SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 13D

Under the Securities Exchange Act of 1934

(Amendment No.       )

APTINYX INC.

(Name of Issuer)

Common Stock, $0.01 par value per share

(Title of Class of Securities)

03836N103

(CUSIP Number)

Patrick G. Enright

Managing Member

Longitude Capital Partners II, LLC

2740 Sand Hill Road, 2^nd Floor

Menlo Park, CA 94025

(650) 854-5700

(Name, Address and Telephone Number of Person

Authorized to Receive Notices and Communications)

June 25, 2018

(Date of Event Which Requires Filing of this Statement)

If the filing person has previously filed a statement on Schedule 13G to report the acquisition that is the subject of this Schedule 13D, and is filing this schedule because of §§ 240.13d-1(e), 240.13d-1(f) or 240.13d-1(g), check the following box ¨

The information required on the remainder of this cover page shall not be deemed to be “filed” for the purpose of Section 18 of the Securities Exchange Act of 1934 (“Act”) or otherwise subject to the liabilities of that section of the Act but shall be subject to all other provisions of the Act (however, see the Notes).

(Continued on following pages)

(Page 1 of 9 Pages)

This Schedule 13D (this “Statement”) is filed with respect to the common stock, par value $0.01 per share (“Common Stock”), of Aptinyx Inc., a Delaware corporation (the “Issuer”). The address of the principal executive offices of the Issuer is 909 Davis Street, Suite 600, Evanston, Illinois 60201.

(a)       This Statement is being filed on behalf of entities Longitude Venture Partners II, L.P. (“Longitude Venture II”) and Longitude Venture II’s sole general partner Longitude Capital Partners II, LLC (“Longitude Capital II”, and together with Longitude Venture II, a “Reporting Entity”), and individuals Patrick G. Enright and Juliet Tammenoms Bakker (each a “Reporting Individual,” and each Reporting Entity or Reporting Individual, a “Reporting Person”). The agreement among the Reporting Persons to file jointly in accordance with the provisions of Rule 13d-1(k)(1) under the Act is attached hereto as Exhibit 1. Each Reporting Person disclaims beneficial ownership of all securities reported in this Statement except to the extent of such Reporting Person’s pecuniary interest therein, other than those securities reported herein as being held directly by such Reporting Person.

(b)       The address of the principal offices of each Reporting Entity and the business address of each Reporting Individual is 2740 Sand Hill Road, 2^nd Floor, Menlo Park, California 94025.

(c)       Each Reporting Entity is a venture capital investment entity. Each Reporting Individual is engaged through venture capital investment entities in acquiring, holding and disposing of interests in various companies for investment purposes. The Reporting Individuals are the managing members of Longitude Capital II and together constitute all officers and directors of Longitude Capital II, the general partner of Longitude Venture II. In addition, Mr. Enright has served as a member of the board of directors of the Issuer (the “Board”) since May 2016 and as a member of the audit and nominating and corporate governance committees of the Board since the effectiveness of the Issuer’s Registration Statement on Form S-1, as amended, declared effective by the Securities and Exchange Commission (the “Commission”) on June 20, 2018 (together with the prospectus dated June 20, 2018 forming a part thereof, the “Registration Statement”).

(d)       During the past five years, none of the Reporting Persons have been convicted in a criminal proceeding (excluding traffic violations or similar misdemeanors).

(e)       None of the Reporting Persons are, nor during the last five years have been, a party to a civil proceeding of a judicial or administrative body of competent jurisdiction and as a result of such proceeding was or is subject to a judgment, decree or final order enjoining future violations of, or prohibiting or mandating activities subject to, federal or state securities laws or finding any violation with respect to such laws.

(f)       Longitude Capital II is a limited liability company organized under the laws of the State of Delaware. Longitude Venture II is a limited partnership organized under the laws of the State of Delaware. Each of the Reporting Individuals is a citizen of the United States of America.

On May 4, 2016, Longitude Venture II entered into a stock purchase agreement with the Issuer and certain other parties thereto, pursuant to which Longitude Venture II purchased from the Issuer, (i) on May 4, 2016, 28,895,188 shares of the Issuer’s Series A-1 convertible preferred stock for an aggregate purchase price of $4,759,615, or $0.16472 per share, and (ii) on February 2, 2017, 33,022,786 shares of the Issuer’s Series A-2 convertible preferred stock for an aggregate purchase price of $7,615,385, or $0.23061 per share.

On December 11, 2017, Longitude Venture II entered into a stock purchase agreement with the Issuer and certain other parties thereto, pursuant to which Longitude Venture II purchased from the Issuer, (i) on December 15, 2017, 21,946,301 shares of the Issuer’s Series B convertible preferred stock for an aggregate purchase price of $6,538,462, or $0.29793 per share.

Upon the closing of the Issuer’s initial public offering of its Common Stock (the “IPO”), which occurred on June 25, 2018, all then-outstanding shares of the Issuer’s Series A-1, Series A-2 and Series B convertible preferred stock converted into shares of Common Stock at a ratio of 27.58621-for-one. As a result, all shares of each such series of the Issuer’s convertible preferred stock held by Longitude Venture II converted into 1,047,450, 1,197,076 and 795,553 shares of Common Stock, respectively, upon the closing of the IPO.

Longitude Venture II purchased 150,000 shares of Common Stock from the Issuer in the IPO for an aggregate purchase price of $2,400,000, or $16.00 per share.

