SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 13D

Under the Securities Exchange Act of 1934

(Amendment No.    )*

Alpine Immune Sciences, Inc.

(Name of Issuer)

Common Stock, $0.001 par value per share

(Title of Class of Securities)

02083G100

(CUSIP Number)

Dr. Mitchell H. Gold

600 Stewart Street, Suite 1503

Seattle, Washington 98101

Telephone: (206) 441-5064

(Name, Address and Telephone Number of Person Authorized to Receive Notices and Communications)

July 24, 2017

(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 Rule 13d-1(e), Rule 13d-1(f) or Rule 13d-1(g), check the following box.    ☐

Note: Schedules filed in paper format shall include a signed original and five copies of the schedule, including all exhibits. See Rule 13d-7 for other parties to whom copies are to be sent.

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).

This statement relates to the common stock, $0.001 par value per share (the “Shares”), of Alpine Immune Sciences, Inc., a Delaware corporation (the “Issuer” or the “Company”), whose principal executive offices are located at 201 Elliott Avenue West, Suite 230, Seattle, Washington 98119.

This Schedule 13D relates to Shares held by Alpine Immunosciences, which is principally engaged in the business of making investments. Alpine BioVentures is the general partner of Alpine Immunosciences. Dr. Gold and Dr. Venkatesan are the Managing Partners of Alpine BioVentures and limited partners of Alpine Immunosciences.

The business address of each of the Alpine Immunosciences and Alpine BioVentures is 600 Stewart Street, Suite 1503, Seattle, Washington 98101.

The business address of each of Dr. Gold and Dr. Venkatesan is 201 Elliott Avenue West, Suite 230, Seattle, Washington 98119.

Alpine Immunosciences is a Delaware limited partnership; Alpine BioVentures is a Delaware limited liability company. Each of Dr. Gold and Venkatesan are citizens of the United States of America.

Prior to the Merger (defined and described in Item 4), Alpine Immunosciences held shares of common stock of Old Alpine (defined in Item 4), which had been acquired over several years through various means. In addition, prior to the Merger, on April 18, 2017, Alpine Immunosciences, together with other Old Alpine stockholders, entered into a Subscription Agreement with Old Alpine (the “Subscription Agreement”), pursuant to which Alpine Immunosciences agreed to purchase 520,045 shares of Old Alpine common stock at a price of $6.327 per Old Alpine share immediately prior to the consummation of the Merger, for a total of approximately $3,290,324.72 (the “Financing”). The closing of the Merger was conditioned upon the closing of the Financing. As a result of the foregoing, immediately prior to consummation of the Merger, Alpine Immunosciences beneficially owned 7,655,276 shares of Old Alpine common stock. The description contained herein of the Subscription Agreement does not purport to be complete and is qualified in its entirety by reference to the form of the document, which is attached as Exhibit B to this Schedule 13D and is incorporated by reference herein.

As a result of the Merger, based on the exchange rate of 0.4969 Shares for each share of Old Alpine common stock (the “Exchange Ratio”), Alpine Immunosciences received an aggregate of 3,803,906 Shares in exchange for its shares of Old Alpine common stock.

All fractional Shares were paid in cash.

The source of funds for the foregoing purchases came from the working capital of Alpine Immunosciences.

In addition, prior to the Merger, each of Dr. Gold and Dr. Venkatesan held shares of common stock of Old Alpine, which had been acquired over several years through various means, and options to acquire shares of common stock of Old Alpine, which had been granted under the Alpine Plan (defined in Item 4). Prior to the Merger, Dr. Gold beneficially owned 196,875 shares of Old Alpine common stock, including options to acquire 1,128,564 shares of Old Alpine common stock, and Dr. Venkatesan beneficially owned 118,750 shares of Old Alpine common stock, including options to acquire 181,250 shares of Old Alpine common stock.

Immediately after the Merger, after giving effect to the Exchange Ratio: (i) Dr. Gold’s options to purchase 605,000 shares of Old Alpine’s common stock granted in March 2017 (“March 2017 Options”) converted into options to purchase 300,624 Shares; (ii) of Dr. Gold’s options to purchase 300,000 shares of Old

Alpine’s common stock granted in December 2015 (“December 2015 Options”), the 196,875 December 2015 options which were exercised prior to the Merger were converted into an aggregate of 97,827 Shares, and the 103,125 December 2015 Options which were outstanding immediately prior to the Merger were converted into options to purchase 51,242 Shares; and (iii) Dr. Gold’s options to purchase 420,439 shares of Old Alpine’s common stock granted in April 2017 (“April 2017 Options”) converted into options to purchase 208,916 Shares. Each of the March 2017 Options, December 2015 Options and April 2017 Options are subject generally to Dr. Gold’s continued employment as the Company’s Executive Chairman and Chief Executive Officer and certain change of control provisions.

