as either a “reorganization” within the meaning of Section 368(a) of the Code or as a non-taxable exchange within the meaning of Section 351(a) of the Code, each Enliven U.S. holder would recognize gain or loss upon the exchange of shares of Enliven common stock for Imara common stock in the Merger equal to the difference between the fair market value of the shares of Imara common stock received in exchange for the shares of Enliven common stock (plus any cash received in lieu of a fractional share) and such Enliven U.S. holder’s adjusted tax basis in the shares of Enliven common stock surrendered. Each Enliven stockholder is urged to consult with his, her or its own tax advisor with respect to the tax consequences of the Merger.

 

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The U.S. federal income tax treatment of the CVRs is unclear, and there can be no assurance that the Internal Revenue Service would not assert, or that a court would not sustain, a position that could result in adverse U.S. federal income tax consequences to holders of the CVRs.

The U.S. federal income tax treatment of the CVRs is unclear. There is no legal authority directly addressing the U.S. federal income tax treatment of the receipt of, and payments on, the CVRs, and there can be no assurance that the IRS would not assert, or that a court would not sustain, a position that could result in adverse U.S. federal income tax consequences to holders of the CVRs. As discussed in the section titled “Agreements Related to the Merger—CVR Agreement—Material U.S. Federal Income Tax Consequences of the Receipt of CVRs,” Imara will treat the issuance of the CVRs as a distribution of property with respect to its stock. However, there is no authority directly addressing whether contingent value rights with characteristics similar to the CVRs should be treated as a distribution of property with respect to the corporation’s stock, a distribution of equity, a “debt instrument” or an “open transaction” for U.S. federal income tax purposes. In addition, although Imara will estimate the value of the CVRs for purposes of reporting the distribution on Form 1099 to Imara stockholders, the value of the CVRs is uncertain, and the IRS or a court could determine that the value of the CVRs at the time of issuance was higher. In such case, the Imara stockholders could be treated as having additional income or gain upon receipt of the CVRs as described further in the section titled “Agreements Related to the Merger—CVR Agreement—Material U.S. Federal Income Tax Consequences of the Receipt of CVRs” beginning on page 223 of this proxy statement/prospectus. Further, notwithstanding Imara’s position that the receipt of CVRs and the proposed reverse stock split are appropriately treated as separate transactions, it is possible that the IRS or a court could determine that the Imara stockholders’ receipt of the CVRs and the proposed reverse stock split constitute a single “recapitalization” for U.S. federal income tax purposes. No assurance can be given that the IRS would not assert, or that a court would not sustain, a position contrary to Imara’s position, which could result in adverse U.S. federal income tax consequences to holders of the CVRs. The tax consequences of such alternative treatments are described below under the section titled “Agreements Related to the Merger—CVR Agreement—Material U.S. Federal Income Tax Consequences of the Receipt of CVRs,” beginning on page 223 of this proxy statement/prospectus.

Risks Related to the Proposed Reverse Stock Split

The reverse stock split may not increase the combined company’s stock price over the long-term.

The principal purpose of the reverse stock split is to increase the per-share market price of Imara’s common stock above the minimum bid price requirement under the Nasdaq rules so that the listing of the combined company and the shares of Imara common stock being issued in the Merger on Nasdaq will be approved. It cannot be assured, however, that the reverse stock split will accomplish this objective for any meaningful period of time. While it is expected that the reduction in the number of outstanding shares of common stock will proportionally increase the market price of the combined company’s common stock, it cannot be assured that the reverse stock split will increase the market price of its common stock by a multiple of the reverse stock split ratio mutually agreed by Imara and Enliven, or result in any permanent or sustained increase in the market price of the combined company’s common stock, which is dependent upon many factors, including the combined company’s business and financial performance, general market conditions and prospects for future success. Thus, while the stock price of the combined company might meet the listing requirements for Nasdaq initially, it cannot be assured that it will continue to do so.

The reverse stock split may decrease the liquidity of the combined company’s common stock.

Although Imara’s board of directors believes that the anticipated increase in the market price of the combined company’s common stock resulting from the proposed reverse stock split could encourage interest in its common stock and possibly promote greater liquidity for its stockholders, such liquidity could also be adversely affected by the reduced number of shares outstanding after the reverse stock split. The reduction in the number of outstanding shares may lead to reduced trading and a smaller number of market makers for the combined

 

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company’s common stock. In addition, the reverse stock split may not result in an increase in the combined company’s stock price necessary to satisfy Nasdaq’s initial listing requirements for the combined company.

The reverse stock split may lead to a decrease in the combined company’s overall market capitalization.

Should the market price of the combined company’s common stock decline after the reverse stock split, the percentage decline may be greater, due to the smaller number of shares outstanding, than it would have been prior to the reverse stock split. A reverse stock split is often viewed negatively by the market and, consequently, can lead to a decrease in the combined company’s overall market capitalization. If the per share market price does not increase in proportion to the reverse stock split ratio, then the value of the combined company, as measured by its stock capitalization, will be reduced. In some cases, the per-share stock price of companies that have effected reverse stock splits subsequently declined back to pre-reverse split levels, and accordingly, it cannot be assured that the total market value of the combined company’s common stock will remain the same after the reverse stock split is effected, or that the reverse stock split will not have an adverse effect on the combined company’s stock price due to the reduced number of shares outstanding after the reverse stock split.

Risks Related to Imara

Risks Related to Imara’s Financial Position and Need for Additional Capital

As described below, if the Merger is not completed, Imara will reconsider its strategic alternatives, including dissolving and liquidating its assets, pursuing another strategic transaction, or operating its business. If the Merger is not completed, Imara will face various risks related to its financial condition and need for capital; its ability to execute on alternative strategies; discovery, development and commercialization of its product candidates; its intellectual property; regulatory and compliance matters; and its status as a public company, all as further discussed in the Risk Factors, including this subsection titled “—Risks Related to Imara.”

Imara has incurred significant losses since its inception. Imara expects to incur operating losses for the foreseeable future and may never achieve or maintain profitability.

Since inception, Imara has incurred significant operating losses. Its net loss was $51.4 million for the year ended December 31, 2021 and $30.7 million for the nine months ended September 30, 2022. As of September 30, 2022, Imara had an accumulated deficit of $178.2 million. To date, Imara has financed its operations primarily through the sale of common stock and the sale of convertible preferred stock. Imara has historically devoted substantially all of its financial resources and efforts to research and development, including clinical trials and preclinical studies of tovinontrine.

In April 2022, Imara made the decision to discontinue development of tovinontrine and is not currently developing product candidates. Imara may never generate revenues that are significant enough to achieve profitability. Imara is unable to accurately predict the timing or amount of increased expenses or when, or if, Imara will be able to achieve profitability.

Even if Imara does achieve profitability, it may not be able to sustain or increase profitability on a quarterly or annual basis. Its failure to become and remain profitable would depress the value of the company and could impair its ability to raise capital, expand its business, maintain its research and development efforts, diversify its pipeline of product candidates or even continue its operations. A decline in the value of the company could also cause its stockholders to lose all or part of their investment.

 

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If the Merger is not completed, Imara will reconsider its strategic alternatives, including dissolving and liquidating its assets, pursuing another strategic transaction, or operating its business. Imara’s future capital requirements depend on many factors, and adequate additional financing may not be available to it on acceptable terms, or at all.

Imara expects to devote significant time and resources to the completion of the Merger. However, there can be no assurances that such activities will result in the completion of the Merger. If the Merger is not completed, Imara will reconsider its strategic alternatives. Imara considers one of the following courses of action to be the most likely alternatives if the Merger is not completed:

 

   

Dissolve and liquidate its assets. If, for any reason, the Merger does not close, Imara’s board of directors may conclude that it is in the best interest of stockholders to dissolve the company and liquidate its assets. In that event, Imara would be required to pay all of its debts and contractual obligations, and to set aside certain reserves for potential future claims. There would be no assurances as to the amount or timing of available cash remaining to distribute to stockholders after paying Imara’s obligations and setting aside funds for reserves.

 

   

Pursue another strategic transaction. Imara may resume the process of evaluating a potential strategic transaction in order to attempt another strategic transaction like the Merger.

 

   

Operate its business. Imara’s board of directors may elect to initiate development of IMR-261 or to seek new product candidates for development.

If Imara’s board of directors elects to seek new product candidates for development, Imara expects that it would incur significant research and development expenses. If Imara is unable to raise capital when needed or on attractive terms, it would be forced to delay, reduce or eliminate any such future research and development programs or commercialization efforts and/or Imara could be forced to revise or abandon its current business strategy.

Identifying potential product candidates and conducting preclinical testing and clinical trials is a time-consuming, expensive and uncertain process that takes years to complete, and Imara may never generate the necessary data or results required to obtain regulatory approval and achieve product sales. In addition, any product candidates, if approved, may not achieve commercial success. Commercial revenues, if any, will not be derived unless and until Imara can achieve sales of products, which it does not anticipate for several years, if at all. Accordingly, if Imara decides to pursue any future product development efforts, it will need to obtain substantial additional funding in connection with its continuing operations.

In April 2021, Imara entered into a sales agreement, or the Sales Agreement, with Cantor Fitzgerald & Co, LLC, as sales agent, providing for the offering, issuance and sale by Imara of up to an aggregate $75.0 million of its common stock from time to time in “at-the-market” offerings under a shelf registration statement on Form S-3. As of September 30, 2022, Imara had issued and sold 231,291 shares of common stock under the Sales Agreement, resulting in net proceeds of $1.4 million after deducting commissions and offering expenses. The extent to which Imara utilizes the Sales Agreement as a source of funding will depend on a number of factors, including the prevailing market price of its common stock, general market conditions, the extent to which Imara is able to secure funds from other sources, and restrictions on Imara’s ability to sell common stock pursuant to the Sales Agreement to the extent it is then subject to restrictions on its ability to utilize the Form S-3 shelf registration statement to sell more than one-third of the market value of its public float, meaning the aggregate market value of voting and non-voting common stock held by non-affiliates, in any trailing 12-month period. Accordingly, Imara may not be able to sell shares under the Sales Agreement at prices or amounts that it deems acceptable, and there can be no assurance that it will sell any further common stock pursuant to the Sales Agreement.

 

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As of September 30, 2022, Imara had cash, cash equivalents and investments of $56.3 million. Imara’s future capital requirements will depend on many factors, including:

 

   

whether it completes the Merger with Enliven and, if the Merger is completed, the capital requirements of the combined company;

 

   

whether Imara realizes the anticipated cost savings in connection with its April 2022 workforce reduction;

 

   

if Imara decides to pursue any future product development efforts, its ability to bring any such product candidate through preclinical and clinical development, and the timing and scope of these research and development activities;

 

   

the costs of obtaining clinical and commercial supplies of any product candidates Imara may develop;

 

   

Imara’s ability to successfully commercialize any product candidates it may develop;

 

   

the manufacturing, selling and marketing costs associated with any product candidates Imara may develop, including the cost and timing of establishing its sales and marketing capabilities;

 

   

the amount and timing of sales and other revenues from any product candidates Imara may develop, including the sales price and the availability of coverage and adequate third-party reimbursement;

 

   

the time and cost necessary to respond to technological and market developments;

 

   

the extent to which Imara may acquire or in-license product candidates and technologies;

 

   

the impact of the COVID-19 pandemic and Imara’s response to it;

 

   

the costs of maintaining, expanding and protecting Imara’s intellectual property portfolio; and

 

   

the costs associated with operating as a public company and maintaining compliance with exchange listing and SEC requirements.

Imara may seek additional financing to achieve its business objectives. Adequate additional financing may not be available to it on acceptable terms, or at all. In addition, Imara may seek additional capital when market conditions are favorable, or for strategic considerations, even if it believes it has sufficient funds for its current or future operating plans. If adequate funds are not available to Imara on a timely basis or on terms acceptable to Imara, it may be required to delay, limit, reduce or terminate any preclinical studies, clinical trials or other activities for any product candidates under development at such time, or delay, limit, reduce or terminate its establishment of sales and marketing capabilities or other activities that may be necessary to commercialize any product candidates.

Raising additional capital may cause dilution to Imara’s stockholders, restrict its operations or require it to relinquish rights to its technologies or product candidates.

Until such time, if ever, as Imara can generate substantial product revenues, Imara expect to finance its cash needs through a combination of the sale of one or more of its product candidates or other assets, equity offerings, debt financings, collaborations, strategic alliances and marketing, distribution or licensing arrangements. Imara does not have any committed external source of funds. To the extent that Imara raises additional capital through the sale of equity or convertible debt securities, its stockholders’ ownership interests will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect its stockholders’ rights as common stockholders. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting Imara’s ability to take specific actions, such as incurring additional debt, selling or licensing its assets, making capital expenditures or declaring dividends.

If Imara raises additional funds through the sale of one or more of its product candidates or other assets, collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, Imara

 

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may have to relinquish valuable rights to its technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to Imara. If Imara is unable to raise additional funds through equity or debt financings when needed or on terms acceptable to it, it may be required to delay, limit, reduce or terminate any product development or future commercialization efforts or grant rights to develop and market product candidates that Imara would otherwise prefer to develop and market itself.

Imara’s limited operating history may make it difficult to evaluate the success of its business to date and to assess its future viability.

Imara commenced activities in 2016 and its operations to date have been limited to organizing and staffing its company, business planning, raising capital, developing its technology, and undertaking preclinical studies and clinical trials of its product candidates. Imara has not yet demonstrated its ability to successfully develop any product candidate, obtain regulatory approvals, manufacture a commercial scale product or arrange for a third-party to do so on its behalf, or conduct sales and marketing activities necessary for successful product commercialization. Consequently, any predictions about its future success or viability may not be as accurate as they could be if Imara had a longer operating history or a history of successfully developing and commercializing products.

Imara expects its financial condition and operating results to fluctuate significantly from quarter-to-quarter and year-to-year due to a variety of factors, many of which are beyond its control. Each of its announcements regarding the termination of development of tovinontrine and the related workforce reduction, the Asset Sale, and the signing of the Merger Agreement are likely to further increase the variability of its operating results in the coming quarters as compared to prior quarters. Accordingly, Imara’s stockholders should not rely upon the results of any quarterly or annual periods as indications of future operating performance.

Imara’s ability to use its net operating losses, or NOLs, and research and development tax credit carryforwards to offset future taxable income may be subject to certain limitations.

Imara has a history of cumulative losses and anticipates that it will continue to incur significant losses in the foreseeable future; thus, it does not know whether or when it will generate taxable income necessary to utilize its net operating losses, or NOLs, or research and development tax credit carryforwards. As of December 31, 2021, it had federal NOLs of $139.2 million and state NOLs of $129.4 million.

In general, under Sections 382 and 383 of the Code and corresponding provisions of state law, a corporation that undergoes an “ownership change,” generally defined as a greater than 50 percentage point change (by value) in its equity ownership by certain stockholders over a three year period, is subject to limitations on its ability to utilize its pre-change NOLs and research and development tax credit carryforwards to offset future taxable income. Imara may have experienced such ownership changes in the past, including as a result of its public offering of shares of common stock in July 2021, and the Merger, if completed, will result in such an ownership change. Imara may experience additional ownership changes in the future as a result of subsequent changes in its stock ownership (which may be outside Imara’s control). As a result, if, and to the extent that, Imara earns net taxable income, its ability to use its pre-change NOLs and research and development tax credit carryforwards to offset such taxable income may be subject to limitations.

There is also a risk that due to regulatory changes, such as suspensions on the use of NOLs, or other unforeseen reasons, Imara’s existing NOLs could expire or otherwise become unavailable to offset future income tax liabilities. As described below in “Changes in tax laws or in their implementation or interpretation may adversely affect Imara’s business and financial condition,” the Tax Cuts and Jobs Act, or TCJA, as amended by the Coronavirus Aid, Relief, and Economic Security Act, or CARES Act, includes changes to U.S. federal tax rates and the rules governing NOL carryforwards that may significantly impact Imara’s ability to utilize its NOLs to offset taxable income in the future. Additionally, state NOLs generated in one state cannot be used to offset

 

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income generated in another state. For these reasons, even if Imara attains profitability, it may be unable to use a material portion of its NOLs and other tax attributes.

Imara’s business and operations have been and may continue to be adversely affected by the COVID-19 pandemic, as may the operations of its third-party service providers.

The COVID-19 pandemic and government measures taken in response to it have had a significant impact, both direct and indirect, on businesses and commerce, as worker shortages have occurred; supply chains have been disrupted; facilities and production have been suspended; and demand for certain goods and services, such as medical services and supplies, has spiked, while demand for other goods and services has fallen. The future progression of the pandemic and its effects on Imara’s business and operations are uncertain.

The COVID-19 pandemic has affected Imara’s operations to date, including by causing delays in the conduct of clinical trials. While Imara has not experienced any significant disruptions with the third parties on which it relies, the COVID-19 pandemic, or the spread of another infectious disease, could also negatively affect the operations of Imara’s third-party manufacturers, which could result in disruptions in the supply of any product candidates Imara may develop. In addition, many of Imara’s employees are currently working remotely. The COVID-19 pandemic continues to rapidly evolve and could more significantly impact Imara’s operations in the future.

Although Imara is not currently developing any product candidates, if it decides to pursue any future product development efforts, the COVID-19 pandemic may adversely affect its development activities, including its ability to recruit and retain patients in clinical trials, as a result of many factors, including:

 

   

diversion of healthcare resources away from the conduct of its clinical trials in order to focus on pandemic concerns, including the availability of necessary materials, the attention of physicians serving as clinical trial investigators, access to hospitals serving as clinical trial sites, availability of hospital staff supporting the conduct of clinical trials and the reluctance of patients enrolled in clinical trials to visit clinical trial sites;

 

   

potential interruptions in global shipping affecting the transport of clinical trial materials, such as investigational drug product, patient samples and other supplies used in clinical trials;

 

   

the impact of further limitations on travel that could interrupt key clinical trial activities, such as clinical trial site initiations and monitoring activities, travel by Imara’s employees, contractors or patients to clinical trial sites, or the ability of employees at any of Imara’s contract manufacturers or contract research organizations, or CROs, to report to work, any of which could delay or adversely impact the conduct or progress of clinical trials, and limit the amount of clinical data Imara will be able to report;

 

   

any future interruption of, or delays in receiving, supplies of clinical trial material from Imara’s contract manufacturing organizations, or CMOs, due to staffing shortages, production slowdowns or stoppages or disruptions in delivery systems; and

 

   

availability of future capacity at contract manufacturers to produce sufficient drug substance and drug product to meet forecasted clinical trial demand if any of these manufacturers elect or are required to divert attention or resources to the manufacture of other pharmaceutical products.

Additionally, while the potential economic impact and the duration of the COVID-19 pandemic is difficult to assess or predict, any impact of the COVID-19 pandemic on the global financial markets may reduce Imara’s ability to access capital, which could negatively impact its short-term and long-term liquidity.

While Imara expects the impacts of COVID-19 will continue to have some adverse effect on its business, the extent to which COVID-19 impacts its operations will depend on future developments, which remain uncertain

 

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and cannot be predicted with confidence, including the duration of the pandemic, new information which may emerge concerning the severity of COVID-19 and variants of COVID-19, the actions to contain COVID-19 or treat its impact and changes in government spending or priorities, among others. The COVID-19 pandemic is a widespread health crisis that continues to adversely affect the global economy and financial markets of many countries, and any economic downturn could also affect Imara’s operations, its ability to raise additional funds through public offerings and the volatility of its stock price and trading in its stock. Even after the COVID-19 pandemic has subsided, Imara may continue to experience adverse impacts to its business as a result of any economic recession or depression that has occurred or may occur in the future.

Risks Related to the Discovery, Development and Commercialization of Imara’s Product Candidates

Imara does not currently have any product candidates in active development. Future clinical trials of its product candidates, if any, may not be successful. If Imara is unable to successfully develop or commercialize its product candidates, or experience significant delays in doing so, its business will be materially harmed.

As discussed above, if the Merger is not completed, Imara will reconsider its strategic alternatives, including dissolving and liquidating its assets, pursuing another strategic transaction, or operating its business. If Imara’s board of directors elects to seek product candidates for development, Imara will face the risks related to discovery, development and commercialization of its product candidates set forth in this section, in addition to other risks described in this Risk Factors section.

Although Imara has invested a significant portion of its efforts and financial resources in the development of its product candidates, Imara is not currently actively developing any of its product candidates. If Imara decides to pursue any future product development efforts, its ability to generate meaningful product revenues will depend heavily on the successful development of its product candidates. To the extent that Imara pursues any development efforts in the future, its success will depend on several factors, including the following:

 

   

successfully completing clinical trials;

 

   

acceptance by the FDA or other regulatory agencies of regulatory filings;

 

   

expanding and maintaining a workforce of experienced clinical-stage drug development professionals and others to continue to develop its product candidates;

 

   

obtaining and maintaining intellectual property protection and regulatory exclusivity for its product candidates;

 

   

making arrangements with third-party manufacturers for, or establishing, commercial manufacturing capabilities;

 

   

establishing sales, marketing and distribution capabilities and successfully launching commercial sales, if and when approved, whether alone or in collaboration with others;

 

   

acceptance of its product candidates, if and when approved, by patients, the medical community and third-party payors;

 

   

effectively competing with other existing therapies, if any;

 

   

obtaining and maintaining coverage, adequate pricing and adequate reimbursement from third-party payors, including government payors;

 

   

patients’ willingness to pay out-of-pocket for its product candidates in the absence of coverage and/or adequate reimbursement from third-party payors; and

 

   

maintaining a continued acceptable safety profile following receipt of any regulatory approvals.

Many of these factors are beyond Imara’s control, including clinical outcomes, the regulatory review process, potential threats to its intellectual property rights and the manufacturing, marketing and sales efforts of any future

 

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collaborator. If Imara is unable to develop, receive marketing approval for and successfully commercialize any product candidates it seeks to develop, or if it experiences delays as a result of any of these factors or otherwise, Imara may need to spend significant additional time and resources to identify additional product candidates, advance them through preclinical and clinical development and apply for regulatory approvals, which would adversely affect its business, prospects, financial condition and results of operations.

Clinical drug development involves a lengthy and expensive process, with an uncertain outcome. Imara may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of any product candidates.

The risk of failure for any product candidates Imara may develop is high. It is impossible to predict when or if any product candidates it may develop will prove effective or safe in humans or will receive regulatory approval. Before obtaining marketing approval from regulatory authorities for the sale of any product candidate, Imara must complete preclinical development and then conduct extensive clinical trials to demonstrate the safety and efficacy of such product candidate in humans. Clinical trials may fail to demonstrate that any product candidates Imara may develop are safe for humans and effective for indicated uses. For example, in April 2022, Imara discontinued development of tovinontrine in SCD and ß-thalassemia based on the results of interim analyses of its Ardent and Forte Phase 2b clinical trial of tovinontrine in patients with SCD and ß-thalassemia. Even if clinical trials are successful, changes in marketing approval policies during the development period, changes in or the enactment or promulgation of additional statutes, regulations or guidance or changes in regulatory review for each submitted product application may cause delays in the approval or rejection of an application.

Before Imara can commence clinical trials for a product candidate, it must complete extensive preclinical testing and studies that support its planned investigational new drug applications, or INDs, and other regulatory filings in the United States and abroad. Imara cannot be certain of the timely completion or outcome of its preclinical testing and studies, and cannot predict if the FDA or other regulatory agencies will accept its proposed clinical programs or if the outcome of its preclinical testing and studies will ultimately support the further development of any product candidates. As a result, Imara cannot be sure that it will be able to submit INDs or similar applications for its preclinical programs on the timelines it expects, if at all, and it cannot be sure that submission of INDs or similar applications will result in the FDA or other regulatory authorities allowing clinical trials to begin. Furthermore, product candidates are subject to continued preclinical safety studies, which may be conducted concurrent with Imara’s clinical testing. The outcomes of these safety studies may delay the launch of or enrollment in future clinical trials and could impact Imara’s ability to continue to conduct its clinical trials.

Clinical trials are expensive, difficult to design and implement, can take many years to complete and are uncertain as to outcome. Imara cannot guarantee that any clinical trials will be conducted as planned or completed on schedule, or at all. A failure of one or more clinical trials can occur at any stage of testing, which may result from a multitude of factors, including, but not limited to, flaws in study design, dose selection issues, placebo effects, patient enrollment criteria and failure to demonstrate favorable safety or efficacy traits.

Imara may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent its ability to receive marketing approval or commercialize any product candidates it may develop, including:

 

   

regulators or institutional review boards, or IRBs, may not authorize Imara or its investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site;

 

   

Imara may experience delays in reaching, or fail to reach, agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites;

 

   

regulators may decide the design of Imara’s clinical trials is flawed, for example, if its trial protocol does not evaluate treatment effects in trial subjects for a sufficient length of time;

 

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clinical trials of any product candidates Imara may develop may produce negative or inconclusive results, and Imara may decide, or regulators may require it, to conduct additional clinical trials or abandon product development programs;

 

   

Imara may be unable to establish clinical endpoints that applicable regulatory authorities would consider clinically meaningful, or, if Imara seeks accelerated approval, biomarker efficacy endpoints that applicable regulatory authorities would consider likely to predict clinical benefit;

 

   

the number of patients required for clinical trials of any product candidates Imara may develop may be larger than it anticipates, enrollment in these clinical trials may be slower than it anticipates or participants may drop out of these clinical trials at a higher rate than it anticipates;

 

   

Imara’s third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to Imara in a timely manner, or at all;

 

   

Imara may decide, or regulators or IRBs may require it, to suspend or terminate clinical trials of any product candidates it may develop for various reasons, including non-compliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks;

 

   

regulators or IRBs may require Imara to perform additional or unanticipated clinical trials to obtain approval or Imara may be subject to additional post-marketing testing requirements to maintain regulatory approval;

 

   

regulators may revise the requirements for approving any product candidates Imara may develop, or such requirements may not be as it anticipates;

 

   

the cost of clinical trials of any product candidates Imara may develop may be greater than it anticipates;

 

   

the supply or quality of any product candidates Imara may develop or other materials necessary to conduct clinical trials of such product candidates may be insufficient or inadequate;

 

   

any product candidates Imara may develop may have undesirable side effects or other unexpected characteristics, causing Imara or its investigators, regulators or IRBs to suspend or terminate the trials; and

 

   

regulators may withdraw their approval of a product or impose restrictions on its distribution, such as in the form of a risk evaluation and mitigation strategy, or REMS.

If Imara is required to conduct additional clinical trials or other testing beyond those that it contemplates, if it is unable to successfully complete clinical trials or other testing of any product candidates it may develop, if the results of these trials or tests are not positive or are only modestly positive or if there are safety concerns, Imara may:

 

   

be delayed in obtaining marketing approval for any product candidates;

 

   

not obtain marketing approval at all;

 

   

obtain approval for indications or patient populations that are not as broad as intended or desired;

 

   

obtain approval with labeling or a REMS that includes significant use or distribution restrictions or safety warnings;

 

   

be subject to additional post-marketing testing requirements; or

 

   

have the product removed from the market after obtaining marketing approval.

Imara’s product development costs will also increase if it experiences delays in testing or in obtaining marketing approvals. Imara does not know whether any of its preclinical studies or clinical trials will begin as planned, will need to be restructured or will be completed on schedule, or at all. Imara may also change the design or protocol

 

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of one or more of its clinical trials, including to add additional patients or arms, which could result in increased costs and expenses and/or delays. Significant preclinical study or clinical trial delays also could shorten any periods during which Imara may have the exclusive right to commercialize any product candidates or allow its competitors to bring products to market before it does and impair its ability to successfully commercialize any product candidates and may harm its business and results of operations.

The outcome of preclinical studies and earlier-stage clinical trials may not be predictive of the success of later-stage clinical trials.

The outcome of preclinical testing and earlier-stage clinical trials may not be predictive of the success of later-stage clinical trials. Any product candidates Imara may develop may fail to show the desired safety and efficacy in clinical development despite positive results in preclinical studies or having successfully advanced through initial clinical trials. For example, data from the interim analysis in Imara’s Ardent Phase 2b clinical trial of tovinontrine in SCD did not replicate its previously observed positive vaso-occlusive crisis data from its Phase 2a and OLE clinical trials of tovinontrine in SCD. Similarly, data from the interim analysis in its Forte Phase 2b clinical trial of tovinontrine in ß-thalassemia showed no meaningful benefit from treatment with tovinontrine as compared to placebo, despite previous positive preclinical data for tovinontrine in ß-thalassemia. In April 2022, Imara discontinued the Ardent and Forte trials as well as the further development of tovinontrine in SCD and ß-thalassemia.

Several companies in the pharmaceutical and biotechnology industries have suffered similar setbacks in late-stage clinical trials even after achieving promising results in preclinical testing and earlier-stage clinical trials, and Imara cannot be certain that it will not face similar setbacks in any future product development it may pursue. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their products. Furthermore, the failure of any product candidate to demonstrate safety and efficacy in any clinical trial could negatively impact the perception of any other product candidates then under development and/or cause the FDA or other regulatory authorities to require additional testing before approving any other such product candidates.

If Imara decides to pursue any future product development efforts and experiences delays or difficulties in the enrollment of patients in clinical trials, its receipt of necessary regulatory approvals could be delayed or prevented.

Although Imara is not currently developing its product candidates, if it decides to pursue any future product development efforts, identifying and qualifying patients to participate in clinical trials for any product candidates it may develop will be critical to its success. Successful and timely completion of clinical trials will require that Imara enroll a sufficient number of patients who remain in the trial until its conclusion. Imara may not be able to initiate or continue clinical trials for any product candidates it may develop if it is unable to locate and enroll a sufficient number of eligible patients to participate in these trials as required by the FDA or similar regulatory authorities outside of the United States. Imara may not be able to identify, recruit, and enroll a sufficient number of patients to complete clinical trials of any product candidate it may develop because of the perceived risks and benefits of such product candidate, the availability of competing therapies and clinical trials, the proximity and availability of clinical trial sites for prospective subjects and the subject referral practices of physicians, among other factors.

Patient enrollment is affected by a variety of other factors, including:

 

   

the prevalence and severity of the disease under investigation;

 

   

the eligibility criteria for the trial in question;

 

   

the perceived risks and benefits of the product candidate under trial;

 

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the requirements of the trial protocols;

 

   

the availability of existing commercially available treatments for the indications for which Imara is conducting clinical trials;

 

   

the ability to recruit clinical trial investigators with the appropriate competencies and experience;

 

   

efforts to facilitate timely enrollment in clinical trials;

 

   

the patient referral practices of physicians;

 

   

the ability to monitor patients adequately during and after treatment;

 

   

the proximity and availability of clinical trial sites for prospective patients;

 

   

the conduct of clinical trials by competitors for product candidates that treat the same indications as any product candidates Imara may develop;

 

   

the ability to identify specific patient populations for biomarker-defined trial cohort(s); and

 

   

the cost to, or lack of adequate compensation for, prospective patients.

Imara’s inability to locate and enroll a sufficient number of patients for its clinical trials would result in significant delays, could require it to abandon one or more clinical trials altogether and could delay or prevent its receipt of necessary regulatory approvals. Enrollment delays in its clinical trials may result in increased development costs for any product candidates it may develop, which would cause the value of the company to decline and limit Imara’s ability to obtain additional financing.

Changes in methods of product candidate manufacturing or formulation may result in additional costs or delay.