All shares of the capital stock of the Issuer purchased by the Reporting Entities have been purchased using investment funds provided to Longitude Venture II by its limited partner investors.

The information set forth in Item 3 of this Statement is incorporated herein by reference.

The Reporting Persons hold the securities of the Issuer for general investment purposes. The Reporting Persons may, from time to time, depending on prevailing market, economic and other conditions, acquire additional shares of Common Stock or other securities of the Issuer, dispose of any such securities, or engage in discussions with the Issuer concerning such acquisitions or dispositions or further investments in the Issuer. The Reporting Persons intend to review their investment in the Issuer on a continuing basis and, depending upon the price and availability of shares of Common Stock or other securities of the Issuer, subsequent developments affecting the Issuer, the Issuer’s business and prospects, other investment and business opportunities available to the Reporting Persons, general stock market and economic conditions, tax considerations and other factors considered relevant, may decide at any time to increase or to decrease the size of their investment in the Issuer.

(a)       According to the Registration Statement, as of June 25, 2018, after giving effect to the issuance of 7,359,998 shares of Common Stock in the IPO and the conversion of all outstanding shares of all series of the Issuer’s convertible preferred stock upon the closing of the IPO, there were 33,496,224 outstanding shares of Common Stock.

Longitude Venture II is the record holder of an aggregate of 3,190,079 shares of Common Stock, which represents beneficial ownership of approximately 9.5% of the Common Stock.

Longitude Capital II, as the general partner of Longitude Venture II, has the power to vote and dispose of securities held by Longitude Venture II and may be deemed to beneficially own the securities held of record by Longitude Venture II.

The Reporting Individuals are the managing members of Longitude Capital II. The Reporting Individuals share the decision-making power of Longitude Capital II with respect to the voting and disposition of the securities of the Issuer beneficially owned by Longitude Capital II. As a result, each of the Reporting Individuals may be deemed to beneficially own the securities of the Issuer held by Longitude Venture II.

(b)       Each of the Reporting Persons has shared power to vote and dispose of an aggregate of 3,190,079 shares of Common Stock.

(c)       Except as reported in this Statement, none of the Reporting Persons has effected any transactions in the Issuer’s securities within the past 60 days.

(d)       Not applicable.

(e)       Not applicable.

The information set forth in Items 3 and 4 of this Statement is incorporated herein by reference.

In connection with its purchase of the various series of the Issuer’s convertible preferred stock, Longitude Venture II and the other purchasers of such convertible preferred stock entered into an Amended and Restated Investors’ Rights Agreement, dated December 11, 2017, with the Issuer (the “Rights Agreement”), pursuant to which such parties have the right, following the completion of the IPO and under certain circumstances as set forth therein, to demand that the Issuer file a registration statement with the Commission and to request that their shares of Common Stock be covered by a registration statement that the Issuer is otherwise filing. The terms and provisions of the Rights Agreement are described more fully in the Registration Statement, and the above summary is qualified by reference to such description and the full text of such agreement, which is filed or incorporated by reference as an exhibit to this Statement.

In connection with the IPO, Longitude Venture II has delivered a lock-up agreement in favor of J.P. Morgan Securities LLC, Cowen and Company, LLC, Leerink Partners LLC and BMO Capital Markets Corp., as representatives of the underwriters of the IPO, pursuant to which such party is prohibited from offering, selling or otherwise transferring or disposing of any shares of Common Stock or any securities convertible into or exercisable or exchangeable for Common Stock beneficially owned by it for a period of 180 days after June 20, 2018 without the prior written consent of certain of such representatives of the underwriters, subject to certain limited exceptions. The terms and provisions of such lock-up agreement are described more fully in the Registration Statement, and the above summary is qualified by reference to such description and the full text of such agreement, which is filed or incorporated by reference as an exhibit to this Statement.

As disclosed in the Registration Statement, the Issuer has not historically compensated its directors for their services as such (other than reimbursement for reasonable travel and out-of-pocket expenses incurred in connection with attending meetings of the Board and applicable committees thereof), but the Board has approved a compensation policy for its non-employee directors, including Mr. Enright, that became effective upon the effectiveness of the Registration Statement. Such compensation policy generally provides for (i) cash compensation, including an annual retainer for service as a member of the Board and supplemental annual retainers for membership and chair positions on certain of the Board’s committees, all of which may, at each director’s election, be provided in cash or in the form of one or more equity awards, and (ii) equity compensation, including stock options and/or restricted stock units, as determined by the Board or a committee thereof, with a specified grant date fair value to be granted upon initial appointment as a director and on an annual basis on each date of the Issuer’s annual meeting of stockholders. In addition, in connection with his service on the Board, Mr. Enright has entered into an indemnification agreement with the Issuer, pursuant to which, among other things, the Issuer is required to indemnify Mr. Enright for certain expenses (including attorneys’ fees), judgments, fines and settlement amounts reasonably incurred by him in any action or proceeding, including any action by or in our right, on account of any services undertaken by him on behalf of the Issuer or his status as a member of the Board, to the maximum extent allowed under Delaware law. The terms and provisions of such director compensation policy and indemnification agreement are described more fully in the Registration Statement, and the above summaries are qualified by reference to such descriptions and the full text of such document or agreement, as applicable, which are filed or incorporated by reference as exhibits to this Statement.

SIGNATURE

After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct.

Dated: July 2, 2018