SC 13D

UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington, D.C. 20549

SCHEDULE 13DUnder the Securities Exchange Act of 1934

Alpine Immune Sciences, Inc.

(Name of Issuer)

Common Stock, par value $0.001 per share

(Title of Class of Securities)

02083G100

(CUSIP Number)

OrbiMed Advisors LLCOrbiMed Capital GP VI LLCSamuel D. Isaly

601 Lexington Avenue, 54th FloorNew York, NY 10022Telephone:  (212) 739‑6400

(Name, Address and Telephone Number of PersonAuthorized 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(b) for other parties to whom copies are to be sent.

*The remainder of this cover page shall be filled out for a reporting person’s initial filing on this form with respect to the subject class of securities, and for any subsequent amendment containing information which would alter disclosures provided in a prior cover page.

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).

SCHEDULE 13D

CUSIP No.  02083G100				Page 2 of 11 Pages
1	NAME OF REPORTING PERSONS OrbiMed Advisors LLC
2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (See Instructions) (a) ☐ (b) ☐
3	SEC USE ONLY
4	SOURCE OF FUNDS (See Instructions) AF
5	CHECK BOX IF DISCLOSURE OF LEGAL PROCEEDINGS IS REQUIRED PURSUANT TO ITEMS 2(d) or 2(e)				☐
6	CITIZENSHIP OR PLACE OF ORGANIZATION Delaware
NUMBER OFSHARESBENEFICIALLYOWNED BYEACHREPORTINGPERSONWITH		7	SOLE VOTING POWER 0
		8	SHARED VOTING POWER 3,298,516
		9	SOLE DISPOSITIVE POWER 0
		10	SHARED DISPOSITIVE POWER 3,298,516
11	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON 3,298,516
12	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (11) EXCLUDES CERTAIN SHARES (See Instructions)				☐
13	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (11) 23.76% *
14	TYPE OF REPORTING PERSON (See Instructions) IA

_______________________

* This percentage is calculated based upon 13,881,645 shares of common stock outstanding of Alpine Immune Sciences, Inc. (the “Issuer”), as set forth in the Issuer’s Current Report on Form 8-K filed with the Securities and Exchange Commission on July 25, 2017.

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SCHEDULE 13D

CUSIP No.  02083G100				Page 3 of 11 Pages
1	NAME OF REPORTING PERSONS OrbiMed Capital GP VI LLC
2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (See Instructions) (a) ☐ (b) ☐
3	SEC USE ONLY
4	SOURCE OF FUNDS (See Instructions) AF
5	CHECK BOX IF DISCLOSURE OF LEGAL PROCEEDINGS IS REQUIRED PURSUANT TO ITEMS 2(d) or 2(e)				☐
6	CITIZENSHIP OR PLACE OF ORGANIZATION Delaware
NUMBER OFSHARESBENEFICIALLYOWNED BYEACHREPORTINGPERSONWITH		7	SOLE VOTING POWER 0
		8	SHARED VOTING POWER 3,298,516
		9	SOLE DISPOSITIVE POWER 0
		10	SHARED DISPOSITIVE POWER 3,298,516
11	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON 3,298,516
12	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (11) EXCLUDES CERTAIN SHARES (See Instructions)				☐
13	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (11) 23.76%*
14	TYPE OF REPORTING PERSON (See Instructions) OO

_______________________

  * This percentage is calculated based upon 13,881,645 shares of common stock outstanding of Alpine Immune Sciences, Inc. (the “Issuer”), as set forth in the Issuer’s Current Report on Form 8-K filed with the Securities and Exchange Commission on July 25, 2017.

