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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

SCHEDULE 14A

(Rule 14a-101)

Proxy Statement Pursuant to Section 14(a) of
the Securities Exchange Act of 1934 (Amendment No.          )

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APTINYX INC.
909 Davis Street, Suite 600
Evanston, Illinois 60201

NOTICE OF 20192020 ANNUAL MEETING OF STOCKHOLDERS
To be held May 15, 201920, 2020

        Notice is hereby given that the 20192020 Annual Meeting of Stockholders, or Annual Meeting, of Aptinyx Inc., a Delaware corporation, or the Company, which will be held on May 15, 201920, 2020 at 8:00 a.m. Central Time at a virtual meeting at which you will be able to attend, vote and submit your questions atwww.virtualshareholdermeeting.com/APTX2019APTX2020. The purposes of the Annual Meeting are the following:

1.

To elect two class IClass II directors to our board of directors, to serve until the 20222023 Annual Meeting of Stockholders and until his or her successor has been duly elected and qualified, or until his or her earlier death, resignation or removal;



2.

To ratify the appointment of Deloitte & Touche LLP as the independent registered public accounting firm of the Company for the fiscal year ending December 31, 2019;2020; and



3.

To transact any other business properly brought before the Annual Meeting or any adjournment or postponement of the Annual Meeting.

        The proposal for the election of directors relates solely to the election of class IClass II directors nominated by the board of directors.

        Only Aptinyx Inc. stockholders of record at the close of business on March 20, 2019,23, 2020, will be entitled to vote at the Annual Meeting and any adjournment or postponement thereof.

        We are pleased to take advantage of Securities and Exchange Commission rules that allow companies to furnish their proxy materials over the Internet. We are mailing to our stockholders a Notice of Internet Availability of Proxy Materials, or Notice, instead of a paper copy of our proxy materials and our 20182019 Annual Report to Stockholders, or 20182019 Annual Report. The Notice contains instructions on how to access those documents and to cast your vote via the Internet. The Notice also contains instructions on how to request a paper copy of our proxy materials and our 20182019 Annual Report. This process allows us to provide our stockholders with the information they need on a more timely basis, while reducing the environmental impact and lowering the costs of printing and distributing our proxy materials.

        Your vote is important. Whether or not you are able to attend the virtual meeting, it is important that your shares be represented. To ensure that your vote is recorded promptly, please vote as soon as possible, even if you plan to attend the virtual meeting, by submitting your proxy via the Internet at the address listed on the proxy card or by signing, dating and returning the proxy card. The proxy statement and Annual Report to stockholders are available athttp://www.proxyvote.com.

Evanston, Illinois
April 1, 20196, 2020

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APTINYX INC.

909 Davis Street, Suite 600
Evanston, Illinois 60201

PROXY STATEMENT

FOR THE 20192020 ANNUAL MEETING OF STOCKHOLDERS
TO BE HELD MAY 15, 201920, 2020

        This proxy statement contains information about the 20192020 Annual Meeting of Stockholders, or the Annual Meeting, of Aptinyx Inc., which will be held via virtual meeting on May 15, 201920, 2020 at 8:00 a.m. Central Time. You may attend the meeting virtually via the Internet at www.virtualshareholdermeeting.com/APTX2019,APTX2020, where you will be able to vote electronically and submit questions. The board of directors of Aptinyx Inc. is using this proxy statement to solicit proxies for use at the Annual Meeting. In this proxy statement, the terms "Aptinyx," "the Company," "we," "us," and "our" refer to Aptinyx Inc. The mailing address of our principal executive offices is Aptinyx Inc., 909 Davis Street, Suite 600, Evanston, Illinois 60201.

        All properly submitted proxies will be voted in accordance with the instructions contained in those proxies. If no instructions are specified, the proxies will be voted in accordance with the recommendation of our board of directors with respect to each of the matters set forth in the accompanying noticeNotice of meeting.Meeting. You may revoke your proxy at any time before it is exercised at the meeting by giving our corporate secretary written notice to that effect.

        We made this proxy statement and our Annual Report to Stockholders for the fiscal year ended December 31, 20182019 available to stockholders on April 1, 2019.6, 2020.

        We are an "emerging growth company" under applicable federal securities laws and therefore permitted to conform with certain reduced public company reporting requirements. As an emerging growth company, we provide in this proxy statement the scaled disclosure permitted under the Jumpstart Our Business Startups Act of 2012 or the(the JOBS Act,Act), including the compensation disclosures required of a "smaller reporting company," as that term is defined in Rule 12b-2 promulgated under the Securities Exchange Act of 1934, as amended or the(the Exchange Act.Act). In addition, as an emerging growth company, we are not required to conduct votes seeking approval, on an advisory basis, of the compensation of our named executive officers or the frequency with which such votes must be conducted. We will remain an "emerging growth company" until the earliest of (i) the last day of the fiscal year following the fifth anniversary of our initial public offering in June 2018; (ii) the last day of the fiscal year in which our total annual gross revenue is equal to or more than $1.07 billion; (iii) the date on which we have issued more than $1 billion in nonconvertible debt during the previous three years; or (iv) the date on which we are deemed to be a large accelerated filer under the rules of the Securities and Exchange Commission, or the SEC.Commission. Even after we are no longer an "emerging growth company," we may remain a "smaller reporting company."

Important Notice Regarding the Availability of Proxy Materials for
the Annual Meeting of Stockholders to be Held on May 15, 2019:20, 2020:

This proxy statement and our 20182019 Annual Report to Stockholders are
available for viewing, printing and downloading at www.proxyvote.com.