As product candidates proceed through preclinical studies to late-stage clinical trials towards potential approval and commercialization, it is common that various aspects of the development program, such as manufacturing methods and formulation, are altered along the way in an effort to optimize processes and results. Such changes carry the risk that they will not achieve these intended objectives. Any of these changes could cause any product candidates Imara may develop to perform differently and affect the results of planned clinical trials or other future clinical trials conducted with the materials manufactured using altered processes. Such changes may also require additional testing, FDA notification or FDA approval. This could delay completion of clinical trials, require the conduct of bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay approval of the affected product candidate and jeopardize Imara’s ability to commence sales and generate revenue.

If serious adverse events or unacceptable side effects are identified during the development of any product candidates Imara may develop, it may need to abandon or limit its development of those product candidates.

Clinical trials by their nature utilize a sample of the potential patient population. Many product candidates that initially showed promise in early-stage testing have later been found to cause side effects that prevented their further development. If Imara decides to pursue any future product development efforts and any product candidates it develops are associated with undesirable side effects in clinical trials or have characteristics that are unexpected in clinical trials or preclinical testing, Imara may need to abandon their development or limit development to more narrow uses or subpopulations in which the side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective. In pharmaceutical development, many compounds that initially show promise in early-stage or clinical testing are later found to cause side effects that delay or prevent further development of the compound.

Additionally, if results of clinical trials reveal unacceptable side effects, Imara, the FDA or similar regulatory authorities outside of the United States, or the IRBs or Ethics Committees at the institutions in which Imara’s

 

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studies are conducted, could suspend or terminate clinical trials or the FDA or similar foreign regulatory authorities could order Imara to cease clinical trials or deny approval of any product candidates Imara may develop for any or all targeted indications. Treatment-related side effects could also affect patient recruitment or the ability of enrolled patients to complete any clinical trials. If Imara elects or is forced to suspend or terminate any clinical trial of any product candidates it may develop, the commercial prospects of such product candidate will be harmed, and Imara’s ability to generate product revenue from such product candidate will be delayed or eliminated. Any of these occurrences could materially harm Imara’s business.

If any product candidate receives marketing approval and Imara, or others, later discovers that the drug is less effective than previously believed or causes undesirable side effects that were not previously identified, Imara’s ability to market the drug could be compromised.

If Imara decides to pursue any future product development efforts, the conduct of any clinical trials of product candidates is likely to be conducted in carefully defined subsets of patients who have agreed to enter into clinical trials. Consequently, it is possible that Imara’s clinical trials may indicate an apparent positive effect of a product candidate that is greater than the actual positive effect, if any, or alternatively fail to identify undesirable side effects. If any product candidate receives regulatory approval, and Imara, or others, later discovers that it is less effective than previously believed, or causes undesirable side effects, a number of potentially significant negative consequences could result, including:

 

   

withdrawal or limitation by regulatory authorities of approvals of such product;

 

   

seizure of the product by regulatory authorities;

 

   

recall of the product;

 

   

restrictions on the marketing of the product or the manufacturing process for any component thereof;

 

   

requirement by regulatory authorities of additional warnings on the label, such as a “black box” warning or contraindication;

 

   

decrease or elimination of third-party reimbursement;

 

   

requirement that Imara implement a REMS or create a medication guide outlining the risks of such side effects for distribution to patients;

 

   

commitment to expensive post-marketing studies as a prerequisite of approval by regulatory authorities of such product;

 

   

the product may become less competitive;

 

   

initiation of regulatory investigations and government enforcement actions;

 

   

initiation of legal action against Imara to hold it liable for harm caused to patients; and

 

   

harm to Imara’s reputation and resulting harm to physician or patient acceptance of its products.

Any of these events could prevent Imara from achieving or maintaining market acceptance of a particular product candidate, if approved, and could significantly harm its business, financial condition, and results of operations.

If Imara decides to pursue any future product development efforts, it may not be successful in its efforts to identify or discover product candidates and may fail to capitalize on programs or product candidates that may present a greater commercial opportunity or for which there is a greater likelihood of success.

If Imara decides to pursue any future product development efforts, there can be no assurance that it will be successful in its efforts to identify or acquire potential product candidates. Even if Imara identifies or acquire additional product candidates, there can be no assurance that its development efforts will be successful.

Additionally, because Imara has limited resources, it may forego or delay pursuit of opportunities with certain programs or product candidates or for indications that later prove to have greater commercial potential. If Imara

 

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does not accurately evaluate the commercial potential for a particular product candidate, it may relinquish valuable rights to that product candidate through a sale, strategic collaboration, licensing or other arrangements in cases in which it would have been more advantageous for Imara to retain sole development and commercialization rights to such product candidate. Alternatively, Imara may allocate internal resources to a product candidate in a therapeutic area in which it would have been more advantageous to enter into a partnering arrangement.

Even if any product candidate receives marketing approval, it may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success.

If any product candidate receives marketing approval, it may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community. Sales of medical products depend in part on the willingness of physicians to prescribe the treatment, which is likely to be based on a determination by these physicians that the products are safe, therapeutically effective and cost effective. In addition, the inclusion or exclusion of products from treatment guidelines established by various physician groups and the viewpoints of influential physicians can affect the willingness of other physicians to prescribe the treatment. Imara cannot predict whether physicians, physicians’ organizations, hospitals, other healthcare providers, government agencies or private insurers will determine that any product it may develop is safe, therapeutically effective and cost effective as compared with competing treatments. Efforts to educate the medical community and third-party payors on the benefits of any product candidates Imara may develop may require significant resources and may not be successful. If any product candidates Imara may develop do not achieve an adequate level of acceptance, Imara may not generate significant product revenues and it may not become profitable. The degree of market acceptance of any product candidates Imara may develop, if approved for commercial sale, will depend on a number of factors, including:

 

   

the efficacy and potential advantages compared to alternative treatments;

 

   

the effectiveness of sales and marketing efforts;

 

   

the cost of treatment in relation to alternative treatments, including any similar generic treatments;

 

   

the clinical indications for which the product is approved;

 

   

the convenience and ease of administration compared to alternative treatments;

 

   

the willingness of the target patient population to try new therapies and to continue treatment over time and of physicians to prescribe these therapies;

 

   

the strength of marketing and distribution support;

 

   

the timing of market introduction of competitive products;

 

   

the availability of third-party coverage and adequate reimbursement, and patients’ willingness to pay out of pocket for required co-payments or in the absence of third-party coverage or adequate reimbursement;

 

   

the prevalence and severity of any side effects; and

 

   

any restrictions on the use of Imara’s products, if approved, together with other medications.

If Imara decides to pursue any future product development efforts and it is unable to establish sales, marketing and distribution capabilities or enter into sales, marketing and distribution agreements with third parties, Imara may not be successful in commercializing any product candidates if and when they are approved.

Imara does not have a sales or marketing infrastructure and has no experience in the sale, marketing or distribution of pharmaceutical products. To achieve commercial success for any product for which Imara has

 

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obtained marketing approval, it will need to establish a sales, marketing and distribution organization, either itself or through collaborations or other arrangements with third parties should Imara pursue developing and commercializing novel therapeutics.

In the future, Imara expects that it would begin to build a sales and marketing infrastructure to market any product candidates it may develop, if and when approved by the applicable regulatory authority. There are risks involved with establishing Imara’s own sales, marketing and distribution capabilities. For example, recruiting and training a sales force is expensive and time-consuming and could delay any product launch. If the commercial launch of a product candidate for which Imara recruits a sales force and establishes marketing capabilities is delayed or does not occur for any reason, Imara would have prematurely or unnecessarily incurred these commercialization expenses. These efforts would be costly, and Imara’s investment would be lost if it cannot retain or reposition its sales and marketing personnel.

Factors that may inhibit Imara’s efforts to commercialize products on its own include:

 

   

Imara’s inability to recruit, train and retain adequate numbers of effective sales, marketing, coverage or reimbursement, customer service, medical affairs and other support personnel;

 

   

the inability of sales personnel to educate adequate numbers of physicians on the benefits of any future products;

 

   

the inability of reimbursement professionals to negotiate arrangements for formulary access, reimbursement and other acceptance by payors;

 

   

the inability to price products at a sufficient price point to ensure an adequate and attractive level of profitability;

 

   

restricted or closed distribution channels that make it difficult to distribute products to segments of the patient population;

 

   

the lack of complementary products to be offered by sales personnel, which may put Imara at a competitive disadvantage relative to companies with more extensive product lines; and

 

   

unforeseen costs and expenses associated with creating an independent sales and marketing organization.

If Imara is unable to establish its own sales, marketing and distribution capabilities and it enters into arrangements with third parties to perform these services, its product revenues and its profitability, if any, are likely to be lower than if Imara were to market, sell and distribute any products that it would develop itself. In addition, Imara may not be successful in entering into arrangements with third parties to sell, market and distribute any product candidates or may be unable to do so on terms that are acceptable to it. Imara likely will have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market Imara’s products effectively. If Imara does not establish sales, marketing and distribution capabilities successfully, either on its own or in collaboration with third parties, it will not be successful in commercializing any product candidates.

Imara faces substantial competition, which may result in others discovering, developing or commercializing products before or more successfully than it does.

The development and commercialization of new drug products is highly competitive. If Imara decides to pursue any future product development efforts, it will face competition with respect to any product candidates that it may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide. Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek

 

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patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization.

Imara’s commercial opportunity could be reduced or eliminated if its competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that it may develop. Imara’s competitors also may obtain FDA or other regulatory approval for their products more rapidly than Imara may obtain approval for its, which could result in Imara’s competitors establishing a strong market position before it is able to enter the market. In addition, Imara’s ability to compete may be affected in many cases by insurers or other third-party payors seeking to encourage the use of generic products. If any product candidates achieve marketing approval, Imara expects that they would be priced at a significant premium over competitive generic products.

Many of the companies against which Imara is competing or against which it may compete in the future have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than Imara does.

Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of Imara’s competitors. Smaller and other early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These third parties compete with Imara in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, Imara’s programs.

Even if Imara is able to commercialize any product candidates, the products may become subject to unfavorable pricing regulations, third-party coverage or reimbursement practices or healthcare reform initiatives, which could harm Imara’s business.

The regulations that govern marketing approvals, pricing, coverage and reimbursement for new drug products vary widely from country to country. Current and future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. Some countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted. As a result, Imara might obtain marketing approval for a product in a particular country, but then be subject to price regulations that delay its commercial launch of the product, possibly for lengthy time periods, and negatively impact the revenues Imara is able to generate from the sale of the product in that country. Adverse pricing limitations may hinder Imara’s ability to recoup its investment in one or more product candidates, even if any product candidates obtain marketing approval.

Imara’s ability to commercialize any product candidates successfully will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations. Government authorities and other third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels. A primary trend in the U.S. healthcare industry and elsewhere is cost containment. Government authorities and other third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products. Coverage and reimbursement may not be available for any product that Imara commercializes and, even if these are available, the level of reimbursement may not be satisfactory. Reimbursement may affect the demand for, or the price of, any product candidate for which Imara obtains marketing approval. Obtaining and maintaining adequate reimbursement for

 

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Imara’s products may be difficult. There can be no assurance that any product candidates, even if they are approved for sale in the United States or in other countries, will be considered medically reasonable and necessary for a specific indication or cost-effective by third-party payors. Imara may be required to conduct expensive pharmacoeconomic studies to justify coverage and reimbursement or the level of reimbursement relative to other therapies. If coverage and adequate reimbursement are not available, Imara may not be able to successfully commercialize any product candidate for which it obtains marketing approval.

There may be significant delays in obtaining coverage and reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which the drug is approved by the FDA or similar regulatory authorities outside of the United States. Moreover, eligibility for coverage and reimbursement does not imply that a drug will be paid for in all cases or at a rate that covers Imara’s costs, including research, development, manufacture, sale and distribution expenses. Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover Imara’s costs and may not be made permanent. Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States. Further, no uniform policy for coverage and reimbursement exists in the United States. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies, but also have their own methods and process apart from Medicare determinations. As a result, obtaining and maintaining coverage and adequate reimbursement is often time-consuming and costly. Imara’s inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for any approved products that it develops could have a material adverse effect on its operating results, its ability to raise capital needed to commercialize products and its overall financial condition.

If Imara decides to pursue any future product development efforts, its success may depend, in part, on its ability to penetrate foreign markets, where it would be subject to additional regulatory burdens and other risks and uncertainties that, if they materialize, could harm its business.

If Imara decides to pursue any future product development efforts, its future profitability may depend, in part, on its ability to commercialize any product candidates it may develop in markets outside of the United States and the European Union. If Imara commercializes any product candidates it may develop in foreign markets, it will be subject to additional risks and uncertainties, including:

 

   

economic weakness, including inflation, or political instability in particular economies and markets;

 

   

the burden of complying with complex and changing foreign regulatory, tax, accounting and legal requirements, many of which vary between countries;

 

   

different medical practices and customs in foreign countries affecting acceptance in the marketplace;

 

   

tariffs and trade barriers, as well as other governmental controls and trade restrictions;

 

   

other trade protection measures, import or export licensing requirements, economic sanctions or other restrictive actions by U.S. or foreign governments;

 

   

longer accounts receivable collection times;

 

   

longer lead times for shipping;

 

   

compliance with tax, employment, immigration and labor laws for employees living or traveling abroad;

 

   

workforce uncertainty in countries where labor unrest is common;

 

   

language barriers for technical training;

 

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reduced protection of intellectual property rights in some foreign countries, and related prevalence of generic alternatives to therapeutics;

 

   

foreign currency exchange rate fluctuations and currency controls;

 

   

differing foreign reimbursement landscapes;

 

   

uncertain and potentially inadequate reimbursement of Imara’s products; and

 

   

the interpretation of contractual provisions governed by foreign laws in the event of a contract dispute.

If risks related to any of these uncertainties materializes, it could have a material adverse effect on Imara’s business.

Clinical trial and product liability lawsuits against Imara could divert its resources, could cause it to incur substantial liabilities and could limit commercialization of any products that Imara may develop.

Imara faces an inherent risk of clinical trial and product liability exposure related to the testing of any product candidates it may develop in clinical trials, and Imara will face an even greater risk if it commercially sells any products that it may develop. While Imara currently is not developing any product candidates and have no products that have been approved for commercial sale, the future use of product candidates by Imara in clinical trials, and the sale of any approved products in the future, may expose Imara to liability claims. These claims might be made by patients that use the product, healthcare providers, pharmaceutical companies or others selling such products. If Imara cannot successfully defend itself against claims that any product candidates or products it may develop caused injuries, it will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:

 

   

decreased demand for any product candidates or products that Imara may develop;

 

   

injury to Imara’s reputation and significant negative media attention;

 

   

withdrawal of clinical trial participants;

 

   

significant costs to defend any related litigation;

 

   

substantial monetary awards to trial participants or patients;

 

   

loss of revenue;

 

   

reduced resources of Imara’s management to pursue its business strategy; and

 

   

the inability to commercialize any products that Imara may develop.

Although Imara currently holds clinical trial liability insurance coverage in amounts it believes to be adequate with respect to completed and discontinued clinical trials, Imara may need to increase its insurance coverage if it decides to pursue any future product development efforts and or if it commences commercialization of any product candidates. Insurance coverage is increasingly expensive. Imara may not be able to maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise. If a successful clinical trial or product liability claim or series of claims is brought against Imara for uninsured liabilities or in excess of insured liabilities, Imara’s assets may not be sufficient to cover such claims and its business operations could be impaired.

 

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Risks Related to Imara’s Dependence on Third Parties

Imara may enter into collaborations with third parties for the development or commercialization of product candidates. If its collaborations are not successful, Imara may not be able to capitalize on the market potential of these product candidates and its business could be adversely affected.

Imara is not currently party to any sales, marketing, distribution, development, licensing or broader collaboration arrangements. However, if Imara does enter into any such arrangements with any third parties in the future, it will likely have limited control over the amount and timing of resources that its collaborators dedicate to the development or commercialization of any product candidates it may develop. Imara’s ability to generate revenues from these arrangements will depend on its collaborators’ abilities and efforts to successfully perform the functions assigned to them in these arrangements.

Collaborations that Imara enters into may not be successful, and any success will depend heavily on the efforts and activities of such collaborators. Collaborations pose a number of risks, including the following:

 

   

collaborators have significant discretion in determining the amount and timing of efforts and resources that they will apply to these collaborations;

 

   

collaborators may not perform their obligations as expected;

 

   

collaborators may not pursue commercialization of any product candidates Imara may develop that achieve regulatory approval or may elect not to continue or renew commercialization programs based on results of clinical trials or other studies, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that may divert resources or create competing priorities;

 

   

collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with any product candidates and products if the collaborators believe that the competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than Imara’s;

 

   

product candidates discovered in collaboration with Imara may be viewed by its collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of any product candidates;

 

   

a collaborator may fail to comply with applicable regulatory requirements regarding the development, manufacture, distribution or marketing of a product candidate or product;

 

   

disagreements with collaborators, including disagreements over intellectual property or proprietary rights, contract interpretation or the preferred course of development, might cause delays or terminations of the research, development or commercialization of product candidates, might lead to additional responsibilities for Imara with respect to product candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive;

 

   

collaborators may not properly obtain, maintain, enforce, defend or protect Imara’s intellectual property or proprietary rights or may use its proprietary information in such a way as to potentially lead to disputes or legal proceedings that could jeopardize or invalidate Imara’s intellectual property or proprietary information or expose it to potential litigation;

 

   

collaborators may infringe, misappropriate or otherwise violate the intellectual property or proprietary rights of third parties, which may expose Imara to litigation and potential liability; and

 

   

collaborations may be terminated for the convenience of the collaborator, and, if terminated, Imara could be required to raise additional capital to pursue further development or commercialization of the applicable product candidates.

Collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner, or at all. If any collaborations that Imara enters into do not result in the successful development

 

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and commercialization of products or if one of its collaborators terminates its agreement with Imara, Imara may not receive any future research funding or milestone or royalty payments under the collaboration. If Imara does not receive the funding it expects under these agreements, its development of any product candidates could be delayed and it may need additional resources to develop any product candidates. All of the risks relating to product development, regulatory approval and commercialization described in this proxy statement/prospectus also apply to the activities of Imara’s collaborators.

Additionally, subject to its contractual obligations to Imara, if a collaborator of Imara’s is involved in a business combination, the collaborator might deemphasize or terminate the development or commercialization of any product candidate licensed to it by Imara. If one of its collaborators terminates its agreement with Imara, Imara may find it more difficult to attract new collaborators and its perception in the business and financial communities could be adversely affected.

If Imara is not able to establish or maintain collaborations, it may have to alter its development and commercialization plans and its business could be adversely affected.

In connection with any future product development efforts, Imara may decide to collaborate with pharmaceutical or biotechnology companies for the development and potential commercialization of those product candidates. Imara faces significant competition in seeking appropriate collaborators, and a number of more established companies may also be pursuing strategies to license or acquire third-party intellectual property rights that Imara considers attractive. These established companies may have a competitive advantage over Imara due to their size, financial resources and greater clinical development and commercialization capabilities. In addition, companies that perceive Imara to be a competitor may be unwilling to assign or license rights to it. Whether Imara reaches a definitive agreement for a collaboration will depend, among other things, upon its assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors. Those factors may include the design or results of clinical trials, the likelihood of approval by the FDA or similar regulatory authorities outside the United States, the potential market for the subject product candidate, the costs and complexities of manufacturing and delivering such product candidate to patients, the potential of competing products, the existence of uncertainty with respect to Imara’s ownership of technology, which can exist if there is a challenge to such ownership without regard to the merits of the challenge, and industry and market conditions generally. The collaborator may also consider alternative product candidates or technologies for similar indications that may be available to collaborate on and whether such a collaboration could be more attractive than the one with Imara for its product candidate. Collaborations are complex and time-consuming to negotiate and document. In addition, there have been a significant number of recent business combinations among large pharmaceutical and biotechnology companies that have resulted in a reduced number of potential future collaborators.

If Imara is unable to reach agreements with suitable collaborators on a timely basis, on acceptable terms or at all, it may have to curtail the development of a product candidate, reduce or delay its development program or one or more of its other development programs, delay its potential commercialization or reduce the scope of any sales or marketing activities, or increase its expenditures and undertake development or commercialization activities at its own expense. If Imara elects to fund and undertake development or commercialization activities on its own, it may need to obtain additional expertise and additional capital, which may not be available to it on acceptable terms or at all. If Imara fails to enter into collaborations and does not have sufficient funds or expertise to undertake the necessary development and commercialization activities, it may not be able to further develop any product candidates or bring them to market.

If Imara decides to pursue any future product development efforts, it expects to rely on third parties to conduct its clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such trials, which may harm Imara’s business.

Imara historically has relied on third-party clinical research organizations to conduct its clinical trials, including its discontinued Ardent and Forte Phase 2b clinical trials in SCD and in ß-thalassemia. If Imara decides to pursue

 

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any future product development efforts, it does not expect to independently conduct clinical trials of any such product candidates. It expects it would rely on third parties, such as clinical research organizations, clinical data management organizations, medical institutions and clinical investigators, to conduct any such clinical trials. These agreements might terminate for a variety of reasons, including a failure to perform by the third parties. If Imara needs to enter into alternative arrangements, its product development activities, should it pursue them, might be delayed.

Imara’s reliance on these third parties for research and development activities would reduce its control over these activities but will not relieve it of its responsibilities. For example, Imara would remain responsible for ensuring that each of its clinical trials is conducted in accordance with the general investigational plan and protocols for the trial. Moreover, the FDA requires Imara to comply with standards, commonly referred to as good clinical practices, or GCPs, for conducting, recording and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial participants are protected. Imara also is required to register clinical trials and post the results of completed clinical trials on a government-sponsored database, ClinicalTrials.gov, within specified timeframes. Failure to do so can result in fines, adverse publicity and civil and criminal sanctions.

If these third parties do not successfully carry out their contractual duties, meet expected deadlines or conduct Imara’s clinical trials in accordance with regulatory requirements or its stated protocols, Imara will not be able to obtain, or may be delayed in obtaining, marketing approvals for any product candidates and will not be able to, or may be delayed in its efforts to, successfully develop and commercialize any product candidates. Furthermore, these third parties may also have relationships with other entities, some of which may be Imara’s competitors.

Imara also expects to rely on other third parties to store and distribute drug supplies for any clinical trials it may conduct. Any performance failure on the part of Imara’s distributors could delay clinical development or marketing approval of any product candidates it may successfully develop and commercialization of its products, producing additional losses and depriving Imara of potential product revenue.

If Imara decides to pursue any future product development efforts, it expects to contract with third parties for the manufacture of any product candidates it may develop for preclinical and clinical testing and would expect to continue to do so for commercialization. This reliance on third parties entails risks, including that such third parties may not be able to comply with applicable regulatory requirements. Any performance failure on the part of Imara’s manufacturers could delay clinical development or marketing approval.

Imara does not have any manufacturing facilities and if it decides to pursue any future product development efforts, it expects to rely on third parties for the manufacture of any product candidates for preclinical and clinical testing. Reliance on third-party manufacturers entails additional risks, including:

 

   

reliance on the third-party for regulatory compliance and quality assurance;

 

   

the possible breach of the manufacturing agreement by the third-party;

 

   

the possible misappropriation of Imara’s proprietary information, including its trade secrets and know-how; and

 

   

the possible termination or nonrenewal of the agreement by the third-party at a time that is costly or inconvenient for Imara.

Third-party manufacturers may not be able to comply with current good manufacturing practices, or cGMP, regulations or similar regulatory requirements outside of the United States. Imara’s failure, or the failure of its third-party manufacturers, to comply with applicable regulations could result in sanctions being imposed on Imara, including clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of Imara’s products.

 

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Any product candidates or products that Imara may develop may compete with other product candidates and products for access to manufacturing facilities. There are a limited number of manufacturers that operate under cGMP regulations and that might be capable of manufacturing for Imara.

Any performance failure on the part of Imara’s existing or future manufacturers could delay clinical development or marketing approval. Historically, Imara relied on a single manufacturer of active pharmaceutical ingredient and a different single manufacturer for finished drug product in the development of its product candidates. If Imara decides to pursue any future product development efforts, it expects it may similarly rely on a single or limited number of manufacturers at each stage of the manufacturing process. If any of Imara’s future contract manufacturers cannot perform as agreed, it may be required to replace such manufacturers. Although Imara believes that there are several potential alternative manufacturers who could manufacture any product candidates it may develop, Imara may incur added costs and delays in identifying and qualifying any such replacement.

Imara’s current and anticipated future dependence upon others for the manufacture of any product candidates or products Imara may develop may adversely affect its future profit margins and its ability to commercialize any products that receive marketing approval on a timely and competitive basis.

Risks Related to Imara’s Intellectual Property

If Imara fails to comply with its obligations under its existing license agreements, or under any future intellectual property licenses, or otherwise experience disruptions to its business relationships with its current or any future licensors, Imara could lose intellectual property rights that are important to its business.

Imara is party to license agreements with the UAB Research Foundation and the University of Pittsburgh with respect to IMR-261. Imara may enter into additional license agreements in the future. Imara’s current license agreements impose, and it expects that future licenses will impose, specified diligence, milestone payment, royalty and other obligations on Imara. Furthermore, Imara’s licensors have the right to terminate these license agreements if it materially breaches the applicable agreement and fails to cure such breach within specified periods or in the event Imara undergoes certain bankruptcy events. In spite of Imara’s best efforts, its current or any future licensors might conclude that it has materially breached its license agreements and might therefore terminate the license agreements, thereby removing Imara’s ability to develop and commercialize product candidates and technology covered by these license agreements. If these in-licenses are terminated, or if the underlying intellectual property fails to provide the intended exclusivity, competitors would have the freedom to seek regulatory approval of, and to market, products and technologies identical to Imara’s. This could have a material adverse effect on Imara’s competitive position, business, financial condition, results of operations and prospects.

Disputes may arise regarding intellectual property subject to a licensing agreement, including:

 

   

the scope of rights granted under the license agreement and other interpretation related issues;

 

   

the extent to which Imara’s technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement;

 

   

the sublicensing of patent and other rights under Imara’s collaborative development relationships;

 

   

Imara’s diligence obligations under the license agreement and what activities satisfy those diligence obligations;

 

   

the inventorship and ownership of inventions and know-how resulting from the joint creation or use of intellectual property by Imara’s current or future licensors and Imara and its partners; and

 

   

the priority of invention of patented technology.

 

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In addition, license agreements are complex, and certain provisions in such agreements may be susceptible to multiple interpretations. The resolution of any contract interpretation disagreement that may arise could narrow what Imara believes to be the scope of its rights to the relevant intellectual property or technology, or increase what it believes to be its financial or other obligations under the relevant agreement, either of which could have a material adverse effect on Imara’s business, financial condition, results of operations and prospects. Moreover, if disputes over intellectual property that Imara has licensed prevent or impair Imara’s ability to maintain its current licensing arrangements on commercially acceptable terms, Imara may be unable to successfully develop and commercialize the affected technology and product candidates, which could have a material adverse effect on its business, financial conditions, results of operations and prospects.

If Imara is unable to obtain, maintain, enforce and protect patent protection for its technology and product candidates or if the scope of the patent protection obtained is not sufficiently broad, Imara’s competitors could develop and commercialize technology and products similar or identical to Imara’s, and Imara’s ability to successfully develop and commercialize its technology and product candidates may be adversely affected.

If Imara decides to pursue any future product development efforts, its success will depend in large part on its ability to obtain and maintain protection of the intellectual property it may own solely and jointly with others or may license from others, particularly patents, in the United States and other countries with respect to any proprietary technology and product candidates it develops. Imara seeks to protect its proprietary position by filing patent applications in the United States and abroad related to any product candidates it may develop that are important to its business and by in-licensing intellectual property related to its technologies and product candidates. If Imara is unable to obtain or maintain patent protection with respect to any proprietary technology or product candidate, its business, financial condition, results of operations and prospects could be materially harmed.

The patent prosecution process is expensive, time-consuming and complex, and Imara may not be able to file, prosecute, maintain, defend or license all necessary or desirable patent applications at a reasonable cost or in a timely manner. It is also possible that Imara will fail to identify patentable aspects of its research and development output before it is too late to obtain patent protection. Moreover, in some circumstances, Imara may not have the right to control the preparation, filing and prosecution of patent applications, or to maintain, enforce and defend the patents, covering technology that it licenses from third parties. Therefore, these in-licensed patents and applications may not be prepared, filed, prosecuted, maintained, defended and enforced in a manner consistent with the best interests of Imara’s business.

The patent position of pharmaceutical and biotechnology companies generally is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation. In addition, the scope of patent protection outside of the United States is uncertain and laws of non-U.S. countries may not protect Imara’s rights to the same extent as the laws of the United States or vice versa. For example, European patent law restricts the patentability of methods of treatment of the human body more than United States law does. With respect to both owned and in-licensed patent rights, Imara cannot predict whether the patent applications it and its licensors are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient protection from competitors. Further, Imara may not be aware of all third-party intellectual property rights potentially relating to any product candidates it may develop. In addition, publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing of the priority application, or in some cases not published at all. Therefore, neither Imara nor its licensors can know with certainty whether either Imara or its licensors were the first to make the inventions claimed in the patents and patent applications Imara owns or in-license now or in the future, or that either Imara or its licensors were the first to file for patent protection of such inventions. As a result, the issuance, scope, validity, enforceability and commercial value of Imara’s owned and in-licensed patent rights are highly uncertain. Moreover, Imara’s owned and in-licensed pending and future patent applications may not result in patents being issued that protect its technology and product candidates, in whole or in part, or that effectively

 

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prevent others from commercializing competitive technologies and products. Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of Imara’s patents and its ability to obtain, protect, maintain, defend and enforce its patent rights, narrow the scope of its patent protection and, more generally, could affect the value of, or narrow the scope of, its patent rights.

Moreover, Imara or its licensors may be subject to a third-party preissuance submission of prior art to the United States Patent and Trademark Office, or USPTO, or become involved in opposition, derivation, revocation, reexamination, inter partes review, post-grant review or interference proceedings challenging its patent rights or the patent rights of others. An adverse determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate, Imara’s patent rights, allow third parties to commercialize its technology or product candidates and compete directly with Imara, without payment to it, or result in Imara’s inability to manufacture or commercialize drugs without infringing third-party patent rights. If the breadth or strength of protection provided by Imara’s patents and patent applications is threatened, regardless of the outcome, it could dissuade companies from collaborating with Imara to license, develop or commercialize current or future product candidates.

Patents may never issue from Imara’s patent applications, or the scope of any patent may not be sufficient to provide a competitive advantage. Additionally, the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can be reinterpreted after issuance. Even if Imara’s owned and in-licensed patent applications issue as patents, they may not issue in a form that will provide Imara with any meaningful protection, prevent competitors from competing with Imara or otherwise provide Imara with any competitive advantage. The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and Imara’s owned and in-licensed patents may be challenged in the courts or patent offices in the United States and abroad. Such challenges may result in loss of exclusivity or freedom to operate or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit Imara’s ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of Imara’s technology and product candidates. Such proceedings also may result in substantial cost and require significant time from Imara’s management and employees, even if the eventual outcome is favorable to Imara. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. Furthermore, Imara’s competitors may be able to circumvent its owned or in-licensed patents by developing similar or alternative technologies or products in a non-infringing manner. As a result, Imara’s owned and in-licensed patent portfolio may not provide it with sufficient rights to exclude others from commercializing technology and products similar or identical to any of Imara’s technology and product candidates.

Patent terms may be inadequate to protect Imara’s competitive position on any product candidates for an adequate amount of time.

