SC 13D/A

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 13D

Under the Securities Exchange Act of 1934

(Amendment No. 2)*

Sierra Oncology, Inc.

(Name of Issuer)

COMMON STOCK

(Title of Class of Securities)

82640U 10 7

(CUSIP Number)

OrbiMed Advisors LLC

OrbiMed Capital GP VII LLC

OrbiMed Genesis GP LLC

OrbiMed Capital LLC

601 Lexington Avenue, 54th Floor

New York, NY 10022

Telephone: (212) 739-6400

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

January 31, 2022

(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).  

CUSIP No.  82640U 10 7

1	Names of Reporting Persons.                  OrbiMed Advisors LLC
2	Check the Appropriate Box if a Member of a Group (See Instructions). (a) o (b) o
3	SEC Use Only
4	Source of Funds (See Instructions) AF
5	Check if Disclosure of Legal Proceedings Is Required Pursuant to Items 2(d) or 2(e)			o
6	Citizenship or Place of Organization                Delaware
NUMBER OF SHARES BENEFICIALLY OWNED BY EACH REPORTING PERSON WITH		7	Sole Voting Power             0
		8	Shared Voting Power                              3,044,753 (1)
		9	Sole Dispositive Power       0
		10	Shared Dispositive Power            3,044,753 (1)
11	Aggregate Amount Beneficially Owned by Each Reporting Person                  3,044,753 (1)
12	Check if the Aggregate Amount in Row (11) Excludes Certain Shares (See Instructions)			o
13	Percent of Class Represented by Amount in Row (11)                     15.3% (2)
14	Type of Reporting Person (See Instructions)                    IA

(1) This total consists of: (i) 1,738,066 shares of the common stock (the “Common Stock”) of Sierra Oncology, Inc. (the “Issuer”) and (ii) 1,306,687 shares of Common Stock issuable upon the exercise of Series A warrants.

(2) This percentage is calculated based upon 18,573,028 shares of Common Stock outstanding, as set forth in the Issuer’s Rule 424(b)(5) Prospectus filed with the Securities and Exchange Commission (“SEC”) on January 27, 2022 and giving effect to the additional 1,306,687 shares of Common Stock that would be outstanding following the exercise of Series A warrants as reported above.

CUSIP No. 82640U 10 7

1	Names of Reporting Persons.                    OrbiMed Capital GP VII LLC
2	Check the Appropriate Box if a Member of a Group (See Instructions). (a) o (b) o
3	SEC Use Only
4	Source of Funds (See Instructions)            AF
5	Check if Disclosure of Legal Proceedings Is Required Pursuant to Items 2(d) or 2(e)			o
6	Citizenship or Place of Organization                                Delaware
NUMBER OF SHARES BENEFICIALLY OWNED BY EACH REPORTING PERSON WITH		7	Sole Voting Power            0
		8	Shared Voting Power                 2,647,612 (1)
		9	Sole Dispositive Power              0
		10	Shared Dispositive Power              2,647,612 (1)
11	Aggregate Amount Beneficially Owned by Each Reporting Person              2,647,612 (1)
12	Check if the Aggregate Amount in Row (11) Excludes Certain Shares (See Instructions)			o
13	Percent of Class Represented by Amount in Row (11)              13.4% (2)
14	Type of Reporting Person (See Instructions)              OO

(1) This total consists of: (i) 1,511,362 shares of the common stock (the “Common Stock”) of Sierra Oncology, Inc. (the “Issuer”) and (ii) 1,136,250 shares of Common Stock issuable upon the exercise of Series A warrants.

(2) This percentage is calculated based upon 18,573,028 shares of Common Stock outstanding, as set forth in the Issuer’s Rule 424(b)(5) Prospectus filed with the Securities and Exchange Commission (“SEC”) on January 27, 2022 and giving effect to the additional 1,136,250 shares of Common Stock that would be outstanding following the exercise of Series A warrants as reported above.

CUSIP No. 82640U 10 7

1	Names of Reporting Persons.                    OrbiMed Genesis GP LLC
2	Check the Appropriate Box if a Member of a Group (See Instructions). (a) o (b) o
3	SEC Use Only
4	Source of Funds (See Instructions)            AF
5	Check if Disclosure of Legal Proceedings Is Required Pursuant to Items 2(d) or 2(e)			o
6	Citizenship or Place of Organization                                Delaware
NUMBER OF SHARES BENEFICIALLY OWNED BY EACH REPORTING PERSON WITH		7	Sole Voting Power            397,141 (1)
		8	Shared Voting Power
		9	Sole Dispositive Power              397,141 (1)
		10	Shared Dispositive Power
11	Aggregate Amount Beneficially Owned by Each Reporting Person              397,141 (1)
12	Check if the Aggregate Amount in Row (11) Excludes Certain Shares (See Instructions)			o
13	Percent of Class Represented by Amount in Row (11)              2.1% (2)
14	Type of Reporting Person (See Instructions)              OO

(1) This total consists of: (i) 226,704 shares of the common stock (the “Common Stock”) of Sierra Oncology, Inc. (the “Issuer”) and (ii) 170,437 shares of Common Stock issuable upon the exercise of Series A warrants.