        A copy of our Annual Report on Form 10-K for the fiscal year ended December 31, 2018,2019, as filed with the SEC,Securities and Exchange Commission (SEC), except for exhibits, will be furnished without charge to any stockholder upon written request to Aptinyx Inc. 909 Davis Street, Suite 600, Evanston, Illinois 60201, Attention: Corporate Secretary. This proxy statement and our Annual Report on Form 10-K for the fiscal year ended December 31, 20182019 are also available on the SEC's website at www.sec.gov.

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APTINYX INC
PROXY STATEMENT
FOR THE 20192020 ANNUAL MEETING OF STOCKHOLDERS

GENERAL INFORMATION

When are this proxy statement and the accompanying materials scheduled to be sent to stockholders?

        We have elected to provide access to our proxy materials to our stockholders via the Internet. Accordingly, on or about April 1, 2019,6, 2020, we will begin mailing a Notice of Internet Availability of Proxy Materials, or Notice. Our proxy materials, including the Notice of 20192020 Annual Meeting of Stockholders, this proxy statement and the accompanying proxy card or, for shares held in street name (i.e. held for your account by a broker or other nominee), a voting instruction form, and the 20182019 Annual Report to Stockholders, or 20182019 Annual Report, will be mailed or made available to stockholders on the Internet on or about the same date.

Why did I receive a Notice of Internet Availability of Proxy Materials instead of a full set of proxy materials?

        Pursuant to rules adopted by the Securities and Exchange Commission, or SEC, for most stockholders, we are providing access to our proxy materials over the Internet rather than printing and mailing our proxy materials. We believe following this process will expedite the receipt of such materials and will help lower our costs and reduce the environmental impact of our annual meeting materials. Therefore, the Notice was mailed to holders of record and beneficial owners of our common stock starting on or about April 1, 2019.6, 2020. The Notice provides instructions as to how stockholders may access and review our proxy materials, including the Notice of 20192020 Annual Meeting of Stockholders, this proxy statement, the proxy card and our 20182019 Annual Report, on the website referred to in the Notice or, alternatively, how to request that a copy of the proxy materials, including a proxy card, be sent to them by mail. The Notice also provides voting instructions. In addition, stockholders of record may request to receive the proxy materials in printed form by mail or electronically by e-mail on an ongoing basis for future stockholder meetings. Please note that, while our proxy materials are available at the website referenced in the Notice, and our Notice of 20192020 Annual Meeting of Stockholders, this proxy statement and our 20182019 Annual Report are available on our website, no other information contained on either website is incorporated by reference in or considered to be a part of this proxy statement.

Who is soliciting my vote?

        Our board of directors is soliciting your vote for the Annual Meeting, including at any adjournments or postponements of the meeting.

When is the record date for the Annual Meeting?

        The record date for determination of stockholders entitled to vote at the Annual Meeting is the close of business on March 20, 2019.23, 2020.

How many votes can be cast by all stockholders?

        There were 33,562,21145,534,432 shares of our common stock, par value $0.01 per share, outstanding on March 20, 2019,23, 2020, all of which are entitled to vote with respect to all matters to be acted upon at the Annual Meeting. Each stockholder of record is entitled to one vote for each share of our common stock held by such stockholder. None of our shares of undesignated preferred stock were outstanding as of March 20, 2019.23, 2020.

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How do I vote?

        If you are a stockholder of record, there are several ways for you to vote your shares.

•

By Telephone.  You may vote using a touch-tone telephone by calling 800-690-6903, 24 hours a day, seven days a week. You will need the 16-digit control number included on your proxy card. Votes submitted by telephone must be received by 11:59 p.m., Eastern Time, on May 14, 2019.19, 2020.



•

By Internet.  You may vote at www.proxyvote.com, 24 hours a day, seven days a week. You will need the 16-digit control number included on your proxy card. Votes submitted through the Internet must be received by 11:59 p.m., Eastern Time, on May 14, 2019.19, 2020.



•

By Mail.  You may vote by mail by completing, signing and dating the enclosed proxy card and returning it in the enclosed prepaid envelope.



•

During the Annual Meeting.  You may vote during the Annual Meeting by going to www.virtualshareholdermeeting.com/APTX2019.APTX2020.com. You will need the 16-digit control number included on your proxy card.

        Telephone and Internet voting for stockholders of record will be available until 11:59 p.m. Eastern Time on May 14, 2019,19, 2020 and mailed proxy cards must be received by May 14, 201919, 2020 in order to be counted at the Annual Meeting. If the Annual Meeting is adjourned or postponed, these deadlines may be extended.

        The voting deadlines and availability of telephone and Internet voting for beneficial owners of shares held in "street name" will depend on the voting processes of the organization that holds your shares. Therefore, we urge you to carefully review and follow the voting instruction card and any other materials that you receive from that organization.If you hold your shares of Aptinyx common stock in multiple accounts, you should vote your shares as described in each set of proxy materials you receive.

        If any other matters are properly presented for consideration at the Annual Meeting, including, among other things, consideration of a motion to adjourn the Annual Meeting to another time or place (including, without limitation, for the purpose of soliciting additional proxies), the persons named in your proxy and acting thereunder will have discretion to vote on those matters in accordance with their best judgment. We do not currently anticipate that any other matters will be raised at the Annual Meeting.

How do I revoke my proxy?

        You may revoke your proxy by (1) following the instructions on the Notice and entering a new vote by mail that we receive before the start of the Annual Meeting or over the Internet by the cutoff time of 11:59 p.m. Eastern Time on May 14, 2019,19, 2020, (2) attending and voting at the Annual Meeting (although attendance at the Annual Meeting will not in and of itself revoke a proxy), or (3) by filing an instrument in writing revoking the proxy or another duly executed proxy bearing a later date with our Corporate Secretary. Any written notice of revocation or subsequent proxy card must be received by our Corporate Secretary prior to the taking of the vote at the Annual Meeting. Such written notice of revocation or subsequent proxy card should be hand delivered to our Corporate Secretary or sent to our principal executive offices at Aptinyx Inc., 909 Davis Street, Suite 600, Evanston, Illinois 60201, Attention: Corporate Secretary.