Patents have a limited lifespan. In the United States, if all maintenance fees are timely paid, the natural expiration of a patent is generally 20 years from its earliest U.S. non-provisional filing date. Various extensions may be available, but the life of a patent, and the protection it affords, is limited. Even if patents covering any product candidates are obtained, once the patent life has expired, Imara may be open to competition from competitive products, including generics or biosimilars. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, Imara’s owned and licensed patent portfolio may not provide it with sufficient rights to exclude others from commercializing products similar or identical to Imara’s. Given the expected expiration date of these patents, and the fact that safe harbor protections in many jurisdictions permit third parties to engage in development, including clinical trials, these patents may not provide Imara with a meaningful competitive advantage.

 

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If Imara is unable to obtain licenses from third parties on commercially reasonable terms or fail to comply with its obligations under such agreements, its business could be harmed.

If Imara decides to pursue any future product development efforts, it may be necessary for Imara to use the patented or proprietary technology of third parties to commercialize its products, in which case Imara would be required to obtain a license from these third parties. If Imara is unable to license such technology, or if Imara is forced to license such technology on unfavorable terms, its business could be materially harmed. If Imara is unable to obtain a necessary license, it may be unable to develop or commercialize the affected product candidates, which could materially harm its business and the third parties owning such intellectual property rights could seek either an injunction prohibiting Imara’s sales or an obligation on Imara’s part to pay royalties and/or other forms of compensation. Even if Imara is able to obtain a license, it may be non-exclusive, thereby giving its competitors access to the same technologies licensed to Imara.

If Imara is unable to obtain rights to required third-party intellectual property rights or maintain the existing intellectual property rights it has, it may be required to expend significant time and resources to redesign its technology, product candidates, or the methods for manufacturing them or to develop or license replacement technology, all of which may not be feasible on a technical or commercial basis. If Imara is unable to do so, it may be unable to develop or commercialize the affected technology and product candidates, which could harm its business, financial condition, results of operations and prospects significantly.

Additionally, if Imara fails to comply with its obligations under license agreements, its counterparties may have the right to terminate these agreements, in which event Imara might not be able to develop, manufacture or market, or may be forced to cease developing, manufacturing or marketing, any product that is covered by these agreements or may face other penalties under such agreements. Such an occurrence could materially adversely affect the value of the product candidate being developed under any such agreement. Termination of these agreements or reduction or elimination of Imara’s rights under these agreements, or restrictions on its ability to freely assign or sublicense its rights under such agreements when it is in the interest of Imara’s business to do so, may result in Imara having to negotiate new or reinstated agreements with less favorable terms, cause Imara to lose its rights under these agreements, including its rights to important intellectual property or technology or impede, or delay or prohibit the further development or commercialization of one or more product candidates that rely on such agreements.

If Imara does not obtain patent term extension in the United States under the Hatch-Waxman Act and in non-U.S. countries under similar legislation, thereby potentially extending the term of its marketing exclusivity for any product candidates it may develop, Imara’s business may be materially harmed.

In the United States, the patent term of a patent that covers an FDA-approved drug may be eligible for limited patent term extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory review process. The Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Act, permits a patent term extension of up to five years beyond the expiration of the patent. The length of the patent term extension is related to the length of time the drug is under regulatory review. Patent extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, and only one patent applicable to an approved drug may be extended and only those claims covering the approved drug, a method for using it, or a method for manufacturing it may be extended. Similar provisions are available in Europe and certain other non-United States jurisdictions to extend the term of a patent that covers an approved drug. While, in the future, if and when any product candidates receive FDA approval, Imara expects to apply for patent term extensions on patents covering those product candidates, there is no guarantee that the applicable authorities will agree with Imara’s assessment of whether such extensions should be granted, and even if granted, the length of such extensions. Imara may not be granted patent term extension either in the United States or in any non-U.S. country because of, for example, failing to exercise due diligence during the testing phase or regulatory review process, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. Moreover, the term of

 

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extension, as well as the scope of patent protection during any such extension, afforded by the governmental authority could be less than Imara requests. If Imara is unable to obtain any patent term extension or the term of any such extension is less than it requests, Imara’s competitors may obtain approval of competing products following the expiration of Imara’s patent rights, and Imara’s business, financial condition, results of operations and prospects could be materially harmed.

It is possible that Imara will not obtain patent term extension under the Hatch-Waxman Act for a U.S. patent covering any product candidates that it may identify even where that patent is eligible for patent term extension, or if Imara obtains such an extension, it may be for a shorter period than it had sought. Further, for Imara’s licensed patents, it may not have the right to control prosecution, including filing with the USPTO a petition for patent term extension under the Hatch-Waxman Act. Thus, if one of Imara’s licensed patents is eligible for patent term extension under the Hatch-Waxman Act, it may not be able to control whether a petition to obtain a patent term extension is filed, or obtained, from the USPTO.

Also, there are detailed rules and requirements regarding the patents that may be submitted to the FDA for listing in the Approved Drug Products with Therapeutic Equivalence Evaluations, or the Orange Book. Imara may be unable to obtain patents covering any product candidates that contain one or more claims that satisfy the requirements for listing in the Orange Book. Even if Imara submits a patent for listing in the Orange Book, the FDA may decline to list the patent, or a manufacturer of generic drugs may challenge the listing. If a product candidate is approved and a patent covering that product candidate is not listed in the Orange Book, a manufacturer of generic drugs would not have to provide advance notice to Imara of any abbreviated new drug application filed with the FDA to obtain permission to sell a generic version of such product candidate.

Changes to patent laws in the United States and other jurisdictions could diminish the value of patents in general, thereby impairing Imara’s ability to protect its products.

Changes in either the patent laws or interpretation of patent laws in the United States, including patent reform legislation such as the Leahy-Smith America Invents Act, or the Leahy-Smith Act, could increase the uncertainties and costs surrounding the prosecution of Imara’s owned and in-licensed patent applications and the maintenance, enforcement or defense of its owned and in-licensed issued patents. The Leahy-Smith Act includes a number of significant changes to United States patent law. These changes include provisions that affect the way patent applications are prosecuted, redefine prior art, provide more efficient and cost-effective avenues for competitors to challenge the validity of patents, and enable third-party submission of prior art to the USPTO during patent prosecution and additional procedures to attack the validity of a patent at USPTO-administered post-grant proceedings, including post-grant review, inter partes review, and derivation proceedings. Assuming that other requirements for patentability are met, prior to March 2013, in the United States, the first to invent the claimed invention was entitled to the patent, while outside the United States, the first to file a patent application was entitled to the patent. After March 2013, under the Leahy-Smith Act, the United States transitioned to a first-to-file system in which, assuming that the other statutory requirements for patentability are met, the first inventor to file a patent application will be entitled to the patent on an invention regardless of whether a third-party was the first to invent the claimed invention. As such, the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of Imara’s patent applications and the enforcement or defense of Imara’s issued patents, all of which could have a material adverse effect on Imara’s business, financial condition, results of operations and prospects.

In addition, the patent positions of companies in the development and commercialization of biologics and pharmaceuticals are particularly uncertain. Recent U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations. This combination of events has created uncertainty with respect to the validity and enforceability of patents once obtained. Depending on future actions by the U.S. Congress, the federal courts, and the USPTO, the laws and regulations governing patents could change in unpredictable ways that could have a material adverse effect on Imara’s patent rights and its ability to protect, defend and enforce its patent rights in the future.

 

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Imara and its licensors, and any future licensors, may become involved in lawsuits to protect or enforce Imara’s patent or other intellectual property rights, which could be expensive, time-consuming and unsuccessful.

Competitors and other third parties may infringe, misappropriate or otherwise violate Imara’s or its current and future licensors’ issued patents or other intellectual property. As a result, Imara or any current or future licensor may need to file infringement, misappropriation or other intellectual property related claims, which can be expensive and time-consuming. Any claims Imara asserts against perceived infringers could provoke such parties to assert counterclaims against Imara alleging that it infringes, misappropriates or otherwise violates their intellectual property. In addition, in a patent infringement proceeding, such parties could counterclaim that the patents Imara or its licensors have asserted are invalid or unenforceable. In patent litigation in the United States, defendant counterclaims alleging invalidity or unenforceability are commonplace. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, or non-enablement. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant information from the USPTO, or made a misleading statement, during prosecution. Third parties may institute such claims before administrative bodies in the United States or abroad, even outside the context of litigation. Such mechanisms include re-examination, post-grant review, inter partes review, interference proceedings, derivation proceedings, and equivalent proceedings in non-U.S. jurisdictions (e.g., opposition proceedings). The outcome following legal assertions of invalidity and unenforceability is unpredictable.

An adverse result in any such proceeding could put one or more of Imara’s owned or in-licensed patents at risk of being invalidated or interpreted narrowly and could put any of its owned or in-licensed patent applications at risk of not yielding an issued patent. A court may also refuse to stop the third-party from using the technology at issue in a proceeding on the grounds that Imara’s owned or in-licensed patents do not cover such technology. Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of Imara’s confidential information or trade secrets could be compromised by disclosure during this type of litigation. Any of the foregoing could allow such third parties to develop and commercialize competing technologies and products and have a material adverse impact on Imara’s business, financial condition, results of operations and prospects.

Interference or derivation proceedings provoked by third parties, or brought by Imara or by its licensors, or declared by the USPTO may be necessary to determine the priority of inventions with respect to Imara’s patents or patent applications. An unfavorable outcome could require Imara to cease using the related technology or to attempt to license rights to it from the prevailing party. Imara’s business could be harmed if the prevailing party does not offer Imara a license on commercially reasonable terms or at all, or if a non-exclusive license is offered and Imara’s competitors gain access to the same technology. Imara’s defense of litigation or interference or derivation proceedings may fail and, even if successful, may result in substantial costs and distract its management and other employees. In addition, the uncertainties associated with litigation could have a material adverse effect on Imara’s ability to raise the funds necessary to continue its clinical trials, continue its research programs, license necessary technology from third parties, or enter into development partnerships that would help Imara bring any product candidates to market.

Third parties may initiate legal proceedings alleging that Imara is infringing, misappropriating or otherwise violating their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of Imara’s business.

If Imara decides to pursue any future product development efforts, its commercial success depends upon its ability and the ability of its collaborators to develop, manufacture, market and sell any product candidates Imara may develop and use its proprietary technologies without infringing, misappropriating or otherwise violating the intellectual property and proprietary rights of third parties. There is considerable patent and other intellectual property litigation in the pharmaceutical and biotechnology industries. Imara may become party to, or threatened

 

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with, adversarial proceedings or litigation regarding intellectual property rights with respect to its technology and product candidates, including interference proceedings, post grant review, inter partes review, and derivation proceedings before the USPTO and similar proceedings in non-U.S. jurisdictions such as oppositions before the European Patent Office. Numerous U.S. and non-U.S. issued patents and pending patent applications, which are owned by third parties, exist in the fields in which Imara is pursuing development candidates. As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that Imara’s technologies or product candidates that it may identify may be subject to claims of infringement of the patent rights of third parties.

The legal threshold for initiating litigation or contested proceedings is low, so that even lawsuits or proceedings with a low probability of success might be initiated and require significant resources to defend. Litigation and contested proceedings can also be expensive and time-consuming, and Imara’s adversaries in these proceedings may have the ability to dedicate substantially greater resources to prosecuting these legal actions than Imara can. The risks of being involved in such litigation and proceedings may increase if and as any product candidates near commercialization and as Imara continues to gain the greater visibility associated with being a public company. Third parties may assert infringement claims against Imara based on existing patents or patents that may be granted in the future, regardless of merit. Imara may not be aware of all such intellectual property rights potentially relating to its technology and product candidates and their uses, or it may incorrectly conclude that third-party intellectual property is invalid or that its activities and product candidates do not infringe such intellectual property. Thus, Imara does not know with certainty that its technology and product candidates, or its development and commercialization thereof, do not and will not infringe, misappropriate or otherwise violate any third-party’s intellectual property.

Third parties may assert that Imara is employing their proprietary technology without authorization. There may be third-party patents or patent applications with claims to materials, formulations or methods, such as methods of manufacture or methods for treatment, related to the discovery, use or manufacture of the product candidates that Imara may identify or related to its technologies. Because patent applications can take many years to issue, there may be currently pending patent applications which may later result in issued patents that the product candidates that Imara may identify may infringe. In addition, third parties may obtain patents in the future and claim that use of Imara’s technologies infringes upon these patents. Moreover, as noted above, there may be existing patents that Imara is not aware of or that Imara has incorrectly concluded are invalid or not infringed by its activities. If any third-party patents were held by a court of competent jurisdiction to cover, for example, the manufacturing process of the product candidates that Imara may identify, any molecules formed during the manufacturing process or any final product itself, the holders of any such patents may be able to block Imara’s ability to commercialize such product candidate unless it obtained a license under the applicable patents, or until such patents expire.

Parties making claims against Imara may obtain injunctive or other equitable relief, which could effectively block Imara’s ability to further develop and commercialize the product candidates that it may identify. Defense of these claims, regardless of their merit, would involve substantial litigation expense and would be a substantial diversion of employee resources from Imara’s business. In the event of a successful claim of infringement against Imara, it may have to pay substantial damages, including treble damages and attorneys’ fees for willful infringement, pay royalties, redesign its infringing products, be forced to indemnify its customers or collaborators or obtain one or more licenses from third parties, which may be impossible or require substantial time and monetary expenditure.

Imara may choose to take a license or, if it is found to infringe, misappropriate or otherwise violate a third-party’s intellectual property rights, it could also be required to obtain a license from such third-party to continue developing, manufacturing and marketing Imara’s technology and product candidates. However, Imara may not be able to obtain any required license on commercially reasonable terms or at all. Even if Imara were able to obtain a license, it could be non-exclusive, thereby giving Imara’s competitors and other third parties access to the same technologies licensed to Imara and could require Imara to make substantial licensing and royalty

 

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payments. Imara could be forced, including by court order, to cease developing, manufacturing and commercializing the infringing technology or product. A finding of infringement could prevent Imara from commercializing any product candidates or force it to cease some of its business operations, which could materially harm its business. In addition, Imara may be forced to redesign any product candidates, seek new regulatory approvals and indemnify third parties pursuant to contractual agreements. Claims that Imara has misappropriated the confidential information or trade secrets of third parties could have a similar material adverse effect on its business, financial condition, results of operations and prospects.

Intellectual property litigation or other legal proceedings relating to intellectual property could cause Imara to spend substantial resources and distract its personnel from their normal responsibilities.

Even if resolved in its favor, litigation or other legal proceedings relating to intellectual property claims may cause Imara to incur significant expenses and could distract its technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of Imara’s common stock. Such litigation or proceedings could substantially increase Imara’s operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities. Imara may not have sufficient financial or other resources to conduct such litigation or proceedings adequately. Some of Imara’s competitors may be able to sustain the costs of such litigation or proceedings more effectively than Imara can because of their greater financial resources and may also have an advantage in such proceedings due to their more mature and developed intellectual property portfolios. Uncertainties resulting from the initiation and continuation of intellectual property litigation or other proceedings could compromise Imara’s ability to compete in the marketplace.

Obtaining and maintaining patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and Imara’s patent protection could be reduced or eliminated for non-compliance with these requirements.

Periodic maintenance, renewal and annuity fees and various other government fees on any issued patent and pending patent application must be paid to the USPTO and non-U.S. patent agencies in several stages or annually over the lifetime of Imara’s owned and in-licensed patents and patent applications. The USPTO and various non-U.S. governmental patent agencies also require compliance with a number of procedural, documentary and other similar provisions during the patent application process. In certain circumstances, Imara may rely on its licensing partners to pay these fees to, or comply with the procedural and documentary rules of, the relevant patent agency. With respect to its patents, Imara relies on an annuity service, outside firms and outside counsel to remind it of the due dates and to make payment after Imara instructs them to do so. While an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which non-compliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Non-compliance events that could result in abandonment or lapse of a patent or patent application include failure to respond to official actions within prescribed time limits, non-payment of fees and failure to properly legalize and submit formal documents. In such an event, potential competitors might be able to enter the market with similar or identical products or technology. If Imara or its current or future licensors fail to maintain the patents and patent applications covering any product candidates, it may have a material adverse effect on Imara’s business, financial condition, results of operations and prospects.

Imara may not be able to protect its intellectual property and proprietary rights throughout the world.

Filing, prosecuting and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and the laws of non-U.S. countries may not protect Imara’s rights to the same extent as the laws of the United States. In addition, the laws of some non-U.S. countries do not protect intellectual property

 

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rights to the same extent as federal and state laws in the United States, and even where such protection is nominally available, judicial and governmental enforcement of such intellectual property rights may be lacking. Consequently, Imara may not be able to prevent third parties from practicing its inventions in all countries outside the United States, or from selling or importing products made using Imara’s inventions in and into the United States or other jurisdictions. Competitors may use Imara’s technologies in jurisdictions where it has not obtained patent protection to develop their own products and, further, may export otherwise infringing products to territories where Imara has patent protection or licenses but enforcement is not as strong as that in the United States. These products may compete with Imara’s products, and Imara’s patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.

Many companies have encountered significant problems in protecting and defending intellectual property rights in non-U.S. jurisdictions. The legal systems of certain countries do not favor the enforcement of patents, trade secrets, and other intellectual property rights, particularly those relating to biotechnology products, which could make it difficult for Imara to stop the infringement of its patents or marketing of competing products in violation of its intellectual property and proprietary rights generally. In addition, certain jurisdictions do not protect to the same extent or at all inventions that constitute new methods of treatment.

Proceedings to enforce Imara’s intellectual property and proprietary rights in non-U.S. jurisdictions could result in substantial costs and divert its efforts and attention from other aspects of its business, could put its patents at risk of being invalidated or interpreted narrowly, could put its patent applications at risk of not issuing, and could provoke third parties to assert claims against Imara. Imara may not prevail in any lawsuits that it initiates, and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, Imara’s efforts to enforce its intellectual property and proprietary rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that Imara develops or licenses.

Many countries have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In addition, many countries limit the enforceability of patents against government agencies or government contractors. In these countries, the patent owner may have limited remedies, which could materially diminish the value of such patent. If Imara or any of its current or future licensors is forced to grant a license to third parties with respect to any patents relevant to Imara’s business, Imara’s competitive position may be impaired, and its business, financial condition, results of operations and prospects may be adversely affected.

Imara may be subject to claims challenging the inventorship or ownership of its patents and other intellectual property.

Imara or its licensors may be subject to claims that former employees, collaborators or other third parties have an interest in Imara’s owned or in-licensed patents, trade secrets or other intellectual property as an inventor or co-inventor. For example, Imara or its licensors may have inventorship disputes arise from conflicting obligations of employees, consultants or others who are involved in developing any product candidates. Litigation may be necessary to defend against these and other claims challenging inventorship or Imara’s or its licensors’ ownership of Imara’s owned or in-licensed patents, trade secrets or other intellectual property. If Imara or its licensors fail in defending any such claims, in addition to paying monetary damages, Imara may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, intellectual property that is important to any product candidates. Even if Imara is successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees. Any of the foregoing could have a material adverse effect on Imara’s business, financial condition, results of operations and prospects.

 

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Imara may be subject to claims by third parties asserting that its employees, consultants or contractors have wrongfully used or disclosed confidential information of third parties, or Imara has wrongfully used or disclosed alleged trade secrets of their current or former employers or claims asserting Imara has misappropriated their intellectual property, or claiming ownership of what Imara regards as its own intellectual property.

Certain of Imara’s employees, consultants and contractors were previously employed at universities or other pharmaceutical or biotechnology companies, including Imara’s competitors or potential competitors. Although Imara tries to ensure that its employees, consultants and contractors do not use the proprietary information or know-how of others in their work for Imara, Imara may be subject to claims that these individuals or Imara have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such individual’s current or former employer. Litigation may be necessary to defend against these claims.

In addition, while it is Imara’s policy to require that its employees, consultants and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to Imara, Imara may be unsuccessful in executing such an agreement with each party who in fact develops intellectual property that Imara regards as its own. Imara’s intellectual property assignment agreements with them may not be self-executing or may be breached, and Imara may be forced to bring claims against third parties, or defend claims they may bring against Imara, to determine the ownership of what Imara regards as its intellectual property. Such claims could have a material adverse effect on Imara’s business, financial conditions, results of operations and prospects.

If Imara fails in prosecuting or defending any such claims, in addition to paying monetary damages, Imara may lose valuable intellectual property rights or personnel, which could have a material adverse effect on its competitive business position and prospects. Such intellectual property rights could be awarded to a third-party, and Imara could be required to obtain a license from such third-party to commercialize its technology or products, which license may not be available on commercially reasonable terms, or at all, or such license may be non-exclusive. Even if Imara is successful in prosecuting or defending against such claims, litigation could result in substantial costs and be a distraction to its management and employees.

If Imara is unable to protect the confidentiality of its trade secrets, its business and competitive position may be harmed.

In addition to seeking patents for any product candidates Imara may seek to develop, Imara also relies on trade secrets and confidentiality agreements to protect its unpatented know-how, technology and other proprietary information, to maintain its competitive position. Imara seeks to protect its trade secrets and other proprietary technology, in part, by entering into non-disclosure and confidentiality agreements with parties who have access to them, such as Imara’s employees, corporate collaborators, outside scientific collaborators, contract research organizations, contract manufacturers, consultants, advisors and other third parties. Imara also enters into confidentiality and invention or patent assignment agreements with its employees and consultants, but it cannot guarantee that it has entered into such agreements with each party that may have or has had access to its trade secrets or proprietary technology. Despite these efforts, any of these parties may breach the agreements and disclose Imara’s proprietary information, including its trade secrets, and Imara may not be able to obtain adequate remedies for such breaches. Detecting the disclosure or misappropriation of a trade secret and enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive and time-consuming, and the outcome is unpredictable. In addition, some courts inside and outside of the United States are less willing or unwilling to protect trade secrets. If any of Imara’s trade secrets were to be lawfully obtained or independently developed by a competitor or other third-party, Imara would have no right to prevent them, or those to whom they communicate it, from using that technology or information to compete with Imara. If any of Imara’s trade secrets were to be disclosed to or independently developed by a competitor or other third-party, Imara’s competitive position may be materially and adversely harmed.

 

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Intellectual property rights do not necessarily address all potential threats.

The degree of future protection afforded by Imara’s intellectual property rights is uncertain because intellectual property rights have limitations and may not adequately protect Imara’s business or permit Imara to maintain its competitive advantage. For example:

 

   

others may be able to make product candidates that are similar to Imara’s but that are not covered by the claims of the patents that Imara owns;

 

   

Imara, or its license partners or current or future collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent applications that Imara licenses or may own in the future;

 

   

Imara, or its license partners or current or future collaborators, might not have been the first to file patent applications covering certain of Imara’s or their inventions;

 

   

Imara, or its license partners or current or future collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent applications that Imara licenses or may own in the future;

 

   

Imara, or its license partners or current or future collaborators, might not have been the first to file patent applications covering certain of Imara’s or their inventions;

 

   

others may independently develop similar or alternative technologies or duplicate any of Imara’s technologies without infringing Imara’s owned or in-licensed intellectual property rights;

 

   

it is possible that Imara’s owned and in-licensed pending patent applications or those Imara may own or in-license in the future will not lead to issued patents;

 

   

issued patents that Imara holds rights to may be held invalid or unenforceable, including as a result of legal challenges by Imara’s competitors;

 

   

Imara’s competitors might conduct research and development activities in countries where Imara does not have patent rights and then use the information learned from such activities to develop competitive products for sale in Imara’s major commercial markets;

 

   

Imara cannot ensure that any of its patents, or any of its pending patent applications, if issued, or those of its licensors, will include claims having a scope sufficient to protect any product candidates;

 

   

Imara cannot ensure that any patents issued to it or its current or future licensors will provide a basis for an exclusive market for its commercially viable product candidates or will provide Imara with any competitive advantages;

 

   

Imara cannot ensure that its commercial activities or product candidates will not infringe upon the patents of others;

 

   

Imara cannot ensure that it will be able to successfully commercialize any product candidates on a substantial scale, if approved, before the relevant patents that Imara owns or licenses expire;

 

   

Imara may not develop additional proprietary technologies that are patentable;

 

   

the patents of others may harm Imara’s business; and

 

   

Imara may choose not to file a patent in order to maintain certain technology as a trade secrets or know-how, and a third-party may subsequently file a patent application covering such technology.

Should any of these events occur, they could have a material adverse effect on Imara’s business, financial condition, results of operations and prospects.

 

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Risks Related to Regulatory Approval of Imara’s Product Candidates and Other Legal Compliance Matters

If Imara decides to pursue any future product development efforts, even if it completes the necessary preclinical studies and clinical trials, the marketing approval process is expensive, time-consuming and uncertain and may prevent Imara from obtaining approvals for the commercialization of any product candidates. If Imara is not able to obtain, or if there are delays in obtaining, required regulatory approvals, Imara will not be able to commercialize any product candidates, and its ability to generate revenue will be materially impaired.

If Imara decides to pursue any future product development efforts, any product candidates it may develop and the activities associated with their development and commercialization, including design, testing, manufacture, packaging, recordkeeping, labeling, storage, approval, advertising, promotion, sale and distribution, export, import and adverse event reporting, are subject to comprehensive regulation by the FDA and other regulatory agencies in the United States and by the EMA and similar regulatory authorities outside of the United States. In addition, regulatory agencies may not approve the labeling claims that are necessary or desirable for the successful commercialization of any such product candidates.

Marketing approval of drugs in the United States requires the submission of a new drug application, or NDA, to the FDA and Imara is not permitted to market any product candidate in the United States until it obtains approval from the FDA of the NDA for that product. An NDA must be supported by extensive clinical and preclinical data, as well as extensive information regarding pharmacology, toxicology, and chemistry, manufacturing and controls. Imara has not submitted an application for or received marketing approval for any product candidates it may develop in the United States or in any other jurisdiction.

Imara has only limited experience in filing and supporting the applications necessary to gain marketing approvals and expects to rely on third-party clinical research organizations or other third-party consultants or vendors to assist Imara in this process. Securing marketing approval requires the submission of extensive preclinical and clinical data and supporting information to regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy. Securing marketing approval also requires the submission of information about the product manufacturing processes to, and inspection of manufacturing facilities by, the regulatory authorities. Imara’s product candidates may not be effective, may be only moderately effective or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude it from obtaining marketing approval or prevent or limit commercial use. If any product candidates receives marketing approval, the accompanying label may limit the approved use of Imara’s drug, which could limit sales of the product.

The process of obtaining marketing approvals, both in the United States and abroad, is expensive, may take many years, if approval is obtained at all, and can vary substantially based upon a variety of factors, including the type, complexity and novelty of the product candidates involved. Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted product application may cause delays in the approval or rejection of an application. Regulatory authorities have substantial discretion in the approval process and may refuse to accept any application or may decide that Imara’s data is insufficient for approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate in various countries. Any marketing approval Imara ultimately obtains may be limited or subject to restrictions or post-approval commitments that render the approved product not commercially viable.

If Imara experiences delays in obtaining approval or if it fails to obtain approval of any product candidates it may develop, the commercial prospects for any product candidates may be harmed and Imara’s ability to generate revenues will be materially impaired.

 

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Imara may not be able to obtain or maintain orphan drug designation or exclusivity for any product candidates and, even if it does, that exclusivity may not prevent the FDA or the EMA from approving other competing products.

If Imara decides to pursue any future product development efforts, it may seek orphan drug designation in indications or for any product candidates it develops. Regulatory authorities in some jurisdictions, including the United States and the European Union, may designate drugs for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may designate a product as an orphan drug if it is a drug intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals in the United States.

Generally, if a product with an orphan drug designation subsequently receives the first marketing approval for the indication for which it has such designation, the product is entitled to a period of marketing exclusivity, which precludes the FDA or the EMA from approving another marketing application for the same drug for that time period. The applicable period is seven years in the United States and ten years in the European Union. The exclusivity period in the European Union can be reduced to six years if a drug no longer meets the criteria for orphan drug designation or if the drug is sufficiently profitable so that market exclusivity is no longer justified.

Even if Imara obtains orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from competition because competing drugs containing a different active ingredient can be approved for the same condition. In addition, even after an orphan drug is approved, the FDA can subsequently approve the same drug for the same condition if the FDA concludes that the later drug is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care. Orphan drug exclusivity may be lost if the FDA or EMA determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the drug to meet the needs of patients with the rare disease or condition.

On August 3, 2017, the U.S. Congress passed the FDA Reauthorization Act of 2017, or FDARA. FDARA, among other things, codified the FDA’s pre-existing regulatory interpretation to require that a drug sponsor demonstrate the clinical superiority of an orphan drug that is otherwise the same as a previously approved drug for the same rare disease in order to receive orphan drug exclusivity. The new legislation reverses prior precedent holding that the Orphan Drug Act unambiguously requires that the FDA recognize the orphan exclusivity period regardless of a showing of clinical superiority.

The FDA may further reevaluate the Orphan Drug Act and its regulations and policies. This may be particularly true in light of a decision from the Court of Appeals for the 11th Circuit in September 2021 finding that, for the purpose of determining the scope of exclusivity, the term “same disease or condition” means the designated “rare disease or condition” and could not be interpreted by the FDA to mean the “indication or use.” Imara does not know if, when or how the FDA may change the orphan drug regulations and policies in the future, and it is uncertain how any changes might affect its business. Depending on what changes the FDA may make to its orphan drug regulations and policies, Imara’s business could be adversely impacted.

A Fast Track designation by the FDA may not lead to a faster development or regulatory review or approval process.

If Imara decides to pursue any future product development efforts, it may seek Fast Track designation for product candidates it may develop. If a drug is intended for the treatment of a serious or life-threatening condition and the drug demonstrates the potential to address unmet medical needs for this condition, the drug sponsor may apply for FDA Fast Track designation. The FDA has broad discretion whether or not to grant this designation, so even if Imara believes a particular product candidate is eligible for this designation, it cannot be certain that the FDA would decide to grant it. Even if Imara does receive Fast Track designation, it may not experience a faster development process, review or approval compared to conventional FDA procedures. The FDA may withdraw Fast Track designation if it believes that the designation is no longer supported by data from Imara’s clinical development program.

 

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Accelerated approval by the FDA, even if granted for any product candidates does not increase the likelihood that any product candidates will ultimately receive full approval.

If Imara decides to pursue any future product development efforts, it may seek approval of any other product candidates it may develop using the FDA’s accelerated approval pathway. A product may be eligible for accelerated approval if it treats a serious or life-threatening condition and generally provides a meaningful advantage over available therapies. In addition, it must demonstrate an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit or on an intermediate clinical endpoint that can be measured earlier than irreversible morbidity or mortality, or IMM, that is reasonably likely to predict an effect on IMM or other clinical benefit. The FDA makes the determination regarding whether to accept a biomarker as a proposed surrogate endpoint.

Prior to seeking such accelerated approval, Imara will request feedback from the FDA regarding the eligibility of the drug product candidate for accelerated approval and otherwise evaluate its ability to seek and receive such accelerated approval. As a condition of accelerated approval, the FDA will require that a sponsor of a drug or biologic product candidate receiving accelerated approval perform adequate and well-controlled post-marketing clinical trials. These confirmatory trials must be completed with due diligence and Imara may be required to evaluate different or additional endpoints in these post-marketing confirmatory trials. In addition, the FDA currently requires Imara a condition for accelerated approval pre-clearance of promotional materials prior to use, which could adversely impact the timing of the commercial launch of the product.

