MTCR Metacrine Inc

NOTICE OF ANNUAL MEETING OF STOCKHOLDERS

AND PROXY STATEMENT

Dear Stockholder:

The 2022 annual meeting of stockholders of Metacrine, Inc. (the “Annual Meeting”) will be held on May 18, 2022 at 8:00 a.m., Pacific Time via a live webcast, for the following purposes:

1. To elect the two nominees for director to serve as Class II directors for a three-year term to expire at the 2025 annual meeting of stockholders;

2. To ratify the selection by the Audit Committee of the Board of Directors of Ernst & Young LLP as our independent registered public accounting firm for our fiscal year ending December 31, 2022; and

3. To conduct any other business properly brought before the meeting.

As noted above, the Annual Meeting will be completely virtual, and will be conducted solely by remote communication via a live webcast. There will not be a physical meeting location and stockholders will not be able to attend the Annual Meeting in person. This means that you can vote your shares, submit questions for consideration, and attend the Annual Meeting online. To be admitted to the live webcast, you must register in advance at www.proxydocs.com/MTCR, as described in the Notice of Internet Availability of Proxy Materials or proxy card. As part of the registration process, you must enter the Control Number shown on your Notice of Internet Availability of Proxy Materials or proxy card. After completion of your registration, further instructions, including a unique link to access the Annual Meeting, will be emailed to you. You will not be able to attend the Annual Meeting in person.

The foregoing items of business are more fully described in the attached Proxy Statement, which forms a part of this notice and is incorporated herein by reference. Our Board of Directors has fixed the close of business on March 29, 2022 as the record date for the determination of stockholders entitled to notice of and to vote at the Annual Meeting or any adjournment or postponement thereof.

Your vote is important. Whether or not you expect to attend our virtual Annual Meeting, please vote as soon as possible. If you received the Notice of Internet Availability, a proxy card was not sent to you and you may vote only via the Internet unless you attend the virtual Annual Meeting, in which case you may vote during the virtual Annual Meeting by following the registration instructions outlined above, or request that a proxy card and proxy materials be mailed to you. If you have requested that a proxy card and proxy materials be mailed to you, and you have received those materials, then you may vote via the Internet, by telephone or by mailing a completed proxy card. For specific voting instructions, please refer to the information provided in the accompanying Proxy Statement and in the Notice of Internet Availability.

All stockholders are cordially invited to virtually attend the meeting. On behalf of the Board of Directors and the employees of Metacrine, Inc., we thank you for your continued support.

San Diego, California

April 7, 2022

Table of Contents

METACRINE, INC.

4225 Executive Square, Suite 600

San Diego, CA 92037

as described in the Notice of Internet Availability of Proxy Materials or proxy card. As part of the registration process, you must enter the Control Number shown on your Notice of Internet Availability of Proxy Materials or proxy card. After completion of your registration, further instructions, including a unique link to access the Annual Meeting, will be emailed to you.

You may submit a question in advance of the meeting at www.proxydocs.com/MTCR after logging in with the Control Number shown on your Notice of Internet Availability of Proxy Materials or proxy card. If you wish to submit a question, on the day of the Annual Meeting, beginning at 8:00 a.m. Pacific Time on Wednesday, May 18, 2022, you may log into the virtual meeting platform using the unique link provided to you via email following the completion of your registration at www.proxydocs.com/MTCR, and follow the instructions there. Our virtual Annual Meeting will be governed by our Rules of Conduct and Procedures, which will be made available on the Annual Meeting’s live webcast on the day of the Annual Meeting and will address the ability of stockholders to ask questions during the meeting, including rules on permissible topics, and rules for how questions and comments will be recognized and disclosed to meeting participants.

Who can vote at the Annual Meeting?

Only stockholders of record at the close of business on March 29, 2022, the record date for the Annual Meeting (the “Record Date”), are entitled to vote at the Annual Meeting.

At the close of business on the Record Date, there were 42,163,510 shares of our common stock outstanding. Common stock is the only class of stock entitled to vote at the Annual Meeting. A list of our stockholders of record will be available for inspection online during the Annual Meeting at www.proxydocs.com/MTCR, and during the ten days prior to the Annual Meeting upon request. If you would like to view the list, please contact our Secretary to schedule an appointment by calling (858) 369-7800 or writing to him at the address above.

Stockholders of Record: Shares Registered in Your Name

If, on the Record Date, your shares were registered directly in your name with the transfer agent for our common stock, American Stock Transfer & Trust Company, LLC, then you are a stockholder of record. As a stockholder of record, you may vote at the Annual Meeting if you attend online or vote by proxy. Whether or not you plan to attend the Annual Meeting online, we encourage you to vote by proxy via the Internet, by telephone or by mail, as instructed below to ensure your vote is counted.

Beneficial Owners: Shares Registered in the Name of a Broker or Bank

If, on the Record Date, your shares were held in an account at a brokerage firm, bank, dealer or other similar organization, then you are the beneficial owner of shares held in “street name” and these proxy materials are being forwarded to you by that organization. The organization holding your account is considered the stockholder of record for purposes of voting at the Annual Meeting. As a beneficial owner, you have the right to direct your broker or other agent on how to vote the shares in your account. As discussed above, if you are a street name stockholder, you are invited to attend and vote your shares at the Annual Meeting online so long as you register to attend the Annual Meeting at www.proxydocs.com/MTCR in advance. However, since you are not the stockholder of record, you may not vote your shares online at the Annual Meeting unless you request and obtain a valid proxy from your broker, bank or other agent.

What am I voting on?

There are two proposals scheduled for a vote:

Proposal 1: Election of two Class II nominees for director to hold office until the 2025 annual meeting of stockholders.