        If a broker, bank, or other nominee holds your shares, you must contact such broker, bank, or nominee in order to find out how to change your vote.

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How is a quorum reached?

        Our Amended and Restated Bylaws, or bylaws, provide that a majority of the shares entitled to vote, present in person or represented by proxy, will constitute a quorum for the transaction of business at the Annual Meeting.

        Under the General Corporation Law of the State of Delaware, shares that are voted "abstain" or "withheld" and broker "non-votes" are counted as present for purposes of determining whether a quorum is present at the Annual Meeting. If a quorum is not present, the meeting may be adjourned until a quorum is obtained.

How is the vote counted?

        Under our bylaws, any proposal other than an election of directors is decided by a majority of the votes properly cast for and against such proposal, except where a larger vote is required by law or by our Amended and Restated Certificate of Incorporation, or certificate of incorporation, or bylaws. Abstentions and broker "non-votes" are not included in the tabulation of the voting results on any such proposal and, therefore, do not have an impact on such proposals. A broker "non-vote" occurs when a nominee holding shares for a beneficial owner does not vote on a particular proposal because the nominee does not have discretionary voting power with respect to that item, and has not received instructions from the beneficial owner.

        If your shares are held in "street name" by a brokerage firm, your brokerage firm is required to vote your shares according to your instructions. If you do not give instructions to your brokerage firm, the brokerage firm will still be able to vote your shares with respect to certain "discretionary" items but will not be allowed to vote your shares with respect to "non-discretionary" items. Proposal No. 1 is a "non-discretionary" item. If you do not instruct your broker how to vote with respect to this proposal, your broker may not vote for this proposal, and those votes will be counted as broker "non-votes." Proposal No. 2 is considered to be a discretionary item, and your brokerage firm will be able to vote on this proposal even if it does not receive instructions from you.

        To be elected, the directors nominated via Proposal No. 1 must receive a plurality of the votes cast and entitled to vote on the proposal, meaning that the director nominees receiving the most votes will be elected. Shares voting "withheld" have no effect on the election of directors.

        The approval of Proposal No. 2 requires that a majority of the votes properly cast vote FOR this proposal. Share voting "abstain" have no effect on the outcome of Proposal No.2.No. 2.

Who pays the cost for soliciting proxies?

        We are making this solicitation and will pay the entire cost of preparing and distributing the Notice and our proxy materials and soliciting votes. If you choose to access the proxy materials or vote over the Internet, you are responsible for any Internet access charges that you may incur. Our officers and employees may, without compensation other than their regular compensation, solicit proxies through further mailings, personal conversations, facsimile transmissions, e-mails, or otherwise. We have hired Broadridge Financial Solutions, Inc. to assist us in the distribution of proxy materials and the solicitation of votes described above. Proxy solicitation expenses that we will pay include those for preparation, mailing, returning, and tabulating the proxies.

How may stockholders submit matters for consideration at an annual meeting?

        The required notice must be in writing and received by our corporate secretary at our principal executive offices not less than 90 days nor more than 120 days prior to the first anniversary of the preceding year's annual meeting. However, in the event that the date of the annual meeting is advanced by more than 30 days, or delayed by more than 60 days, from the first anniversary of the

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preceding year's annual meeting, or if no annual meeting were held in the preceding year, a stockholder's notice must be so received no earlier than the 120th day prior to such annual meeting and not later than the close of business on the later of (A) the 90th day prior to such annual meeting and (B) the tenth day following the day on which notice of the date of such annual meeting was mailed or public disclosure of the date of such annual meeting was made, whichever first occurs.

        In addition, any stockholder proposal intended to be included in the proxy statement for the next annual meeting of our stockholders in 20202021 must also satisfy the requirements of SEC Rule 14a-8 under the Securities Exchange Act of 1934, as amended, or the Exchange Act, and be received not later than December 3, 2019.7, 2020 If the date of the annual meeting is moved by more than 30 days from the date contemplated at the time of the previous year's proxy statement, then notice must be received within a reasonable time before we begin to print and send proxy materials. If that happens, we will publicly announce the deadline for submitting a proposal in a press release or in a document filed with the SEC.

How can I know the voting results?

        We plan to announce preliminary voting results at the Annual Meeting and will publish final results in a Current Report on Form 8-K to be filed with the SEC within four business days following the Annual Meeting.

OVERVIEW OF PROPOSALS

        This Proxy Statement contains two proposals requiring stockholder action. Proposal No. 1 requests the election of two Class III directors to our board of directors. Proposal No. 2 requests the ratification of the appointment of Deloitte & Touche LLP as our independent registered public accounting firm for the fiscal year ending December 31, 2019.2020. Each of the proposals is discussed in more detail in the pages that follow.

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PROPOSAL NO. 1 — ELECTION OF CLASS III DIRECTORS

        Our board of directors currently consists of sevennine members. In accordance with the terms of our certificate of incorporation and bylaws, our board of directors is divided into three classes, classClass I, classClass II and classClass III, with members of each class serving staggered three-year terms. The current members of the classes are divided as follows:

•

the classClass I directors are Wilbur H. Gantz III, and Norbert G. Riedel, Ph.D., and theirRachel E. Sherman, M.D., M.P.H.; Mr. Gantz has resigned from the board of directors due to his retirement, effective as of the Annual Meeting, and Dr. Riedel's and Dr. Sherman's terms will expire at the Annual Meeting;annual meeting of stockholders to be held in 2022;



•

the classClass II directors are Patrick G. Enright, Adam M. Koppel, M.D., Ph.D., and James N. Topper, M.D., Ph.D., and their terms will expire at the annual meeting of stockholders to be held in 2020;Annual Meeting; and



•

the classClass III directors are Elisha P. Gould III, and Robert J. Hombach, and Henry O. Gosebruch, and their terms will expire at the annual meeting of stockholders to be held in 2021.