Also immediately after the Merger, after giving effect to the Exchange Ratio, of Dr. Venkatesan’s options to purchase 300,000 shares of Old Alpine’s common stock granted in December 2015: (i) the 118,750 of which options were exercised prior to the Merger were converted into an aggregate of 59,005 Shares; and (ii) the 181,250 of which options were outstanding immediately prior to the Merger were converted into options to purchase 90,063 Shares. Such options are subject generally to Dr. Venkatesan’s continued employment as the Company’s President and certain change of control provisions.

The source of funds for the purchases by Dr. Gold came from the personal funds of Dr. Gold, and the source of funds for the purchases by Dr. Venkatesan came from the personal funds of Dr. Venkatesan.

On July 24, 2017, the Company (which was formerly known as Nivalis Therapeutics, Inc.) completed a business combination with what was then known as Alpine Immune Sciences, Inc. and currently known as AIS Operating Co., Inc. (“Old Alpine”) in accordance with the terms of the Agreement and Plan of Merger and Reorganization, dated as of April 18, 2017, by and among the Company, Nautilus Merger Sub, Inc. (“Merger Sub”), and Old Alpine (the “Merger Agreement”), pursuant to which Merger Sub merged with and into Old Alpine, with Old Alpine surviving as a wholly owned subsidiary of the Company (the “Merger”).

On July 24, 2017, in connection with, and prior to the completion of, the Merger, the Company effected a 1-for-4 reverse stock split (the “Reverse Stock Split”). Also on July 24, 2017, immediately after completion of the Merger, the Company changed its name to “Alpine Immune Sciences, Inc.”

Under the terms of the Merger Agreement, the Company issued Shares to Old Alpine’s stockholders, including Alpine Immunosciences, Dr. Gold and Dr. Venkatesan, at the Exchange Ratio and after taking into account the Reverse Stock Split, for each share of Old Alpine common stock outstanding immediately prior to the Merger. The Company also assumed all of the stock options outstanding under the Old Alpine Amended and Restated 2015 Stock Plan, as amended (the “Old Alpine Plan”), including those held by Dr. Gold and Dr. Venkatesan, with such stock options henceforth representing the right to purchase a number of Shares equal to the Exchange Ratio multiplied by the number of shares of Old Alpine common stock previously represented by such options. The Company also assumed the Old Alpine Plan.

On July 24, 2017, effective as of the effective time of the Merger: (i) each of Dr. Gold and Dr. Venkatesan were appointed to the Company’s board of directors (the “Board”) with a term that expires at the Company’s 2020 annual meeting of stockholders; (ii) the Board appointed Dr. Gold as the Executive Chairman of the Board and the Company’s Chief Executive Officer and Assistant Secretary; and (iii) the Board appointed Dr. Venkatesan as the Company’s President. Dr. Gold served as Old Alpine’s acting Chief Executive Officer since June 2016 and has served as Executive Chairman and as a member of Old Alpine’s board of directors since January 2015. Dr. Venkatesan served as Old Alpine’s Chief Executive Officer from November 2015 to June 2016 before transitioning to Old Alpine’s President in June 2016. Dr. Venkatesan has served as a member of Old Alpine’s board of directors since November 2015.

The Reporting Persons acquired the Shares for investment purposes, and such purchases have been made in the Reporting Persons’ ordinary course of business. The Reporting Persons expect to review from time to time their investment in the Company and may, depending on the market and other conditions: (i) purchase additional Shares, options or related derivatives in the open market, in privately negotiated transactions or otherwise and (ii) sell all or a portion of the Shares, options or related derivatives now beneficially owned or hereafter acquired by them.

Also, consistent with their investment intent, the Reporting Persons may engage in communications with, without limitation, one or more shareholders of the Company, one or more officers of the Company and/or one or more members of the Board regarding the Company, including but not limited to its operations, governance and control.

Except as set forth above, none of the Reporting Persons has any plans or proposals which relate to, or could result in, any of the matters referred to in paragraphs (a) through (j), inclusive, of the instructions to Item 4 of Schedule 13D. The Reporting Persons may, at any time and from time to time, review or reconsider their position and/or change their purpose and/or formulate plans or proposals with respect thereto.

As of the date hereof, Alpine BioVentures may be deemed to indirectly beneficially own the 3,803,906 Shares directly beneficially owned by Alpine Immunosciences, representing approximately 27.4% of the outstanding Shares.

