UNITED STATES

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

(Title of Class of Securities)

02083G 100

(CUSIP Number)

Steve R. Bailey

Frazier Healthcare Partners

601 Union Street, Suite 3200

Seattle, WA 98101

Telephone: (206) 621-7200

(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 §§240.13d-1(e), 240.13d-1(f) or 240.13d-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 §240.13d-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).

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This statement relates to the Common Stock of Alpine Immune Sciences, Inc. (the “Issuer”), having its principal executive office at 201 Elliott Avenue West, Suite 230, Seattle, WA 98119.

c/o Frazier Healthcare Partners

601 Union Street, Suite 3200

Seattle, WA 98101

FLS-VIII had purchased from a company then known as Alpine Immune Sciences, Inc. (“Old Alpine”) in a series of private transactions 3,558,719 shares of Series A-1 Preferred Stock (“Series A-1 Stock”) and 866,741 shares of Common Stock (the “Old Alpine Common Stock”) for an aggregate purchase price of $15,483,870.

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Pursuant to the terms of that certain Agreement and Plan of Merger and Reorganization, dated as of April 18, 2017, by and among the Issuer, Nautilus Merger Sub, Inc. and Old Alpine (the “Merger Agreement”), at the closing of the merger provided for in the Merger Agreement (the “Merger”), each share of Old Alpine’s Common Stock and Series A-1 Stock held by FLS-VIII was automatically converted into 0.4969 shares of the Issuer’s Common Stock, which resulted in FLS-VIII holding a total of 2,199,011 shares of the Issuer’s Common Stock as of July 24, 2017. FLS-VIII holds 2,199,011 shares of the Issuer’s Common Stock as of the date of this filing (the “Frazier Shares”).

The working capital of FLS-VIII was the source of the funds for the purchase of the Frazier Shares. No part of the purchase price of the Frazier Shares were represented by funds or other consideration borrowed or otherwise obtained for the purpose of acquiring, holding, trading or voting the Frazier Shares.

FLS-VIII acquired the Frazier Shares for investment purposes. Depending on market conditions, its continuing evaluation of the business and prospects of the Issuer and other factors, FLS-VIII and other Reporting Persons may dispose of or acquire additional shares of the Issuer. Except as set forth above, none of the Reporting Persons has any present plans which relate to or would result in:

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The percentage of outstanding Common Stock of the Issuer, which may be deemed to be beneficially owned by each Reporting Person, is set forth on Line 13 of such Reporting Person’s cover sheet. Such percentage was calculated based on the 13,881,645 shares of Common Stock outstanding as of July 24, 2017 as set forth in the Issuer’s Form 8-K filed on July 24, 2017.

Lockup Agreements

FLS-VIII, along with all of the Issuer’s directors (including Topper), executive officers and certain of the Issuer’s stockholders have entered into agreements (the “Lockup Agreements”) pursuant to which such parties have agreed not to, except in limited circumstances, sell or transfer, or engage in swap or similar transactions with respect to, shares of the Issuer’s Common Stock, including, as applicable, shares received in the merger and issuable upon exercise of certain warrants and options, from the closing of the merger until 180 days from the closing date of the Merger.

The foregoing description of the Lockup Agreements is only a summary and is qualified in its entirety by the form of Lockup Agreement, filed herewith as Exhibit C, which is incorporated by reference herein.

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

Exhibit A - Agreement regarding filing of joint Schedule 13D.

Exhibit B - Power of Attorney regarding filings under the Securities Exchange Act of 1934, as amended.

Exhibit C - Form of Lock-up Agreement.

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SIGNATURES

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.

This Schedule 13D was executed by Steve R. Bailey on behalf of the individuals listed above pursuant to a Power of Attorney a copy of which is attached as Exhibit B.

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Exhibit Index

Exhibit A - Agreement regarding filing of joint Schedule 13D.

Exhibit B - Power of Attorney regarding filings under the Securities Exchange Act of 1934, as amended.

Exhibit C - Form of Lock-up Agreement.

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EXHIBIT A

AGREEMENT

Pursuant to Rule 13d-1(k)(1) under the Securities Exchange Act of 1934, the undersigned hereby agree that only one statement containing the information required by Schedule 13D need to be filed with respect to the ownership by each of the undersigned of shares of Common Stock of Alpine Immune Sciences, Inc.

This Schedule 13D was executed by Steve R. Bailey on behalf of the individuals listed above pursuant to a Power of Attorney a copy of which is attached as Exhibit B.

EXHIBIT B

POWER OF ATTORNEY

KNOW ALL BY THESE PRESENTS, that each person whose signature appears below hereby constitutes and appoints Steve R. Bailey with full power to act singly, his true and lawful attorney-in-fact, with full power of substitution, to: (i) sign any and all instruments, certificates and documents that may be necessary, desirable or appropriate to be executed on behalf of himself as an individual or in his capacity as a general partner of any partnership or limited liability company, pursuant to Section 13 or 16 of the Securities Exchange Act of 1934, as amended, and any and all regulations promulgated thereunder, (ii) file the same (including any amendments thereto), with all exhibits thereto, and any other documents in connection therewith, with the Securities and Exchange Commission, and any stock exchange or similar authority and (iii) take any other action of any type whatsoever in connection with the foregoing which, in the opinion of such attorney-in-fact, may be of benefit to, in the best interest of, or legally required by, the undersigned, it being understood that the documents executed by such attorney-in-fact on behalf of the undersigned pursuant to this power of attorney shall be in such form and shall contain such terms and conditions as such attorney-in-fact may approve in such attorney-in-fact’s discretion, granting unto said attorney-in-fact full power and authority to do and perform each and every act and thing necessary, desirable or appropriate.

Each of the undersigned hereby grant to the attorney-in-fact full power and authority to do and perform any and every act and thing whatsoever requisite, necessary or proper to be done in the exercise of any of the rights and powers herein granted, as fully to all intents and purposes as the undersigned might or could do if personally present with full power of substitution or revocation, hereby ratifying and confirming all that such attorney-in-fact or such attorney-in-fact’s substitute or substitutes, shall lawfully do or cause to be done by virtue of this power of attorney and the rights and powers herein granted.

This power of attorney shall remain in full force and effect until revoked by the undersigned in a signed writing delivered to the attorney-in-fact.

IN WITNESS WHEREOF, this Power of Attorney has been signed as of the 28th day of July, 2017.

EXHIBIT C

FORM OF LOCK-UP AGREEMENT

FORM OF LOCK-UP AGREEMENT

July 24, 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:

(a)    transfers of the Undersigned’s Shares:

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)

[Signature Page to Lock-up Agreement]