        Upon the expiration of the term of a class of directors, directors in that class will be eligible to be elected for a new three-year term at the annual meeting of stockholders in the year in which their term expires. As disclosed on March 29, 2019, Dr. Ratcliffe notified us of his decision to retire from service on our board of directors as of March 31, 2019.

        Our certificate of incorporation and bylaws provide that the authorized number of directors may be changed only by resolution of our board of directors. Our certificate of incorporation also provides that our directors may be removed only for cause by the affirmative vote of the holders of at least two-thirds (²/3) of the outstanding shares then entitled to vote in an annual election of directors, and that any vacancy on our board of directors, including a vacancy resulting from an enlargement of our board of directors, may be filled only by vote of a majority of our directors then in office.

        James N. Topper, M.D., Ph.D., who is currently a Class II director, is not standing for reelection to the board of directors at the Annual Meeting, and his term will end following the Annual Meeting. In addition, Wilbur H. Gantz III, who is currently chairman of the board and a Class I director, has resigned from the board due to his retirement, effective as of the Annual Meeting. Patrick G. Enright has been appointed to serve as chairman of the board following the effectiveness of Mr. Gantz's resignation.

Our board of directors has nominated Wilbur H. Gantz IIIPatrick G. Enright and Norbert G. Riedel,Adam, M. Koppel, M.D., Ph.D. for election as the class IClass II directors at the Annual Meeting. The nominees are presently directors and have indicated a willingness to continue to serve as directors, if elected. If the nominees become unable or unwilling to serve, however, the proxies may be voted for a substitute nominee selected by our board of directors.

Nominees for Election as Class III Directors

        The following table identifies our nominees to serve as Class II directors and sets forth their principal occupation and business experience during the last five years and their ages as of April 1, 2019.March 23, 2020.

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Class II Directors (Term Expires at 2020 Annual Meeting)

Patrick G. Enright has served as a member of our board of directors since May 2016. Since 2007, Mr. Enright has served as a Managing Director of Longitude Capital, a venture capital firm, of which he is a founder. From 2002 through 2006, Mr. Enright was a Managing Director of Pequot Ventures, a venture capital investment firm, where he co-led the life sciences investment practice. He currently serves on the boards of directors of Aimmune Therapeutics, Inc., Jazz Pharmaceuticals plc, and several privately-held companies. During the past five years, Mr. Enright has served on the boards of directors of Esperion Therapeutics, Inc. and Corcept Therapeutics Incorporated. Mr. Enright received a B.S. from Stanford University and an M.B.A. from the Wharton School at the University of Pennsylvania. We believe Mr. Enright is qualified to serve on our board due to his experience as a venture capital investor focused on life sciences companies and his past work in the pharmaceutical industry.

Adam M. Koppel, M.D., Ph.D., joined our board of directors in December 2017. Dr. Koppel rejoined Bain Capital in 2016 as a managing director of Bain Capital Life Sciences. He had initially joined Bain Capital Public Equity in 2003 where he was a leader within the healthcare sector until mid-2014. During the period mid-2014 to mid-2016, Dr. Koppel worked at Biogen, Inc. where he served as executive vice president of corporate development and chief strategy officer. Prior to joining Bain Capital Public Equity in 2003, Dr. Koppel was an associate principal at McKinsey & Co in New Jersey where he served a variety of healthcare companies. Dr. Koppel currently serves on the board of directors of Cerevel Therapeutics, Inc., Dicerna Pharmaceuticals, Inc., Foghorn Therapeutics, Solid BioSciences, Inc. and ViaCyte, Inc. Dr. Koppel previously served on the board of directors of Trevena, Inc. and PTC Therapeutics, Inc. Dr. Koppel received an M.D. and Ph.D. in neuroscience from the University of Pennsylvania School of Medicine, as well as an M.B.A. from The Wharton School at the University of Pennsylvania, where he was a Palmer Scholar. He graduated magna cum laude from Harvard University with an A.B. and A.M. in History and Science. We believe that Dr. Koppel's background as an executive officer, director and venture capital investor in biopharmaceutical companies, as well as his scientific and medical background, provide him with the qualifications and skills to serve as a member of our board of directors.

Vote Required and Board of Directors' Recommendation

        To be elected, the directors nominated via Proposal No. 1 must receive a plurality of the votes cast and entitled to vote on the proposal, meaning that the director nominees receiving the most votes will be elected. Shares voting "withheld" have no effect on the election of directors.

        The proxies will be voted in favor of the above nominees unless a contrary specification is made in the proxy. The nominees have consented to serve as our directors if elected. However, if the nominees are unable to serve or for good cause will not serve as a director, the proxies will be voted for the election of such substitute nominee as our board of directors may designate.

        The proposal for the election of directors relates solely to the election of Class II directors nominated by our board of directors.

The board of directors recommends voting "FOR" the election of Patrick G. Enright and Adam M. Koppel, M.D., Ph.D. as the Class II directors, to serve for a three-year term ending at the annual meeting of stockholders to be held in 2023.

Class I and Class II Directors

        The following table identifies our current Class I and Class III directors and sets forth their principal occupation and business experience during the last five years and their ages as of March 23,

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2020. Wilbur H. Gantz III, who is currently chairman of the board and a Class I director, has resigned from the board due to his retirement, effective as of the Annual Meeting.