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Proposal 2: Ratification of the selection of Ernst and Young LLP as our independent registered public accounting firm for the fiscal year ending December 31, 2022.

How many votes do I have?

Each share of Metacrine common stock that you own as of March 29, 2022, the Record Date, entitles you to one vote at the Annual Meeting.

How do I vote?

With respect to the election of two Class II director nominees, you may either vote “FOR” the nominees to the Board or you may “WITHHOLD” your vote for any nominee you specify. With respect to the ratification of the appointment of Ernst & Young, LLP as our independent registered public accounting firm, you may vote “FOR,” “AGAINST” or abstain from voting.

Stockholders of Record: Shares Registered in Your Name

If you are a stockholder of record, there are several ways for you to vote your shares. Whether or not you plan to attend the virtual Annual Meeting, we urge you to vote by proxy prior to the Annual Meeting to ensure that your vote is counted.

Beneficial Owners: Shares Registered in the Name of a Broker, Bank or Other Agent

If you are a beneficial owner of shares registered in the name of your broker, bank or other agent, you should have received voting instructions from that organization rather than directly from us. Please check with your bank, broker, or other agent and follow the voting instructions they provide to vote your shares. Generally, you have three options for returning your proxy.

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May I revoke my proxy?

If you give us your proxy, you may revoke it at any time before it is exercised. You may revoke your proxy in any one of the four following ways:

What constitutes a quorum?

The presence at the Annual Meeting, by virtual attendance or by proxy, of holders representing a majority of our outstanding common stock as of March 29, 2022, or approximately 21,081,756 shares, constitutes a quorum at the meeting, permitting us to conduct our business.

What vote is required to approve each proposal?

Proposal 1: Election of Nominees for Director. Directors are elected by a plurality vote. “Plurality” means that the two director nominees for Class II who receives the largest number of votes cast “FOR” such nominee will be elected as a director. As a result, any shares not voted “FOR” a particular nominee, whether as a result of a “WITHHOLD” vote or a broker non-vote (in other words, where a brokerage firm has not received voting instructions from the beneficial owner and for which the brokerage firm does not have discretionary power to vote on a particular matter), will not be counted in such nominee’s favor and will have no effect on the outcome of the election. You may vote “FOR” or “WITHHOLD” on the two nominees for election as a director.

Proposal 2: Ratification of Independent Registered Public Accounting Firm. The ratification of the selection of Ernst & Young LLP as our independent registered public accounting firm for the fiscal year ending December 31, 2022 requires the affirmative vote of a majority of the voting power of the shares of our common stock present virtually or by proxy during the Annual Meeting and entitled to vote thereon to be approved. Abstentions are considered shares present and entitled to vote on this proposal, and thus, will have the same effect as a vote “AGAINST” this proposal. Broker non-votes will have no effect on the outcome of this proposal.

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Voting results will be tabulated and certified by the inspector of election appointed for the Annual Meeting.

How will my shares be voted if I do not specify how they should be voted?

If you are a stockholder of record and you indicate when voting on the Internet or by telephone that you wish to vote as recommended by the Board, then your shares will be voted at the Annual Meeting in accordance with the Board’s recommendation on all matters presented for a vote at the Annual Meeting. Similarly, if you sign and return a proxy card but do not indicate how you want to vote your shares for a particular proposal or for any of the proposals, then for any proposal for which you do not so indicate, your shares will be voted in accordance with the Board’s recommendation.

If you are a beneficial owner of shares held in street name and do not provide the organization that holds your shares with specific voting instructions, then, the organization that holds your shares may generally vote your shares in their discretion on “routine” matters, but may not use its discretion to vote your shares on “non-routine” matters under the rules of the New York Stock Exchange (the “NYSE”). If the organization that holds your shares does not receive instructions from you on how to vote your shares on a non-routine matter, that organization will inform the inspector of election that it does not have the authority to vote on that matter with respect to your shares. This is generally referred to as a “broker non-vote.” Under the rules and interpretations of the NYSE, “non-routine” matters are matters that may substantially affect the rights or privileges of stockholders, such as mergers, stockholder proposals, elections of directors (even if not contested), executive compensation (including any advisory stockholder votes on executive compensation and on the frequency of stockholder votes on executive compensation), and certain corporate governance proposals, even if management-supported.

What is the effect of withheld votes, abstentions and broker non-votes?

Shares of common stock held by persons attending the virtual Annual Meeting but not voting, and shares represented by proxies that reflect withheld votes or abstentions as to a particular proposal, will be counted as present for purposes of determining the presence of a quorum. Abstentions are not an affirmative or negative vote on a proposal, so abstaining does not count as a vote cast and has no effect for purposes of determining whether our stockholders have ratified the appointment of Ernst & Young, LLP, our independent registered public accounting firm. The election of directors is determined by a plurality of votes cast, so a “WITHHOLD” vote will not be counted in determining the outcome of such proposal.

Shares represented by proxies that reflect a broker non-vote will be counted as present for purposes of determining the presence of a quorum exists. As discussed above, a broker non-vote occurs when an organization holding shares for a beneficial owner has not received instructions from the beneficial owner and does not have discretionary authority to vote the shares for certain non-routine matters. With regard to the election of directors, which is considered a non-routine matter, broker non-votes will not be counted as votes cast and will have no effect on the result of the vote. Ratification of the appointment of Ernst & Young, LLP is considered a routine matter on which a broker or other nominee has discretionary authority to vote. If there are broker non-votes for this proposal, they will not be counted as votes cast and will have no effect on the result of the vote.

How does the Board recommend that I vote?