There can be no assurance that the FDA will agree with Imara’s surrogate endpoints or intermediate clinical endpoints, or that Imara will decide to pursue or submit an NDA for accelerated approval or any other form of expedited development, review or approval. Similarly, there can be no assurance that, after feedback from FDA, Imara will continue to pursue or apply for accelerated approval or any other form of expedited development, review or approval, even if Imara initially decides to do so. Furthermore, if Imara decides to submit an application for accelerated approval or under another expedited regulatory designation, there can be no assurance that such submission or application will be accepted or that any expedited review or approval will be granted on a timely basis, or at all.

Moreover, as noted above, for drugs granted accelerated approval, the FDA requires post-marketing trials to confirm the benefit of the drug. These confirmatory trials must be completed with due diligence. Imara may be required to evaluate additional or different clinical endpoints in these post-marketing confirmatory trials. These confirmatory trials may require enrollment of more patients than Imara currently anticipates and will result in additional costs, which may be greater than the estimated costs Imara currently anticipates. The FDA may withdraw approval of a product candidate approved under the accelerated approval pathway if, for example, the trial required to verify the predicted clinical benefit of Imara’s product candidate fails to verify such benefit or does not demonstrate sufficient clinical benefit to justify the risks associated with the drug. The FDA may also withdraw approval if other evidence demonstrates that Imara’s product candidate is not shown to be safe or effective under the conditions of use, Imara fails to conduct any required post approval trial of its product candidate with due diligence or Imara disseminates false or misleading promotional materials relating to its product candidate. A failure to obtain accelerated approval or any other form of expedited development, review or approval for any product candidates Imara may develop, or withdrawal of a product candidate, would result in a longer time period for commercialization of such product candidate, could increase the cost of development of such product candidate and could harm Imara’s competitive position in the marketplace. Even if Imara does receive accelerated approval, it may not ultimately be able to obtain full FDA approval.

If Imara decides to pursue any future product development efforts, a failure to obtain marketing approval in foreign jurisdictions would prevent any product candidates from being marketed abroad.

If Imara decides to pursue any future product development efforts, in order to market and sell its products in the European Union and many other foreign jurisdictions, Imara or its potential third-party collaborators must obtain

 

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separate marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional testing. The time required to obtain approval may differ substantially from that required to obtain FDA approval. The regulatory approval process outside of the United States generally includes all of the risks associated with obtaining FDA approval. In addition, in many countries outside of the United States, it is required that the product be approved for reimbursement before the product can be made available for sale in that country. Imara or its potential third-party collaborators may not obtain approvals from regulatory authorities outside of the United States on a timely basis, if at all. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside of the United States does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA. However, a failure or delay in obtaining regulatory approval in one country may have a negative effect on the regulatory process in other countries. Imara may not be able to file for marketing approvals and may not receive necessary approvals to commercialize its products in any market.

Additionally, Imara could face heightened risks with respect to seeking marketing approval in the United Kingdom as a result of the withdrawal of the United Kingdom from the European Union, commonly referred to as Brexit. The United Kingdom is no longer part of the European Single Market and European Union Customs Union. As of January 1, 2021, the Medicines and Healthcare products Regulatory Agency, or the MHRA, became responsible for supervising medicines and medical devices in Great Britain, comprising England, Scotland and Wales under domestic law, whereas Northern Ireland will continue to be subject to European Union rules under the Northern Ireland Protocol. The MHRA will rely on the Human Medicines Regulations 2012 (SI 2012/1916) (as amended), or the HMR, as the basis for regulating medicines. The HMR has incorporated into the domestic law of the United Kingdom the body of European Union law governing medicinal products that pre-existed prior to the United Kingdom’s withdrawal from the European Union. Any delay in obtaining, or an inability to obtain, any marketing approvals, as a result of Brexit or otherwise, may force Imara to restrict or delay efforts to seek regulatory approval in the United Kingdom for its product candidates, which could significantly and materially harm its business.

Imara expects that it will be subject to additional risks in commercializing any of its product candidates that receive marketing approval outside the United States, including tariffs, trade barriers and regulatory requirements; economic weakness, including inflation, or political instability in particular foreign economies and markets; compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; and workforce uncertainty in countries where labor unrest is more common than in the United States.

Inadequate funding for the FDA, the SEC and other government agencies, including from government shut downs, or other disruptions to these agencies’ operations, could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of Imara’s business may rely, which could negatively impact Imara’s business.

The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory and policy changes. Average review times at the FDA have fluctuated in recent years as a result. Disruptions at the FDA and other agencies may also slow the time necessary for new product candidates to be reviewed and/or approved by necessary government agencies, which would adversely affect Imara’s business. In addition, government funding of the SEC and other government agencies on which Imara’s operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable. For example, over the last several years the U.S. government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical activities. If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process

 

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Imara’s regulatory submissions, which could have a material adverse effect on Imara’s business. Further, future government shutdowns could impact Imara’s ability to access the public markets and obtain necessary capital in order to properly capitalize and continue its operations.

Separately, in response to the COVID-19 pandemic, a number of companies announced receipt of complete response letters due to the FDA’s inability to complete required inspections for their applications. As of May 26, 2021, the FDA noted it was continuing to ensure timely reviews of applications for medical products during the COVID-19 pandemic in line with its user fee performance goals and conducting mission critical domestic and foreign inspections to ensure compliance of manufacturing facilities with FDA quality standards. However, the FDA may not be able to continue its current pace and review timelines could be extended, including where a pre-approval inspection or an inspection of clinical sites is required and due to the COVID-19 pandemic and travel restrictions, the FDA is unable to complete such required inspections during the review period. Regulatory authorities outside the United States may adopt similar restrictions or other policy measures in response to the COVID-19 pandemic and may experience delays in their regulatory activities.

Accordingly, if a prolonged government shutdown or other disruption occurs, it could significantly impact the ability of the FDA to timely review and process Imara’s regulatory submissions, which could have a material adverse effect on Imara’s business. Future shutdowns or other disruptions could also affect other government agencies such as the SEC, which may also impact Imara’s business by delaying review of its public filings, to the extent such review is necessary, and Imara’s ability to access the public markets.

If Imara decides to pursue any future product development efforts, any product candidate for which Imara obtains marketing approval could be subject to post-marketing restrictions or withdrawal from the market and Imara may be subject to substantial penalties if it fails to comply with regulatory requirements or if it experiences unanticipated problems with its products, when and if any of them are approved.

If Imara decides to pursue any future product development efforts, any product candidate for which Imara obtains marketing approval, along with the manufacturing processes, post-approval clinical data, labeling, advertising and promotional activities for such product, will be subject to continual requirements of and review by the FDA and other regulatory authorities. These requirements include submissions of safety and other post-marketing information and reports, registration and listing requirements, cGMP requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, requirements regarding the distribution of samples to physicians and recordkeeping. Even if marketing approval of a product candidate is granted, the approval may be subject to limitations on the indicated uses for which the product may be marketed or to the conditions of approval, including the requirement to implement a REMS. If any product candidate receives marketing approval, the accompanying label may limit the approved use of the drug, which could limit sales of the product.

The FDA may also impose requirements for costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of the product, including the adoption and implementation of REMS. The FDA and other agencies, including the Department of Justice, or the DOJ, closely regulate and monitor the post-approval marketing and promotion of drugs to ensure, among other things, that they are marketed and distributed only for the approved indications and in accordance with the provisions of the approved labeling. The FDA and other agencies impose and enforce stringent restrictions on manufacturers’ communications regarding off-label use, and if Imara promotes its products beyond their approved indications, it may be subject to enforcement action or prosecution arising from off-label promotion. In September 2021, the FDA published final regulations which describe the types of evidence that the agency will consider in determining the intended use of a drug product. Violations of the FDCA and other statutes and regulations relating to the promotion and advertising of prescription drugs may lead to investigations and enforcement actions alleging violations of federal and state healthcare fraud and abuse laws, including the False Claims Act, as well as state consumer protection laws.

 

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In addition, later discovery of previously unknown adverse events or other problems with Imara’s products, manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may have various consequences, including:

 

   

suspension of or restrictions on such products, manufacturers or manufacturing processes;

 

   

restrictions and warnings on the labeling or marketing of a product;

 

   

restrictions on product distribution or use;

 

   

requirements to conduct post-marketing studies or clinical trials;

 

   

warning letters or untitled letters;

 

   

withdrawal of the products from the market;

 

   

refusal to approve pending applications or supplements to approved applications that Imara submits;

 

   

recall of products;

 

   

fines, restitution or disgorgement of profits or revenues;

 

   

suspension of any ongoing clinical trials;

 

   

suspension or withdrawal of marketing approvals;

 

   

damage to relationships with any potential collaborators;

 

   

unfavorable press coverage and damage to Imara’s reputation;

 

   

refusal to permit the import or export of Imara’s products;

 

   

product seizure or detention;

 

   

injunctions or the imposition of civil or criminal penalties; or

 

   

litigation involving patients using Imara’s products.

In addition, manufacturers of approved products and those manufacturers’ facilities are required to comply with extensive FDA requirements, including ensuring that quality control and manufacturing procedures conform to cGMPs applicable to drug manufacturers or quality assurance standards applicable to medical device manufacturers, which include requirements relating to quality control and quality assurance as well as the corresponding maintenance of records and documentation and reporting requirements. Imara, any contract manufacturers it may engage in the future, its future collaborators and their contract manufacturers will also be subject to other regulatory requirements, including submissions of safety and other post-marketing information and reports, registration and listing requirements, requirements regarding the distribution of samples to clinicians, recordkeeping, and costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of the product such as the requirement to implement a REMS.

Similar restrictions apply to the approval of Imara’s products in the European Union. The holder of a marketing authorization is required to comply with a range of requirements applicable to the manufacturing, marketing, promotion and sale of medicinal products. These include compliance with the European Union’s stringent pharmacovigilance or safety reporting rules, which can impose post-authorization studies and additional monitoring obligations; the manufacturing of authorized medicinal products, for which a separate manufacturer’s license is mandatory; and the marketing and promotion of authorized drugs, which are strictly regulated in the European Union and are also subject to European Union Member State laws. The failure to comply with these and other European Union requirements can also lead to significant penalties and sanctions.

 

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Imara may be subject to certain healthcare laws and regulations, which could expose it to criminal sanctions, civil penalties, contractual damages, reputational harm, fines, disgorgement, exclusion from participation in government healthcare programs, curtailment or restricting of Imara’s operations, and diminished profits and future earnings.

Healthcare providers, third-party payors and others will play a primary role in the recommendation and prescription of any products for which Imara obtains marketing approval. Imara’s future arrangements with healthcare providers and third-party payors will expose it to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which Imara markets, sells and distributes any products for which it obtains marketing approval. Potentially applicable U.S. federal and state healthcare laws and regulations include the following:

 

   

the federal Anti-Kickback Statute, prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under a federal healthcare programs such as Medicare and Medicaid;

 

   

the federal false claims laws, including the civil False Claims Act, impose criminal and civil penalties, including those from civil whistleblower or qui tam actions against individuals or entities for knowingly presenting, or causing to be presented to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;

 

   

the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for executing or attempting to execute a scheme to defraud any healthcare benefit program;

 

   

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or the HITECH Act, also imposes obligations on certain types of individuals and entities, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;

 

   

the federal false statements statute prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services;

 

   

the federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program (with specific exceptions) to report annually to the U.S. Department of Health and Human Services information related to payments and other transfers of value made by that entity to physicians, other healthcare providers and teaching hospitals and ownership and investment interests held by physicians, other healthcare providers and their family members; and

 

   

analogous state laws and regulations, such as state anti- kickback and false claims laws, and transparency laws, may apply to sales or marketing arrangements, and claims involving healthcare items or services reimbursed by non-governmental third party payors, including private insurers and some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, in addition to requiring manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures. Many state laws also govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts. Foreign laws also govern the privacy and security of health information in many circumstances.

The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is prohibited in the European Union.

 

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Payments made to physicians in certain European Union Member States must be publicly disclosed. Moreover, agreements with physicians often must be the subject of prior notification and approval by the physician’s employer, his or her competent professional organization and/or the regulatory authorities of the individual European Union Member States. These requirements are provided in the national laws, industry codes or professional codes of conduct applicable in the European Union Member States. Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.

Efforts to ensure that Imara’s business arrangements with third parties, and its business generally, will comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that Imara’s business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If Imara’s operations are found to be in violation of any of these laws or any other governmental regulations that may apply to it, Imara may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, disgorgement, contractual damages, and reputational harm, any of which could substantially disrupt Imara’s operations. If any of the physicians or other providers or entities with whom Imara expects to do business is found not to be in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.

Compliance with global privacy and data security requirements could result in additional costs and liabilities to Imara or inhibit its ability to collect and process data globally, and the failure to comply with such requirements could subject Imara to significant lawsuits or fines and penalties, which may have a material adverse effect on Imara’s business, financial condition or results of operations.

The regulatory framework for the collection, use, safeguarding, sharing, transfer and other processing of information worldwide is rapidly evolving and is likely to remain uncertain for the foreseeable future. Globally, virtually every jurisdiction in which Imara operates has established its own data security and privacy frameworks with which Imara must comply. For example, the collection, use, disclosure, transfer, or other processing of personal data regarding data subjects in the European Union, including personal health data, is subject to the European Union General Data Protection Regulation, or the GDPR, which took effect across all member states of the European Economic Area, or EEA, in May 2018. The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, and taking certain measures when engaging third-party processors. The GDPR increases Imara’s obligations with respect to clinical trials conducted in the EEA by expanding the definition of personal data to include coded data and requiring changes to informed consent practices and more detailed notices for clinical trial subjects and investigators. In addition, the GDPR also imposes strict rules on the transfer of personal data to countries outside the European Union, including the United States and, as a result, increases the scrutiny that such rules should apply to transfers of personal data from clinical trial sites located in the EEA to the United States. The GDPR also permits data protection authorities to require destruction of improperly gathered or used personal information and/or impose substantial fines for violations of the GDPR, which can be up to four percent of global revenues or 20 million Euros, whichever is greater, and confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR. In addition, the GDPR provides that European Union member states may make their own further laws and regulations limiting the processing of personal data, including genetic, biometric or health data.

Given the breadth and depth of changes in data protection obligations, complying with the GDPR’s requirements is rigorous and time intensive and requires significant resources and an ongoing review of Imara’s technologies, systems and practices, as well as those of any third-party collaborators, service providers, contractors or

 

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consultants that process or transfer personal data collected in the European Union. The GDPR and other changes in laws or regulations associated with the enhanced protection of certain types of sensitive data, such as healthcare data or other personal information from Imara’s clinical trials, could require Imara to change its business practices and put in place additional compliance mechanisms, may interrupt or delay Imara’s development, regulatory and commercialization activities and increase its cost of doing business, and could lead to government enforcement actions, private litigation and significant fines and penalties against Imara and could have a material adverse effect on Imara’s business, financial condition or results of operations.

Similar privacy and data security requirements are either in place or underway in the United States. There are a broad variety of data protection laws that may be applicable to Imara’s activities, and a range of enforcement agencies at both the state and federal levels that can review companies for privacy and data security concerns based on general consumer protection laws. The Federal Trade Commission and state Attorneys General all are aggressive in reviewing privacy and data security protections for consumers. New laws also are being considered at both the state and federal levels. For example, the California Consumer Privacy Act, or CCPA, which became effective on January 1, 2020, is creating similar risks and obligations as those created by GDPR, although the CCPA does exempt certain information collected as part of a clinical trial subject to the Federal Policy for the Protection of Human Subjects (the Common Rule). Many other states have passed similar legislation. A broad range of legislative measures also have been introduced at the federal level. Accordingly, failure to comply with current and any future federal and state laws regarding privacy and security of personal information could expose Imara to fines and penalties. Imara also faces a threat of consumer class actions related to these laws and the overall protection of personal data. Even if Imara is not determined to have violated these laws, investigations into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm Imara’s reputation and its business.

Current and future legislation may increase the difficulty and cost for Imara and any future collaborators to obtain reimbursement for any of Imara’s candidate products that do receive marketing approval and Imara’s ability to generate revenue will be materially impaired.

In the United States and foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of Imara’s product candidates, restrict or regulate post-approval activities and affect Imara’s ability to profitably sell any product candidates for which it obtains marketing approval. Imara expects that current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that Imara, or any collaborators, may receive for any approved products. If reimbursement of its products is unavailable or limited in scope, Imara’s business could be materially harmed.

In March 2010, President Obama signed into law the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, or collectively the ACA. In addition, other legislative changes have been proposed and adopted since the ACA was enacted. In August 2011, the Budget Control Act of 2011, among other things, created measures for spending reductions by Congress. A Joint Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s automatic reduction to several government programs. These changes included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect in April 2013 and will remain in effect through 2031 under the CARES Act. These Medicare sequester reductions were suspended through the end of March 2022. From April 2022 through June 2022 a 1% sequester cut will be in effect, with the full 2% cut resuming thereafter. The American Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. These laws may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices Imara may obtain for any of its product candidates for which it may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used.

 

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Since enactment of the ACA, there have been and continue to be, numerous legal challenges and Congressional actions to repeal and replace provisions of the law. For example, with enactment of the TCJA in 2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effective in 2019. Further, on December 14, 2018, a U.S. District Court judge in the Northern District of Texas ruled that the individual mandate portion of the ACA is an essential and inseverable feature of the ACA and therefore because the mandate was repealed as part of the TCJA, the remaining provisions of the ACA are invalid as well. The U.S. Supreme Court heard this case on November 10, 2020 and on June 17, 2021, dismissed this action after finding that the plaintiffs do not have standing to challenge the constitutionality of the ACA. Litigation and legislation over the ACA are likely to continue, with unpredictable and uncertain results.

The Trump Administration also took executive actions to undermine or delay implementation of the ACA, including directing federal agencies with authorities and responsibilities under the ACA to waive, defer, grant exemptions from, or delay the implementation of any provision of the ACA that would impose a fiscal or regulatory burden on states, individuals, healthcare providers, health insurers, or manufacturers of pharmaceuticals or medical devices. On January 28, 2021, however, President Biden issued a new Executive Order which directs federal agencies to reconsider rules and other policies that limit Americans’ access to health care, and consider actions that will protect and strengthen that access. Under this Order, federal agencies are directed to re-examine: policies that undermine protections for people with pre-existing conditions, including complications related to COVID-19; demonstrations and waivers under Medicaid and the ACA that may reduce coverage or undermine the programs, including work requirements; policies that undermine the Health Insurance Marketplace or other markets for health insurance; policies that make it more difficult to enroll in Medicaid and the ACA; and policies that reduce affordability of coverage or financial assistance, including for dependents.

Current and future legislative efforts may limit the costs for Imara’s products, if and when they are licensed for marketing, and that could materially impact Imara’s ability to generate revenues.

The prices of prescription pharmaceuticals have also been the subject of considerable discussion in the United States. There have been several recent U.S. congressional inquiries, as well as proposed and enacted state and federal legislation designed to, among other things, bring more transparency to pharmaceutical pricing, review the relationship between pricing and manufacturer patient programs, and reduce the costs of pharmaceuticals under Medicare and Medicaid. In 2020, President Trump issued several executive orders intended to lower the costs of prescription products and certain provisions in these orders have been incorporated into regulations. These regulations include an interim final rule implementing a most favored nation model for prices that would tie Medicare Part B payments for certain physician-administered pharmaceuticals to the lowest price paid in other economically advanced countries, effective January 1, 2021. That rule, however, has been subject to a nationwide preliminary injunction and, on December 29, 2021, the Centers for Medicare & Medicaid Services, or CMS, issued a final rule to rescind it. With the issuance of this rule, CMS stated that it will explore all options to incorporate value into payments for Medicare Part B pharmaceuticals and improve beneficiaries’ access to evidence-based care.

In addition, in October 2020, the Department of Health and Human Services, or HHS, and the FDA published a final rule allowing states and other entities to develop a Section 804 Importation Program, or SIP, to import certain prescription drugs from Canada into the United States. The final rule is currently the subject of ongoing litigation, but at least six states (Vermont, Colorado, Florida, Maine, New Mexico, and New Hampshire) have passed laws allowing for the importation of drugs from Canada with the intent of developing SIPs for review and approval by the FDA. Further, on November 20, 2020, HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law. The implementation of the rule has been delayed by the Biden administration from January 1, 2022 to January 1, 2023 in response to ongoing litigation. The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers, the implementation of which have also been delayed by the Biden administration until January 1, 2023.

 

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At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. These measures could reduce the ultimate demand for Imara’s products, once approved, or put pressure on its product pricing. Imara expects that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for any product candidates or additional pricing pressures.

Finally, outside the United States, in some nations, including those of the EU, the pricing of prescription pharmaceuticals is subject to governmental control and access. In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product. To obtain reimbursement or pricing approval in some countries, Imara or its collaborators may be required to conduct a clinical trial that compares the cost-effectiveness of its product to other available therapies. If reimbursement of Imara’s products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, Imara’s business could be materially harmed.

If Imara or any third-party manufacturers it engages fail to comply with environmental, health and safety laws and regulations, Imara could become subject to fines or penalties or incur costs or liabilities that could harm its business.

If Imara decides to pursue any future product development efforts, Imara and any third-party manufacturers it may engage will be subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. If Imara decides to pursue any future product development efforts, its operations may involve the use of hazardous and flammable materials, including chemicals and biological materials. Imara’s operations may also produce hazardous waste products. Imara expects it would contract with third parties for the disposal of these materials and wastes. Imara cannot eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from Imara’s use of hazardous materials, Imara could be held liable for any resulting damages, and any liability could exceed its resources. Liability under certain environmental laws governing the release and cleanup of hazardous materials is joint and several and could be imposed without regard to fault. Imara also could incur significant costs associated with civil or criminal fines and penalties or become subject to injunctions limiting or prohibiting Imara’s activities for failure to comply with such laws and regulations.

Although Imara currently maintains general liability insurance as well as workers’ compensation insurance to cover it for costs and expenses it may incur due to injuries to its employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. Imara currently does not maintain insurance for environmental liability or toxic tort claims that may be asserted against it in connection with its storage or disposal of biological, hazardous or radioactive materials.

In addition, Imara may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. These current or future laws and regulations may impair Imara’s research, development or production efforts. Imara’s failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions.

Further, with respect to the operations of any third-party contract manufacturers, it is possible that if they fail to operate in compliance with applicable environmental, health and safety laws and regulations or properly dispose of wastes associated with Imara’s products, Imara could be held liable for any resulting damages, suffer

 

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reputational harm or experience a disruption in the manufacture and supply of any product candidates or products. In addition, Imara’s supply chain could be adversely impacted if any of its third-party contract manufacturers become subject to injunctions or other sanctions as a result of their non-compliance with environmental, health and safety laws and regulations.

Imara is subject to anti-corruption laws, as well as export control laws, customs laws, sanctions laws and other laws governing its operations. If Imara fails to comply with these laws, it could be subject to civil or criminal penalties, other remedial measures and legal expenses, be precluded from developing manufacturing and selling certain products outside the United States or be required to develop and implement costly compliance programs, which could adversely affect Imara’s business, results of operations and financial condition.

Imara’s operations are subject to anti-corruption laws, including the U.K. Bribery Act 2010, or Bribery Act, the U.S. Foreign Corrupt Practices Act, or FCPA, and other anti-corruption laws that apply in countries where Imara does business and may do business in the future. The Bribery Act, FCPA and these other laws generally prohibit Imara, its officers, and its employees and intermediaries from bribing, being bribed or making other prohibited payments to government officials or other persons to obtain or retain business or gain some other business advantage. Compliance with the FCPA, in particular, is expensive and difficult, particularly in countries in which corruption is a recognized problem. In addition, the FCPA presents particular challenges in the pharmaceutical industry, because, in many countries, hospitals are operated by the government, and doctors and other hospital employees are considered foreign officials. Certain payments to hospitals in connection with clinical trials and other work have been deemed to be improper payments to government officials and have led to FCPA enforcement actions.

Imara may in the future operate in jurisdictions that pose a high risk of potential Bribery Act or FCPA violations, and it may participate in collaborations and relationships with third parties whose actions could potentially subject it to liability under the Bribery Act, FCPA or local anti-corruption laws. In addition, Imara cannot predict the nature, scope or effect of future regulatory requirements to which its international operations might be subject or the manner in which existing laws might be administered or interpreted. If Imara expands its operations outside of the United States, it will need to dedicate additional resources to comply with numerous laws and regulations in each jurisdiction in which it plans to operate.

Imara is also subject to other laws and regulations governing its international operations, including regulations administered by the governments of the United Kingdom and the United States, and authorities in the European Union, including applicable export control regulations, economic sanctions on countries and persons, customs requirements and currency exchange regulations, collectively referred to as the Trade Control laws. In addition, various laws, regulations and executive orders also restrict the use and dissemination outside of the United States, or the sharing with certain non-U.S. nationals, of information classified for national security purposes, as well as certain products and technical data relating to those products. If Imara expands its presence outside of the United States, it will require Imara to dedicate additional resources to comply with these laws, and these laws may preclude Imara from developing, manufacturing, or selling certain products and product candidates outside of the United States, which could limit Imara’s growth potential and increase its development costs.

There is no assurance that Imara will be completely effective in ensuring its compliance with all applicable anti-corruption laws, including the Bribery Act, the FCPA or other legal requirements, including Trade Control laws. If Imara is not in compliance with the Bribery Act, the FCPA and other anti-corruption laws or Trade Control laws, it may be subject to criminal and civil penalties, disgorgement and other sanctions and remedial measures, and legal expenses, which could have an adverse impact on Imara’s business, financial condition, results of operations and liquidity. The Securities and Exchange Commission, or SEC, also may suspend or bar issuers from trading securities on U.S. exchanges for violations of the FCPA’s accounting provisions. Any investigation of any potential violations of the Bribery Act, the FCPA, other anti-corruption laws or Trade Control laws by United Kingdom, U.S. or other authorities could also have an adverse impact on Imara’s reputation, its business, results of operations and financial condition.

 

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Imara’s employees, independent contractors, consultants and vendors may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements and insider trading, which could cause significant liability for Imara and harm its reputation.

Imara is exposed to the risk of fraud or other misconduct by its employees, independent contractors, consultants and vendors. Misconduct by these partners could include intentional failures to comply with FDA regulations or similar regulations of comparable foreign regulatory authorities, provide accurate information to the FDA or similar foreign regulatory authorities, comply with manufacturing standards, comply with federal and state healthcare fraud and abuse laws and regulations and similar laws and regulations established and enforced by comparable foreign regulatory authorities, report financial information or data accurately or disclose unauthorized activities to Imara. Employee misconduct could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to Imara’s reputation. This could include violations of HIPAA, other U.S. federal and state law, and requirements of non-U.S. jurisdictions, including the European Union Data Protection Directive. Imara is also exposed to risks in connection with any insider trading violations by employees or others affiliated with Imara. It is not always possible to identify and deter employee misconduct, and the precautions Imara takes to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting Imara from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws, standards, regulations, guidance or codes of conduct. If any such actions are instituted against Imara, and Imara is not successful in defending itself or asserting its rights, those actions could have a significant impact on Imara’s business and results of operations, including the imposition of significant fines or other sanctions.

Imara’s internal computer systems, or those of its collaborators or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of Imara’s product development programs.

Imara’s internal computer systems and those of any collaborators, contractors or consultants are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. Such systems are also vulnerable to service interruptions or to security breaches from inadvertent or intentional actions by Imara’s employees, third-party vendors and/or business partners, or from cyberattacks by malicious third parties. Cyber incidents are increasing in their frequency, sophistication and intensity, and have become increasingly difficult to detect. For example, Imara has experienced attempts at phishing and e-mail fraud with the goal of causing payments to be transmitted to an unintended recipient. Cyber incidents could also include the deployment of harmful malware, ransomware, denial-of-service attacks, unauthorized access to or deletion of files, social engineering and other means to affect service reliability and threaten the confidentiality, integrity and availability of information. The risk of cyber incidents could also be increased by cyberwarfare in connection with the ongoing conflict between Russia and Ukraine, including potential proliferation of malware from the conflict into systems unrelated to the conflict.

While Imara has not experienced any material system failure, accident, cyber incidents or security breach to date, if such an event were to occur and cause interruptions in its operations, it could result in a material disruption of Imara’s development programs and its business operations, whether due to a loss of its trade secrets or other proprietary information or other similar disruptions. For example, the loss of clinical trial data from completed or future clinical trials could result in delays in Imara’s regulatory approval efforts and significantly increase Imara’s costs to recover or reproduce the data. To the extent that any disruption or security breach were to result in a loss of, or damage to, Imara’s data or applications, or inappropriate disclosure of confidential or proprietary information, Imara could incur liability, its competitive position and reputation could be harmed and the further development and commercialization of any product candidates it may develop could be delayed.

 

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Risks Related to Imara’s Common Stock and Status as a Public Company

An active trading market for Imara’s common stock may not continue to develop or be sustained.

Imara’s common stock began trading on the Nasdaq Global Select Market on March 12, 2020. Prior to March 12, 2020, there was no public market for its common stock, and Imara cannot be certain that an active trading market for its shares will continue to develop or be sustained. As a result, it may be difficult for Imara’s stockholders to sell their shares without depressing the market price for the shares or at all.

If securities analysts do not publish or cease publishing research or reports or publish misleading, inaccurate or unfavorable research about Imara’s business or if they publish negative evaluations of its stock, the price and trading volume of Imara’s stock could decline.

The trading market for Imara’s common stock relies, in part, on the research and reports that industry or financial analysts publish about Imara or its business. Imara does not have control over these analysts. There can be no assurance that existing analysts will continue to cover Imara or that new analysts will begin to cover Imara. There is also no assurance that any covering analyst will provide favorable coverage. If one or more of the analysts covering Imara’s business downgrade their evaluations of its stock or publish inaccurate or unfavorable research about its business, or provides more favorable relative recommendations about its competitors, the price of Imara’s stock could decline. If one or more of these analysts cease to cover Imara’s stock, Imara could lose visibility in the market for its stock, which in turn could cause Imara’s stock price and trading volume to decline.

The price of Imara’s common stock may be volatile and fluctuate substantially, which could result in substantial losses for its stockholders.

Imara’s stock price is likely to be volatile. The stock market in general and the market for smaller biopharmaceutical companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies. As a result of this volatility, Imara’s stockholders may not be able to sell their common stock at or above the price paid for their shares. The market price for Imara’s common stock may be influenced by many factors, including:

 

   

results of or developments in preclinical studies and clinical trials of any product candidates Imara may develop or those of its competitors or potential collaborators;

 

   

timing of the results of Imara’s preclinical studies and clinical trials or those of its competitors;

 

   

Imara’s success in commercializing any product candidates, if and when approved;

 

   

the success of competitive products or technologies;

 

   

regulatory or legal developments in the United States and other countries;

 

   

developments or disputes concerning patent applications, issued patents or other intellectual property or proprietary rights;

 

   

the recruitment or departure of key personnel;

 

   

the level of expenses related to any product candidates Imara may develop;

 

   

the results of Imara’s efforts to discover, develop, acquire or in-license products, product candidates, technologies or data referencing rights, the costs of commercializing any such products and the costs of development of any such product candidates or technologies;

 

   

actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts;

 

   

variations in Imara’s financial results or the financial results of companies that are perceived to be similar to Imara;

 

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sales of common stock by Imara, its executive officers, directors or principal stockholders, or others;

 

   

changes in the structure of healthcare payment systems;

 

   

market conditions in the pharmaceutical and biotechnology sectors;

 

   

general economic, industry and market conditions, including, without limitation, the current adverse impact of the COVID-19 pandemic and political and economic instability caused by the current conflict between Russia and Ukraine and economic sanctions adopted in response to the conflict; and

 

   

the other factors described in this “Risk Factors” section.