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SCHEDULE 13D

CUSIP No.  02083G100				Page 4 of 11 Pages
1	NAME OF REPORTING PERSONS Samuel D. Isaly
2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (See Instructions) (a) ☐ (b) ☐
3	SEC USE ONLY
4	SOURCE OF FUNDS (See Instructions) AF
5	CHECK BOX IF DISCLOSURE OF LEGAL PROCEEDINGS IS REQUIRED PURSUANT TO ITEMS 2(d) or 2(e)				☐
6	CITIZENSHIP OR PLACE OF ORGANIZATION United States
NUMBER OFSHARESBENEFICIALLYOWNED BYEACHREPORTINGPERSONWITH		7	SOLE VOTING POWER 0
		8	SHARED VOTING POWER 3,298,516
		9	SOLE DISPOSITIVE POWER 0
		10	SHARED DISPOSITIVE POWER 3,298,516
11	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON 3,298,516
12	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (11) EXCLUDES CERTAIN SHARES (See Instructions)				☐
13	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (11) 23.76%*
14	TYPE OF REPORTING PERSON (See Instructions) IN

_______________________

* This percentage is calculated based upon 13,881,645 shares of common stock outstanding of Alpine Immune Sciences, Inc. (the “Issuer”), as set forth in the Issuer’s Current Report on Form 8-K filed with the Securities and Exchange Commission on July 25, 2017.

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Item 1. Security and Issuer

This Schedule 13D (the “Statement”) relates to the common stock, par value $0.001 per share (the “Shares”), of Alpine Immune Sciences, Inc., a Delaware corporation (the “Issuer”), with its principal offices located at 201 Elliott Avenue West, Suite 230, Seattle, WA 98119.  The Shares are listed on the NASDAQ Global Market under the ticker symbol “ALPN”.

Item 2. Identity and Background

(a)This Statement is being filed by OrbiMed Advisors LLC (“Advisors”), a limited liability company organized under the laws of Delaware, OrbiMed Capital GP VI LLC (“GP VI”), a limited liability company organized under the laws of Delaware, and Samuel D. Isaly (“Isaly”), an individual (collectively, the “Reporting Persons”).

(b) – (c)      Advisors, a registered investment adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP VI, which is the sole general partner of OrbiMed Private Investments VI, LP (“OPI VI”), which holds Shares,  as more particularly described in Item 3 below.  Advisors has its principal offices at 601 Lexington Avenue, 54th Floor, New York, New York 10022.

GP VI has its principal offices at 601 Lexington Avenue, 54th Floor, New York, New York 10022.

Isaly, a natural person, is the managing member of Advisors and owns a controlling interest in Advisors.

The directors and executive officers of Advisors and GP VI are set forth on Schedules I and II, attached hereto.  Schedules I and II set forth the following information with respect to each such person:

(i)              name;

(ii)             business address;

(iii)            present principal occupation or employment and the name, principal business and address of any corporation or other organization in which such employment is conducted; and

(iv)            citizenship.

(d) – (e)  During the last five years, neither the Reporting Persons nor any person named in Schedule I or II have been (i) convicted in a criminal proceeding (excluding traffic violations or similar misdemeanors) or (ii) 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)Isaly is a citizen of the United States.

Item 3. Source and Amount of Funds or Other Consideration

Prior to the Merger (as defined below), OPI VI had purchased from a company then known as Alpine Immune Sciences, Inc. (“Old Alpine”), in a series of private transactions, 5,338,078 shares of Series A-1 Preferred Stock (“Series A-1 Stock”) and 1,300,112 shares of common stock (the “Old Alpine Common Stock”) for an aggregate purchase price of $23,225,808.  On July 24, 2017, Nivalis Therapeutics, Inc. (“Nivalis”) completed its business combination with 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 Nivalis, Nautilus Merger Sub, Inc. (“Merger Sub”), and Old Alpine (the “Merger Agreement”), pursuant to which Merger Sub merged with and into Old Alpine, with the Issuer surviving as a wholly owned subsidiary of Nivalis (the “Merger”).  On July 24, 2017, in connection with, and prior to the completion of, the Merger, Nivalis effected a 1:4 reverse stock split of its Shares (the “Reverse Stock Split”), and on July 24, 2017, immediately after completion of the Merger, Nivalis changed its name to “Alpine Immune Sciences, Inc.”  Under the terms of the Merger Agreement, Nivalis issued Shares to Old Alpine’s stockholders, at an exchange rate of 0.4969 Shares, after taking into account the Reverse Stock Split, for each share of Old Alpine Common Stock and Series A-1 Stock outstanding immediately prior to the Merger.

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The source of funds for such purchases was the working capital of OPI VI and capital contributions made to OPI VI.