The Board recommends that you vote:

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If you vote via the Internet, by telephone, or sign and return a proxy card by mail but do not make specific choices, your shares, as permitted, will be voted as recommended by our Board. If any other matter is presented at the Annual Meeting, your proxy will vote in accordance with his or her best judgment. As of the date of this Proxy Statement, we know of no matters that needed to be acted on at the Annual Meeting, other than those discussed in this Proxy Statement.

Who is paying the costs of soliciting these proxies?

We will pay all of the costs of soliciting these proxies. Our directors, officers and other employees may solicit proxies in person or by mail, telephone, fax or email. We will not pay our directors, officers and other employees any additional compensation for these services. We will ask banks, brokers and other institutions, nominees and fiduciaries to forward these proxy materials to their principals and to obtain authority to execute proxies. We will then reimburse them for their expenses. Our costs for forwarding proxy materials will not be significant.

How do I obtain the 2021 Annual Report?

If you would like a copy of our 2021 Annual Report that we filed with the SEC on March 30, 2022, we will send you one without charge. Please write to:

Metacrine, Inc.

4225 Executive Square, Suite 600

San Diego, CA 92037

Attn: Secretary

All of our SEC filings are also available free of charge in the “Investors—Financial Information—SEC Filings” section of our website at www.metacrine.com.

When are stockholder proposals and director nominations due for the 2023 annual meeting of stockholders?

To be considered for inclusion in next year’s proxy materials, your proposal must be submitted in writing by December 9, 2022, to the attention of our Secretary at 4225 Executive Square, Suite 600, San Diego, CA 92037. If you wish to submit a proposal (including a director nomination) at the 2023 annual meeting of stockholders that is not to be included in next year’s proxy materials, your written request must be received by our Secretary between January 18, 2023 and February 17, 2023, provided that, if our 2023 annual meeting of stockholders is earlier than April 18, 2023 or later than June 17, 2023, your written request must be received by our Secretary not earlier than the close of business on the 120th day prior to such annual meeting and not later than the close of business on the later of the 90th day prior to such annual meeting or the 10th day following the day on which public announcement of the date of such meeting is first made. You are also advised to review our amended and restated bylaws, which contain additional requirements about advance notice of stockholder proposals and director nominations. In addition to satisfying the foregoing requirements under our amended and restated bylaws, to comply with the universal proxy rules (once effective), stockholders who intend to solicit proxies in support of director nominees other than our Board’s nominees must provide notice that sets forth the information required by Rule 14a-19 promulgated under the Securities Exchange Act of 1934, as amended (the “Exchange Act”), no later than March 19, 2023.

How can I find out the results of the voting at the Annual Meeting?

Preliminary voting results will be announced at the Annual Meeting. We will publish the final voting results in a Current Report on Form 8-K to be filed with the SEC within four business days after the Annual

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Meeting. If final voting results are not available to us in time to file a Form 8-K within four business days after the Annual Meeting, we will file a Form 8-K to publish the preliminary voting results and, within four business days after the final results are known to us, file an additional Form 8-K to publish the final results.

and other qualities that our Nominating and Corporate Governance Committee views as critical to effective functioning of the Board. The brief biographies below include information, as of the date of this Proxy Statement, regarding the specific and particular experience, qualifications, attributes or skills of each director/nominee that led the Nominating and Corporate Governance Committee to recommend that person as a nominee. However, each of the members of our Nominating and Corporate Governance Committee may have a variety of reasons why he or she believes a particular person would be an appropriate nominee for our Board, and these views may differ from the views of other members.

Set forth below are the names, ages, and positions of our director nominees as of the date of this Proxy Statement:

Nominees for Election to the Board of Directors for a Three-Year Term Expiring at the 2025 Annual Meeting of Stockholders (Class II)

Set forth below is biographical information for each of our director nominees and a summary of the specific qualifications, attributes, skills, and experiences which led our Nominating and Corporate Governance Committee and our Board to conclude that each director nominee should serve on our Board at this time. There are no familial relationships among any of the directors or executive officers of the Company.

Ronald Evans, Ph.D., one of our co-founders, has served as a member of our Board of Directors since September 2014. Dr. Evans is a professor, director and biologist at The Salk Institute for Biological Studies (“The Salk”), a scientific research institute, where he holds the March of Dimes Chair in Molecular and Developmental Biology. He became a faculty member of The Salk in 1978. Dr. Evans was also a Howard Hughes Medical Institute Investigator from 1985 to 2020. Dr. Evans was elected to the National Academy of Sciences in 1989. He received his B.S. and Ph.D. degrees from UCLA in 1970 and 1974, respectively, followed by a postdoctoral training at Rockefeller University from 1975-1978. The Nominating and Corporate Governance Committee and the Board of Directors believe that Dr. Evans’ scientific and research expertise qualify him to serve on our Board of Directors.

Richard Heyman, Ph.D., one of our co-founders, has served as a member of our Board of Directors since September 2014 and has served as our Chairman since June 2015. From 2013 to 2015, he served as the Chief Executive Officer of Seragon Pharmaceuticals Inc., which he co-founded. Prior to joining Seragon, Dr. Heyman served as the Chief Executive Officer of Aragon Pharmaceuticals, Inc., which he co-founded in 2009. He has served as Chairman of the Board of Directors of ORIC Pharmaceuticals, Inc., a public company focused on the discovery and development of novel therapies for treatment-resistant cancers, since November 2014. He serves as Vice Chair of the Board of Trustees of, and is a Board member of Gritstone Oncology, Inc., a publicly traded biotechnology company, and serves as a Board member of Yumanity Therapeutics Inc., a publicly traded biopharmaceuticals company, Amunix Pharmaceuticals, Inc., a privately held immune-oncology company, and PMV Pharmaceuticals, Inc., a publicly traded precision oncology company. He also serves on the Executive Committee of the Board of Visitors at the UCSD Moores Cancer Center. Dr. Heyman received a Ph.D. in pharmacology from the University of Minnesota and a B.S. in Chemistry from the University of Connecticut. The Nominating and Corporate Governance Committee and the Board of Directors believe that Dr. Heyman’s operational, clinical and research expertise qualify him to serve on our Board of Directors.