Class I Directors (Term Expires at 2022 Annual Meeting, except that Mr. Gantz has resigned from our board of directors, effective as of the Annual Meeting)

        Norbert G. Riedel, Ph.D., has served as a member of our board of directors and our President and Chief Executive Officer since June 2015. Dr. Riedel previously served as Chief Executive Officer and President of Naurex Inc., our predecessor company, from January 2014 to July 2015. From 2001 to January 2013, he served as Corporate Vice President and Chief Scientific Officer of Baxter International Inc., a diversified healthcare company, where from 1998 to 2001, he also served as President and General Manager of the recombinant therapeutic proteins business unit and Vice President of Research and Development of the bioscience business unit. From 1996 to 1998, Dr. Riedel served as head of worldwide biotechnology and worldwide core research functions at Hoechst-Marion Roussel, now Sanofi, a global pharmaceutical company. Dr. Riedel served on the board of directors of Ariad Pharmaceuticals, Inc., an oncology company, from May 2011 until the company was acquired in February 2017. Dr. Riedel also serves on the board of directors of Jazz Pharmaceuticals plc, Eton

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Pharmaceuticals, Inc., Cerevel Therapeutics, LLC,Inc., and the Illinois Biotechnology Innovation Organization and is also a member of the Austrian Academy of Sciences. Dr. Riedel is an Adjunct Professor at Boston University School of Medicine and an Adjunct Professor of Medicine at Northwestern University's Feinberg School of Medicine. Dr. Riedel previously served as an associate professor of medicine at Boston University School of Medicine and a visiting associate professor at the Massachusetts Institute of Technology. Dr. Riedel holds a diplomaDiploma in biochemistry and a Ph.D. in biochemistry from the University of Frankfurt. Dr. Riedel brings significant scientific, drug discovery and development, and commercial expertise to our board of directors with over 20 years of experience in the biotechnology and pharmaceutical industries.

        Wilbur H. Gantz III has served as a member of our board of directors since July 2015. Mr. Gantz has been the President of PathoCapital, an investor in healthcare companies, since March 2009. He previously served as Executive Chairman and Chief Executive Officer of Ovation Pharmaceuticals, Inc., which was sold to Lundbeck, AG in 2009, and as Chairman, Chief Executive Officer and President of PathoGenesis Corporation, a biopharmaceutical company that was sold to Chiron, Inc. in 2000. Prior to founding PathoGenesis, from 1987 to 1992 he served as President of Baxter International, Inc., a manufacturer and marketer of healthcare products. During the past five years, Mr. Gantz has served on the board of directors of Aevi Genomic Medicine, Inc. and W.W. Grainger, Inc. He currently serves on the boards of private companies Harmony Biosciences, LLC, and ReliefBand Technologies LLC. He is a trustee of The Field Museum of Natural History and Brain Research Foundation. Mr. Gantz holds a B.A. degree from Princeton University, where he graduated cum laude, and an M.B.A. from Harvard Business School. We believe that Mr. Gantz is qualified to serve on our board of directors due to his extensive experience managing biopharmaceutical and healthcare companies.

Vote Required and Board of Directors' RecommendationRachel Sherman, M.D., M.P.H.,

        To be elected, the directors nominated via Proposal No. 1 must receive a plurality of the votes cast and entitled to vote on the proposal, meaning that the director nominees receiving the most votes will be elected. Shares voting "withheld" have no effect on the election of directors.

        The proxies will be voted in favor of the above nominees unless a contrary specification is made in the proxy. The nominees have consented to serve as our directors if elected. However, if the nominees are unable to serve or for good cause will not serve as a director, the proxies will be voted for the election of such substitute nominee as joined our board of directors may designate.

        The proposal for the election of directors relates solely to the election of class I directors nominated by our board of directors.

The board of directors recommends voting "FOR" the election of Wilbur H. Gantz III and Norbert G. Riedel, Ph.D. as the class I directors, to serve forin August 2019. Dr. Sherman is a three-year term endingrenowned expert in medical policy who served at the annual meeting of stockholders to be held in 2022.FDA for nearly 30 years until her retirement early

Directors Continuing in Office

       ��The following table identifies our directors and sets forth their principal occupation and business experience during the last five years and their ages as of April 1, 2019.

global private equity firm, and has been employed by Adams Street Partners or its predecessor organizations since 1994. Since 2014, Mr. Gould has served on the board of directors of Corvus Pharmaceuticals, Inc. and in the past five years, he has also served on the board of directors of OncoMed Pharmaceuticals, Inc. He also currently serves on the board of directors of several private companies. Mr. Gould received an A.B. in Engineering Science from Dartmouth College and an M.B.A. from the Stanford University Graduate School of Business. We believe Mr. Gould's experience in the venture capital industry and as director of a pharmaceutical company provides him with the qualifications and skills to serve as a member of our board of directors.

        Robert J. Hombach has served as a member of our board of directors since May 2018. Mr. Hombach is the retired Executive Vice President, Chief Financial Officer and Chief Operations Officer of Baxalta Inc., a biopharmaceutical company, a position he held from July 2015 until the acquisition of Baxalta by Shire plc in June 2016. Baxalta was spun off from its parent, Baxter International Inc., in July 2015, where Mr. Hombach served as Vice President and Chief Financial Officer from June 2010 until the Baxalta spin off. Mr. Hombach began his career at Baxter in 1989 and served in a number of roles there, including as Vice President of Finance EMEA from 2004 to 2007 and Treasurer from 2007 to 2010. Mr. Hombach currently serves on the board of directors of BioMarin Pharmaceutical Inc. and Carmax Inc. Mr. Hombach earned an M.B.A. from Northwestern University's J.L. Kellogg Graduate School of Management, and a B.S. in finance cum laude from the University of Colorado. Mr. Hombach is qualified to serve on our board of directors due to his extensive experience in finance and accounting, capital markets, and managing large biotechnology and pharmaceutical organizations.