(2) This percentage is calculated based upon 18,573,028 shares of Common Stock outstanding, as set forth in the Issuer’s Rule 424(b)(5) Prospectus filed with the Securities and Exchange Commission (“SEC”) on January 27, 2022 and giving effect to the additional 170,437 shares of Common Stock that would be outstanding following the exercise of Series A warrants as reported above.

CUSIP No. 82640U 10 7
1	Names of Reporting Persons.                OrbiMed Capital LLC
2	Check the Appropriate Box if a Member of a Group (See Instructions). (a) o (b) o
3	SEC Use Only
4	Source of Funds (See Instructions)                  AF
5	Check if Disclosure of Legal Proceedings Is Required Pursuant to Items 2(d) or 2(e)			o
6	Citizenship or Place of Organization                     Cayman Islands
NUMBER OF SHARES BENEFICIALLY OWNED BY EACH REPORTING PERSON WITH		7	Sole Voting Power             397,141 (1)
		8	Shared Voting Power            0
		9	Sole Dispositive Power              397,141 (1)
		10	Shared Dispositive Power            0
11	Aggregate Amount Beneficially Owned by Each Reporting Person                  397,141 (1)
12	Check if the Aggregate Amount in Row (11) Excludes Certain Shares (See Instructions)			o
13	Percent of Class Represented by Amount in Row (11)              2.1%*
14	Type of Reporting Person (See Instructions)               IA

(1) This total consists of: (i) 226,704 shares of the common stock (the “Common Stock”) of Sierra Oncology, Inc. (the “Issuer”) and (ii) 170,437 shares of Common Stock issuable upon the exercise of Series A warrants.

(2) This percentage is calculated based upon 18,573,028 shares of Common Stock outstanding, as set forth in the Issuer’s Rule 424(b)(5) Prospectus filed with the Securities and Exchange Commission (“SEC”) on January 27, 2022 and giving effect to the additional 170,437 shares of Common Stock that would be outstanding following the exercise of Series A warrants as reported above.

Item 1.  Security and Issuer

This Amendment No. 2 to Schedule 13D supplements and amends the Statement of Schedule 13D of OrbiMed Advisors LLC, OrbiMed Capital GP VII LLC, OrbiMed Global Healthcare GP LLC (“OrbiMed Global Healthcare”), and OrbiMed Capital LLC originally filed with the Securities and Exchange Commission (the “SEC”) on November 27, 2019 and amended by Amendment No. 1 thereto filed with the SEC on November 5, 2021 (“Amendment No. 1”). The Statement relates to the common stock, par value $0.001 per share (the “Shares”) of Sierra Oncology, Inc., a corporation organized under the laws of Delaware (the “Issuer”), with its principal executive offices located at 885 West Georgia Street, Suite 2150, Vancouver, BC V6C 3E8.  The Shares are listed on the NASDAQ Global Market under the ticker symbol “SRRA”. Information given in response to each item shall be deemed incorporated by reference in all other items, as applicable.

On January 31, 2022, the Issuer completed a public offering pursuant to which the Issuer agreed to issue and sell to the participants 4,074,075 Shares (the “Offering”) at a price to the public of $27.00, as well pre-funded warrants to purchase 925,925 Shares. In addition, the Issuer granted the underwriters an option to purchase, at the public offering price less any underwriting discounts and commissions, up to an additional 750,000 Shares. The Reporting Persons (as defined below) did not participate in the Offering. As a result of the Offering, the Issuer’s total number of outstanding Shares increased to 18,573,028 (the “Outstanding Share Increase”). As a result of the Outstanding Share Increase, the percentage of outstanding Shares that the Reporting Persons may be deemed to beneficially own was reduced by more than one percent of the Issuer since the filing of Amendment No. 1.

In addition, on January 26, 2022, the Reporting Persons exercised their Series B Warrants at an exercise price of $13.20 per share. Because the Reporting Persons had previously reported the Series B Warrants on Amendment No. 1, the exercise of the Series B Warrants did not change the beneficial ownership of the Reporting Persons with respect to the Shares.

Item 2.  Identity and Background

(a) This Schedule 13D is being filed by OrbiMed Advisors LLC (“OrbiMed Advisors”), OrbiMed Capital GP VII LLC (“OrbiMed GP”), OrbiMed Genesis GP LLC (“Genesis GP”), and OrbiMed Capital LLC (“OrbiMed Capital”) (collectively, the “Reporting Persons”).