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THE BOARD OF DIRECTORS UNANIMOUSLY

RECOMMENDS A VOTE “FOR” THE ELECTION OF EACH NOMINEE UNDER PROPOSAL ONE

Information about Members of the Board of Directors Continuing in Office

Set forth below is biographical information for each of our directors continuing in office along with a summary of the specific qualifications, attributes, skills and experiences which led our Nominating and Corporate Governance Committee and our Board to conclude that each director nominee should serve on our Board at this time. There are no familial relationships among any of the directors or executive officers of the Company.

Julia Owens, Ph.D. has served as a member of our Board of Directors since April 2021. Dr. Owens currently serves as an advisor to several biotech companies and investors. From February until June 2021, she was the Executive Chair of the Board of Directors of Millendo Therapeutics, Inc., a publicly traded biopharmaceutical company that she co-founded in 2012. From 2012 until January 2021, she served as the President and Chief Executive Officer of Millendo Therapeutics, Inc. From 2010 to 2012, Dr. Owens served as the Senior Vice President of Corporate Development and Strategy at Lycera Corp., a biopharmaceutical company. Prior to that, from 2004 to 2010, Dr. Owens served in a number of business development positions at QuatRx Pharmaceuticals Co., a biopharmaceutical company, including as Head of Business Development from 2009 to 2010. From 1999 to 2004, Dr. Owens served in a number of business development positions at Tularik Inc., a biotechnology company, which was acquired by Amgen, Inc. in 2004. Prior to that, from July to October 1999, Dr. Owens served as a Licensing Officer in the Office of Technology Management at the University of California, San Francisco. Dr. Owens received a B.S. in Chemistry and a B.A. in Molecular and Cellular Biology from the University of California, Berkeley, and a Ph.D. in Biochemistry from the University of California, San Francisco. The Nominating and Corporate Governance Committee and the Board of Directors believe that Dr. Owens’ business and technical expertise qualify her to serve on our Board of Directors.

Andrew Guggenhime has served as a member of our Board of Directors since July 2018. Mr. Guggenhime has served as President and Chief Financial Officer of Vaxcyte, Inc., a public vaccine company, since January 2021, and from May 2020 to December 2020 served as Vaxcyte’s Chief Operating Officer and Chief Financial Officer. From April 2014 to May 2020, Mr. Guggenhime served as Chief Financial Officer of Dermira, Inc., a medical dermatology company, and from April 2014 to May 2018 he also served as Chief Operating Officer. From September 2011 to April 2014, Mr. Guggenhime served as Chief Financial Officer of CardioDx, Inc., a molecular diagnostics life sciences company, and as a member of the CardioDx Board of Directors from April 2014 until July 2016. From September 2010 to April 2011, Mr. Guggenhime served as Chief Financial Officer of Calistoga Pharmaceuticals, Inc., a biotechnology company acquired in April 2011 by Gilead Sciences, Inc. From December 2008 to June 2010, Mr. Guggenhime served as Senior Vice President and Chief Financial Officer of Facet Biotech Corporation, a biotechnology company acquired in April 2010 by Abbott Laboratories. Facet Biotech Corporation was spun off from PDL BioPharma, Inc. at which Mr. Guggenhime served as Senior Vice President and Chief Financial Officer from April 2006 to December 2008. From October 2000 to March 2006, Mr. Guggenhime served as Chief Financial Officer of Neoforma, Inc., a provider of supply-chain management solutions for the healthcare industry acquired by Global Healthcare Exchange, LLC in March 2006. From January to October 2000, Mr. Guggenhime served as Neoforma’s Vice President, Corporate Development. Mr. Guggenhime serves on the Board of Directors of Directors of Caribou Biosciences, Inc., a publicly traded biotechnology company. Mr. Guggenhime began his career in financial services at Merrill Lynch & Co. and Wells Fargo & Company. Mr. Guggenhime holds a B.A. in International Politics and Economics from Middlebury College and holds an M.B.A. from the J.L. Kellogg Graduate School of Management at Northwestern University. The Nominating and Corporate Governance Committee and the Board of Directors believe that Mr. Guggenhime’s financial expertise and experience in the life sciences industry qualifies him to serve on our Board of Directors.