Henry O. Gosebruch joined our board of directors in May 2019. Since 2015, Mr. Gosebruch has served as executive vice president and chief strategy officer at AbbVie, a global biopharmaceutical company. As a member of AbbVie's Executive Team, he is responsible for corporate strategy, business development and acquisitions, search and evaluation, alliance management, early-stage collaborations, and the company's corporate strategic venture capital arm, AbbVie Ventures. Prior to joining AbbVie, Mr. Gosebruch spent more than 20 years as a member of J.P. Morgan's North American M&A Group, most recently as its co-head. Mr. Gosebruch currently serves as a member of the Advisory Board for the Life Sciences & Management Program at the University of Pennsylvania. Mr. Gosebruch graduated from the Wharton School at the University of Pennsylvania.

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        There are no family relationships between or among any of our directors or executive officers. The principal occupation and employment during the past five years of each of our directors was carried on, in each case except as specifically identified above, with a corporation or organization that is not a parent, subsidiary or other affiliate of us. There is no arrangement or understanding between any of our directors and any other person or persons pursuant to which he or she is to be selected as a director.

        There are no material legal proceedings to which any of our directors is a party adverse to us in which any such person has a material interest adverse to us.

Executive Officers Who Are Not Directors

        The following table identifies our executive officers, other than as otherwise noted above, and sets forth their current positions at Aptinyx and their ages as of April 1, 2019.March 23, 2020.

        Ashish Khanna has served as our Chief Business Officer since July 2015 and as our Chief Financial Officer since February 2018. He was previously Vice President of Corporate Development at Naurex and managed its financing and transaction efforts between 2010 and 2015, culminating in the company's acquisition by Allergan plc. Prior to Naurex, Mr. Khanna served as Director of Business Development at Vanda Pharmaceuticals. He was formerly a member of the cardiology strategic marketing team at Cordis Corporation, a Johnson & Johnson company. Earlier, Mr. Khanna was a strategy consultant with the Palladium Group and with the Strategic Advisory Services practice of Ernst & Young (now Capgemini). He serves on the board of directors of the Illinois Biotechnology Innovation Organization. Mr. Khanna received a B.S. in finance and B.A.S. in systems engineering from the University of Pennsylvania, as well as an M.B.A. from the Wharton School.

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        Andrew Kidd has served as our Chief Commercial Officer since November 2017 and as our Chief Operating Officer as of March 2019. He was previously at Baxter International for over ten years, most recently as senior vice president of strategy and business development. Prior to that he held a number of commercial leadership positions including general manager of Baxter Canada, global franchise head for surgical care, and general manager of U.S. anesthesia and cardiovascular. Before joining Baxter he worked at The Boston Consulting Group both in London and then Chicago focused on pharmaceutical and other healthcare clients. Mr. Kidd received a BM BCh medical degree from the University of Oxford and a B.A. in medical sciences from the University of Cambridge.

Joseph R. Moskal, Ph.D., has served as our Chief Scientific Officer since July 2015. He founded Naurex in September 2006 and served as its chief scientific officer until the company was acquired by Allergan plc in July 2015. He is also a professor of biomedical engineering at Northwestern University and director of the university's Falk Center for Molecular Therapeutics. Dr. Moskal previously served as assistant professor and director of the neurosurgery laboratories at the Albert Einstein College of Medicine. Earlier, he was a staff fellow at the National Institutes of Health. Dr. Moskal is well known for his research on the NMDAr. He received a B.S. and a Ph.D. from the University of Notre Dame.

        The principal occupation and employment during the past five years of each of our executive officers was carried on, in each case except as specifically identified above, with a corporation or organization that is not a parent, subsidiary or other affiliate of us. There is no arrangement or understanding between any of our executive officers and any other person or persons pursuant to which he was or is to be selected as an executive officer.

        There are no material legal proceedings to which any of our executive officers is a party adverse to us in which any such person has a material interest adverse to us.

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PROPOSAL NO. 2 — RATIFICATION OF THE APPOINTMENT OF DELOITTE & TOUCHE LLP
AS APTINYX'S INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM FOR THE
FISCAL YEAR ENDING DECEMBER 31, 20192020

        Aptinyx's stockholders are being asked to ratify the appointment by the audit committee of the board of directors of Deloitte & Touche LLP as Aptinyx's independent registered public accounting firm for the fiscal year ending December 31, 2019.2020. Deloitte & Touche LLP has served as Aptinyx's independent registered public accounting firm since 2017.

        The audit committee is solely responsible for selecting Aptinyx's independent registered public accounting firm for the fiscal year ending December 31, 2019.2020. Stockholder approval is not required to appoint Deloitte & Touche LLP as Aptinyx's independent registered public accounting firm. However, the board of directors believes that submitting the appointment of Deloitte & Touche LLP to the stockholders for ratification is good corporate governance. If the stockholders do not ratify this appointment, the audit committee will reconsider whether to retain Deloitte & Touche LLP. If the selection of Deloitte & Touche LLP is ratified, the audit committee, at its discretion, may direct the appointment of a different independent registered public accounting firm at any time it decides that such a change would be in the best interest of Aptinyx and its stockholders.

        A representative of Deloitte & Touche LLP is expected to be present at the Annual Meeting and will have an opportunity to make a statement if he or she desires to do so and to respond to appropriate questions from our stockholders.

        Aptinyx incurred the following fees from Deloitte & Touche LLP, and their respective affiliates (the "Deloitte Entities"), for the audit of the financial statements, and for fees billed for other services provided by the Deloitte Entities during the years ended December 31, 20182019 and 2017.2018.

Audit Committee Pre-approval Policy and Procedures

        Our audit committee has adopted policies and procedures relating to the approval of all audit and non-audit services that are to be performed by our independent registered public accounting firm. This policy provides that we will not engage our independent registered public accounting firm to render audit or non-audit services unless the service is specifically approved in advance by our audit committee or the engagement is entered into pursuant to the pre-approval procedure described below.