As a result of the transactions described in this Item 3, (i) GP VI, as the general partner of OPI VI, (ii) Advisors, as the managing member of GP VI, and (iii) Isaly, as the managing member of Advisors and the owner of a controlling interest in Advisors, may each be deemed to be the beneficial owner of approximately 23.76% of the outstanding Shares.

Item 4. Purpose of Transaction

The Reporting Persons caused OPI VI to acquire Shares for the purpose of making an investment in the Issuer and not with the intention of acquiring control of the Issuer’s business on behalf of OPI VI.

The Reporting Persons from time to time intend to review their investment in the Issuer on the basis of various factors, including the Issuer’s business, financial condition, results of operations and prospects, general economic and industry conditions, the securities markets in general and those for the Issuer’s Shares in particular, as well as other developments and other investment opportunities.  Based upon such review, the Reporting Persons will take such actions in the future as the Reporting Persons may deem appropriate in light of the circumstances existing from time to time.  If the Reporting Persons believe that further investment in the Issuer is attractive, whether because of the market price of the Shares or otherwise, they may acquire Shares or other securities of the Issuer either in the open market or in privately negotiated transactions.  Similarly, depending on market and other factors, the Reporting Persons may determine to dispose of some or all of the Shares currently owned by the Reporting Persons or otherwise acquired by the Reporting Persons either in the open market or in privately negotiated transactions.

Except as set forth in this Statement, the Reporting Persons have not formulated any plans or proposals which relate to or would result in: (a) the acquisition by any person of additional securities of the Issuer or the disposition of securities of the Issuer; (b) an extraordinary corporate transaction, such as a merger, reorganization or liquidation, involving the Issuer or any of its subsidiaries; (c) a sale or transfer of a material amount of the assets of the Issuer or any of its subsidiaries; (d) any change in the present Board of Directors or management of the Issuer, including any plans or proposals to change the number or term of directors or to fill any existing vacancies on the board; (e) any material change in the Issuer’s capitalization or dividend policy of the Issuer; (f) any other material change in the Issuer’s business or corporate structure; (g) any change in the Issuer’s charter or bylaws or other instrument corresponding thereto or other action which may impede the acquisition of control of the Issuer by any person; (h) causing a class of the Issuer’s securities to be deregistered or delisted from a national securities exchange or to cease to be authorized to be quoted in an inter‑dealer quotation system of a registered national securities association; (i) a class of equity securities of the Issuer becoming eligible for termination of registration pursuant to Section 12(g)(4) of the Act; or (j) any action similar to any of those enumerated above.

Item 5. Interest in Securities of the Issuer

(a)‑(b)        As of the date of this filing, the Reporting Persons may be deemed, for purposes of Rule 13d-3 of the Exchange Act, directly or indirectly, including by reason of their mutual affiliation, to be the beneficial owners of the Shares described in Item 6 below  Based upon information contained in the Issuer’s on Form 8-K, filed with the Securities and Exchange Commission on July 25, 2017, such Shares deemed to be indirectly beneficially owned by the Reporting Persons constitutes approximately 23.76% of the issued and outstanding Shares. Advisors, pursuant to its authority as the sole managing member of GP VI, the sole general partner of OPI VI, may be deemed to indirectly beneficially own the Shares held by OPI VI.  GP VI, pursuant to its authority as the general partner of OPI VI, may be deemed to indirectly beneficially own the Shares held by OPI VI.  Isaly, pursuant to his authority as the managing member of Advisors and owner of a controlling interest in Advisors, pursuant to its limited liability company agreement, may also be deemed to indirectly beneficially own the Shares attributable to Advisors.  As a result, Isaly, Advisors and GP VI share the power to direct the vote and to direct the disposition of the Shares described in Item 3 above.

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(c)Except as disclosed in Item 3, the Reporting Persons have not effected any transactions in the Shares during the past sixty (60) days.

(d)Not applicable.

(e)Not applicable.