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Amir Nashat, Ph.D. has served as a member of our Board of Directors since January 2015. Dr. Nashat is a managing partner at Polaris Partners, a venture capital firm, where he has worked since 2002. Dr. Nashat currently represents Polaris as a director of Agbiome, Inc., Brain Games Corporation, CAMP4 Therapeutics, Inc., Dewpoint Therapeutics, Inc., Morphic Holding, Inc., a publicly traded biopharmaceutical company, Paratus Sciences Corporation, Primmune Therapeutics, Inc., Pursuit Talent, Inc., Soufflé Therapeutics, Inc. and Syros Pharmaceuticals, Inc., a publicly traded biotechnology company. Additionally, Dr. Nashat previously served as director of 1366 Technologies, Inc., Adnexus Therapeutics, Inc. (Bristol Myers Squibb), Athenix Corporation, Inc. (Bayer), aTyr Pharmaceuticals, Inc., a publicly traded biotherapeutics company, Avila Therapeutics, Inc. (Celgene), Fate Therapeutics, Inc., a publicly traded biotechnology company, Scholar Rock Holding Corporation, a publicly traded biotechnology company, Jnana Therapeutics, Inc., Living Proof (Unilever), Olivo Laboratories, LLC, Pervasis Therapeutics, Inc. (Shire Pharmaceuticals), Promedior Pharmaceuticals, Receptos (Celgene), Selecta Biosciences, Inc., a publicly traded biotechnology company, Sofregen and Sun Catalytix (Lockheed Martin), and Taris Holdings, LLC. At Dewpoint, Living Proof, Sun Catalytix, Olivo Labs and Jnana, Dr. Nashat served as, and at Soufflé and Paratus is currently serving as, the company’s initial Chief Executive Officer and President, respectively. Outside of Polaris, he serves on the BIO Emerging Companies Section Governing Board, the nonprofit Institute for Protein Innovation Board, the Living Proof Advisory Board, the Partners Healthcare Innovation Fund Board, the Investment Advisory Committee for The Engine at MIT, and helped launch the MIT Sandbox Innovation Fund as its active president. Dr. Nashat received a M.S. and B.S. in materials science and mechanical engineering from the University of California, Berkeley and a Sc.D. as a Hertz Fellow in Chemical Engineering at the Massachusetts Institute of Technology with a minor in Biology under Dr. Robert Langer. Our Board of Directors believes that Dr. Nashat’s biotechnology investment experience qualifies him to serve on our Board of Directors.

Preston Klassen, M.D. has served as our President and Chief Executive Officer and as a member of our Board of Directors since June 2020. From March 2017 to June 2020, Dr. Klassen served as Executive Vice President, Head of Research and Development and Chief Medical Officer of Arena Pharmaceuticals, Inc., a biopharmaceutical company. From June 2016 to March 2017, he was Chief Medical Officer of Laboratoris Sanifit S.L., a biotechnology company, and prior to that, from November 2009 to May 2016, was Executive Vice President, Head of Global Development at Orexigen Therapeutics, Inc. Dr. Klassen also held several positions of increasing responsibility at Amgen Inc., including Therapeutic Area Head for Nephrology. Before joining Amgen, he was a faculty member in the Division of Nephrology at Duke University Medical Center. From February 2014 to May 2020, Dr. Klassen served on the board of directors of Conatus Pharmaceuticals Inc., a publicly traded biotechnology company that merged with Histogen Inc. in May 2020. Dr. Klassen holds a B.S. in Chemistry from Central University of Iowa. Dr. Klassen received his medical degree from the University of Nebraska College of Medicine and completed his residency in internal medicine, fellowship in nephrology, and Master of Health Sciences degree at Duke University. The Nominating and Corporate Governance Committee and the Board of Directors believe that Dr. Klassen’s experience as our Chief Executive Officer and his clinical and research expertise qualify him to serve on our Board of Directors.

John McHutchison, M.D. has served as a member of our Board of Directors since February 2020. Since August 2019, Dr. McHutchison has served as the President and Chief Executive Officer and as a director of Assembly Biosciences, Inc. a publicly traded clinical-stage biotechnology company. Prior to joining Assembly Biosciences, Inc., Dr. McHutchison was the Chief Scientific Officer and Head of Research and Development of Gilead Sciences, Inc., a pharmaceutical company. Prior to joining Gilead in 2010, Dr. McHutchison worked at Duke University Medical Center, where he served as Associate Director of the Duke Clinical Research Institute. He also held the positions of Professor of Medicine in the Division of Gastroenterology at Duke University Medical Center, Associate Director at Duke Clinical Research Institute

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and Co-Director of the Duke Clinical and Translational Science Award. Prior to his positions at Duke University, Dr. McHutchison spent nearly 10 years at Scripps Clinic, most recently as Medical Director, Liver Transplantation. He also previously held an Assistant Professorship in Medicine at the University of Southern California. In June 2018, Dr. McHutchison was appointed an Officer of the Order of Australia in recognition of his distinguished service to medical research in gastroenterology and hepatology. Dr. McHutchison has undergraduate degrees in medicine and surgery from the University of Melbourne in Australia and completed his residency in internal medicine and fellowship in gastroenterology at the Royal Melbourne Hospital. He is a member of the Royal Australasian College of Physicians. The Nominating and Corporate Governance Committee and the Board of Directors believe Dr. McHutchison’s expertise and experience in the life sciences industry qualify him to serve on our Board of Directors.

Jeffrey Jonker, J.D. has served as a member of our Board of Directors since March 2021. Mr. Jonker is the Chief Executive Officer of Belharra Therapeutics, Inc. Mr. Jonker previously served as President and Chief Executive Officer of Ambys Medicines, Inc., a biotechnology company, from November 2018 until June 2020. Prior to joining Ambys, Mr. Jonker served as President of NGM Biopharmaceuticals, Inc., a pharmaceutical company, from 2014 to 2018. Prior to joining NGM, Mr. Jonker was Senior Vice President, Corporate and Business Development at Theravance Biopharma, Inc., a biopharmaceutical company that emerged from a June 2014 spin-off transaction that also created Innoviva, Inc. From 2010 to 2013, he served as Chief Business Officer of Satori Pharmaceuticals, Inc., and Vice President of Business Development and Corporate Strategy for Gloucester Pharmaceuticals, Inc., prior to its acquisition by Celgene Corporation. From 2003 to 2009, he served in multiple leadership positions in the business development and legal groups at Genentech, Inc. Prior to Genentech, Mr. Jonker was a member of the Technology Transactions Group at Wilson, Sonsini, Goodrich & Rosati, representing clients in the life science and high-tech industries. Mr. Jonker holds a J.D. from Columbia University School of Law, an M.LITT. from the University of St. Andrews and a B.A. from Claremont McKenna College. The Nominating and Corporate Governance Committee and the Board of Directors believe Mr. Jonker’s business expertise and experience in the life sciences industry qualify him to serve on our Board of Directors.