In the past, following periods of volatility in the market price of a company’s securities, securities class-action litigation has often been instituted against that company. Any lawsuit to which Imara is a party, with or without merit, may result in an unfavorable judgment. Imara also may decide to settle lawsuits on unfavorable terms. Any such negative outcome could result in payments of substantial damages or fines, damage to its reputation or adverse changes to its offerings or business practices. Such litigation may also cause Imara to incur other substantial costs to defend such claims and divert management’s attention and resources.

Imara’s executive officers, directors and principal stockholders, if they choose to act together, have the ability to control all matters submitted to stockholders for approval.

As of September 30, 2022, Imara’s executive officers and directors and its stockholders who owned more than 5% of Imara’s outstanding common stock, in the aggregate, beneficially owned shares representing approximately 55.1% of Imara’s common stock. As a result, if these stockholders were to choose to act together, they would be able to significantly influence all matters submitted to Imara’s stockholders for approval, as well as its management and affairs. For example, these persons, if they choose to act together, would have significant influence over the election of directors and approval of any merger, consolidation or sale of all or substantially all of Imara’s assets.

This concentration of ownership control may:

 

   

delay, defer or prevent a change in control;

 

   

entrench Imara’s management and board of directors; or

 

   

delay or prevent a merger, consolidation, takeover or other business combination involving Imara that other stockholders may desire.

This concentration of ownership may also adversely affect the market price of Imara’s common stock.

Imara has broad discretion in the use of its cash, cash equivalents and investments and may not use them effectively.

Imara’s management has broad discretion in the application of its cash, cash equivalents and investments and could use such funds in ways that do not, despite the exercise of reasonable judgement, improve its results of operations or enhance the value of its common stock. The failure by Imara’s management to apply these funds effectively could result in financial losses that could cause the price of Imara’s common stock to decline and delay the development of any product candidates Imara may develop. Pending their use, Imara may invest its cash, cash equivalents and investments in a manner that does not produce income or that loses value.

Because Imara does not anticipate paying any cash dividends on its capital stock in the foreseeable future, capital appreciation, if any, will be the sole source of gain for its stockholders.

Imara has never declared or paid cash dividends on its capital stock and it has no current plans to pay cash dividends on its common stock. As a result, capital appreciation, if any, of Imara’s common stock will be the sole source of gain for its stockholders for the foreseeable future.

 

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Sales of a substantial number of shares of Imara’s common stock in the public market could cause its stock price to fall, even if its business is doing well.

Sales of a substantial number of shares of Imara’s common stock in the public market, or the perception in the market that the holders of a large number of shares intend to sell shares, could reduce the market price of Imara’s common stock, impair its ability to raise capital through the sale of additional equity securities, and make it more difficult for Imara’s stockholders to sell their common stock at a time and price that they deem appropriate. Persons who were Imara’s stockholders prior to its initial public offering continue to hold a substantial number of shares of Imara’s common stock. If such persons sell, or indicate an intention to sell, substantial amounts of Imara’s common stock in the public market, the trading price of its common stock could decline.

Imara currently has on file with the SEC a universal shelf registration statement which allows it to offer and sell registered common stock, preferred stock, debt securities, warrants and/or units from time to time pursuant to one or more offerings up to an aggregate of $200 million, at prices and terms to be determined at the time of sale, subject to restrictions that may apply from time to time on Imara’s ability to utilize the shelf registration statement to sell more than one-third of the market value of its public float, meaning the aggregate market value of voting and non-voting common stock held by non-affiliates, in any trailing 12-month period. In July 2021, Imara issued and sold 8,333,333 shares of common stock with aggregate gross proceeds of approximately $50 million under this universal shelf registration statement.

Moreover, holders of an aggregate of 11,005,600 shares of Imara’s common stock have rights, subject to specified conditions, to require Imara to file registration statements covering their shares or to include their shares in registration statements that Imara may file for itself or other stockholders. Imara has also registered all 4,654,296 shares of common stock that it may issue under its equity compensation plans and such shares can be freely sold in the public market upon issuance, subject to volume limitations applicable to affiliates, vesting arrangements and exercise of options.

Imara is an “emerging growth company” and a “smaller reporting company,” and the reduced disclosure requirements applicable to emerging growth companies and smaller reporting companies may make its common stock less attractive to investors.

Imara is an “emerging growth company,” or EGC, as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act. It may remain an EGC until December 31, 2025, although if the market value of its common stock that is held by non-affiliates exceeds $700.0 million as of any September 30 before that time or if Imara has annual gross revenues of $1.235 billion or more in any fiscal year, it would cease to be an EGC as of December 31 of the applicable year. Imara also would cease to be an EGC if it issues more than $1.0 billion of non-convertible debt over a three-year period. For so long as Imara remains an EGC, it is permitted and intends to rely on exemptions from certain disclosure requirements that are applicable to other public companies that are not EGCs. These exemptions include:

 

   

being permitted to provide only two years of audited financial statements, in addition to any required unaudited interim financial statements, with correspondingly reduced “Management’s Discussion and Analysis of Financial Condition and Results of Operations” disclosure;

 

   

not being required to comply with the auditor attestation requirements in the assessment of Imara’s internal control over financial reporting;

 

   

not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements;

 

   

reduced disclosure obligations regarding executive compensation; and

 

   

exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and stockholder approval of any golden parachute payments not previously approved.

 

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Imara may choose to take advantage of some or all of the available exemptions. Imara cannot predict whether investors will find its common stock less attractive if it relies on these exemptions. If some investors find its common stock less attractive as a result, there may be a less active trading market for Imara’s common stock and its stock price may be more volatile.

In addition, the JOBS Act permits an EGC to take advantage of an extended transition period to comply with new or revised accounting standards applicable to public companies until those standards would otherwise apply to private companies. Imara has elected to take advantage of such extended transition period, which means that when a standard is issued or revised and it has different application dates for public or private companies, Imara will adopt the new or revised standard at the time private companies adopt the new or revised standard and will do so until such time that Imara either (1) irrevocably elects to “opt out” of such extended transition period or (2) no longer qualifies as an EGC.

Imara is also a smaller reporting company, and it will remain a smaller reporting company until the fiscal year following the determination that either (i) its voting and non-voting common shares held by non-affiliates is more than $250 million measured on the last business day of its second fiscal quarter, or (ii) its annual revenues are less than $100 million during the most recently completed fiscal year and its voting and non-voting common shares held by non-affiliates is more than $700 million measured on the last business day of its second fiscal quarter. Similar to emerging growth companies, smaller reporting companies have reduced disclosure obligations, such as an exemption from providing selected financial data and an ability to provide simplified executive compensation information and only two years of audited financial statements.

Imara has incurred and will continue to incur costs as a result of operating as a public company, and its management has devoted and will continued to be required to devote substantial time to new compliance initiatives and corporate governance practices.

As a public company, and particularly after it is no longer an EGC, Imara will incur significant legal, accounting and other expenses that it did not incur as a private company. The Sarbanes-Oxley Act of 2002, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements of the Nasdaq Global Select Market and other applicable securities rules and regulations impose various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance practices. Imara’s management will need to devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations will increase Imara’s legal and financial compliance costs, particularly as it hires additional financial and accounting employees to meet public company internal control and financial reporting requirements, and will make some activities more time-consuming and costly.

Imara continuously evaluates these rules and regulations, and cannot predict or estimate the amount of additional costs it may incur or the timing of such costs. These rules and regulations are often subject to varying interpretations, in many cases due to their lack of specificity, and, as a result, their application in practice may evolve over time as new guidance is provided by regulatory and governing bodies. This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.

Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002, or Section 404, Imara is required to furnish a report by its management on its internal control over financial reporting with its Annual Reports on Form 10-K. However, while Imara remains an EGC, it will not be required to include an attestation report on internal control over financial reporting issued by its independent registered public accounting firm. To comply with Section 404, Imara is engaged in a process to document and evaluate its internal control over financial reporting, which is both costly and challenging. In this regard, Imara will need to continue to dedicate internal resources, including through hiring additional financial and accounting personnel, potentially engage outside consultants and adopt a detailed work plan to assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing that controls are functioning as

 

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documented and implement a continuous reporting and improvement process for internal control over financial reporting. Despite its efforts, there is a risk that Imara will not be able to conclude, within the prescribed timeframe or at all, that its internal control over financial reporting is effective as required by Section 404. If Imara identifies one or more material weaknesses in its internal control over financial reporting, it could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of its financial statements.

If Imara fails to maintain an effective system of internal control over financial reporting, it may not be able to accurately report its financial results or prevent fraud. As a result, stockholders could lose confidence in its financial and other public reporting, which would harm Imara’s business and the trading price of its common stock.

Effective internal controls over financial reporting are necessary for Imara to provide reliable financial reports and, together with adequate disclosure controls and procedures, are designed to prevent fraud. Any failure to implement required new or improved controls, or difficulties encountered in their implementation could cause Imara to fail to meet its reporting obligations. In addition, any testing by Imara conducted in connection with Section 404 of the Sarbanes-Oxley Act of 2002, or any subsequent testing by its independent registered public accounting firm, may reveal deficiencies in its internal controls over financial reporting that are deemed to be material weaknesses or that may require prospective or retroactive changes to Imara’s financial statements or identify other areas for further attention or improvement. Inferior internal controls could also cause investors to lose confidence in Imara’s reported financial information, which could have a negative effect on the trading price of its stock.

Imara is required to disclose changes made in its internal controls and procedures on a quarterly basis and its management is required to assess the effectiveness of these controls annually. However, for as long as Imara is an “emerging growth company” under the JOBS Act, its independent registered public accounting firm will not be required to attest to the effectiveness of its internal controls over financial reporting pursuant to Section 404. Imara could be an “emerging growth company” for up to five years. An independent assessment of the effectiveness of its internal controls over financial reporting could detect problems that Imara’s management’s assessment might not. Undetected material weaknesses in Imara’s internal controls over financial reporting could lead to financial statement restatements and require Imara to incur the expense of remediation.

Imara’s disclosure controls and procedures may not prevent or detect all errors or acts of fraud.

As a public company, Imara is subject to certain reporting requirements of the Exchange Act. Imara’s disclosure controls and procedures are designed to reasonably assure that information required to be disclosed by Imara in reports it files or submits under the Exchange Act is accumulated and communicated to management, recorded, processed, summarized and reported within the time periods specified in the rules and forms of the SEC. Imara believes that any disclosure controls and procedures or internal controls and procedures, no matter how well conceived and operated, can provide only reasonable, not absolute, assurance that the objectives of the control system are met. These inherent limitations include the realities that judgments in decision-making can be faulty, and that breakdowns can occur because of simple error or mistake. Additionally, controls can be circumvented by the individual acts of some persons, by collusion of two or more people or by an unauthorized override of the controls. Accordingly, because of the inherent limitations in Imara’s control system, misstatements or insufficient disclosures due to error or fraud may occur and not be detected.

Changes in tax laws or in their implementation or interpretation may adversely affect Imara’s business and financial condition.

Changes in tax law may adversely affect Imara’s business or financial condition. On December 22, 2017, the U.S. government enacted the TCJA, which significantly reformed the Code. The TCJA, as amended by the CARES Act, among other things, contained significant changes to corporate taxation, including a reduction of

 

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the corporate tax rate from a top marginal rate of 35% to a flat rate of 21%, the limitation of the tax deduction for net interest expense to 30% of adjusted taxable income (except for certain small businesses), the limitation of the deduction for NOLs to 80% of current year taxable income and the elimination of NOL carrybacks, in each case, for NOLs arising in taxable years beginning after December 31, 2017 (though any such NOLs may be carried forward indefinitely and such NOLs arising in taxable years beginning before January 1, 2021 are generally eligible to be carried back up to five years), the imposition of a one-time taxation of offshore earnings at reduced rates regardless of whether they are repatriated, the elimination of U.S. tax on foreign earnings (subject to certain important exceptions), the allowance of immediate deductions for certain new investments instead of deductions for depreciation expense over time, and the modification or repeal of many business deductions and credits.

In addition to the CARES Act, as part of Congress’ response to the COVID-19 pandemic, economic relief legislation has been enacted in 2020 and 2021 containing tax provisions. In addition, the Inflation Reduction Act, or the IRA, was signed into law in August 2022. The IRA introduced new tax provisions, including a 1% excise tax imposed on certain stock repurchases by publicly traded companies. In the absence of regulatory guidance, the 1% excise tax generally applies to certain acquisitions of stock by the publicly traded company (or certain of its affiliates) from a stockholder of the company in exchange for money or other property (other than stock of the company itself), subject to a de minimis exception. Thus, the excise tax could apply to certain transactions that are not traditional stock repurchases. Regulatory guidance under the TCJA and such additional legislation, is and continues to be forthcoming, and such guidance could ultimately increase or lessen the impact of these laws on Imara’s business and financial condition. In addition, it is uncertain if and to what extent various states will conform to the TCJA and additional tax legislation.

Provisions in Imara’s corporate charter documents and under Delaware law could make an acquisition of the company, which may be beneficial to Imara’s stockholders, more difficult and may prevent attempts by Imara’s stockholders to replace or remove its current directors and members of management.

Provisions in Imara’s restated certificate of incorporation and its amended and restated bylaws may discourage, delay or prevent a merger, acquisition or other change in control of the company that stockholders may consider favorable, including transactions in which Imara’s stockholders might otherwise receive a premium for their shares. These provisions could also limit the price that investors might be willing to pay in the future for shares of Imara’s common stock, thereby depressing the market price of its common stock. In addition, because Imara’s board of directors is responsible for appointing the members of its management team, these provisions may frustrate or prevent any attempts by Imara’s stockholders to replace or remove its current management by making it more difficult for stockholders to replace members of Imara’s board of directors. Among other things, these provisions:

 

   

establish a classified board of directors such that only one of three classes of directors is elected each year;

 

   

allow the authorized number of Imara’s directors to be changed only by resolution of its board of directors;

 

   

limit the manner in which stockholders can remove directors from Imara’s board of directors;

 

   

establish advance notice requirements for stockholder proposals that can be acted on at stockholder meetings and nominations to Imara’s board of directors;

 

   

require that stockholder actions must be effected at a duly called stockholder meeting and prohibit actions by Imara’s stockholders by written consent;

 

   

limit who may call stockholder meetings;

 

   

authorize Imara’s board of directors to issue preferred stock without stockholder approval, which could be used to institute a “poison pill” that would work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approved by Imara’s board of directors; and

 

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require the approval of the holders of at least 75% of the votes that all Imara’s stockholders would be entitled to cast to amend or repeal specified provisions of Imara’s restated certificate of incorporation or for stockholders to amend or repeal Imara’s amended and restated bylaws.

Moreover, because Imara is incorporated in Delaware, it is governed by the provisions of Section 203 of the DGCL, which generally prohibits a person who, together with their affiliates and associates, owns 15% or more of a company’s outstanding voting stock from, among other things, merging or combining with the company for a period of three years after the date of the transaction in which the person acquired ownership of 15% or more of the company’s outstanding voting stock, unless the merger or combination is approved in a prescribed manner.

Imara’s restated certificate of incorporation designates the state courts in the State of Delaware as the sole and exclusive forum for certain types of actions and proceedings that may be initiated by its stockholders, which could discourage lawsuits against the company and its directors, officers and employees.

Imara’s restated certificate of incorporation provides that, unless Imara consents in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware (or, if the Court of Chancery of the State of Delaware does not have jurisdiction, the federal district court for the District of Delaware) will be the sole and exclusive forum for the following types of proceedings: (1) any derivative action or proceeding brought on Imara’s behalf, (2) any action asserting a claim of breach of a fiduciary duty owed by any of Imara’s directors, officers, employees or stockholders to the company or its stockholders, (3) any action asserting a claim arising pursuant to any provision of the DGCL or as to which the DGCL confers jurisdiction on the Court of Chancery of the State of Delaware or (4) any action asserting a claim arising pursuant to any provision of Imara’s restated certificate of incorporation or amended and restated bylaws (in each case, as they may be amended from time to time) or governed by the internal affairs doctrine. These choice of forum provisions will not apply to suits brought to enforce a duty or liability created by the Securities Act, the Exchange Act or any other claim for which federal courts have exclusive jurisdiction.

These exclusive-forum provisions may make it more expensive for stockholders to bring a claim than if the stockholders were permitted to select another jurisdiction and may limit the ability of Imara’s stockholders to bring a claim in a judicial forum that such stockholders find favorable for disputes with Imara or its directors, officers or employees, which may discourage such lawsuits against Imara and its directors, officers and employees. Alternatively, if a court were to find the choice of forum provisions contained in Imara’s restated certificate of incorporation to be inapplicable or unenforceable in an action, Imara may incur additional costs associated with resolving such action in other jurisdictions, which could materially adversely affect its business, financial condition and operating results.

Risks Related to Enliven

Risks Related to Enliven’s Limited Operating History, Financial Position and Need for Additional Capital

Enliven is early in its development efforts, with a limited operating history, and it has no products approved for commercial sale, which may make it difficult for you to evaluate its current business and likelihood of success and future viability.

Enliven is a clinical stage biopharmaceutical company with a limited operating history upon which you can evaluate its business and prospects.

Enliven commenced operations in June 2019, has never completed a clinical trial, has no products approved for commercial sale and has never generated any revenue. Drug development is a highly uncertain undertaking and involves a substantial degree of risk. To date, Enliven has devoted substantially all of its resources to developing ELVN-001 and ELVN-002, its research and development activities, business planning, establishing and maintaining its intellectual property portfolio, hiring personnel, raising

 

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capital, and providing general and administrative support for these operations. Enliven is currently evaluating ELVN-001 in a Phase 1 clinical trial in adults with CML and Enliven filed an IND with the FDA for ELVN-002 in the fourth quarter of 2022. Enliven has not initiated clinical trials for any other product candidate.

Enliven has not yet demonstrated its ability to complete any clinical trials, obtain marketing approvals, manufacture a commercial-scale product or arrange for a third party to do so on its behalf, or conduct sales and marketing activities necessary for successful product commercialization. As a result, it may be more difficult for investors to accurately predict Enliven’s likelihood of success and viability than it could be if it had a longer operating history.

In addition, Enliven may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors and risks frequently experienced by early-stage biopharmaceutical companies in rapidly evolving fields. Enliven also expects that, as it advances its product candidates, it will need to transition from a company with a research and development focus to a company capable of supporting commercial activities. Enliven has not yet demonstrated an ability to successfully overcome such risks and difficulties, or to make such a transition. If Enliven does not adequately address these risks and difficulties or successfully make such a transition, its business will suffer.

Enliven has incurred significant net losses in each period since its inception, and it expects to continue to incur significant net losses for the foreseeable future.

Enliven has incurred significant net losses in each reporting period since its inception, has not generated any revenue to date and has financed its operations principally through private placements of its preferred stock. Enliven’s net loss was $24.7 million for the year ended December 31, 2021. As of September 30, 2022, Enliven had an accumulated deficit of $73.3 million. Enliven is still in the very early stages of development of its product candidates and has not yet completed any clinical trials. As a result, it expects that it will be many years, if ever, before it has commercialized product and generate revenue from product sales. Even if it succeeds in receiving marketing approval for and commercializing one or more of its product candidates, it expects that it will continue to incur substantial research and development and other expenses in order to discover, develop and market additional potential products.

Enliven expects to continue to incur significant expenses and increasing operating losses for the foreseeable future. The net losses Enliven incurs may fluctuate significantly from quarter to quarter such that a period-to-period comparison of its results of operations may not be a good indication of its future performance. The size of Enliven’s future net losses will depend, in part, on the rate of future growth of its expenses and its ability to generate revenue. Enliven’s prior losses and expected future losses have had and will continue to have an adverse effect on its working capital, its ability to fund the development of its product candidates and its ability to achieve and maintain profitability and the performance of its stock.

Enliven has never generated revenue from product sales and may never achieve or maintain profitability.

Enliven has never generated any revenue from commercial product sales. To become and remain profitable, Enliven must develop and eventually commercialize product candidates with significant market potential, which will require it to be successful in a range of challenging activities. These activities can include completing preclinical studies and clinical trials of Enliven’s product candidates, obtaining marketing approval for these product candidates, manufacturing, marketing and selling those products that are approved and satisfying any post-marketing requirements. Enliven does not anticipate generating any revenue from product sales for many years, if ever. Enliven’s ability to generate revenue and achieve profitability depends significantly on its ability to achieve several objectives, including:

 

   

successful and timely completion of clinical development of ELVN-001 and ELVN-002 and preclinical and clinical development of other research programs and any other future programs;

 

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establishing and maintaining relationships with CROs and clinical sites for the clinical development of ELVN-001, ELVN-002 and any other future programs;

 

   

timely receipt of marketing approvals from applicable regulatory authorities for any product candidates for which Enliven successfully completes clinical development;

 

   

developing an efficient and scalable manufacturing process for Enliven’s product candidates, including obtaining finished products that are appropriately packaged for sale;

 

   

establishing and maintaining commercially viable supply and manufacturing relationships with third parties that can provide adequate, in both amount and quality, products and services to support clinical development and meet the market demand for Enliven’s product candidates, if approved;

 

   

successful commercial launch following any marketing approval, including the development of a commercial infrastructure, whether in-house or with one or more collaborators;

 

   

a continued acceptable safety profile following any marketing approval of Enliven’s product candidates;

 

   

commercial acceptance of Enliven’s product candidates by patients, the medical community and third-party payors;

 

   

satisfying any required post-marketing approval commitments to applicable regulatory authorities;

 

   

identifying, assessing and developing new product candidates;

 

   

obtaining, maintaining and expanding patent protection, trade secret protection and regulatory exclusivity, both in the United States and internationally;

 

   

defending against third-party interference or infringement claims, if any;

 

   

entering into, on favorable terms, any collaboration, licensing or other arrangements that may be necessary or desirable to develop, manufacture or commercialize Enliven’s product candidates;

 

   

obtaining and maintaining coverage and adequate reimbursement by third-party payors for Enliven’s product candidates;

 

   

addressing any competing therapies and technological and market developments; and

 

   

attracting, hiring and retaining qualified personnel.

Enliven may never be successful in achieving its objectives and, even if it does, may never generate revenue that is significant or large enough to achieve profitability. If Enliven does achieve profitability, it may not be able to sustain or increase profitability on a quarterly or annual basis. Enliven’s failure to become and remain profitable would decrease the value of its company and could impair its ability to maintain or further its research and development efforts, raise additional necessary capital, grow its business and continue its operations.

Any changes in the manufacturing process, suppliers, or facilities will require further comparability analysis and approval by the FDA before implementation, which could delay Enliven’s clinical trials and product candidate development, and could require additional clinical trials, including bridging studies, to demonstrate consistent and continued safety and efficacy.

Enliven has not previously submitted a New Drug Application (NDA) to the FDA or similar approval filings to a comparable foreign regulatory authority for any product candidate. An NDA or other relevant regulatory filing must include extensive nonclinical and clinical data and supporting information to establish that the product candidate is safe and effective for each desired indication. The NDA or other relevant regulatory filing must also include significant information regarding the chemistry, manufacturing and controls for the product candidate. Enliven cannot be certain that its current or future product candidates will be successful in clinical trials or receive regulatory approval. If Enliven does not receive regulatory approvals for current or future product

 

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candidates, it may not be able to continue its operations. Even if Enliven successfully obtains regulatory approval to market a product candidate, its revenue will depend, in part, upon the size of the markets in the territories for which it receives regulatory approval and has commercial rights, the availability of competitive therapies and whether there are sufficient levels of reimbursement and adoption by physicians.

Risks Related to the Discovery, Development and Commercialization of Enliven’s Product Candidates

Enliven is very early in its development efforts. In addition, Enliven is substantially dependent on ELVN-001 and ELVN-002. If Enliven is unable to advance ELVN-001 or ELVN-002 through clinical development, obtain regulatory approval and ultimately commercialize such product candidates, or experience significant delays in doing so, Enliven’s business will be materially harmed.

Enliven is very early in its development efforts. Enliven is currently evaluating ELVN-001 in a Phase 1 clinical trial in adults with CML and Enliven filed an IND with the FDA for ELVN-002 in the fourth quarter of 2022. Enliven has not initiated clinical trials for any other product candidate and Enliven may experience unexpected or adverse results in the future. Enliven will be required to demonstrate thorough, adequate and well-controlled clinical trials that its product candidates are safe and effective, with a favorable benefit-risk profile, for use in their target indications before Enliven can seek regulatory approvals for their commercial sale. Enliven’s initial clinical trials will begin with relatively small cohorts before expanding in size in subsequent cohorts. If safety issues arise in an early cohort, Enliven may be delayed or prevented from subsequently expanding into larger trial cohorts. Enliven’s ability to generate product revenue, which it does not expect will occur for many years, if ever, will depend heavily on the successful clinical development and eventual commercialization of ELVN-001 and ELVN-002. Enliven is not permitted to market or promote any product candidate before it receives marketing approval from the FDA, EMA or any comparable foreign regulatory authorities, and Enliven may never receive such marketing approvals.

The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and the results of Enliven’s clinical trials may not satisfy the requirements of the FDA, EMA or other comparable foreign regulatory authorities.

Enliven will be required to demonstrate with substantial evidence through well-controlled clinical trials that its product candidates are safe and effective for use in a diverse population before it can seek marketing approvals for their commercial sale. Preclinical and clinical testing is expensive and can take many years to complete, and its outcome is inherently uncertain. Failure can occur at any time during the preclinical study and clinical trial processes, and, because Enliven’s product candidates are in early stages of developments, there is a high risk of failure and Enliven may never succeed in developing marketable products.

The results of preclinical studies may not be predictive of the results of clinical trials of Enliven’s product candidates. Moreover, the results of early clinical trials may not be predictive of the results of later-stage clinical trials. Although product candidates may demonstrate promising results in preclinical studies and early clinical trials, they may not prove to be safe or effective in subsequent clinical trials. Favorable results from certain animal studies may not accurately predict the results of other animal studies or of human trials, due to the inherent biologic differences in species, the differences between testing conditions in animal studies and human trials, and the particular goals, purposes, and designs of the relevant studies and trials.

There is typically an extremely high rate of attrition from the failure of product candidates proceeding through preclinical studies and clinical trials. Product candidates in later stages of clinical trials may fail to show the desired safety and efficacy profile despite having progressed through preclinical studies and initial clinical trials. Likewise, early, smaller-scale clinical trials may not be predictive of eventual safety or effectiveness in large-scale pivotal clinical trials. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their

 

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drugs. A number of companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy, insufficient durability of efficacy or unacceptable safety issues, notwithstanding promising results in earlier trials. Most product candidates that commence preclinical studies and clinical trials are never approved as products. The development of Enliven’s product candidates and Enliven’s stock price may also be impacted by inferences, whether correct or not, that are drawn between the success or failure of preclinical studies or clinical trials of Enliven’s competitors or other companies in the biopharmaceutical industry, in addition to Enliven’s own preclinical studies and clinical trials.

In some instances, there can be significant variability in safety and efficacy results between different clinical trials of the same product candidate due to numerous factors, including changes in trial protocols, differences in size and type of the patient populations, differences in and adherence to the dose and dosing regimen and other trial protocols and the rate of dropout among clinical trial participants. Patients treated with Enliven’s product candidates may also be undergoing surgical, radiation and chemotherapy treatments and may be using other approved products or investigational new drugs, which can cause side effects or adverse events that are unrelated to Enliven’s product candidates. As a result, assessments of efficacy can vary widely for a particular patient, and from patient to patient and site to site within a clinical trial. This subjectivity can increase the uncertainty of, and adversely impact, Enliven’s clinical trial outcomes.

Any preclinical studies or clinical trials that Enliven conducts may not demonstrate the safety and efficacy necessary to obtain regulatory approval to market its product candidates. If the results of Enliven’s ongoing or future preclinical studies and clinical trials are inconclusive with respect to the safety and efficacy of its product candidates, if it does not meet the clinical endpoints with statistical and clinically meaningful significance, or if there are safety concerns associated with its product candidates, Enliven may be prevented or delayed in obtaining marketing approval for such product candidates. In some instances, there can be significant variability in safety or efficacy results between different preclinical studies and clinical trials of the same product candidate due to numerous factors, including changes in trial procedures set forth in protocols, differences in the size and type of the patient populations, changes in and adherence to the clinical trial protocols and the rate of dropout among clinical trial participants.

Enliven does not know whether any preclinical studies or clinical trials it may conduct will demonstrate consistent or adequate efficacy and safety sufficient to obtain approval to market any of its product candidates.

Enliven has limited resources and is currently focusing its efforts on ELVN-001 and ELVN-002 for development in particular indications and advancing its other research programs. As a result, Enliven may fail to capitalize on programs, product candidates or indications that may be more profitable or for which there is a greater likelihood of success.

Enliven is currently focusing its resources and efforts on ELVN-001, ELVN-002 and advancing its other research programs. Because Enliven has limited financial and managerial resources, it must focus on a limited number of research programs and product candidates and on specific indications. As a result, Enliven may forgo or delay pursuit of opportunities for other indications or with other product candidates that may have greater commercial potential. Enliven’s resource allocation decisions may cause it to fail to capitalize on viable commercial products or profitable market opportunities. Enliven’s spending on current and future research and development activities for ELVN-001, ELVN-002 and its other research programs may not yield any commercially viable products. If Enliven does not accurately evaluate the commercial potential or target markets for ELVN-001, ELVN-002 and its other research programs, or the product candidates it is currently developing in these programs, Enliven may relinquish valuable rights to its product candidates or programs through collaboration, licensing or other strategic arrangements in cases in which it would have been more advantageous for it to retain sole development and commercialization rights to such product candidate or program.

 

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Enliven’s prospects depend in large part upon developing and commercializing ELVN-001 and ELVN-002 and discovering, developing and commercializing product candidates from its other research programs, and failure to successfully identify, develop and commercialize additional product candidates could impair Enliven’s ability to grow.

Enliven’s future operating results are dependent on its ability to successfully discover, develop, obtain regulatory approval for and commercialize product candidates including ELVN-001, ELVN-002 and product candidates from its research programs. A product candidate can unexpectedly fail at any stage of development. The historical failure rate for product candidates is high due to risks relating to safety, efficacy, clinical execution, changing standards of medical care and other unpredictable variables. The results from preclinical testing or early clinical trials of a product candidate may not be predictive of the results that will be obtained in later stage clinical trials of the product candidate.

The success of ELVN-001, ELVN-002 and other product candidates Enliven may develop will depend on many factors, including the following:

 

   

successful and timely completion of preclinical studies, including generating sufficient data to support the initiation or continuation of preclinical studies and clinical trials, including data that demonstrates improved efficacy, safety, and patient convenience compared to Enliven’s competitors’ products;

 

   

obtaining IRB approval at each clinical trial site;

 

   

approval of INDs for Enliven’s planned clinical trials and future clinical trials;

 

   

addressing any potential delays resulting from factors related to the COVID-19 pandemic;

 

   

the timely manufacture of sufficient quantities of a product candidate for use in clinical trials;

 

   

successful initiation and completion of clinical trials;

 

   

successful and timely patient selection and enrollment in and completion of clinical trials;

 

   

maintaining and establishing relationships with CROs and clinical sites for the clinical development of Enliven’s product candidates both in the United States and internationally;

 

   

the frequency and severity of adverse events in clinical trials;

 

   

demonstrating efficacy, safety and tolerability profiles that are satisfactory to the FDA, EMA or any comparable foreign regulatory authority for marketing approval;

 

   

the timely receipt of marketing approvals from applicable regulatory authorities;

 

   

the extent of any required post-marketing approval commitments to applicable regulatory authorities;

 

   

the maintenance of existing or the establishment of new supply arrangements with third-party drug product suppliers and manufacturers for clinical development and, if approved, commercialization of Enliven’s product candidates;

 

   

obtaining and maintaining patent protection, trade secret protection and regulatory exclusivity, both in the United States and internationally;

 

   

the protection of Enliven’s rights in its intellectual property portfolio;

 

   

the successful launch of commercial sales following any marketing approval;

 

   

a continued acceptable safety profile following any marketing approval;

 

   

commercial acceptance by patients, the medical community and third-party payors; and

 

   

Enliven’s ability to compete with other therapies, as detailed in the section titled “Enliven’s Business—Competition”, particularly since some of Enliven’s product candidates will be aimed to be best-in-class and first-in-class.