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        From time to time, our audit committee may pre-approve specified types of services that are expected to be provided to us by our independent registered public accounting firm during the next 12 months. Any such pre-approval details the particular service or type of services to be provided and is also generally subject to a maximum dollar amount.

        During our 20182019 and 20172018 fiscal years, no services were provided to us by Deloitte & Touche LLP other than in accordance with the pre-approval policies and procedures described above.

Vote Required and Board of Directors' Recommendation

        The approval of Proposal No. 2 requires that a majority of the votes properly cast vote FOR this proposal. Shares voting "abstain" have no effect on the outcome of Proposal No. 2.

        The board of directors recommends voting "FOR" Proposal No. 2 to ratify the appointment of Deloitte & Touche LLP as Aptinyx's independent registered public accounting firm for the fiscal year ending December 31, 2019.2020.

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CORPORATE GOVERNANCE

Director Nomination Process

        Our nominating and corporate governance committee is responsible for identifying individuals qualified to serve as directors, consistent with criteria approved by our board, of directors, and recommending such persons to be nominated for election as directors, except where we are legally required by contract, law or otherwise to provide third parties with the right to nominate.

        The process followed by our nominating and corporate governance committee to identify and evaluate director candidates includes requests to board members and others for recommendations, meetings from time to time to evaluate biographical information and background material relating to potential candidates, and interviews of selected candidates by management, recruiters, members of the committee and our board of directors.board. The qualifications, qualities and skills that our nominating and corporate governance committee believes must be met by a committee-recommended nominee for a position on our board of directors are as follows:

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Nominees should demonstrate high standards of personal and professional ethics and integrity.



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Nominees should have proven achievement and competence in the nominee's field and the ability to exercise sound business judgment.



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Nominees should have skills that are complementary to those of the existing board of directors.board.



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Nominees should have the ability to assist and support management and make significant contributions to the Company's success.



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Nominees should have an understanding of the fiduciary responsibilities that is required of a member of the board of directors and the commitment of time and energy necessary to diligently carry out those responsibilities.

        Stockholders may recommend individuals to the nominating and corporate governance committee for consideration as potential director candidates. Any such proposals should be submitted to our corporate secretary at our principal executive offices no later than the close of business on the 90th90^th day nor earlier than the close of business on the 120th day prior to the one-year anniversary of the date of the preceding year's annual meeting and should include appropriate biographical and background material to allow the nominating and corporate governance committee to properly evaluate the potential director candidate and the number of shares of our stock beneficially owned by the stockholder proposing the candidate. Stockholder proposals should be addressed to Aptinyx Inc., 909 Davis Street, Suite 600, Evanston, Illinois 60201, Attention: Corporate Secretary. Assuming that biographical and background material has been provided on a timely basis in accordance with our bylaws, any recommendations received from stockholders will be evaluated in the same manner as potential nominees proposed by the nominating and corporate governance committee. If our board of directors determines to nominate a stockholder-recommended candidate and recommends his or her election, then his or her name will be included on our proxy card for the next annual meeting of stockholders. See "Stockholder Proposals" for a discussion of submitting stockholder proposals.

Director Independence

        Applicable Nasdaq Stock Market LLC, or Nasdaq, rules require a majority of a listed company's board of directors be comprised of independent directors within one year of listing. In addition, the Nasdaq rules require that, subject to specified exceptions, each member of a listed company's audit, compensation and nominating and corporate governance committees be independent, that audit committee members also satisfy independence criteria set forth in Rule 10A-3 under the Exchange Act and that compensation committee members satisfy independence criteria set forth in Rule 10C-1 under the Exchange Act. Under applicable Nasdaq rules, a director will only qualify as an "independent

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director" if, in the opinion of the listed company's board of directors based upon the recommendation of the nominating and corporate governance committee, that person does not have a relationship which would interfere with the exercise of independent judgment in carrying out the responsibilities of a director. In order to be considered independent for purposes of Rule 10A-3, a member of an audit committee of a listed company may not, other than in his or her capacity as a member of the audit committee, the board of directors, or any other board committee, accept, directly or indirectly, any consulting, advisory, or other compensatory fee from the listed company or any of its subsidiaries or otherwise be an affiliated person of the listed company or any of its subsidiaries. In addition, in affirmatively determining the independence of any director who will serve on a company's compensation committee, Rule 10C-1 under the Exchange Act requires that a company's board of directors must consider all factors specifically relevant to determining whether a director has a relationship to such company which is material to that director's ability to be independent from management in connection with the duties of a compensation committee member, including: the source of compensation to the director, including any consulting, advisory or other compensatory fee paid by such company to the director, and whether the director is affiliated with the company or any of its subsidiaries or affiliates.

        Our board of directors has determined that all members of the board of directors, except Dr. Riedel, are independent directors, including for purposes of the rules of Nasdaq and the SEC. In making such independence determination, our board of directors considered the relationships that each non-employee director has with us and all other facts and circumstances that our board of directors deemed relevant in determining their independence, including the beneficial ownership of our capital stock by each non-employee director. In considering the independence of the directors listed above, our board of directors considered the association of our directors with the holders of more than 5% of our common stock. There are no family relationships among any of our directors or executive officers. Dr. Riedel is not an independent director under these rules because he is an executive officer of the Company.

Board Committees

        Our board of directors has established an audit committee, a compensation and management development committee, and a nominating and corporate governance committee. Each of the audit committee, compensation and management development committee, and nominating and corporate governance committee operates under a charter that satisfies the applicable standards of the SEC and Nasdaq. Each such committee reviews its respective charter at least annually. A current copy of the charter for each of the audit committee, compensation and management development committee, and nominating and corporate governance committee is posted on the corporate governance section of our website, www.ir.aptinyx.com/corporate-governance/documents-charters.