As of the date hereof, Dr. Gold, may be deemed to beneficially own 4,462,515 Shares, representing approximately 30.9% of the outstanding Shares. These Shares are held as follows:

As of the date hereof, Dr. Venkatesan, may be deemed to beneficially own 3,952,974 Shares, representing approximately 28.3% of the outstanding Shares. These Shares are held as follows:

The foregoing beneficial ownership percentage is based on 13,881,645 Shares outstanding immediately after the Merger, as reported in the Issuer’s current report on Form 8-K, filed with the SEC on July 25, 2017.

The response to Items 3 and 4 of this Schedule 13D are incorporated by reference herein.

Each of Alpine Immunosciences, Dr. Gold and Dr. Venkatesan entered into a lock-up agreement, pursuant to which each agreed, except in limited circumstances, not to sell or transfer, or engage in swap or similar transactions with respect to, the Shares, including, as applicable, Shares received in the Merger and issuable upon exercise of certain warrants and options, for a period of 180 days following the completion of the Merger (the “Lock-Up Agreements”).

In addition, each of Dr. Gold and Dr. Venkatesan entered into an indemnification agreement with the Company on July 24, 2017 immediately following the Merger (the “Indemnification Agreements”).

The descriptions contained herein of the Lock-Up Agreements and the Indemnification Agreements do not purport to be complete and are qualified in their entirety by reference to the form of such documents, which are attached as Exhibits C and D, respectively, to this Schedule 13D and are incorporated by reference herein.

Except as described in this Schedule 13D, there are no contracts, arrangements, understandings or relationships (legal or otherwise) among the persons named in Item 2 of this Statement or between such persons and any other person with respect to any securities of the Issuer.

SIGNATURES

After reasonable inquiry and to the best of his or its knowledge and belief, each of the undersigned certifies that the information set forth in this statement is true, complete and correct.

Date: August 3, 2017

EXHIBIT A

JOINT FILING AGREEMENT

The undersigned hereby agree that the statement on Schedule 13D with respect to the common stock, $0.001 par value per share of Alpine Immune Sciences, Inc. dated as of August 3, 2017 is, and any amendments thereto (including amendments on schedule 13G) signed by each of the undersigned shall be, filed on behalf of each of us pursuant to and in accordance with the provisions of Rule 13d-1(k) under the Securities Exchange Act of 1934, as amended.

Date: August 3, 2017

EXHIBIT C

FORM OF LOCK-UP AGREEMENT

                    , 2017

Nivalis Therapeutics, Inc.

PO Box 18387

Boulder, Colorado 80308

Ladies and Gentlemen:

The undersigned signatory of this lock-up agreement (this “Lock-Up Agreement”) understands that Nivalis Therapeutics, Inc., a Delaware corporation (“Nivalis”) has entered into an Agreement and Plan of Merger and Reorganization, dated as of April 18, 2017 (as the same may be amended from time to time, the “Merger Agreement”) with Nautilus Merger Sub, Inc., a Delaware corporation and a wholly owned subsidiary of Nivalis, and Alpine Immune Sciences, Inc., a Delaware corporation. Capitalized terms used but not otherwise defined herein shall have the respective meanings ascribed to such terms in the Merger Agreement.

As a material inducement to each of the Parties to enter into the Merger Agreement and to consummate the Contemplated Transactions, and for other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the undersigned hereby irrevocably agrees that, subject to the exceptions set forth herein, without the prior written consent of Nivalis, the undersigned will not, during the period commencing upon the Closing and ending on the date that is 180 days after the Closing Date (the “Restricted Period”) (the actions set forth in clauses (i) through (iii) below, the “Restricted Actions”):

The restrictions and obligations contemplated by this Lock-Up Agreement shall not apply to:

provided that, in the case of any transfer or distribution pursuant to this clause (a), such transfer is not for value and each donee, heir, beneficiary or other transferee or distributee shall sign and deliver to Nivalis a lock-up agreement in the form of this Lock-Up Agreement with respect to the shares of Nautilus Common Stock or such other securities that have been so transferred or distributed;

(b) the exercise of an option (including a net or cashless exercise of an option) to purchase shares of Nautilus Common Stock, and any related transfer of shares of Nautilus Common Stock to Nivalis for the purpose of paying the exercise price of such options or for paying taxes (including estimated taxes) due as a result of the exercise of such options (or the disposition to Nivalis of any shares of restricted stock granted pursuant to the terms of any employee benefit plan or restricted stock purchase agreement); provided that, for the avoidance of doubt, the underlying shares of Nautilus Common Stock shall continue to be subject to the restrictions on transfer set forth in this Lock-Up Agreement;