INFORMATION REGARDING THE BOARD OF DIRECTORS AND CORPORATE GOVERNANCE

Independence of the Board of Directors

As required under the Nasdaq Stock Market (“Nasdaq”) listing standards, a majority of the members of a listed company’s board of directors must qualify as “independent,” as affirmatively determined by the board of directors of such company. Our Board consults with outside counsel to ensure that our Board’s determinations are consistent with relevant securities and other laws and regulations regarding the definition of “independent,” including those set forth in pertinent Nasdaq listing standards, as in effect from time to time.

Consistent with these considerations, after review of all relevant identified transactions or relationships between each director, or any of his or her family members, and our company, our senior management and our independent registered public accounting firm, the Board has affirmatively determined that all of our directors, other than Dr. Klassen, are independent within the meaning of the applicable Nasdaq listing standards. In making this determination, the Board found that none of these directors had a material or other disqualifying relationship with our company. There are no family relationships among any of our directors or executive officers.

Board Leadership Structure

The roles of Chairman and Chief Executive Officer are currently separated. Dr. Richard Heyman serves as Chairman of our Board of Directors and Dr. Preston Klassen serves as our Chief Executive Officer. We believe that separating these positions allows our Chief Executive Officer to focus on our day-to-day business, while allowing the Chairman of our Board to lead the Board in its fundamental role of providing advice to and independent oversight of management. Our Board recognizes the time, effort and energy that the Chief Executive Officer is required to devote to his position, as well as the commitment required to serve as our Chairman of our Board of Directors, particularly as the Board’s oversight responsibilities continue to grow. While our amended and restated bylaws do not require that our Chairman and Chief Executive Officer positions be separate, our Board believes that having separate positions is the appropriate leadership structure for us at this time and demonstrates our commitment to good corporate governance.

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Role of the Board of Directors in Risk Oversight

Our Audit Committee is primarily responsible for overseeing our risk management processes on behalf of the full Board. Our Audit Committee receives reports from management at least annually regarding our assessment of risks. In addition, our Audit Committee reports regularly to the full Board, which also considers our risk profile. Our Audit Committee and the full Board focus on the most significant risks we face and our general risk management strategies. While our Board oversees our risk management, management is responsible for day-to-day risk management processes. Our Board expects management to consider risk and risk management in each business decision, to proactively develop and monitor risk management strategies and processes for day-to-day activities and to effectively implement risk management strategies adopted by our Audit Committee and our Board. We believe this division of responsibilities is the most effective approach for addressing the risks we face and that our Board leadership structure, which also emphasizes the independence of the Board of Directors in its oversight of our business and affairs, supports this approach.

Meetings of the Board of Directors

Our Board oversees our business and monitors the performance of our management. Our executive officers and management oversee our day-to-day operations. The independent directors meet quarterly in executive sessions without management or any non-independent directors. The purpose of these executive sessions is to promote open and candid discussion among the non-employee directors. During the 2021 fiscal year, our independent non-employee directors met three times in regularly scheduled executive sessions at which only independent directors were present. Our Board held six meetings during the fiscal year ended December 31, 2021. Each of the incumbent directors attended at least 75% of the total of the meetings of the Board and the meetings of the committees of our Board on which he or she served during the fiscal year ended December 31, 2021 (in each case, which were held during the period for which he or she was a director and/or a member of the applicable committee). It is our policy to encourage our directors to attend the annual meetings of stockholders. We anticipate that a majority of the members of our Board will attend the Annual Meeting.

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Each of the committees has authority to engage legal counsel or other experts or consultants, as it deems appropriate to carry out its responsibilities. Our Board has determined that each member of each committee meets the applicable Nasdaq rules and regulations regarding “independence” and that each member is free of any relationship that would impair his or her individual exercise of independent judgment with regard to us.

Below is a description of each Board committee.

Audit Committee

The Audit Committee of our Board of Directors was established by the Board in accordance with Section 3(a)(58)(A) of the Exchange Act to oversee our corporate accounting and financial reporting processes and audits of our financial statements. For this purpose, the Audit Committee performs several functions which include, among other things:

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The current members of our Audit Committee are Messrs. Guggenhime and Jonker and Dr. Nashat, with Mr. Guggenhime serving as the chair. Dr. Gallagher served as a member of our Audit Committee until April 2021. Ms. Burow served as a member of our Audit Committee until February 2022. Our Board has determined that each member of our Audit Committee is an independent director under Rule 5605(c)(2)(A)(i) and (ii) of the Nasdaq listing standards and under Rule 10A-3 promulgated under the Exchange Act. Each member of our Audit Committee can read and understand fundamental financial statements in accordance with the requirements applicable to audit committees under the relevant Nasdaq listing standards. In arriving at this determination, our Board has examined each Audit Committee member’s scope of experience and the nature of their employment in the corporate finance sector.

Our Board has determined that Mr. Guggenhime qualifies as an “audit committee financial expert” within the meaning of SEC regulations and meets the financial sophistication requirements of the Nasdaq listing standards. In making this determination, our Board has considered Mr. Guggenhime’s prior experience, business acumen and independence. Both our independent registered public accounting firm and management periodically meet privately with our Audit Committee.

The Charter of the Audit Committee can be found on our website at www.metacrine.com in the Corporate Governance section. The inclusion of our website address here and elsewhere in this proxy statement does not include or incorporate by reference the information on our website into this proxy statement.

Committee concerning independence, and has discussed with the independent registered public accounting firm the accounting firm’s independence. Based on the foregoing, the Audit Committee has recommended to the Board of Directors that the audited financial statements be included in the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2021.

Audit Committee

Andrew Guggenhime, Chair

Jeffrey Jonker

Amir Nashat, M.D.