Enliven does not have complete control over many of these factors, including certain aspects of preclinical and clinical development and the regulatory submission process, potential threats to its intellectual property rights

 

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and the manufacturing, marketing, distribution and sales efforts of any future collaborator. If Enliven is not successful with respect to one or more of these factors in a timely manner or at all, it could experience significant delays or an inability to successfully commercialize any product candidates from its lead programs, which would materially harm its business. If Enliven does not receive marketing approvals for such product candidates, it may not be able to continue its operations.

Although a substantial amount of Enliven’s efforts will focus on the continued preclinical and clinical testing and potential approval of its product candidates in its current pipeline, Enliven expects to continue to innovate and potentially expand its portfolio. Because Enliven has limited financial and managerial resources, research programs to identify product candidates may require substantial additional technical, financial and human resources, whether or not any new potential product candidates are ultimately identified. Enliven’s success may depend in part upon its ability to identify, select and develop promising product candidates and therapeutics. Enliven may expend resources and ultimately fail to discover and generate additional product candidates suitable for further development. Even if Enliven successfully advances any product candidates into preclinical and clinical development, their success will be subject to all of the preclinical, clinical, regulatory and commercial risks described elsewhere in this section. All product candidates are prone to risks of failure typical of biotechnology product development, including the possibility that a product candidate may not be suitable for clinical development as a result of its harmful side effects, limited efficacy or other characteristics indicating that it is unlikely to receive approval by the FDA, the EMA and other comparable foreign regulatory authorities and achieve market acceptance. If Enliven does not successfully develop and commercialize ELVN-001 or ELVN-002, or successfully identify, develop and commercialize new product candidates, Enliven’s business, prospects, financial condition and results of operations could be adversely affected.

If clinical trials of Enliven’s product candidates fail to demonstrate safety and efficacy to the satisfaction of regulatory authorities or do not otherwise produce positive results, Enliven would incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of its product candidates.

Before obtaining marketing approval from regulatory authorities for the sale of Enliven’s product candidates, Enliven must conduct preclinical studies in animals and extensive clinical trials in humans to demonstrate the safety and efficacy of the product candidates. Clinical testing is expensive and difficult to design and implement, can take many years to complete and has uncertain outcomes. The outcome of preclinical studies and early clinical trials may not predict the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. A number of companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in advanced clinical trials due to lack of efficacy or unacceptable safety profiles, notwithstanding promising results in earlier trials. Enliven does not know whether the clinical trials it may conduct will demonstrate adequate efficacy and safety to result in regulatory approval to market any of its product candidates in any jurisdiction. Enliven’s product candidates may fail to demonstrate efficacy in humans, and particularly across tumor types. A product candidate may fail for safety or efficacy reasons at any stage of the testing process. A major risk Enliven faces is the possibility that none of its product candidates under development will successfully gain market approval from the FDA, EMA or other comparable foreign regulatory authorities, resulting in Enliven being unable to derive any commercial revenue from them after investing significant amounts of capital in their development.

If the results of Enliven’s ongoing or future preclinical studies and future clinical trials are inconclusive with respect to the safety and efficacy of its product candidates, if it does not meet the clinical endpoints with statistical and clinically meaningful significance, or if there are safety concerns associated with its product candidates, Enliven may be prevented or delayed in obtaining marketing approval for such product candidates. In some instances, there can be significant variability in safety or efficacy results between different preclinical studies and clinical trials of the same product candidate due to numerous factors, including changes in trial procedures set forth in protocols, differences in the size and type of the patient populations, changes in and adherence to the clinical trial protocols and the rate of dropout among clinical trial participants.

 

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It is likely that there will be side effects associated with the use of Enliven’s product candidates. Results of Enliven’s future trials could reveal a high and unacceptable severity and prevalence of side effects or adverse events. In such an event, Enliven’s trials could be suspended or terminated and the FDA, EMA or comparable foreign regulatory authorities could order Enliven to cease further development of or deny approval of its product candidates for any or all targeted indications. Treatment-related side effects could also affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Any of these occurrences may harm Enliven’s business, financial condition and prospects significantly.

Further, Enliven’s product candidates could cause undesirable side effects in clinical trials related to on-target toxicity. If on-target toxicity is observed, or if Enliven’s product candidates have characteristics that are unexpected, Enliven may need to abandon their development or limit development to more narrow indications or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective. Many compounds that initially showed promise in early stage testing for treating cancer have later been found to cause side effects that prevented further development of the compound.

The regulatory approval processes of the FDA, EMA and other comparable foreign regulatory authorities are lengthy, time consuming and inherently unpredictable. If Enliven is ultimately unable to obtain regulatory approval of its product candidates, Enliven will be unable to generate product revenue and its business will be substantially harmed.

Enliven’s product candidates are and will continue to be subject to extensive governmental regulations relating to, among other things, research, testing, development, manufacturing, safety, efficacy, approval, recordkeeping, reporting, labeling, storage, packaging, advertising and promotion, pricing, marketing and distribution of drugs. Rigorous preclinical testing and clinical trials and an extensive regulatory approval process must be successfully completed in the United States and in many foreign jurisdictions before a new drug can be approved for marketing.

Obtaining approval by the FDA, EMA and other comparable foreign regulatory authorities is unpredictable, typically takes many years following the commencement of clinical trials and depends upon numerous factors, including the type, complexity and novelty of the product candidates involved. In addition, approval policies, regulations or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions, which may cause delays in the approval or the decision not to approve an application. For example, FDA’s Oncology Center of Excellence initiated Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development and Project FrontRunner to help develop and implement strategies to support approvals in early clinical setting, among other goals. How the FDA plans to implement these goals and their impact on specific clinical programs and the industry are unclear. Regulatory authorities have substantial discretion in the approval process and may refuse to accept any application or may decide that Enliven’s data are insufficient for approval and require additional preclinical, clinical or other data. Even if Enliven eventually completes clinical testing and receives approval for Enliven’s product candidates, the FDA, EMA and other comparable foreign regulatory authorities may approve its product candidates for a more limited indication or a narrower patient population than it originally requested or may impose other prescribing limitations or warnings that limit the product candidate’s commercial potential. Enliven has not submitted for, or obtained, regulatory approval for any product candidate, and it is possible that none of its product candidates will ever obtain regulatory approval. Further, development of Enliven’s product candidates and/or regulatory approval may be delayed for reasons beyond its control.

Applications for Enliven’s product candidates could fail to receive regulatory approval for many reasons, including the following:

 

   

the FDA, EMA or other comparable foreign regulatory authorities may disagree with the design, implementation or results of Enliven’s clinical trials;

 

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the FDA, EMA or other comparable foreign regulatory authorities may determine that Enliven’s product candidates are not safe and effective, are only moderately effective or have undesirable or unintended side effects, toxicities or other characteristics that preclude its obtaining marketing approval or prevent or limit commercial use;

 

   

the population studied in the clinical trial may not be sufficiently broad or representative to assure efficacy and safety in the full population for which Enliven seeks approval;

 

   

the FDA, EMA or other comparable foreign regulatory authorities may disagree with Enliven’s interpretation of data from preclinical studies or clinical trials;

 

   

Enliven may be unable to demonstrate to the FDA, EMA or other comparable foreign regulatory authorities that a product candidate’s risk-benefit ratio for its proposed indication is acceptable;

 

   

the FDA, EMA or other comparable foreign regulatory authorities may fail to approve the manufacturing processes, test procedures and specifications or facilities of third-party manufacturers with which Enliven contracts for clinical and commercial supplies;

 

   

the FDA, EMA or other comparable regulatory authorities may fail to approve companion diagnostic tests required for Enliven’s product candidates; and

 

   

the approval policies or regulations of the FDA, EMA or other comparable foreign regulatory authorities may significantly change in a manner rendering Enliven’s clinical data insufficient for approval.

This lengthy approval process, as well as the unpredictability of the results of clinical trials, may result in Enliven failing to obtain regulatory approval to market any of its product candidates, which would significantly harm its business, results of operations and prospects.

Enliven is also subject to numerous foreign regulatory requirements governing, among other things, the conduct of clinical trials, manufacturing and marketing authorization, pricing and third-party reimbursement. The foreign regulatory approval process varies among countries, and generally includes all of the risks associated with FDA approval described above as well as risks attributable to the satisfaction of local regulations in foreign jurisdictions. Moreover, the time required to obtain approval may differ from that required to obtain FDA approval.

Enliven has limited experience as a company in designing and conducting clinical trials.

The design and implementation of clinical trials is a complex process. Enliven has limited experience as a company in designing and conducting clinical trials. Enliven is currently evaluating ELVN-001 in a Phase 1 clinical trial in adults with CML and Enliven filed an IND with the FDA for ELVN-002 in the fourth quarter of 2022. However, Enliven has not initiated clinical trials for any other product candidate and Enliven may experience unexpected or adverse results in the future. In part because of this lack of experience as a company and its limited infrastructure, Enliven cannot be certain that its ongoing and planned preclinical studies and clinical trials will be completed on time, that it will successfully or cost-effectively design and implement clinical trials that achieve the desired clinical endpoints efficiently, or at all. Large-scale clinical trials would require significant additional financial and management resources and reliance on CROs and consultants. Relying on third-party clinical investigators, CROs and consultants may force Enliven to encounter delays that are outside of its control. Enliven may be unable to identify and contract with sufficient investigators, CROs and consultants on a timely basis or at all. There can be no assurance that Enliven will be able to negotiate and enter into any necessary services agreement with CROs on terms that are acceptable to it on a timely basis or at all.

 

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Any delays in the commencement or completion, or termination or suspension, of Enliven’s planned or future clinical trials could result in increased costs, delay or limit its ability to generate revenue and adversely affect its commercial prospects. Enliven may not be able to file INDs to commence clinical trials on the timelines it expects, and even if it is able to, the FDA, EMA or other comparable foreign regulatory authorities may not permit it to proceed.

Before Enliven can initiate clinical trials of a product candidate in any indication, it must submit the results of preclinical studies to the FDA, EMA or other comparable foreign regulatory authorities along with other information, including information about the product candidate’s chemistry, manufacturing and controls and its proposed clinical trial protocol, as part of an IND or similar regulatory submission under which it must receive authorization to proceed with clinical development. Enliven filed an IND with the FDA for ELVN-002 in the fourth quarter of 2022, and, subject to IND clearance, it plans to initiate a Phase 1 clinical trial thereafter. However, the FDA, EMA or other comparable foreign regulatory authorities may require Enliven to conduct additional preclinical studies before they allow it to initiate clinical trials under any IND, clinical trial authorization or comparable application, if ever, which may lead to additional delays and increase the costs of Enliven’s preclinical development programs. Before obtaining marketing approval from the FDA of ELVN-001, ELVN-002 or any other programs, Enliven must conduct extensive clinical studies to demonstrate safety and efficacy. Clinical testing is expensive, time consuming and uncertain as to outcome. In addition, Enliven expects to rely in part on preclinical, clinical and quality data generated by its CROs and other third parties for regulatory submissions for its product candidates. While Enliven has or will have agreements governing these third parties’ services, Enliven has limited influence over their actual performance. If these third parties do not make data available to Enliven, or, if applicable, make regulatory submissions in a timely manner, in each case pursuant to Enliven’s agreements with them, Enliven’s development programs may be significantly delayed and it may need to conduct additional studies or collect additional data independently. In either case, Enliven’s development costs would increase. Enliven may not be able to file INDs for future product candidates on the timelines it expects. For example, Enliven may experience manufacturing delays or other delays with IND enabling studies. Moreover, Enliven cannot be sure that submission of an IND will result in the FDA allowing clinical trials to begin, or that, once begun, issues will not arise that suspend or terminate clinical trials. Additionally, even if the FDA agrees with the design and implementation of the clinical trials set forth in an IND, Enliven cannot guarantee that it will not change its requirements in the future. These considerations also apply to new clinical trials Enliven may submit as amendments to existing INDs or to a new IND. Any failure to file INDs on the timelines Enliven expects or to obtain regulatory approvals for its planned clinical trials may prevent Enliven from initiating or completing its clinical trials or commercializing its product candidates on a timely basis, if at all.

Enliven could also encounter delays if a clinical trial is suspended or terminated by Enliven, by the IRBs or independent ethics committees of the institutions in which such trials are being conducted, by a Data Safety Monitoring Board for such trial or by the FDA or foreign regulatory authorities. Such authorities may impose such a suspension or termination due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or Enliven’s clinical protocols, inspection of the clinical trial operations or trial site by the FDA or foreign regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse events, failure to demonstrate a benefit from using a pharmaceutical, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial. In addition, changes in regulatory requirements and policies may occur, and Enliven may need to amend clinical trial protocols to comply with these changes. Amendments may require Enliven to resubmit its clinical trial protocols to IRBs or ethics committees for reexamination, which may impact the costs, timing or successful completion of a clinical trial. From time to time, certain of Enliven’s current or future scientific advisors or consultants who receive compensation from Enliven may become investigators for Enliven’s future clinical trials. Under certain circumstances, Enliven may be required to report some of these relationships to the FDA. Although Enliven expects any such relationships to be within the FDA’s guidelines, the FDA may conclude that a financial relationship between Enliven and a principal investigator has created a conflict of interest or otherwise affected interpretation of the study. The FDA may therefore question the integrity of the data generated at the applicable clinical trial site and the utility of the clinical trial itself may be jeopardized. This could result in a

 

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delay in approval, or rejection, of Enliven’s marketing applications by the FDA and may ultimately lead to the denial of marketing approval of Enliven’s product candidates. If Enliven experiences delays in the completion of, or termination of, any clinical trial of any product candidate, the commercial prospects of such product candidate will be harmed, and Enliven’s ability to generate product revenues will be delayed. Moreover, any delays in completing Enliven’s clinical trials will increase its costs, slow down its development and approval process and jeopardize its ability to commence product sales and generate revenues which may harm Enliven’s business, financial condition, results of operations and prospects significantly.

Enliven’s product candidates may cause significant adverse events, toxicities or other undesirable side effects when used alone or in combination with other approved products or investigational new drugs that may result in a safety profile that could prevent regulatory approval, prevent market acceptance, limit their commercial potential or result in significant negative consequences.

If Enliven’s product candidates are associated with undesirable side effects or have unexpected characteristics in preclinical studies or clinical trials when used alone or in combination with other approved products or investigational new drugs Enliven may need to interrupt, delay or abandon their development or limit development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk- benefit perspective. Treatment-related side effects could also affect patient recruitment or the ability of enrolled subjects to complete the trial or result in potential product liability claims. Any of these occurrences may prevent Enliven from achieving or maintaining market acceptance of the affected product candidate and may harm its business, financial condition and prospects significantly. It is likely that there will be side effects associated with the use of Enliven’s product candidates as is typically the case with oncology drugs. Results of Enliven’s studies or trials could reveal a high and unacceptable severity and prevalence of side effects or adverse events. In such an event, Enliven’s trials could be suspended or terminated and the FDA, EMA or comparable foreign regulatory authorities could order Enliven to cease further development of or deny approval of its product candidates for any or all targeted indications. Drug-related side effects could also affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Any of these occurrences may harm Enliven’s business, financial condition and prospects significantly.

In addition, Enliven’s product candidates may be used in populations for which safety concerns may be particularly scrutinized by regulatory agencies. In addition, Enliven’s product candidates may be studied in combination with other therapies, which may exacerbate adverse events associated with the therapy. Patients treated with Enliven’s product candidates may also be undergoing surgical, radiation and chemotherapy treatments, which can cause side effects or adverse events that are unrelated to Enliven’s product candidate but may still impact the success of Enliven’s clinical trials. The inclusion of critically ill patients in Enliven’s clinical trials may result in deaths or other adverse medical events due to other therapies or medications that such patients may be using or due to the gravity of such patients’ illnesses. For example, it is expected that some of the patients to be enrolled in Enliven’s future clinical trials will die or experience major clinical events either during the course of Enliven’s clinical trials or after participating in such trials for non-treatment related reasons.

If significant adverse events or other side effects are observed in any of Enliven’s current or future clinical trials, Enliven may have difficulty recruiting patients to the clinical trials, patients may drop out of Enliven’s trials, or Enliven may be required to abandon the trials or its development efforts of that product candidate altogether. Enliven, the FDA, EMA, other comparable foreign regulatory authorities or an IRB may suspend clinical trials of a product candidate at any time for various reasons, including a belief that subjects in such trials are being exposed to unacceptable health risks or adverse side effects. Some potential therapeutics developed in the biotechnology industry that initially showed therapeutic promise in early- stage trials have later been found to cause side effects that prevented their further development. Even if the side effects do not preclude the product candidate from obtaining or maintaining marketing approval, undesirable side effects may inhibit market acceptance due to its tolerability versus other therapies. Any of these developments could materially harm Enliven’s business, financial condition and prospects. Further, if any of Enliven’s product candidates obtains

 

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marketing approval, toxicities associated with such product candidates previously not seen during clinical testing may also develop after such approval and lead to a requirement to conduct additional clinical safety trials, additional contraindications, warnings and precautions being added to the drug label including “black box” warnings, significant restrictions on the use of the product or the withdrawal of the product from the market. Enliven cannot predict whether its product candidates will cause toxicities in humans that would preclude or lead to the revocation of regulatory approval based on preclinical studies or early-stage clinical trials.

Interim, topline and preliminary data from Enliven’s preclinical studies and clinical trials that Enliven announces or publishes from time to time may change as more data become available and are subject to audit and verification procedures that could result in material changes in the final data.

From time to time, Enliven may publicly disclose preliminary, interim or topline data from its preclinical studies and clinical trials. These interim updates are based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular study or trial. For example, Enliven may report responses in certain patients that are unconfirmed at the time and which do not ultimately result in confirmed responses to treatment after follow-up evaluations. Enliven also makes assumptions, estimations, calculations and conclusions as part of its analyses of data, and Enliven may not have received or had the opportunity to fully and carefully evaluate all data. As a result, the topline results that Enliven reports may differ from future results of the same studies or trials, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. Topline data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data Enliven previously published. As a result, topline data should be viewed with caution until the final data are available. In addition, Enliven may report interim analyses of only certain endpoints rather than all endpoints. Interim data from clinical trials that Enliven may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available. Adverse changes between interim data and final data could significantly harm Enliven’s business and prospects. Further, additional disclosure of interim data by Enliven or by its competitors in the future could result in volatility in the price of Enliven’s common stock.

In addition, the information Enliven chooses to publicly disclose regarding a particular study or trial is typically selected from a more extensive amount of available information. Investors may not agree with what Enliven determines is the material or otherwise appropriate information to include in its disclosure, and any information Enliven determines not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product candidate or its business. If the preliminary or topline data that Enliven reports differ from late, final or actual results, or if others, including regulatory authorities, disagree with the conclusions reached, Enliven’s ability to obtain approval for, and commercialize, any of its product candidates may be harmed, which could harm Enliven’s business, financial condition, results of operations and prospects.

If Enliven experiences delays or difficulties in the enrollment or maintenance of patients in clinical trials, its regulatory submissions or receipt of necessary marketing approvals could be delayed or prevented.

Enliven may not be able to initiate or continue clinical trials for its product candidates if it is unable to locate and enroll a sufficient number of eligible patients to participate in these trials to such trial’s conclusion as required by the FDA, EMA or other comparable foreign regulatory authorities. Patient enrollment is a significant factor in the timing of clinical trials. Enliven’s ability to enroll eligible patients may be limited or may result in slower enrollment than it anticipates. Because there are approved drugs and ongoing clinical trials being conducted for CML, it may make it difficult for Enliven to enroll patients. For example, patient enrollment could have been and will likely be affected by the recent approval of asciminib as well as Enliven’s competitors that have ongoing clinical trials for programs that are under development for the same indications as its product candidates since patients who would otherwise be eligible for its clinical trials instead enroll in clinical trials of its competitors’ programs. Additionally, the CML patient population is relatively small and certain clinical trials for future

 

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product candidates may be focused on indications with relatively small patient populations, which may further limit enrollment of eligible patients or may result in slower enrollment than Enliven anticipates. In Enliven’s ELVN-001 and ELVN-002 programs, Enliven will utilize genomic profiling of patients’ tumors to identify suitable patients for recruitment into its clinical trials. Enliven cannot be certain (1) how many patients will have the requisite alterations for inclusion in its clinical trials, (2) that the number of patients enrolled in each program will suffice for regulatory approval or (3) whether each specific BCR-ABL or HER2 mutation will be included in the approved drug label. If Enliven’s strategies for patient identification and enrollment prove unsuccessful, Enliven may have difficulty enrolling or maintaining patients appropriate for its product candidates.

Enliven’s ability to enroll patients may also be significantly delayed by the evolving COVID-19 pandemic and Enliven does not know the extent and scope of such delays at this point. In addition, patients may not be able or willing to visit clinical trial sites for dosing or data collection purposes due to limitations on travel and physical distancing imposed or recommended by federal or state governments or patients’ reluctance to visit the clinical trial sites during the pandemic. These factors resulting from the COVID-19 pandemic could delay Enliven’s clinical trials and its regulatory submissions.

Patient enrollment for Enliven’s current or any future clinical trials may be affected by other factors, including:

 

   

size and nature of the patient population;

 

   

severity of the disease under investigation;

 

   

availability and efficacy of approved drugs for the disease under investigation;

 

   

patient eligibility criteria for the trial in question as defined in the protocol, including biomarker- driven identification and/or certain highly-specific criteria related to stage of disease progression, which may limit the patient populations eligible for Enliven’s clinical trials to a greater extent than competing clinical trials for the same indication that do not have biomarker-driven patient eligibility criteria;

 

   

perceived risks and benefits of the product candidate under study;

 

   

clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new products that may be approved or other product candidates being investigated for the indications Enliven is investigating;

 

   

clinicians’ willingness to screen their patients for biomarkers to indicate which patients may be eligible for enrollment in Enliven’s clinical trials;

 

   

patient referral practices of physicians;

 

   

the ability to monitor patients adequately during and after treatment;

 

   

proximity and availability of clinical trial sites for prospective patients; and

 

   

the risk that patients enrolled in clinical trials will drop out of the trials before completion or, because they may be late-stage cancer patients, will not survive the full terms of the clinical trials.

Enliven’s inability to enroll a sufficient number of patients for its clinical trials would result in significant delays or may require it to abandon one or more clinical trials altogether. Enrollment delays in Enliven’s clinical trials may result in increased development costs for its product candidates and jeopardize its ability to obtain marketing approval for the sale of its product candidates. Furthermore, even if Enliven is able to enroll a sufficient number of patients for its clinical trials, Enliven may have difficulty maintaining participation in its clinical trials through the treatment and any follow-up periods.

 

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Enliven faces substantial competition which may result in others discovering, developing or commercializing products before or more successfully than Enliven does.

The pharmaceutical and biotechnology industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products. In particular, precision oncology is a very competitive space and Enliven has chosen to prioritize addressing well-validated biological targets, and therefore expects to face competition from existing products and products in development for each of its product candidates. While Enliven believes that its technology, the expertise of its team, and its development experience and scientific knowledge provide it with competitive advantages, Enliven faces increasing competition from many different sources, including pharmaceutical and biotechnology companies, academic institutions, governmental agencies and public and private research institutions. Product candidates that Enliven successfully develops and commercializes may compete with existing therapies and new therapies that may become available in the future.

Many of Enliven’s competitors, either alone or with their collaborators, have significantly greater financial resources, established presence in the market, and expertise in research and development, manufacturing, preclinical and clinical testing, obtaining regulatory approvals and reimbursement and marketing approved products than Enliven does. These competitors also compete with Enliven in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, its programs. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. Additional mergers and acquisitions may result in even more resources being concentrated in Enliven’s competitors. As a result of all of these factors, Enliven’s competitors may succeed in obtaining approval from the FDA, EMA or other comparable foreign regulatory authorities or in discovering, developing and commercializing product candidates in its field before Enliven does.

Enliven’s commercial potential could be reduced or eliminated if its competitors develop and commercialize products that are safer or more effective, have fewer or less severe side effects, and are more convenient or less expensive than products that Enliven may develop. Enliven’s competitors also may obtain FDA or other regulatory approval for their products more rapidly than Enliven can, which could result in its competitors establishing a strong market position before Enliven is able to enter the market or could otherwise make its development more complicated. Enliven believes the key competitive factors affecting the success of all of its programs are likely to be efficacy, safety and patient convenience. Even if the product candidates Enliven develops achieve marketing approval, they may be priced at a significant premium over competitive products if any have been approved by then, resulting in reduced competitiveness.

There are currently six BCR-ABL TKIs approved for use in CML: Novartis AG’s Gleevac (imatinib), Tasigna (nilotinib), and Scemblix (asciminib), Bristol Myers Squibb’s Sprycel (dasatinib), Pfizer’s Bosulif (bosutinib), and Takeda’s Iclusig (ponatinib).

There are no approved TKIs for HER2 mutant NSCLC. Enhertu (fam-trastuzumab deruxtecan), an antibody drug conjugate, marketed by AstraZeneca and Daiichi-Sankyo, received accelerated approval from the FDA for this patient population in August 2022. Most of the investigational TKIs for this population are all dual EGFR and HER2 inhibitors such as Spectrum’s poziotinib, Takeda’s mobocertinib, Black Diamond’s BDTX-189 and Jiangsu HengRui Medicine Co., Ltd’s pyrotinib. The FDA is currently reviewing Poziotinib’s NDA and has a Prescription Drug User Fee Act (PDUFA) date in November 2022. Pyrotinib is currently being investigated in a Phase 3 pivotal study. Finally, Boehringer Ingelheim recently initiated clinical development on a HER2 selective, irreversible TKI, BI-1810631, for HER2 mutant NSCLC and other cancers.

For HER2 amplified and overexpressing tumors, such as breast cancer (BRC), there are several FDA-approved antibodies, antibody drug conjugates, and TKIs. For example, Genentech’s Herception (trastuzumab) and Perjecta (pertuzumab) are approved HER2-antibodies. Approved HER2-antibody drug conjugates include

 

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Genentech’s Kadcyla (ado-trastuzumab emtansine) and Daiichi Sankyo’s Enhertu (fam-trastuzumab deruxtecan). Approved TKIs for HER2 BRC include Puma’s Nerlynx (neratinib), Novartis AG’s Tykerb (lapatinib), and Seagen’s Tukysa (tucatinib). Several of these drugs are approved for other HER2-driven indications such as gastric and colorectal cancer.

Finally, there are numerous other investigational therapies, spanning many modalities, that are being evaluated preclinically and in clinical trials for various HER2-altered cancers.

Technological advances or products developed by Enliven’s competitors may render Enliven’s technologies or product candidates obsolete, less competitive or not economical. If Enliven is unable to compete effectively, its opportunity to generate revenue from the sale of its products it may develop, if approved, could be adversely affected. For additional information regarding Enliven’s competition, see the section titled “Enliven’s Business—Competition.

The COVID-19 pandemic could adversely impact Enliven’s business, including its ongoing and planned preclinical and clinical trials.

The COVID-19 pandemic and government measures taken in response have had a significant impact, both direct and indirect, on businesses and commerce, as worker shortages have occurred; supply chains have been disrupted; facilities and production have been suspended; and demand for certain goods and services, such as medical services and supplies, has spiked, while demand for other goods and services, such as travel, has fallen. Enliven may experience disruptions that could severely impact its business and clinical trials, including:

 

   

delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff;

 

   

delays or difficulties in enrolling and retaining patients in any clinical trials, particularly elderly subjects, who are at a higher risk of severe illness or death from COVID-19;

 

   

difficulties interpreting data from Enliven’s clinical trials due to the possible effects of COVID-19 on patients;

 

   

diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as Enliven’s clinical trial sites and hospital staff supporting the conduct of clinical trials;

 

   

interruption of key clinical trial activities, such as clinical trial site monitoring, due to limitations on travel imposed or recommended by federal or state governments, employers and others;

 

   

interruption or delays in the operations of the FDA, EMA or other regulatory authorities, which may impact review and approval timelines;

 

   

limitations in resources that would otherwise be focused on the conduct of Enliven’s business, its preclinical studies or its clinical trials, including because of sickness or the desire to avoid contact with large groups of people or as a result of government-imposed “shelter in place” or similar working restrictions;

 

   

interruptions, difficulties or delays arising in Enliven’s existing operations and company culture as a result of all of its employees working remotely, including those hired during the COVID-19 pandemic;

 

   

delays in receiving approval from regulatory authorities to initiate Enliven’s clinical trials;

 

   

delays in clinical sites receiving the supplies and materials needed to conduct Enliven’s clinical trials;

 

   

interruptions in preclinical studies or clinical trials due to restricted or limited operations at the CROs conducting such studies;

 

   

interruption in global freight and shipping that may affect the transport of clinical trial materials, such as investigational drug product to be used in Enliven’s clinical trials;

 

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changes in regulations as part of a response to the COVID-19 pandemic which may require Enliven to change the ways in which its clinical trials are to be conducted, or to discontinue the clinical trials altogether, or which may result in unexpected costs;

 

   

delays in necessary interactions with regulators, ethics committees and other important agencies and contractors due to limitations in employee resources or forced furlough of government or contractor personnel; and

 

   

refusal of the FDA, EMA or other regulatory authorities to accept data from clinical trials in affected geographies outside of their respective jurisdictions.

Enliven continues to assess the impact that the COVID-19 pandemic may have on its ability to effectively conduct its business operations as planned and there can be no assurance that it will be able to avoid a material impact on its business from the spread of COVID-19 or its consequences, including disruption to its business and downturns in business sentiment generally or in its industry or due to shutdowns that may be requested or mandated by federal, state and local governmental authorities. As a result of the COVID-19 pandemic, an increased number of Enliven’s employees could telecommute, which may impact certain of its operations over the near term and long term.

Additionally, certain third parties with whom Enliven engages or may engage, including collaborators, contract organizations, third-party manufacturers, suppliers, clinical trial sites, regulators and other third parties are similarly adjusting their operations and assessing their capacity in light of the COVID-19 pandemic. If these third parties experience shutdowns or continued business disruptions, Enliven’s ability to conduct its business in the manner and on the timelines presently planned could be materially and negatively impacted. For example, as a result of the COVID-19 pandemic, Enliven could experience delays in the procurement of certain animals for its preclinical studies. Such delays could materially impact Enliven’s preclinical studies and clinical trials and similarly, delays in the procurement of materials or manufacturing supply chain could materially adversely impact Enliven’s preclinical studies and clinical trials. For example, Enliven uses third parties including Pharmaron to conduct preclinical studies and clinical trials and to Pharmaron has previously experienced delays as a result of COVID-19 which resulted in a minor delay in Enliven’s preclinical studies.