Item 6. Contracts, Arrangements, Understandings or Relationship with Respect to Securities of the Issuer

In addition to the relationships between the Reporting Persons described in Items 2, 3 and 5 above, GP VI is the sole general partner of OPI VI, pursuant to the terms of the limited partnership agreement of OPI VI.  Advisors is the sole managing member of GP VI, pursuant to the terms of the limited liability company agreement of GP VI.  Pursuant to these agreements and relationships, Advisors and GP VI have discretionary investment management authority with respect to the assets of OPI VI.  Such authority includes the power of GP VI to vote and otherwise dispose of securities purchased by OPI VI.  The number of Shares attributable to OPI VI is 3,298,516.  Advisors and GP VI may each be considered to hold indirectly 3,298,516 Shares.  Isaly, pursuant to his authority as the managing member of, and owner of a controlling interest in, Advisors, also has shared discretionary power to direct the vote and the disposition of the securities of the Issuer held by OPI V.

Peter Thompson (“Thompson”), a Private Equity Partner of Advisors, has been a member of the Board of Directors of the Issuer since June 2016 and, accordingly, the Reporting Persons may have the ability to affect and influence control of the Issuer.  From time to time, Thompson may receive stock options or other awards of equity‑based compensation pursuant to the Issuer’s compensation arrangements for non‑employee directors.  Thompson is obligated to transfer any securities issued under any such stock options or other awards, or the economic benefit thereof, to the Reporting Persons, which will in turn ensure that such securities or economic benefits are provided to OPI VI.

Lock‑up Agreement

In connection with the Merger, certain of Nivalis’ stockholders and Alpine’s stockholders, including OPI VI, entered into an agreement (the “Lock‑Up Agreement”), 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 Nivalis’ 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 Lock‑Up Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Lock‑Up Agreement, a copy of which is included in this Statement as Exhibit 2 and incorporated herein by reference.

Item 7. Materials to Be Filed as Exhibits

Exhibit	Description
1.	Joint Filing Agreement among OrbiMed Advisors LLC, OrbiMed Capital GP VI LLC and Samuel D. Isaly.
2.	Form of Lock-Up Agreement.

                          

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SIGNATURE

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

Dated:  August 3, 2017

OrbiMed Advisors LLC
By:	/s/ Samuel D. Isaly
	Name:	Samuel D. Isaly
	Title:	Managing Member

OrbiMed Capital GP VI LLC
By:	OrbiMed Advisors LLC its Managing Member
By:	/s/ Samuel D. Isaly
	Name:	Samuel D. Isaly
	Title:	Managing Member

Samuel D. Isaly
By:	/s/ Samuel D. Isaly
	Name:	Samuel D. Isaly

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Schedule I

The name and present principal occupation of each of the executive officers and directors of OrbiMed Advisors LLC are set forth below.  Unless otherwise noted, each of these persons are United States citizens and have as their business address 601 Lexington Avenue, 54th Floor, New York, NY 10022.

Name	Position with ReportingPerson	Principal Occupation
Samuel D. Isaly	Managing Member	Managing MemberOrbiMed Advisors LLC
Carl L. Gordon	Member	MemberOrbiMed Advisors LLC
Sven H. BorhoGerman and Swedish Citizen	Member	MemberOrbiMed Advisors LLC
Jonathan T. Silverstein	Member	MemberOrbiMed Advisors LLC
W. Carter Neild	Member	MemberOrbiMed Advisors LLC
Geoffrey C. Hsu	Member	MemberOrbiMed Advisors LLC
Evan D.  Sotiriou	Chief Financial Officer	Chief Financial OfficerOrbiMed Advisors LLC

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Schedule II

The business and operations of OrbiMed Capital GP VI LLC are managed by the executive officers and directors of its managing member, OrbiMed Advisors LLC, set forth on Schedule I attached hereto.

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EXHIBIT INDEX

Exhibit	Description
1.	Joint Filing Agreement among OrbiMed Advisors LLC, OrbiMed Capital GP VI LLC and Samuel D. Isaly.
2.	Form of Lock-Up Agreement.