(c) the establishment of a trading plan pursuant to Rule 10b5-1 under the Exchange Act for the transfer of Nautilus Common Stock; provided that such plan does not provide for any transfers of Nautilus Common Stock during the Restricted Period; or

(d) transfers by the undersigned of shares of Nautilus Common Stock purchased by the undersigned on the open market following the Closing Date;

and provided, further, that, with respect to each of (a), (b) and (c) above, no filing by any party (including any donor, donee, transferor, transferee, distributor or distributee) under the Exchange Act or other public announcement shall be required or shall be made voluntarily in connection with such transfer or disposition during the Restricted Period (other than (i) any exit filings or public announcements that may be required under applicable federal and state securities laws or (ii) in respect of a required filing under the Exchange Act in connection with the exercise of an option to purchase Nivalis Common Stock following such individual’s termination of employment with Nivalis that would otherwise expire during the Restricted Period, provided that reasonable notice shall be provided to Nivalis prior to any such filing).

Any attempted transfer in violation of this Lock-Up Agreement will be of no effect and null and void, regardless of whether the purported transferee has any actual or constructive knowledge of the transfer restrictions set forth in this Lock-Up Agreement, and will not be recorded on the share register of Nivalis. In furtherance of the foregoing, the undersigned agrees that Nivalis and any duly appointed transfer agent for the registration or transfer of the securities described herein are hereby authorized to decline to make any transfer of securities if such transfer would constitute a violation or breach of this Lock-Up Agreement. Nivalis may cause the legend set forth below, or a legend substantially equivalent thereto, to be placed upon any certificate(s) or other documents, ledgers or instruments evidencing the undersigned’s ownership of Nautilus Common Stock:

THE SHARES REPRESENTED BY THIS CERTIFICATE ARE SUBJECT TO AND MAY ONLY BE TRANSFERRED IN COMPLIANCE WITH A LOCK-UP AGREEMENT, A COPY OF WHICH IS ON FILE AT THE PRINCIPAL OFFICE OF THE COMPANY.

The undersigned hereby represents and warrants that the undersigned has full power and authority to enter into this Lock-Up Agreement. All authority herein conferred or agreed to be conferred and any obligations of the undersigned shall be binding upon the successors, assigns, heirs or personal representatives of the undersigned.

In the event that any holder of Nautilus Common Stock or securities convertible into or exercisable or exchangeable for Nautilus Common Stock that is subject to a substantially similar letter agreement entered into by such holder, other than Nivalis or the undersigned, is permitted by Nivalis to sell or otherwise transfer or dispose of shares of Nautilus Common Stock or securities convertible into or exercisable or exchangeable for Nautilus Common Stock for value other than as permitted by this Lock-Up Agreement or a substantially similar letter agreement entered into by such holder, the same percentage of shares of Nautilus Common Stock or securities convertible into or exercisable or exchangeable for Nautilus Common Stock held by the undersigned (the “Pro-rata Release”) shall be immediately and fully released on the same terms from any remaining restrictions set forth herein.

The undersigned understands that if the Merger Agreement is terminated for any reason, or if the Merger is not consummated by April 18, 2018, the undersigned shall be released from all obligations under this Lock-Up Agreement. The undersigned understands that Nivalis is proceeding with the Contemplated Transactions in reliance upon this Lock-Up Agreement.

Any and all remedies herein expressly conferred upon Nivalis will be deemed cumulative with and not exclusive of any other remedy conferred hereby, or by law or equity, and the exercise by Nivalis of any one remedy will not preclude the exercise of any other remedy. The undersigned agrees that irreparable damage would occur to Nivalis in the event that any provision of this Lock-Up Agreement were not performed in accordance with its specific terms or were otherwise breached. It is accordingly agreed that Nivalis shall be entitled to an injunction or injunctions to prevent breaches of this Lock-Up Agreement and to enforce specifically the terms and provisions hereof in any court of the United States or any state having jurisdiction, this being in addition to any other remedy to which Nivalis is entitled at law or in equity, and the undersigned waives any bond, surety or other security that might be required of Nivalis with respect thereto.

This Lock-Up Agreement and any claim, controversy or dispute arising under or related to this Lock-Up Agreement shall be governed by and construed in accordance with the laws of the State of Delaware, without regard to the conflict of laws principles thereof.

This Lock-Up Agreement may be executed in several counterparts, each of which shall be deemed an original and all of which shall constitute one and the same instrument. The exchange of a fully executed Lock-Up Agreement (in counterparts or otherwise) by Nivalis and the undersigned by facsimile or electronic transmission in .pdf format shall be sufficient to bind such parties to the terms and conditions of this Lock-Up Agreement.

(Signature Page Follows)