Additionally, many of Enliven’s preclinical studies and clinical trials are conducted by CROs, which could be discontinued or delayed as a result of the pandemic. It is also possible that the disproportionate impact of COVID-19 on hospitals and clinical sites will have an impact on recruitment and retention for Enliven’s clinical trials. In addition, certain clinical trial sites for product candidates similar to Enliven’s have experienced, and others may experience in the future, delays in collecting, receiving and analyzing data from patients enrolled in clinical trials due to limited staff at such sites, limitation or suspension of on-site visits by patients, or patients’ reluctance to visit the clinical trial sites during the pandemic and Enliven may experience similar delays. CROs have also made certain adjustments to the operation of such trials in an effort to ensure the monitoring and safety of patients and minimize risks to trial integrity during the pandemic in accordance with the guidance issued by the FDA and may need to make further adjustments in the future that could impact the timing or enrollment of Enliven’s clinical trials. Many of these adjustments are new and untested, may not be effective, may increase costs, and may have unforeseen effects on the enrollment, progress and completion of these trials and the findings from these trials. Enliven may experience delays in the completion of its preclinical studies, clinical trials, patient selection or enrollment or in the progression of its activities related to its planned clinical trials, may need to suspend its clinical trials, and may encounter other negative impacts to such trials due to the effects of the COVID-19 pandemic.

Enliven may be required to develop and implement additional clinical trial policies and procedures designed to help protect subjects from COVID-19. For example, in March 2020, the FDA issued a guidance, which the FDA subsequently updated, on conducting clinical trials during the pandemic, which describes a number of considerations for sponsors of clinical trials impacted by the pandemic, including the requirement to include in the clinical trial report contingency measures implemented to manage the clinical trial, and any disruption of the

 

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clinical trial as a result of the COVID-19 pandemic, among other requirements. In June 2020, the FDA also issued a guidance on good manufacturing practice considerations (cGMPs) for responding to COVID-19 infection in employees in drug products manufacturing, including recommendations for manufacturing controls to prevent contamination of drugs. In view of the spread of the COVID-19 variants, FDA may issue additional guidance and policies that may materially impact Enliven’s business, clinical trials, and clinical development timelines. Changes to existing policies and regulations can increase Enliven’s compliance costs or delay its clinical plans.

Furthermore, the COVID-19 pandemic may also impact the timelines of FDA regulatory inspections and reviews. Since March 2020 when foreign and domestic inspections were largely placed on hold, the FDA has been working to resume routine surveillance, bioresearch monitoring and pre-approval inspections on a prioritized basis. In May 2021, the FDA issued an updated guidance on manufacturing, supply chain, and drug and biological product inspections, indicating that it intends to continue using other tools and approaches where possible for pre-approval inspections, and that it will continue to conduct “mission-critical” inspections on a case-by-case basis, or, where possible to do so safely, resume prioritized domestic inspections, such as pre-approval and surveillance inspections. While the FDA has largely caught up with domestic preapproval inspections, it continues to work through its backlog of foreign inspections. Regulatory authorities outside the United States may adopt similar restrictions or other policy measures in response to COVID-19. If public health concerns or other factors prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities in a timely manner, including due to travel restrictions, foreign COVID-19-related policies, or staffing shortages, it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process Enliven’s regulatory submissions, which could have a material adverse effect on Enliven’s business and clinical development plans.

While the extent of the impact of the current COVID-19 pandemic on Enliven’s business and financial results is uncertain, a continued and prolonged public health crisis such as the COVID-19 pandemic could have a material negative impact on Enliven’s business, financial condition and operating results.

To the extent the COVID-19 pandemic adversely affects Enliven’s business, financial condition and operating results, it may also have the effect of heightening many of the risks described in this section.

The manufacture of drugs is complex, and Enliven’s third-party manufacturers may encounter difficulties in production. If any of Enliven’s third-party manufacturers encounter such difficulties, Enliven’s ability to provide adequate supply of its product candidates for clinical trials or its products for patients, if approved, could be delayed or prevented.

Manufacturing drugs, especially in large quantities, is complex and may require the use of innovative technologies. Each lot of an approved drug product must undergo thorough testing for identity, strength, quality, purity and potency. Manufacturing drugs requires facilities specifically designed for and validated for this purpose, as well as sophisticated quality assurance and quality control procedures. Slight deviations anywhere in the manufacturing process, including filling, labeling, packaging, storage and shipping and quality control and testing, may result in lot failures, product recalls or spoilage. When changes are made to the manufacturing process, Enliven may be required to provide preclinical and clinical data showing the comparable identity, strength, quality, purity or potency of the products before and after such changes. If microbial, viral or other contaminations are discovered at the facilities of Enliven’s manufacturer, such facilities may need to be closed for an extended period of time to investigate and remedy the contamination, which could delay clinical trials and adversely harm Enliven’s business. The use of biologically derived ingredients can also lead to allegations of harm, including infections or allergic reactions, or closure of product facilities due to possible contamination.

If Enliven’s third-party manufacturers are unable to produce sufficient quantities for clinical trials or for commercialization as a result of these challenges, or otherwise, Enliven’s development and commercialization efforts would be impaired, which would have an adverse effect on its business, financial condition, results of operations and prospects.

 

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Changes in methods of product candidate manufacturing or formulation may result in additional costs or delay.

As product candidates progress through preclinical and clinical trials to marketing approval and commercialization, it is common that various aspects of the development program, such as manufacturing methods and formulation, are altered along the way in an effort to optimize yield and manufacturing batch size, minimize costs and achieve consistent quality and results. For example, Enliven may introduce an alternative formulation of one or more of its product candidates during the course of its clinical trials. Such changes carry the risk that they will not achieve these intended objectives. Any of these changes could cause Enliven’s product candidates to perform differently and affect the results of clinical trials conducted with the altered materials. This could delay completion of clinical trials, require the conduct of bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay approval of Enliven’s product candidates and jeopardize Enliven’s ability to commercialize its product candidates, if approved, and generate revenue.

Enliven’s product candidates may not achieve adequate market acceptance among physicians, patients, healthcare payors and others in the medical community necessary for commercial success.

Even if Enliven’s product candidates receive regulatory approval, they may not gain adequate market acceptance among physicians, patients, third-party payors and others in the medical community. The degree of market acceptance of any of Enliven’s approved product candidates will depend on a number of factors, including:

 

   

the efficacy and safety profile as demonstrated in clinical trials compared to alternative treatments, particularly since Enliven’s product candidates will be focused on being best-in-class;

 

   

the timing of market introduction of the product candidate as well as competitive products;

 

   

the clinical indications for which a product candidate is approved;

 

   

restrictions on the use of product candidates in the labeling approved by regulatory authorities, such as boxed warnings or contraindications in labeling, or a risk evaluation and mitigation strategy, if any, which may not be required of alternative treatments and competitor products;

 

   

the potential and perceived advantages of Enliven’s product candidates over alternative treatments;

 

   

the cost of treatment in relation to alternative treatments;

 

   

the availability of coverage and adequate reimbursement by third-party payors, including government authorities;

 

   

the availability of an approved product candidate for use as a combination therapy;

 

   

relative convenience and ease of administration;

 

   

the willingness of the target patient population to try new therapies and undergo required diagnostic screening to determine treatment eligibility and of physicians to prescribe these therapies and diagnostic tests;

 

   

the effectiveness of sales and marketing efforts;

 

   

unfavorable publicity relating to Enliven’s product candidates; and

 

   

the approval of other new therapies for the same indications.

If any of Enliven’s product candidates are approved but do not achieve an adequate level of acceptance by physicians, hospitals, healthcare payors and patients, Enliven may not generate or derive sufficient revenue from that product candidate and its financial results could be negatively impacted.

 

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The market opportunities for any product candidates Enliven develops, if approved, may be limited to certain smaller patient subsets and may be smaller than Enliven estimates them to be.

When cancer is detected early (referred to as localized disease), conventional treatments which include chemotherapy, hormone therapy, surgery and radiation therapy and/or selected targeted therapies may be adequate to cure the patient in many cases. However, once cancer has spread to other areas (advanced or metastatic disease), cancer treatments may not be sufficient to provide a cure but often can significantly prolong life without curing the cancer. First-line (1L) therapies designate treatments that are initially administered to patients with advanced or metastatic disease, while second-line (2L) and 3L therapies are administered to patients when the prior therapies lose their effectiveness. The FDA, EMA and other comparable foreign regulatory bodies often approve cancer therapies for a particular line of treatment. Typically, drug approvals are initially granted for use in later lines of treatment, but with additional evidence of significant efficacy from clinical trials, biopharmaceutical companies can successfully seek and gain approval for use in earlier lines of treatment.

Enliven plans to initially seek approval of its product candidates in most instances at least as a second- or third-line therapy, for use in patients with advanced or metastatic cancer where at least one prior therapy has limited clinical benefit or has lost its effectiveness. For those product candidates that prove to be sufficiently safe and effective, if any, Enliven would expect to seek approval as a 2L therapy and potentially ultimately as a 1L therapy. There is no guarantee that Enliven’s product candidates, even if approved as a second, third or subsequent line of therapy would be approved for an earlier line of therapy, and prior to any such approvals Enliven may have to conduct additional clinical trials that may be costly, time-consuming and subject to risk.

Enliven’s projections of both the number of people who have the cancers it is targeting, as well as the subset of people with these cancers in a position to receive a particular line of therapy and who have the potential to benefit from treatment with its product candidates, are based on its beliefs and estimates. These estimates have been derived from a variety of sources, including scientific literature, surveys of clinics, patient foundations or market research, and may prove to be incorrect. Further, new studies may change the estimated incidence or prevalence of the cancers that Enliven is targeting. The potentially addressable patient population for Enliven’s product candidates may be limited or may not be amenable to treatment with its product candidates. Consequently, even if Enliven’s product candidates are approved, the number of patients that may be eligible for treatment with its product candidates may turn out to be much lower than expected. In addition, Enliven has not yet conducted market research to determine how treating physicians would expect to prescribe a product that is approved for multiple tumor types if there are different lines of approved therapies for each such tumor type. Even if Enliven obtains significant market share for its products, if approved, if the potential target populations are small, Enliven may never achieve profitability without obtaining regulatory approval for additional indications.

Any product candidates Enliven develops may become subject to unfavorable third-party coverage and reimbursement practices, as well as pricing regulations.

The availability and extent of coverage and adequate reimbursement by third-party payors, including government health administration authorities, private health coverage insurers, managed care organizations and other third-party payors is essential for most patients to be able to afford expensive treatments. Sales of any of Enliven’s product candidates that receive marketing approval will depend substantially, both in the United States and internationally, on the extent to which the costs of such product candidates will be covered and reimbursed by third-party payors. If reimbursement is not available, or is available only to limited levels, Enliven may not be able to successfully commercialize its product candidates. Even if coverage is provided, the approved reimbursement amount may not be high enough to allow Enliven to establish or maintain pricing sufficient to realize an adequate return on its investment. Coverage and reimbursement may impact the demand for, or the price of, any product candidate for which Enliven obtains marketing approval. If coverage and reimbursement are not available or reimbursement is available only to limited levels, Enliven may not successfully commercialize any product candidate for which it obtains marketing approval.

 

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There is significant uncertainty related to third-party payor coverage and reimbursement of newly approved products. In the United States, for example, principal decisions about reimbursement for new products are typically made by the Centers for Medicare & Medicaid Services (CMS), an agency within the U.S. Department of Health and Human Services (HHS). CMS decides whether and to what extent a new product will be covered and reimbursed under Medicare, and private third-party payors often follow CMS’s decisions regarding coverage and reimbursement to a substantial degree. However, one third-party payor’s determination to provide coverage for a product candidate does not assure that other payors will also provide coverage for the product candidate. As a result, the coverage determination process is often time-consuming and costly. This process will require Enliven to provide scientific and clinical support for the use of its products to each third-party payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.

As federal and state governments implement additional health care cost containment measures, including measures to lower prescription drug pricing, Enliven cannot be sure that its products, if approved, will be covered by private or public payors, and if covered, whether the reimbursement will be adequate or competitive with other marketed products. Any actions by federal and state governments and health plans aimed at putting additional downward pressure on pharmaceutical pricing and health care costs could negatively impact coverage and reimbursement for Enliven’s product candidates if approved, its revenue, and its ability to compete with other marketed products and to recoup the costs of its research and development. For further discussion, see “—Enliven may face difficulties from changes to current regulations and future legislation. Healthcare legislative measures aimed at reducing healthcare costs may have a material adverse effect on Enliven’s business and results of operations.”

Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products. Further, such payors are increasingly challenging the price, examining the medical necessity and reviewing the cost effectiveness of medical product candidates. There may be especially significant delays in obtaining coverage and reimbursement for newly approved drugs. Third-party payors may limit coverage to specific product candidates on an approved list, known as a formulary, which might not include all FDA-approved drugs for a particular indication. Enliven may need to conduct expensive pharmaco-economic studies to demonstrate the medical necessity and cost effectiveness of its products. Nonetheless, Enliven’s product candidates may not be considered medically necessary or cost effective. Enliven cannot be sure that coverage and reimbursement will be available for any product that it commercializes and, if reimbursement is available, what the level of reimbursement will be.

In addition, companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical or biological products. Similar challenges to obtaining coverage and reimbursement, applicable to pharmaceutical or biological products, will apply to companion diagnostics. Additionally, if any companion diagnostic provider is unable to obtain reimbursement or is inadequately reimbursed, that may limit the availability of such companion diagnostic, which would negatively impact prescriptions for Enliven’s product candidates, if approved.

Outside the United States, the commercialization of therapeutics is generally subject to extensive governmental price controls and other market regulations, and Enliven believes the increasing emphasis on cost containment initiatives in Europe, Canada and other countries has and will continue to put pressure on the pricing and usage of therapeutics such as its product candidates. In many countries, particularly the countries of the European Union (EU), medical product prices are subject to varying price control mechanisms as part of national health systems. In these countries, pricing negotiations with governmental authorities can take considerable time after a product receives marketing approval. To obtain reimbursement or pricing approval in some countries, Enliven may be required to conduct a clinical trial that compares the cost-effectiveness of its product candidate to other available therapies. In general, product prices under such systems are substantially lower than in the United States. Other countries allow companies to fix their own prices for products but monitor and control company profits. Additional foreign price controls or other changes in pricing regulation could restrict the amount that

 

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Enliven is able to charge for its product candidates. Accordingly, in markets outside the United States, the reimbursement for Enliven’s products may be reduced compared with the United States and may be insufficient to generate commercially reasonable revenue and profits.

If Enliven is unable to establish or sustain coverage and adequate reimbursement for any product candidates from third-party payors, the adoption of those products and sales revenue will be adversely affected, which, in turn, could adversely affect the ability to market or sell those product candidates, if approved. Coverage policies and third-party payor reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which Enliven receives regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

Enliven’s business entails a significant risk of product liability and if it is unable to obtain sufficient insurance coverage such inability could have an adverse effect on Enliven’s business and financial condition.

Enliven’s business exposes it to significant product liability risks inherent in the development, testing, manufacturing and marketing of therapeutic treatments. Product liability claims could delay or prevent completion of Enliven’s development programs. If Enliven succeeds in marketing products, such claims could result in an FDA, EMA or other regulatory authority investigation of the safety and effectiveness of Enliven’s products, its manufacturing processes and facilities or its marketing programs. FDA, EMA or other regulatory authority investigations could potentially lead to a recall of Enliven’s products or more serious enforcement action, limitations on the approved indications for which they may be used or suspension or withdrawal of approvals. Regardless of the merits or eventual outcome, liability claims may also result in decreased demand for Enliven’s products, injury to Enliven’s reputation, costs to defend the related litigation, a diversion of management’s time and Enliven’s resources and substantial monetary awards to trial participants or patients. Enliven currently has product liability insurance that it believes is appropriate for its stage of development and may need to obtain higher levels prior to advancing its product candidates into clinical trials or marketing any of its product candidates, if approved. Any insurance Enliven has or may obtain may not provide sufficient coverage against potential liabilities. Furthermore, clinical trial and product liability insurance is becoming increasingly expensive. As a result, Enliven may be unable to obtain sufficient insurance at a reasonable cost to protect it against losses caused by product liability claims that could have an adverse effect on its business and financial condition.

Risks Related to Regulatory Approval and Other Legal Compliance Matters

Enliven may develop its current or future product candidates in combination with other therapies, which would expose it to additional risks.

Enliven may develop or it may seek strategic collaborations to develop its current or future product candidates in combination with one or more currently approved cancer therapies or therapies in development. Even if any of Enliven’s current or future product candidates were to receive marketing approval or be commercialized for use in combination with other existing therapies, Enliven would continue to be subject to the risks that the FDA, EMA or other comparable foreign regulatory authorities could revoke approval of the therapy used in combination with any of Enliven’s product candidates, or safety, efficacy, manufacturing or supply issues could arise with these existing therapies. In addition, it is possible that existing therapies with which Enliven’s product candidates are approved for use could themselves fall out of favor or be relegated to later lines of treatment. This could result in the need to identify other combination therapies for Enliven’s product candidates or its own products being removed from the market or being less successful commercially.

Enliven or its future third party collaborators may also evaluate its current or future product candidates in combination with one or more other cancer therapies that have not yet been approved for marketing by the FDA, EMA or comparable foreign regulatory authorities. Enliven will not be able to market and sell any product candidate in combination with any such unapproved cancer therapies that do not ultimately obtain marketing approval.

 

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If the FDA, EMA or other comparable foreign regulatory authorities do not approve or withdraw their approval of these other therapies, or if safety, efficacy, commercial adoption, manufacturing or supply issues arise with the therapies Enliven chooses to evaluate in combination with any of its current or future product candidates, Enliven may be unable to obtain approval of or successfully market any one or all of the current or future product candidates it develops. Additionally, if the third-party providers of therapies or therapies in development used in combination with Enliven’s current or future product candidates are unable to produce sufficient quantities for clinical trials or for commercialization of Enliven’s current or future product candidates, or if the cost of combination therapies are prohibitive, Enliven’s development and commercialization efforts would be impaired, which would have an adverse effect on its business, financial condition, results of operations and growth prospects.

Enliven has never commercialized a product candidate as a company before and currently lacks the necessary expertise, personnel and resources to successfully commercialize any products on its own or together with suitable collaborators.

Enliven has never commercialized a product candidate as a company. Enliven may license certain rights with respect to its product candidates to collaborators, and, if so, Enliven will rely on the assistance and guidance of those collaborators. For product candidates for which Enliven retains commercialization rights and marketing approval, Enliven will have to develop its own sales, marketing and supply organization or outsource these activities to a third party.

Factors that may affect Enliven’s ability to commercialize its product candidates, if approved, on its own include recruiting and retaining adequate numbers of effective sales and marketing personnel, developing adequate educational and marketing programs to increase public acceptance of its approved product candidates, ensuring regulatory compliance of its company, employees and third parties under applicable healthcare laws, and other unforeseen costs associated with creating an independent sales and marketing organization. Developing a sales and marketing organization will be expensive and time-consuming and could delay the launch of Enliven’s product candidates upon approval. Enliven may not be able to build an effective sales and marketing organization. If Enliven is unable to build its own distribution and marketing capabilities or to find suitable partners for the commercialization of its product candidates, it may not generate revenues from them or be able to reach or sustain profitability.

The FDA, EMA and other comparable foreign regulatory authorities may not accept data from trials conducted in locations outside of their jurisdiction.

Enliven currently conducts its clinical trial for ELVN-001 in the United States and internationally and plans to conduct its clinical trial for ELVN-002 in the United States and internationally. The acceptance of study data by the FDA, EMA or other comparable foreign regulatory authority from clinical trials conducted outside of their respective jurisdictions may be subject to certain conditions. In cases where data from United States clinical trials are intended to serve as the basis for marketing approval in the foreign countries outside the United States, the standards for clinical trials and approval may be different. There can be no assurance that any United States or foreign regulatory authority would accept data from trials conducted outside of its applicable jurisdiction. If the FDA, EMA or any applicable foreign regulatory authority does not accept such data, it would result in the need for additional trials, which would be costly and time-consuming and delay aspects of Enliven’s business plan, and which may result in Enliven’s product candidates not receiving approval or clearance for commercialization in the applicable jurisdiction.

Obtaining and maintaining regulatory approval of Enliven’s product candidates in one jurisdiction does not mean that it will be successful in obtaining regulatory approval of its product candidates in other jurisdictions.

Obtaining and maintaining regulatory approval of Enliven’s product candidates in one jurisdiction does not guarantee that it will be able to obtain or maintain regulatory approval in any other jurisdiction. For example,

 

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even if the FDA or EMA grants marketing approval of a product candidate, comparable regulatory authorities in foreign jurisdictions must also approve the manufacturing, marketing and promotion and reimbursement of the product candidate in those countries. However, a failure or delay in obtaining regulatory approval in one jurisdiction may have a negative effect on the regulatory approval process in others. Approval procedures vary among jurisdictions and can involve requirements and administrative review periods different from those in the United States, including additional preclinical studies or clinical trials as clinical trials conducted in one jurisdiction may not be accepted by regulatory authorities in other jurisdictions. In many jurisdictions outside the United States, a product candidate must be approved for reimbursement before it can be approved for sale in that jurisdiction. In some cases, the price that Enliven intends to charge for its products is also subject to approval.

Obtaining foreign regulatory approvals and establishing and maintaining compliance with foreign regulatory requirements could result in significant delays, difficulties and costs for Enliven and could delay or prevent the introduction of Enliven’s products in certain countries. If Enliven or any future collaborator fails to comply with the regulatory requirements in international markets or fail to receive applicable marketing approvals, Enliven’s target market will be reduced and its ability to realize the full market potential of its potential product candidates will be harmed.

Even if Enliven’s product candidates receive regulatory approval, they will be subject to significant post-marketing regulatory requirements and oversight.

Any regulatory approvals that Enliven may receive for its product candidates will require the submission of reports to regulatory authorities and on-going surveillance to monitor the safety and efficacy of the product candidate, may contain significant limitations related to use restrictions for specified age groups, warnings, precautions or contraindications, and may include burdensome post- approval study or risk management requirements and regulatory inspection. For example, the FDA may require a REMS in order to approve Enliven’s product candidates, which could entail requirements for a medication guide, physician training and communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools.

In addition, if the FDA, EMA or foreign regulatory authorities approve Enliven’s product candidates, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion, import, export and recordkeeping for Enliven’s product candidates will be subject to extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as on-going compliance with current cGMPs and good clinical practices (GCPs) for any clinical trials that Enliven conducts post-approval.

In addition, manufacturers of drug products and their facilities are subject to continual review and periodic, unannounced inspections by the FDA, EMA and other regulatory authorities for compliance with cGMP regulations and standards. If Enliven or a regulatory agency discover previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, or problems with the facilities where the product is manufactured, a regulatory agency may impose restrictions on that product, the manufacturing facility or Enliven, including requiring recall or withdrawal of the product from the market or suspension of manufacturing. In addition, failure to comply with FDA, EMA and other comparable foreign regulatory requirements may subject Enliven to administrative or judicially imposed sanctions, including:

 

   

delays in or the rejection of product approvals;

 

   

suspension or restrictions on Enliven’s ability to conduct clinical trials, including full or partial clinical holds on ongoing or planned trials;

 

   

restrictions on the products, manufacturers or manufacturing process;

 

   

warning or untitled letters;

 

   

fines, restitution, or disgorgement of profits or revenues;

 

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consent decrees, injunctions or imposition of civil or criminal penalties;

 

   

suspension or withdrawal of regulatory approvals;

 

   

product seizures, detentions, or export or import bans;

 

   

voluntary or mandatory product recalls, withdrawals, and/or publicity requirements;

 

   

total or partial suspension of production;

 

   

imposition of restrictions on operations, including costly new manufacturing requirements;

 

   

restrictions or revisions to the labeling, including limitation on approved uses or the addition of additional warnings, contraindications or other safety information, including boxed warnings;

 

   

imposition of a REMS, which may include distribution or use restrictions; and

 

   

requirements to conduct additional post-market clinical trials to assess the safety of the product.

The FDA, EMA and other regulatory authorities’ policies may change, and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of Enliven’s product candidates. Enliven cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or abroad. If Enliven is slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if Enliven is not able to maintain regulatory compliance, it may lose any marketing approval that it may have obtained and it may not achieve or sustain profitability.

Enliven may be required to develop and implement additional clinical trial policies and procedures designed to help protect subjects from the COVID-19 virus. For example, in March 2020, the FDA issued a guidance, which the FDA subsequently updated, on conducting clinical trials during the pandemic, which describes a number of considerations for sponsors of clinical trials impacted by the pandemic. In June 2020, FDA also issued a guidance on cGMPs for responding to COVID-19 infection in employees in drug products manufacturing, including recommendations for manufacturing controls to prevent contamination of drugs. In view of the spread of the COVID-19 variants, FDA may issue additional guidance and policies that may materially impact Enliven’s business, clinical trials, and its clinical development timelines. Changes to existing policies and regulations can increase Enliven’s compliance costs or delay its clinical plans.

Moreover, the FDA strictly regulates the promotional claims that may be made about drug products. In particular, a product may not be promoted in the United States for uses that are not approved by the FDA as reflected in the product’s approved labeling, or in other jurisdictions for uses that differ from the labeling or uses approved by the applicable regulatory agencies. While physicians may prescribe products for off-label uses, the FDA, EMA and other regulatory agencies actively enforce laws and regulations that prohibit the promotion of off-label uses by companies, including promotional communications made by companies’ sales force with respect to off-label uses that are not consistent with the approved labeling, and a company that is found to have improperly promoted off-label uses may be subject to significant civil, criminal and administrative penalties. The occurrence of any event or penalty described above may inhibit Enliven’s ability to commercialize its product candidates, if approved, and generate revenue.

The FDA, EMA and other regulatory agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses.

If any of Enliven’s product candidates are approved and Enliven is found to have improperly promoted off-label uses of those products, Enliven may become subject to significant liability. The FDA, EMA and other regulatory agencies strictly regulate the promotional claims that may be made about prescription products, such as Enliven’s product candidates, if approved. If Enliven is found to have promoted such off-label uses, Enliven may become subject to significant liability. The United States federal government has levied large civil and criminal fines

 

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against companies for alleged improper promotion of off-label use and has enjoined several companies from engaging in off-label promotion. The FDA has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed. If Enliven cannot successfully manage the promotion of its product candidates, if approved, Enliven could become subject to significant liability, which would materially adversely affect its business and financial condition.

Where appropriate, Enliven plans to secure approval from the FDA, EMA or comparable foreign regulatory authorities through the use of accelerated registration pathways. If Enliven is unable to obtain such approval, it may be required to conduct additional preclinical studies or clinical trials beyond those that it contemplates, which could increase the expense of obtaining, and delay the receipt of, necessary marketing approvals. Even if Enliven receives accelerated approval from the FDA, EMA or comparable regulatory authorities, if its confirmatory trials do not verify clinical benefit, or if it does not comply with rigorous post-marketing requirements, the FDA, EMA or such other regulatory authorities may seek to withdraw accelerated approval.

Where possible, Enliven plans to pursue accelerated development strategies in areas of high unmet need. Enliven may seek an accelerated approval pathway for one or more of its product candidates from the FDA, EMA or comparable foreign regulatory authorities. Under the accelerated approval provisions in the Federal Food, Drug, and Cosmetic Act, and the FDA’s implementing regulations, the FDA may grant accelerated approval to a product candidate designed to treat a serious or life- threatening condition that provides meaningful therapeutic benefit over available therapies upon a determination that the product candidate has an effect on a surrogate endpoint or intermediate clinical endpoint that is reasonably likely to predict clinical benefit. The FDA considers a clinical benefit to be a positive therapeutic effect that is clinically meaningful in the context of a given disease, such as irreversible morbidity or mortality. For the purposes of accelerated approval, a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit. An intermediate clinical endpoint is a clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit. The accelerated approval pathway may be used in cases in which the advantage of a new drug over available therapy may not be a direct therapeutic advantage but is a clinically important improvement from a patient and public health perspective. If granted, accelerated approval is usually contingent on the sponsor’s agreement to conduct, in a diligent manner, additional post-approval confirmatory studies to verify and describe the drug’s clinical benefit. If such post-approval studies fail to confirm the drug’s clinical benefit, the FDA may withdraw its approval of the drug.

Prior to seeking accelerated approval, Enliven will seek feedback from the FDA, EMA or comparable foreign regulatory authorities and will otherwise evaluate Enliven’s ability to seek and receive such accelerated approval. There can be no assurance that after Enliven’s evaluation of the feedback and other factors it will decide to pursue or submit an NDA for accelerated approval or any other form of expedited development, review or approval. Similarly, there can be no assurance that after subsequent feedback from the FDA, EMA or comparable foreign regulatory authorities, Enliven will continue to pursue or apply for accelerated approval or any other form of expedited development, review or approval, even if it initially decides to do so. Furthermore, if Enliven decides to submit an application for accelerated approval or under another expedited regulatory designation (e.g., Fast Track designation, Breakthrough Therapy designation or orphan drug designation), there can be no assurance that such submission or application will be accepted or that any expedited development, review or approval will be granted on a timely basis, or at all. The FDA, EMA or other comparable foreign regulatory authorities could also require Enliven to conduct further studies prior to considering its application or granting approval of any type. A failure to obtain accelerated approval or any other form of expedited development, review or approval for Enliven’s product candidate would result in a longer time period to commercialization of such product candidate, could increase the cost of development of such product candidate and could harm Enliven’s competitive position in the marketplace.

 

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Enliven may seek Fast Track designation from the FDA for one or more of its product candidates. Even if one or more of Enliven’s product candidates receive Fast Track designation, Enliven may be unable to obtain or maintain the benefits associated with the Fast Track designation.

Fast Track designation is designed to facilitate the development and expedite the review of therapies for serious conditions and fill an unmet medical need. Programs with Fast Track designation may benefit from early and frequent communications with the FDA, potential priority review and the ability to submit a rolling application for regulatory review. Fast Track designation applies to both the product candidate and the specific indication for which it is being studied. If any of Enliven’s product candidates receive Fast Track designation but do not continue to meet the criteria for Fast Track designation, or if Enliven’s clinical trials are delayed, suspended or terminated, or put on clinical hold due to unexpected adverse events or issues with clinical supply, Enliven will not receive the benefits associated with the Fast Track program. Furthermore, Fast Track designation does not change the standards for approval. Fast Track designation alone does not guarantee qualification for the FDA’s priority review procedures.

Enliven may seek a Breakthrough Therapy designation from the FDA, which even if granted for any of Enliven’s product candidates, may not lead to a faster development or regulatory review or approval process and it does not increase the likelihood that Enliven’s product candidates will receive marketing approval.

Enliven may seek Breakthrough Therapy designation for one or more of its current or future product candidates. A breakthrough therapy is defined as a drug or biologic that is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug or biologic may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. For product candidates that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens. Drugs designated as breakthrough therapies by the FDA may also be eligible for other expedited approval programs, including accelerated approval.

Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if Enliven believes one of its product candidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead determine not to make such designation. In any event, the receipt of a Breakthrough Therapy designation for a product candidate may not result in a faster development process, review or approval compared to candidate products considered for approval under non-expedited FDA review procedures and does not assure ultimate approval by the FDA. In addition, even if one or more of Enliven’s product candidates qualify as breakthrough therapies, the FDA may later decide that the product no longer meets the conditions for qualification. Thus, even though Enliven may seek Breakthrough Therapy designation for one or more of its current or future product candidates, there can be no assurance that it will receive Breakthrough Therapy designation.