Compensation Committee

Our Compensation Committee currently consists of Drs. McHutchison, Heyman and Owens, with Dr. McHutchison serving as the chair. Dr. Adelman served as a member of our Compensation Committee until March 2021. Our Board has determined that each of the members of our Compensation Committee is a non-employee director, as defined in Rule 16b-3 promulgated under the Exchange Act, and satisfies the Nasdaq independence requirements. The Charter of the Compensation Committee is reviewed and updated annually, or as may be warranted from time to time. The functions of our Compensation Committee include, among other things:

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Typically, we will plan for our Compensation Committee to meet quarterly and with greater frequency if necessary. The agenda for each meeting is usually developed by the Chair of our Compensation Committee, in consultation with our Chief Executive Officer. Our Chief Executive Officer may not participate in, or be present during, any deliberations or determinations of our Compensation Committee regarding his compensation or individual performance objectives. The Charter of the Compensation Committee grants our Compensation Committee full access to all our books, records, facilities and personnel. In addition, under the Charter of the Compensation Committee, our Compensation Committee has the authority to obtain, at our expense, advice and assistance from internal and external legal, accounting or other advisors and other external resources that our Compensation Committee considers necessary or appropriate in the performance of its duties. Our Compensation Committee has direct responsibility for the oversight of the work of any advisers engaged for the purpose of advising our Compensation Committee. In particular, our Compensation Committee has the authority, in its sole discretion, to retain compensation consultants to assist in its evaluation of executive and director compensation, including the authority to approve the consultant’s reasonable fees and other retention terms. Under the Charter of the Compensation Committee, our Compensation Committee may select, or receive advice from, a compensation consultant, legal counsel or other adviser to our Compensation Committee, other than in-house legal counsel and certain other types of advisers, only after taking into consideration six factors, prescribed by the SEC and Nasdaq, that bear upon the adviser’s independence; however, there is no requirement that any adviser be independent.

Our Compensation Committee, or our Board upon recommendation from the Compensation Committee, makes the significant adjustments to annual compensation, determines bonus and equity awards and establishes new performance objectives at one or more meetings held during the first quarter of the year. Generally, our Compensation Committee’s process comprises two related elements: the determination of compensation levels and the establishment of performance objectives for the current year. For executives other than our Chief Executive Officer, our Compensation Committee solicits and considers evaluations and recommendations submitted to our Compensation Committee by our Chief Executive Officer. In the case of our Chief Executive Officer, the evaluation of his performance is conducted by our Board upon recommendation from our Compensation Committee, which determines any adjustments to his compensation as well as awards to be granted. For all executives, as part of its deliberations, our Compensation Committee may review and consider, as appropriate, materials such as financial reports and projections, operational data, tax and accounting information, tally sheets that set forth the total compensation that may become payable to executives in various hypothetical scenarios, executive and director stock ownership information, company stock performance data, analyses of historical executive compensation levels and current Company-wide compensation levels and recommendations of our Compensation Committee’s compensation consultant, including analyses of executive compensation paid at other companies identified by the consultant.

Our Compensation Committee enlists the services of a third-party compensation consultant to conduct an analysis of our compensation practices compared with current market practices. In May 2020, our Compensation Committee engaged the services of Radford, which is part of the Rewards Solutions practice at Aon plc, to conduct a review and analysis of our executive and director compensation compared with current market practices and a peer group of companies, to be used for setting 2020 executive and director compensation levels in connection with our initial public offering (“IPO”) in September 2020. The 2020 peer

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group was chosen based on several characteristics including: comparable stage in key product and corporate development, similar growth and performance potential and market capitalization. Radford reports directly to the Chair of our Compensation Committee. In September 2021, our Compensation Committee reviewed and confirmed the use of the previous peer group for purposes of setting 2022 executive and director level compensation levels. Our Compensation Committee assesses the independence of Radford after taking into consideration six factors mandated by SEC and Nasdaq listing standards that bear upon Radford’s independence.

Radford’s review, which consisted of an analysis of our compensation practices against prevailing market practices of identified peer group companies and broader industry trends, analyzed total direct compensation (inclusive of salary, cash bonuses and equity awards) of our executive officers and was based on an assessment of market trends through analysis of available public information in addition to proprietary data provided by Radford. As guidelines for our executives and directors, we set target cash compensation, when considering salary and bonus potential (or retainers, in the instance of directors), and equity compensation, delivered through equity-based awards, after generally referencing the 50th percentile of compensation paid to executives and directors within our compensation peer group. We target equity compensation for our executives, delivered through equity-based awards between the 50th and 75th percentiles of equity compensation paid to executives in our compensation peer group. We believe that our emphasis on equity compensation serves to retain our executives and directors and align their interests with those of our stockholders. We also believe that generally referencing the 50th percentile in setting salary and bonus compensation and the 50th to 75th percentiles in setting equity compensation for our executives, appropriately reflects our position and performance. We may deviate from setting actual compensation levels at these target percentiles of the peer group with respect to our executives to reflect experience, performance levels, existing equity holdings, and market factors as deemed appropriate by our Compensation Committee or our Board. In any given year, our Compensation Committee may consider the experience and performance levels of our executives and other factors deemed appropriate and make a subjective determination that it would be appropriate for any Named Executive Officer’s (as defined below) compensation elements or targeted total compensation and equity levels to deviate from the targeted percentile of the compensation paid to similarly situated officers employed by our peer companies.

The Charter of the Compensation Committee can be found on our website at www.metacrine.com in the Corporate Governance section. The inclusion of our website address here and elsewhere in this proxy statement does not include or incorporate by reference the information on our website into this proxy statement.