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EX-99.1

EXHIBIT 1

JOINT FILING AGREEMENT

The undersigned hereby agree that the Statement on this Schedule 13D, dated August 3, 2017 (the “Schedule 13D”), with respect to the Shares of Alpine Immune Sciences, Inc. is filed, and all amendments thereto will be filed, on behalf of each of us pursuant to and in accordance with the provisions of Rule 13d‑1(k) under the Securities and Exchange Act of 1934, as amended, and that this Agreement shall be included as an Exhibit to this Schedule 13D.  Each of the undersigned agrees to be responsible for the timely filing of the Schedule 13D, and for the completeness and accuracy of the information concerning itself contained therein.  This Agreement may be executed in any number of counterparts, all of which taken together shall constitute one and the same instrument.

IN WITNESS WHEREOF, the undersigned have executed this Agreement as of the 3^rd day of August, 2017.

OrbiMed Advisors LLC
By:	/s/ Samuel D. Isaly
	Name:	Samuel D. Isaly
	Title:	Managing Member

OrbiMed Capital GP VI LLC
By:	OrbiMed Advisors LLC its Managing Member
By:	/s/ Samuel D. Isaly
	Name:	Samuel D. Isaly
	Title:	Managing Member
Samuel D. Isaly
By:	/s/ Samuel D. Isaly
	Samuel D. Isaly

EX-99.2

EXHIBIT 2

LOCK-UP AGREEMENT

July __, 2017

PETER THOMPSON, M.D.

c/o Alpine Immune Sciences, Inc.

201 Elliott Ave. W., Ste. 230

Seattle, WA 98119

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”):

(i) offer, pledge, sell, contract to sell, sell any option or contract to purchase, purchase any option or contract to sell, grant any option, right or warrant to purchase, or otherwise transfer or dispose of, directly or indirectly, any shares of Common Stock or any securities convertible into or exercisable or exchangeable for Nautilus Common Stock (including without limitation, Nautilus Common Stock or such other securities which may be deemed to be beneficially owned by the undersigned in accordance with the rules and regulations of the SEC and securities of Nautilus which may be issued upon exercise of a stock option or warrant) that are currently or hereafter owned by the undersigned (collectively, the “Undersigned’s Shares”), or publicly disclose the intention to make any such offer, sale, pledge, grant, transfer or disposition;

(ii) enter into any swap, short sale, hedge or other agreement that transfers, in whole or in part, any of the economic consequences of ownership of the Undersigned’s Shares regardless of whether any such transaction described in clause (i) above or this clause (ii) is to be settled by delivery of Nautilus Common Stock or such other securities, in cash or otherwise; or

(iii) make any demand for or exercise any right with respect to the registration of any shares of Nautilus Common Stock or any security convertible into or exercisable or exchangeable for Nautilus Common Stock.

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

(a) transfers of the Undersigned’s Shares:

(i) if the undersigned is a natural person, (A) to any person related to the undersigned by blood or adoption who is an immediate family member of the undersigned, or by marriage or domestic partnership (a “Family Member”), or to a trust formed for the benefit of the undersigned or any of the undersigned’s Family Members, (B) to the undersigned’s estate, following the death of the undersigned, by will, intestacy or other operation of law, (C) as a bona fide gift to a charitable organization, (D) by operation of law pursuant to a qualified domestic order or in connection with a divorce settlement or (E) to any partnership, corporation or limited liability company which is controlled by the undersigned and/or by any such Family Member(s);

(ii) if the undersigned is a corporation, partnership or other business entity, (A) to another corporation, partnership or other business entity that is an affiliate (as defined under Rule 12b-2 of the Exchange Act) of the undersigned, including investment funds or other entities under common control or management with the undersigned, (B) as a distribution or dividend to equity holders (including, without limitation, general or limited partners and members) of the undersigned (including upon the liquidation and dissolution of the undersigned pursuant to a plan of liquidation approved by the undersigned’s equity holders) or (C) as a bona fide gift to a charitable organization; or

(iii) if the undersigned is a trust, to any grantors or beneficiaries of the trust;

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); providedthat, 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;

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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.

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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)

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	Very truly yours,
Print Name of Stockholder:	PETER THOMPSON, M.D.
	Signature (for individuals):
	Signature (for entities):
	By:
		Name:
		Title:

Accepted and Agreed by

Nivalis Therapeutics, Inc.:

By

Name:

Title:

[Signature Page to Lock-up Agreement]