Enliven may pursue an orphan indication for its product candidates to treat CML and potentially others. However, Enliven may not be able to obtain orphan drug designation or obtain or maintain orphan drug exclusivity for its product candidates and, even if it does, that exclusivity may not prevent the FDA, EMA or other comparable foreign regulatory authorities, from approving competing products.

Enliven may pursue an orphan indication for its product candidates to treat CML and potentially others. Regulatory authorities in some jurisdictions, including the United States and the EU, may designate drugs for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may designate a product candidate as an orphan drug if it is a drug intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals annually in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States. Enliven’s target indications may include diseases with large patient populations or may include orphan indications. However, there can be no assurances that Enliven will be able to obtain orphan designations for its product candidates.

 

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In the United States, orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers. In addition, if a product candidate that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product candidate is entitled to orphan drug exclusivity. Orphan drug exclusivity in the United States provides that the FDA may not approve any other applications, including a full NDA, to market the same drug for the same indication for seven years, except in limited circumstances. The applicable exclusivity period is 10 years in Europe. The European exclusivity period can be reduced to six years if a drug no longer meets the criteria for orphan drug designation or if the drug is sufficiently profitable so that market exclusivity is no longer justified.

Even if Enliven obtains orphan drug designation for a product candidate, it may not be able to obtain or maintain orphan drug exclusivity for that product candidate. Enliven may not be the first to obtain marketing approval of any product candidate for which it has obtained orphan drug designation for the orphan-designated indication due to the uncertainties associated with developing pharmaceutical products. In addition, exclusive marketing rights in the United States may be limited if Enliven seeks approval for an indication broader than the orphan-designated indication or may be lost if the FDA later determines that the request for designation was materially defective or if Enliven is unable to ensure that it will be able to manufacture sufficient quantities of the product to meet the needs of patients with the rare disease or condition. Further, even if Enliven obtains orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from competition because different drugs with different active moieties may be approved for the same condition. Even after an orphan drug is approved, the FDA can subsequently approve the same drug with the same active moiety for the same condition if the FDA concludes that the later drug is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care or the manufacturer of the product with orphan exclusivity is unable to maintain sufficient product quantity. Orphan drug designation neither shortens the development time or regulatory review time of a drug nor gives the product candidate any advantage in the regulatory review or approval process or entitles the product candidate to priority review.

Enliven may face difficulties from changes to current regulations and future legislation. Healthcare legislative measures aimed at reducing healthcare costs may have a material adverse effect on Enliven’s business and results of operations.

Existing regulatory policies may change, and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of Enliven’s product candidates. Enliven cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or abroad. If Enliven is slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if Enliven is not able to maintain regulatory compliance, it may lose any marketing approval that it may have obtained, and it may not achieve or sustain profitability.

For example, in March 2010, the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010 (collectively, the ACA), was passed, which substantially changed the way healthcare is financed by both the government and private insurers, and continues to significantly impact the United States pharmaceutical industry. The ACA, which, among other things, extended the Medicaid Drug Rebate program to utilization of prescriptions of individuals enrolled in Medicaid managed care organizations; subjected manufacturers to new annual fees and taxes for certain branded prescription drugs; created a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% (increased to 70% pursuant to the Bipartisan Budget Act of 2018, effective as of January 1, 2019) point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; and provided incentives to programs that increase the federal government’s comparative effectiveness research.

Since its enactment, there have been executive, judicial and Congressional challenges to certain aspects of the ACA. On June 17, 2021, the U.S. Supreme Court dismissed the most recent judicial challenge to the ACA

 

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brought by several states without specifically ruling on the constitutionality of the ACA. Thus, the ACA will remain in effect in its current form. Prior to the Supreme Court’s decision, President Biden issued an Executive Order to initiate a special enrollment period from February 15, 2021 through August 15, 2021 for purposes of obtaining health insurance coverage through the ACA marketplace. The Executive Order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA. It is possible that the ACA will be subject to judicial or Congressional challenges in the future. It is unclear how such challenges and healthcare measures initiated by the Biden administration will impact the ACA, Enliven’s business, financial condition and results of operations. Complying with any new legislation or change in regulatory requirements could be time-intensive and expensive, resulting in a material adverse effect on Enliven’s business.

In addition, other legislative changes have been proposed and adopted in the United States since the ACA was enacted. For example, the Budget Control Act of 2011 was signed into law, which, among other things, resulted in aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, effective April 1, 2013, which, due to subsequent legislative amendments, will stay in effect through 2031, with the exception of a temporary suspension implemented under various COVID-19 relief legislation from May 1, 2020 through March 31, 2022. Under current legislation, the reduction in Medicare payments varies from 1% in 2022 up to 4% in the final fiscal year of the sequester, unless additional congressional action is taken. In January 2013, the American Taxpayer Relief Act of 2012, among other things, increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

Moreover, there has been heightened governmental scrutiny recently over the manner in which drug manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products. For example, under the American Rescue Plan Act of 2021, a sunset provision, effective January 1, 2024, would eliminate the statutory cap on Medicaid Drug Rebate Program rebates that manufacturers pay to state Medicaid programs. Elimination of this cap may require pharmaceutical manufacturers to pay more in rebates than it receives on the sale of products, which could have a material impact on Enliven’s business. Further, in July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at increasing competition for prescription drugs. In August 2022, Congress passed the Inflation Reduction Act of 2022, which includes prescription drug provisions that have significant implications for the pharmaceutical industry and Medicare beneficiaries, including allowing the federal government to negotiate a maximum fair price for certain high-priced single-source Medicare drugs, imposing penalties and excise tax for manufacturers that fail to comply with the drug price negotiation requirements, requiring inflation rebates for all Medicare Part B and Part D drugs, with limited exceptions, if their drug prices increase faster than inflation, and redesigning Medicare Part D to reduce out-of-pocket prescription drug costs for beneficiaries, among other changes. At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. In 2021, many states have passed or are considering state drug price transparency and reporting laws that substantially increase the compliance burdens on pharmaceutical manufacturers. The impact of these legislative, executive, and administrative actions and any future healthcare measures and agency rules implemented by the Biden administration on Enliven and the pharmaceutical industry as a whole is unclear. The implementation of cost containment measures or other healthcare reforms may prevent Enliven from being able to generate revenue, attain profitability, or commercialize its product candidates if approved. Complying with any new legislation and regulatory changes could be time-intensive and expensive, resulting in a material adverse effect on Enliven’s business, and expose Enliven to greater liability.

 

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Enliven is unable to predict the future course of federal or state healthcare legislation in the United States directed at broadening the availability of healthcare and containing or lowering the cost of healthcare, particularly as a result of the recent presidential election. These and any further changes in the law or regulatory framework that reduce Enliven’s revenue or increase its costs could also have a material and adverse effect on its business, financial condition and results of operations. The continuing efforts of the government, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce costs of healthcare and/or impose price controls may adversely affect:

 

   

the demand for Enliven’s product candidates, if Enliven obtains regulatory approval;

 

   

Enliven’s ability to set a price that it believes is fair for its products;

 

   

Enliven’s ability to obtain coverage and reimbursement approval for a product;

 

   

Enliven’s ability to generate revenue and achieve or maintain profitability;

 

   

the level of taxes that Enliven is required to pay; and

 

   

the availability of capital.

Enliven expects that the ACA, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that it receives for any approved product. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent Enliven from being able to generate revenue, attain profitability or commercialize its product candidates. It is also possible that additional governmental action is taken in response to the COVID-19 pandemic.

Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for biotechnology products. Enliven cannot be sure whether additional legislative changes will be enacted, or whether FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals of Enliven’s product candidates, if any, may be. In addition, increased scrutiny by Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject Enliven to more stringent product labeling and post-marketing testing and other requirements.

The withdrawal of the United Kingdom (UK) from the EU, commonly referred to as “Brexit,” may adversely impact Enliven’s ability to obtain regulatory approvals for its product candidates in the EU, result in restrictions or imposition of taxes and duties for importing its product candidates into the EU, and may require it to incur additional expenses in order to develop, manufacture and commercialize its product candidates in the EU.

Inadequate funding for the FDA, the SEC and other United States government agencies or the EMA or comparable foreign regulatory authorities could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of Enliven’s business may rely, which could negatively impact its business.

The ability of the FDA, EMA or comparable foreign regulatory authorities to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory, and policy changes. Average review times at the agency have fluctuated in recent years as a result. In addition, government funding of the SEC and other government agencies on which Enliven’s operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable.

Disruptions at the FDA, EMA and other agencies may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect Enliven’s business. For

 

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example, in recent years, including in 2018 and 2019, the United States government shut down several times and certain regulatory agencies, such as the FDA and the SEC, had to furlough critical employees and stop critical activities. If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process Enliven’s regulatory submissions, which could have a material adverse effect on Enliven’s business. Further, future government shutdowns could impact the combined company’s ability to access the public markets and obtain necessary capital in order to properly capitalize and continue its operations.

Enliven’s relationships with employees, independent contractors, consultants, commercial collaborators, healthcare professionals, clinical investigators, CROs, suppliers, vendors and third-party payors in connection with its current and future business activities may be subject to federal and state healthcare fraud and abuse laws, false claims laws, transparency laws, government price reporting, and health information privacy and security laws, which could expose Enliven to significant losses, including, among other things, criminal sanctions, civil penalties, contractual damages, exclusion from governmental healthcare programs, reputational harm, administrative burdens and diminished profits and future earnings.

Enliven is exposed to the risk that its employees, independent contractors, consultants, commercial collaborators, healthcare professionals, clinical investigators, CROs, suppliers, vendors and third-party payors may engage in misconduct or other improper activities. Healthcare providers and third-party payors play a primary role in the recommendation and prescription of any product candidates for which Enliven obtains marketing approval. Enliven’s current and future arrangements with healthcare professionals, clinical investigators, CROs, third-party payors and customers may expose Enliven to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which Enliven researches, as well as markets, sells and distributes its product candidates for which it obtains marketing approval.

The laws that may affect Enliven’s ability to operate include, but are not limited to:

 

   

the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying any remuneration (including any kickback, bribe, or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce, or in return for, either the referral of an individual, or the purchase, lease, order or recommendation of any good, facility, item or service for which payment may be made, in whole or in part, under a federal healthcare program, such as the Medicare and Medicaid programs. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. In addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act (FCA). There are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution, but the exceptions and safe harbors are drawn narrowly and require strict compliance in order to offer protection. Failure to meet all of the requirements of a particular applicable statutory exception or regulatory safe harbor does not make the conduct per se illegal under the Anti-Kickback Statute. Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances. Enliven’s practices may not in all cases meet all of the criteria for protection under a statutory exception or regulatory safe harbor;

 

   

federal civil and criminal false claims laws, including the FCA, which can be enforced through civil “qui tam” or “whistleblower” actions, and civil monetary penalty laws, including the Civil Monetary Penalties Law, impose criminal and civil penalties against individuals or entities for, among other things, knowingly presenting, or causing to be presented, claims for payment or approval from Medicare, Medicaid, or other federal health care programs that are false or fraudulent, knowingly making or causing a false statement material to a false or fraudulent claim or an obligation to pay money to the federal government, or knowingly concealing or knowingly and improperly avoiding or decreasing such an obligation. Manufacturers can be held liable under the FCA even when they do not

 

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submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. The FCA also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the FCA and to share in any monetary recovery. When an entity is determined to have violated the federal civil FCA, the government may impose civil fines and penalties for each false claim, plus treble damages, and exclude the entity from participation in Medicare, Medicaid and other federal healthcare programs;

 

   

the Health Insurance Portability and Accountability Act of 1996, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and the regulations that implement both laws (collectively, HIPAA), which created additional federal criminal statutes that prohibit, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters. Similar to the federal Anti-Kickback Statute, a person or entity can be found guilty of violating HIPAA without actual knowledge of the statute or specific intent to violate it;

 

   

HIPAA, which impose requirements on certain covered healthcare providers, health plans, and healthcare clearinghouses and their respective business associates that perform services for them that involve the use, or disclosure of, individually identifiable health information as well as their covered subcontractors, relating to the privacy, security and transmission of individually identifiable health information without appropriate authorization. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions;

 

   

the federal Physician Payments Sunshine Act, created under the ACA and its implementing regulations, which require applicable manufacturers of drugs, devices, biologicals and medical supplies for which reimbursement is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to CMS in HHS information related to payments or other transfers of value made to covered recipients, including physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician healthcare providers (such as physician assistants and nurse practitioners), and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; and

 

   

analogous state and foreign laws and regulations, such as state and foreign anti-kickback, false claims, consumer protection and unfair competition laws which may apply to pharmaceutical business practices, including but not limited to, research, distribution, sales and marketing arrangements as well as submitting claims involving healthcare items or services reimbursed by any third-party payor, including commercial insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government that otherwise restricts payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to file reports with states regarding pricing and marketing information, such as the tracking and reporting of gifts, compensations and other remuneration and items of value provided to healthcare professionals and entities; state and local laws requiring the registration of pharmaceutical sales representatives; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

 

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Enliven may also be subject to federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers.

Efforts to ensure that Enliven’s current and future business arrangements with third parties will comply with applicable healthcare and data privacy and security laws and regulations will involve on-going substantial costs. Because of the breadth of these laws and the narrowness of the statutory exceptions and safe harbors available, it is possible that governmental authorities will conclude that Enliven’s business practices do not comply with current or future statutes, regulations, agency guidance or case law involving applicable fraud and abuse or other healthcare laws and regulations. If Enliven’s operations are found to be in violation of any of the federal and state healthcare laws described above or any other governmental regulations that apply to it, Enliven may be subject to significant penalties, including without limitation, civil, criminal and/or administrative penalties, damages, fines, disgorgement, imprisonment, exclusion from participation in government programs, such as Medicare and Medicaid, injunctions, private “qui tam” actions brought by individual whistleblowers in the name of the government, exclusion, debarment or refusal to allow Enliven to enter into government contracts, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings, additional reporting requirements and/or oversight if Enliven becomes subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and the curtailment or restructuring of Enliven’s operations, any of which could adversely affect Enliven’s ability to operate its business and its results of operations. Defending against any such actions can be costly, time-consuming and may require significant financial and personnel resources. Therefore, even if Enliven is successful in defending against any such actions that may be brought against it, its business may be impaired. Further, if any of the physicians or other healthcare providers or entities with whom Enliven expects to do business is found to be not in compliance with applicable laws, they may be subject to significant criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.

Enliven is subject to stringent and changing privacy, data protection and data security laws, regulations and standards as well as policies, contracts and other obligations related to data privacy, data protection and data security. Enliven’s actual or perceived failure to comply with such obligations could lead to enforcement or litigation (that could result in fines or penalties), a disruption or cancellation of clinical trials or commercialization of products, reputational harm, or other adverse business effects.

Enliven collects, receives, retains, stores, uses, shares, discloses, transfers, makes accessible, disseminates, and otherwise processes data (including personal and clinical trial information) relating to its employees and contractors, and other persons. Accordingly, Enliven is, or may become, subject to numerous legal and contractual obligations regarding the privacy, security, protection and appropriate collection, storing, sharing, use, processing, transfer, and disclosure of certain data, including personal information. For example, Enliven is, or may become, subject to various federal, state, local, and foreign laws, directives, and regulations regarding privacy, data protection, and data security, the scope of which are changing, subject to differing interpretations, and may be inconsistent among jurisdictions or conflict with other legal and regulatory requirements. Enliven is also subject to certain contractual obligations to third parties related to privacy, data protection and data security and it strives to comply with its applicable policies and applicable laws, regulations, contractual obligations, and other legal obligations relating to privacy, data protection, and data security, to the extent possible. The regulatory framework for privacy, data protection and data security worldwide is evolving and is likely to remain complex and uncertain for the foreseeable future. Any perception of privacy, data security, or data protection concerns or an inability, by Enliven or third parties that it relies on, to comply with applicable laws, regulations, policies, industry standards, contractual obligations, or other legal obligations, even if unfounded, may result in additional cost and liability to Enliven, harm its reputation, and adversely affect its business, financial condition, and results of operations.

Enliven is not currently classified as a covered entity or business associate under HIPAA. Thus, Enliven is not directly subject to HIPAA’s requirements or penalties. The healthcare providers, including certain research institutions from which Enliven may obtain patient or subject health information, may be subject to privacy,

 

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security, and breach notification requirements under HIPAA. Additionally, any person may be prosecuted under HIPAA’s criminal provisions either directly or under aiding-and-abetting or conspiracy principles. Consequently, depending on the facts and circumstances, Enliven could face substantial penalties if it knowingly receives individually identifiable health information from a HIPAA covered entity, business associate or subcontractor that has not satisfied HIPAA’s requirements for disclosure of individually identifiable health information. In addition, Enliven maintains sensitive personally identifiable information, including health and genetic information, that it receives throughout the clinical trial process and in the course of its research collaborations, and may maintain sensitive personally identifiable information received directly from individuals (or their healthcare providers) who may enroll in patient assistance programs if Enliven chooses to implement such programs. In addition, Enliven may be subject to state laws requiring security and protection of personal information and notification of affected individuals and state regulators in the event of a breach of personal information, which is a broader class of information than the health information protected by HIPAA.

Furthermore, certain health privacy laws, data breach notification laws, consumer protection laws and genetic information laws may apply directly to Enliven’s operations and/or those of its collaborators and may impose restrictions on Enliven’s collection, receipt, retention, storage, use, sharing, disclosure, dissemination, transfer or other processing of individuals’ personal information, including health information. Individuals from whom Enliven or its collaborators may obtain personal information, including health information, as well as the healthcare providers who may share this information with Enliven, may have statutory or contractual rights that require certain security measures to protect such information or limit the ability to collect, retain, store, use, share, disclose, disseminate, transfer and otherwise process the information. Enliven may be required to expend significant capital and other resources to ensure ongoing compliance with applicable privacy, data protection, and data security laws. Claims that Enliven has violated individuals’ privacy rights or breached its contractual obligations, even if it is not found liable, could be expensive and time-consuming to defend and could result in adverse publicity that could harm its business.

Additionally, Enliven is subject to additional restrictions and requirements relating to privacy, data protection and data security in other jurisdictions outside the United States in connection with its clinical trials. For example, the collection, use, storage, disclosure, transfer (including cross-border), or other processing of personal data regarding individuals in the EU, including personal health data, is subject to the General Data Protection Regulation (GDPR). The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of certain personal data breaches (including to supervisory authorities and potentially affected individuals), and taking certain measures when engaging third-party processors. The GDPR also imposes strict rules on the transfer of personal data outside the European Economic Area (EEA) to third countries that have not been found to provide adequate protection to such personal data, including the United States, and permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global revenues, whichever is greater, for the most serious of violations. The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR.

While the GDPR applies uniformly across the EU, each EU Member State is permitted to issue nation-specific data protection legislation, which has created inconsistencies on a country-by-country basis. Additionally, the UK’s exit from the EU, often referred to as Brexit, has created further uncertainty and could result in the application of new data privacy and protection laws, regulations and standards, if Enliven decides to conduct clinical trials and enroll patients in the UK in its future clinical trials. While the UK General Data Protection Regulation (the UK GDPR) largely mirrors the GDPR, Brexit and the subsequent implementation of the UK GDPR will expose Enliven to two parallel data protection regimes, each of which potentially authorizes similar significant fines and other potentially divergent enforcement actions for certain violations. In addition, on

 

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July 16, 2020, the European Court of Justice invalidated the EU-US Privacy Shield Framework, a mechanism under which personal data could be transferred from the EEA to entities in the United States that had self-certified under the Privacy Shield Framework. The Court also called into question the Standard Contractual Clauses (SCCs), noting adequate safeguards must be met for SCCs to be valid. Use of the SCCs must now be assessed on a case-by-case basis taking into account the legal regime applicable in the destination country, in particular, applicable surveillance laws and rights of individuals and additional measures and/or contractual provisions may need to be put in place. Additionally, the European Commission has adopted new SCCs that are required to be implemented. The UK also has issued new standard contractual clauses, similar to the SCCs, that also are required to be implemented in place of previously issued standard contractual clauses. As supervisory authorities issue further guidance on personal data export mechanisms, including on the new SCCs, and/or start taking enforcement action, Enliven’s compliance costs could increase, Enliven may be subject to complaints and/or regulatory investigations or fines, and/or if Enliven is otherwise unable to transfer personal data between and among countries and regions in which it may conduct clinical trials, this could negatively impact its business. Furthermore, On June 28, 2021, the European Commission issued an adequacy decision under the GDPR and the Law Enforcement Directive, pursuant to which personal data generally may be transferred from the EU to the UK without restriction; however, this adequacy decision is subject to a four-year “sunset” period, after which the European Commission’s adequacy decision may be renewed. During that period, the European Commission will continue to monitor the legal situation in the UK and may intervene at any time with respect to its adequacy decision. The UK’s adequacy determination therefore is subject to future uncertainty and may be subject to modification or revocation in the future, with the UK potentially being considered an inadequate third country under the GDPR and transfers of personal data from the EEA to the UK will require a transfer mechanism, such as SCCs. Furthermore, there will be increasing scope for divergence in application, interpretation, and enforcement of the data protection law as between the UK and the EEA. This may increase the complexity of transferring personal data across borders.

Similar laws have been proposed in other foreign jurisdictions. For example, on August 20, 2021, the Personal Information Protection Law (PIPL) of the People’s Republic of China (PRC) was adopted and went into effect on November 1, 2021. The PIPL shares similarities with the GDPR, including extraterritorial application, data minimization, data localization, and purpose limitation requirements, and obligations to provide certain notices and rights to citizens of the PRC. The PIPL allows for fines of up to 50 million renminbi or 5% of covered company’s revenue in the prior year. If additional laws are passed, such laws may have potentially conflicting requirements that would make compliance challenging. Such laws may require Enliven to modify its operations, and may limit its ability to collect, retain, store, use, share, disclose, transfer, disseminate, and otherwise process personal data, may require additional investment of resources in compliance programs, impact strategies and could result in increased compliance costs and/or changes in its ongoing or planned business practices and policies.

Enliven may also be subject to federal and state privacy, data protection and data security laws and regulations in the United States including, without limitation, laws that regulate personal information, including health information. For example, California has enacted the California Consumer Privacy Act (CCPA), which creates new individual privacy rights for California consumers (as defined in the law) and places increased privacy, data protection, and data security obligations on entities handling personal information of California consumers, devices, or households. The CCPA requires covered companies to provide new disclosures to California consumers about such companies’ data collection, use and sharing practices and provide such consumers new ways to opt-out of certain sales of personal information. The CCPA also provides consumers with a private right of action in certain data breach situations. The CCPA went into effect on January 1, 2020, and the California Attorney General commenced enforcement actions for violations on July 1, 2020. Moreover, the California Privacy Rights Act (CPRA), which significantly modifies the CCPA, including by imposing additional obligations on covered companies and expanding consumers’ rights with respect to certain sensitive personal information, becomes operative on January 1, 2023, potentially resulting in further uncertainty and requiring Enliven to incur additional costs and expenses in an effort to comply. The CPRA also creates a new state agency that will be vested with authority to implement and enforce the CCPA and the CPRA.

 

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The CCPA and CPRA could mark the beginning of a trend toward more stringent privacy legislation in the United States. The CCPA has prompted a number of proposals for federal and state privacy legislation. For example, in 2021 and 2022, Virginia passed its Consumer Data Protection Act, Colorado enacted the Colorado Privacy Act, Utah passed the Utah Consumer Privacy Act, and Connecticut passed the Act Concerning Personal Data and Online Monitoring, all of which differ from the CPRA and become effective in 2023. Similar laws also have been proposed in other states and at the federal level. Collectively, these reflect a trend toward more stringent privacy legislation in the United States. The enactment of such laws could have potentially conflicting requirements that would make compliance challenging.

Enliven may also publish privacy policies and other documentation regarding its collection, processing, use and disclosure of personal information. Although Enliven endeavors to comply with its published policies and documentation, it may at times fail to do so or may be perceived to have failed to do so. Moreover, despite Enliven’s efforts, it may not be successful in achieving compliance if its employees or contractors fail to comply with its published policies and documentation. Such failures can subject Enliven to potential foreign, local, state and federal action if they are found to be deceptive, unfair, or misrepresentative of its actual practices.

The number and scope of obligations related to privacy, data protection and data security are changing, subject to differing applications and interpretations, and may be inconsistent between jurisdictions or in conflict with each other. As a result, compliance with United States and foreign privacy, data protection, and data security laws and regulations could require Enliven to take on more onerous obligations in its contracts, restrict its ability to collect, retain, store, use, share, disclose, transfer, disseminate, and otherwise process data, or in some cases, impact its ability to operate in certain jurisdictions. Although Enliven endeavors to comply with its published policies, other documentation, and all applicable privacy and security laws and regulations, it may at times fail to do so or may be perceived to have failed to do so. Any actual or alleged failure to comply with such obligations could result in governmental investigations, proceedings and enforcement actions (which could include civil or criminal fines or penalties), private litigation or adverse publicity, harm to Enliven’s reputation, and could negatively affect its operating results and business. Moreover, clinical trial subjects about whom Enliven or its potential collaborators obtain information, as well as the providers who share this information with Enliven, may contractually limit Enliven’s ability to use and disclose the information or impose other obligations or restrictions in connection with Enliven’s use, retention and other processing of information, and Enliven may otherwise face contractual restrictions applicable to its use, retention, and other processing of information. Claims that Enliven has violated individuals’ privacy rights, failed to comply with data protection laws, or breached its contractual obligations, even if it is not found liable, could be expensive and time-consuming to defend and could result in adverse publicity that could harm Enliven’s business.

Enliven’s business activities may be subject to the U.S. Foreign Corrupt Practices Act (FCPA) and similar anti-bribery and anti-corruption laws and anti-money laundering laws, including laws of other countries in which Enliven operates, as well as U.S. and certain foreign export controls, trade sanctions, and import laws and regulations. Compliance with these legal requirements could limit Enliven’s ability to compete in foreign markets and subject it to liability if it violates them.

Enliven is subject to the FCPA, the U.S. domestic public corruption and commercial bribery statutes contained in 18 U.S.C. § 201, the U.S. Travel Act and possibly other anti-bribery and anti-corruption laws and anti-money laundering laws in countries outside of the United States in which where Enliven conducts its activities. Anti-corruption and anti-bribery laws have been enforced aggressively in recent years and are interpreted broadly to generally prohibit companies, their employees, agents, representatives, business partners, and third-party intermediaries from authorizing, offering, or providing, directly or indirectly, improper payments or benefits to recipients in the public or private sector.

Enliven may leverage third parties to sell its products and conduct its business abroad. Enliven, its employees, agents, representatives, business partners and third-party intermediaries may have direct or indirect interactions with officials and employees of government agencies or state-owned or affiliated entities and may be held liable

 

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for the corrupt or other illegal activities of these employees, agents, representatives, business partners or third-party intermediaries even if Enliven does not explicitly authorize such activities. Enliven’s business activities may be subject to the FCPA and similar anti-bribery or anti-corruption laws, regulations or rules of other countries in which it operates. The FCPA generally prohibits companies and their employees and third-party intermediaries from offering, promising, giving or authorizing others to give anything of value, either directly or indirectly, to a non-U.S. government official in order to influence official action or otherwise obtain or retain business. The FCPA also requires public companies to make and keep books and records that accurately and fairly reflect the transactions of the corporation and to devise and maintain an adequate system of internal accounting controls. Enliven’s business is heavily regulated and therefore may involve significant interaction with public officials, including officials of non-U.S. governments. Additionally, in many other countries, hospitals are owned and operated by the government, and doctors and other hospital employees would be considered foreign officials under the FCPA. Recently, the SEC and DOJ have increased their FCPA enforcement activities with respect to biotechnology and pharmaceutical companies. Enliven cannot assure you that all of its employees, agents, representatives, business partners or third-party intermediaries will not take actions in violation of applicable law for which Enliven may be ultimately held responsible. As Enliven commercializes its product candidates and increases its international sales and business, its risks under these laws may increase. There is no certainty that all of Enliven’s employees, agents or contractors, or those of its affiliates, will comply with all applicable laws and regulations, particularly given the high level of complexity of these laws. Violations of these laws and regulations could result in fines, criminal sanctions against Enliven, its officers or its employees, disgorgement, and other sanctions and remedial measures, and prohibitions on the conduct of its business. Any such violations could include prohibitions on Enliven’s ability to offer its products in one or more countries and could materially damage its reputation, its brand, its international activities, its ability to attract and retain employees and its business, prospects, operating results and financial condition.

These laws also require that Enliven keep accurate books and records and maintain internal controls and compliance procedures designed to prevent any such actions. While Enliven has policies and procedures to address compliance with such laws, Enliven cannot assure you that none of its employees, agents, representatives, business partners or third-party intermediaries will take actions in violation of its policies and applicable law, for which Enliven may be ultimately held responsible.

Any allegations or violation of the FCPA or other applicable anti-bribery and anti-corruption laws and anti-money laundering laws could result in whistleblower complaints, sanctions, settlements, prosecution, enforcement actions, fines, damages, adverse media coverage, investigations, loss of export privileges, severe criminal or civil sanctions, or suspension or debarment from government contracts, all of which may have an adverse effect on Enliven’s reputation, business, results of operations, and prospects. Responding to any investigation or action will likely result in a materially significant diversion of management’s attention and resources and significant defense costs and other professional fees.

In addition, Enliven’s products may be subject to U.S. and foreign export controls, trade sanctions and import laws and regulations. Governmental regulation of the import or export of Enliven’s products, or Enliven’s failure to obtain any required import or export authorization for its products, when applicable, could harm Enliven’s international or domestic sales and adversely affect its revenue. Compliance with applicable regulatory requirements regarding the export of Enliven’s products may create delays in the introduction of its products in international markets or, in some cases, prevent the export of its products to some countries altogether. Furthermore, United States export control laws and economic sanctions prohibit the shipment of certain products and services to countries, governments, and persons targeted by United States sanctions. If Enliven fails to comply with export and import regulations and such economic sanctions, penalties could be imposed, including fines and/or denial of certain export privileges. Moreover, any new export or import restrictions, new legislation or shifting approaches in the enforcement or scope of existing regulations, or in the countries, persons, or products targeted by such regulations, could result in decreased use of Enliven’s products by, or in Enliven’s decreased ability to export its products to, existing or potential customers with international operations. Any decreased use of Enliven’s products or limitation on Enliven’s ability to export or sell its products would likely adversely affect its business.

 

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If Enliven fails to comply with environmental, health and safety laws and regulations, it could become subject to fines or penalties or incur costs that could have a material adverse effect on the success of its business.

Enliven is subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Enliven’s operations involve the use of hazardous and flammable materials, including chemicals and biological and radioactive materials. Enliven’s operations also produce hazardous waste products. Enliven generally contracts with third parties for the disposal of these materials and wastes. Enliven cannot eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from Enliven’s use of hazardous materials, Enliven could be held liable for any resulting damages, and any liability could exceed its resources. Enliven also could incur significant costs associated with civil or criminal fines and penalties.

Although Enliven maintains workers’ compensation insurance to cover it for costs and expenses it may incur due to injuries to its employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. Enliven does not maintain insurance for environmental liability or toxic tort claims that may be asserted against it in connection with its storage or disposal of biological, hazardous or radioactive materials.

Any legal proceedings or claims against Enliven could be costly and time-consuming to defend and could harm its reputation regardless of the outcome.

Enliven may in the future become subject to legal proceedings and claims that arise in the ordinary course of business, including intellectual property, product liability, employment, class action, whistleblower and other litigation claims, and governmental and other regulatory investigations and proceedings. Such matters can be time-consuming, divert management’s attention and resources, cause Enliven to incur signi