Audit Committee

        Patrick G. Enright, Wilbur H. Gantz III, and Robert J. Hombach currently serve on the audit committee, which is chaired by Robert J. Hombach. Mr. Gantz has resigned from the board due to his retirement, effective as of the Annual Meeting. Henry O. Gosebruch has been appointed to serve on the audit committee effective as of the Annual Meeting. Our board of directors has determined that each member of the audit committee is "independent" for audit committee purposes as that term is defined in the rules of the SEC and the applicable Nasdaq rules, and each has sufficient knowledge in financial and auditing matters to serve on the audit committee. Our board of directors has designated Robert J. Hombach as an "audit committee financial expert," as defined under the applicable rules of the SEC. During the fiscal year ended December 31, 2018,2019, the audit committee met four times. The

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report of the audit committee is included in this proxy statement under "Report of the Audit Committee." The audit committee's responsibilities include:

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appointing, approving the compensation of, and assessing the independence of our independent registered public accounting firm;

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•

pre-approving auditing and permissible non-audit services, and the terms of such services, to be provided by our independent registered public accounting firm;



•

reviewing the overall audit plan with our independent registered public accounting firm and members of management responsible for preparing our financial statements;



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reviewing and discussing with management and our independent registered public accounting firm our annual and quarterly financial statements and related disclosures as well as critical accounting policies and practices used by us;



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coordinating the oversight and reviewing the adequacy of our internal control over financial reporting;



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establishing policies and procedures for the receipt and retention of accounting-related complaints and concerns;



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recommending based upon the audit committee's review and discussions with management and our independent registered public accounting firm whether our audited financial statements shall be included in our Annual Report on Form 10-K;



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monitoring the integrity of our financial statements and our compliance with legal and regulatory requirements as they relate to our financial statements and accounting matters;



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preparing the audit committee report required by SEC rules to be included in our annual proxy statement;



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reviewing all related person transactions for potential conflict of interest situations and approving all such transactions; and



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reviewing quarterlydiscussing earnings releases.press releases and financial information and earnings guidance provided to analysts and rating agencies.

        All audit and non-audit services, other thande minimis non-audit services, to be provided to us by our independent registered public accounting firm must be approved in advance by our audit committee.

Compensation and Management Development Committee

        Elisha P. Gould III, and Adam M. Koppel, M.D., Ph.D. currently, and Henry O. Gosebruch serve on the compensation and management development committee, which is chaired by Adam M. Koppel, M.D., Ph.D. As of March 31, 2019, Liam Ratcliffe, M.D., Ph.D. resigned from our board of directors, and no longer serves on the compensation and management development committee. Our board of directors has determined that each member of the compensation and management development committee is "independent" as defined in the applicable Nasdaq rules. During the fiscal year ended December 31, 2018,2019, the compensation and management development committee met foursix times. The compensation and management development committee's responsibilities include:

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annually reviewing and recommending to the board of directors corporate goals and objectives relevant to the compensation of our chief executive officer;



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evaluating the performance of our chief executive officer in light of such corporate goals and objectives and recommending to the board of directors the compensation of our chief executive officer;



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reviewing and approving the compensation of our other executive officers;



•

reviewing and establishing our overall management compensation, philosophy, and policy;



•

overseeing and administering our compensation and similar plans;

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•

reviewing and making recommendations to the board of directors with regard to the grant of equity-based awards and the size of equity-based plans;



•

overseeing compensation of senior management;



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evaluating and assessing potential and current compensation advisors in accordance with the independence standards identified in the applicable Nasdaq rules;



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retaining and approving the compensation of any compensation advisors;



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reviewing and making recommendations to our board of directors about our policies and procedures for the grant of equity-based awards;



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evaluating and making recommendations to the board of directors about director compensation;



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preparing the compensation and management development committee report required by SEC rules, if and when required, to be included in our annual proxy statement;



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reviewing and reassessing the adequacy of the compensation and management development committee's charter;



•

performing periodic evaluations of the compensation and management development committee and report results to the board of directors;Board;



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reviewing and approving the retention or termination of any consulting firm or outside advisor to assist in the evaluation of compensation matters; and



•

reviewing and discussing with the board of directors corporate succession plans for our chief executive officer and our other key officers.

Nominating and Corporate Governance Committee

        Patrick G. Enright, Rachel Sherman, M.D., M.P.H, and James Topper, M.D., Ph.D. currently serve on the nominating and corporate governance committee, which is chaired by James Topper, M.D., Ph.D. Dr. Topper is not standing for reelection to the board of directors at the Annual Meeting, and his term will end following the Annual Meeting. Rachel Sherman, M.D., M.P.H., and Adam M. Koppel, M.D., Ph.D., have been appointed to serve on the nominating and corporate governance committee effective as of the Annual Meeting, and Dr. Sherman has been appointed to serve as the chair of the nominating and corporate governance committee effective as of the Annual Meeting. Our board of directors has determined that each member of the nominating and corporate governance committee is "independent" as defined in the applicable Nasdaq rules. During the fiscal year ended December 31, 2018,2019, the nominating and corporate governance committee did not hold anyheld two meetings. The nominating and corporate governance committee's responsibilities include:

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developing and recommending to the board of directors criteria for board and committee membership;



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establishing procedures for recommending, identifying and evaluating board of director candidates, including nominees recommended by stockholders;



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reviewing the size and composition ofrecommending to the board of directors, to ensure that it is composed of members containing the appropriate skills and expertise to advise us;annually reassessing, criteria for board and committee membership;



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reviewing and identifying and considering individuals qualifiedproposed to become members of the board of directors or the board's committees based on the criteria approved by the board of directors and all facts and circumstances that it deems appropriate, including, among other things, the skills of the proposed candidate, relevant business experience, and independence determination;