Our Nominating and Corporate Governance Committee believes that the candidates for director, both individually and collectively, have the integrity, experience, judgment, commitment (including having sufficient time to devote to us and level of participation), skills, diversity and expertise appropriate for us. In assessing the directors, both individually and collectively, our Nominating and Corporate Governance Committee considers our current needs and the needs of our Board, to maintain a balance of knowledge, experience, capability, race, gender, geography, thought, viewpoints, backgrounds, skills, and expertise. However, our Nominating and Corporate Governance Committee retains the right to modify these qualifications from time to time. Candidates for director nominees are reviewed in the context of the current composition of the Board, our operating requirements and the long-term interests of our stockholders. In conducting this assessment, our Nominating and Corporate Governance Committee typically considers diversity (including with respect to race, gender, geography, thought, viewpoints and backgrounds), age, skills and such other factors as it deems appropriate given our current needs and the needs of the Board, to maintain a balance of knowledge, experience and capability. In the case of incumbent directors whose terms of office are set to expire, our Nominating and Corporate Governance Committee reviews these directors’ overall service to us during their terms and any other relationships and transactions that might impair the directors’ independence.

In the case of new director candidates, our Nominating and Corporate Governance Committee also determines whether the nominee is independent for Nasdaq purposes, which determination is based upon applicable Nasdaq listing standards, applicable SEC rules and regulations and the advice of counsel, if necessary. Our Nominating and Corporate Governance Committee then uses its network of contacts to compile a list of potential candidates, but may also engage, if it deems appropriate, a professional search firm. Any search firm retained to assist our Nominating and Corporate Governance Committee in seeking candidates for the Board will be instructed to seek to include diverse candidates in terms of race, gender, geography, thought, viewpoints, backgrounds, skills, experience and expertise from, among other areas, professional and academic areas relevant to Metacrine’s area of focus. In addition, our Nominating and Corporate Governance Committee conducts any appropriate and necessary inquiries into the backgrounds and qualifications of possible candidates after considering the function and needs of the Board. Our Nominating and Corporate Governance Committee meets to discuss and consider the candidates’ qualifications and then selects a nominee for recommendation to the Board by majority vote.

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Our Nominating and Corporate Governance Committee will consider director candidates recommended by stockholders. Our Nominating and Corporate Governance Committee does not intend to alter the manner in which it evaluates candidates, including the minimum criteria set forth above, based on whether or not the candidate was recommended by a stockholder. Stockholders who wish to recommend individuals for consideration by our Nominating and Corporate Governance Committee to become nominees for election to the Board may do so by delivering a written recommendation to our Nominating and Corporate Governance Committee at the following address: 4225 Executive Square, Suite 600, San Diego, CA 92037, Attn: Secretary, no later than the 90th day and no earlier than the 120th day prior to the one year anniversary of the preceding year’s annual meeting of stockholders. Submissions must include the information specified in Article III, Section 5 of our amended and restated bylaws. For additional information about our director nomination requirements, please see refer to our amended and restated bylaws. We may require any proposed nominee to furnish such other information as we may reasonably require to determine the eligibility of such proposed nominee to serve as our independent director or that could be material to a reasonable stockholder’s understanding of the independence, or lack thereof, of such proposed nominee.

The Charter of the Nominating and Corporate Governance Committee can be found on our website at www.metacrine.com in the Corporate Governance section. The inclusion of our website address here and elsewhere in this proxy statement does not include or incorporate by reference the information on our website into this proxy statement.

Board Diversity

Our Board believes that a diverse board of directors is better able to effectively oversee our management and strategy, and position us to deliver long-term value for our stockholders. Our Board considers diversity, including gender and ethnic diversity, as adding to the overall mix of perspectives of our Board as a whole. With the assistance of our Nominating and Corporate Governance Committee, our Board regularly reviews trends in board composition, including on director diversity. Our Board currently includes one director who self-identifies as female and one director who self-identifies as a member of an underrepresented community (as defined in California Assembly Bill 979).

The Board Diversity Matrix below provides the diversity statistics for our Board:

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Stockholder Communications with our Board of Directors

Our Board has adopted a formal process by which stockholders may communicate with our Board or any of its directors. Stockholders who wish to communicate with our Board may do so by sending written communications addressed to the Secretary of Metacrine, Inc. at 4225 Executive Square, Suite 600, San Diego, CA 92037. Each communication must set forth: the name and address of the stockholder on whose behalf the communication is sent and the number of our shares that are owned beneficially by such stockholder as of the date of the communication. Each communication will be reviewed by our Secretary to determine whether it is appropriate for presentation to our Board or such director. Communications determined by our Secretary to be appropriate for presentation to the Board or such director will be submitted to the Board or such director on a periodic basis.

Anti-Hedging and Pledging Prohibition

Pursuant to our Insider Trading Policy, our officers, directors, employees and consultants are prohibited from engaging in short sales, transactions in publicly traded options, such as puts or calls, hedging transactions, margin accounts, pledges or other inherently speculative transactions with respect to our common stock at any time.

CODE OF BUSINESS CONDUCT AND ETHICS

We have adopted a Code of Business Conduct and Ethics that applies to all officers, directors and employees, including our principal executive officer, principal financial officer, principal accounting officer or controller, or person performing similar functions. Our Code of Business Conduct and Ethics is available on our website at www.metacrine.com. If we make any substantive amendments to the Code of Business Conduct and Ethics or grant any waiver from a provision of the Code of Business Conduct and Ethics to any principal executive officer, principal financial officer, principal accounting officer or controller or persons performing similar functions or our directors, we will promptly disclose the nature of the amendment or waiver on our website. The inclusion of our website address here and elsewhere in this proxy statement does not include or incorporate by reference the information on our website into this proxy statement.

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