 (b) — (c), (f) OrbiMed Advisors, a limited liability company organized under the laws of Delaware and a registered investment adviser under the Investment Advisers Act of 1940, as amended, is the managing member or general partner of certain entities as more particularly described in Item 6 below.  OrbiMed Advisors has its principal offices at 601 Lexington Avenue, 54th Floor, New York, New York 10022.

OrbiMed GP, a limited liability company organized under the laws of Delaware, is the general partner of a limited partnership as more particularly described in Item 6 below.  OrbiMed GP has its principal offices at 601 Lexington Avenue, 54th Floor, New York, New York 10022.

Genesis GP, a limited liability company organized under the laws of Delaware, is the general partner of a limited partnership as more particularly described in Item 6 below.  Genesis GP has its principal offices at 601 Lexington Avenue, 54th Floor, New York, New York 10022.

OrbiMed Capital, a limited liability company organized under the laws of Delaware and a registered investment adviser under the Investment Advisers Act of 1940, as amended, is the investment adviser of certain entities as more particularly described in Item 6 below.  OrbiMed Capital has its principal offices at 601 Lexington Avenue, 54th Floor, New York, New York 10022.

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

(i)          name;

(ii)         business address;

(iii)        present principal occupation of 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 Schedules I through IV has 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.

Item 3.  Source and Amount of Funds or Other Consideration

The source of the funds for the exercise of the Series B Warrants was the working capital of OrbiMed Private Investments VII, LP (“OPI VII”), OrbiMed Genesis Master Fund, L.P. (“Genesis”), and OrbiMed Partners Master Fund Limited (“OPM”).

Item 4.  Purpose of Transaction

The Shares were initially acquired by the Reporting Persons 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 the Reporting Persons’ respective advisory clients.

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 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 Schedule 13D, 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) The following disclosure is based upon 18,573,028 outstanding Shares of the Issuer, as set forth in the Rule 424(b)(5) Prospectus filed with the Securities and Exchange Commission on January 27, 2022 and giving effect to an additional 1,477,124 Shares that may be issued upon the exercise of Series A Warrants.

As of the date of this filing, OPI VII, a limited partnership organized under the laws of Delaware, holds 1,511,362 Shares and is the beneficial owner of an additional 1,136,250 Shares that may be issued upon the exercise of Series A Warrants. Such Shares constitute approximately 13.4% of the issued and outstanding Shares.  OrbiMed GP is the general partner of OPI VII, pursuant to the terms of the limited partnership agreement of OPI VII, and OrbiMed Advisors is the managing member of OrbiMed GP, pursuant to the terms of the limited liability company agreement of OrbiMed GP.  As a result, OrbiMed Advisors and OrbiMed GP share power to direct the vote and disposition of the Shares held by OPI VII and may be deemed directly or indirectly, including by reason of their mutual affiliation, to be the beneficial owners of the Shares held by OPI VII.  OrbiMed Advisors exercises this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and W. Carter Neild, each of whom disclaims beneficial ownership of the Shares held by OPI VII.

As of the date of this filing, Genesis, a limited partnership organized under the laws of the Cayman Islands, holds 226,704 Shares and is the beneficial owner of an additional 170,437 Shares that may be issued upon the exercise of Series A Warrants. Such Shares constitute approximately 2.1% of the issued and outstanding Shares.  Genesis GP is the general partner of Genesis, pursuant to the terms of the limited partnership agreement of Genesis, and OrbiMed Advisors is the managing member of Genesis GP, pursuant to the terms of the limited liability company agreement of Genesis GP.  As a result, OrbiMed Advisors and Genesis GP share power to direct the vote and disposition of the Shares held by Genesis and may be deemed, directly or indirectly, including by reason of their mutual affiliation, to be the beneficial owners of the Shares held by Genesis. OrbiMed Advisors exercises this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and W. Carter Neild, each of whom disclaims beneficial ownership of the Shares held by Genesis.

As of the date of this filing, OPM, an exempted company organized under the laws of Bermuda, holds 226,704 Shares and is the beneficial owner of an additional 170,437 Shares that may be issued upon the exercise of Series A Warrants. Such Shares constitute approximately 2.1% of the issued and outstanding Shares.  OrbiMed Capital is the investment advisor of OPM. As a result, OrbiMed Capital has the power to direct the vote and disposition of the Shares held by OPM and may be deemed directly or indirectly, including by reason of mutual affiliation, to be the beneficial owner of the Shares held by OPM.  OrbiMed Capital disclaims any beneficial ownership over the shares of the other Reporting Persons.  OrbiMed Capital exercises this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and W. Carter Neild, each of whom disclaims beneficial ownership of the Shares held by OPM.

(c) Other than as described in Item 1, the Reporting Persons have not effected any transactions during the past sixty (60) days in any Shares.

(d) Not applicable.

(e) Not applicable.

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

The terms and provisions of the Series A Warrants are qualified by the full text of the Series A Warrant, which is filed as Exhibit 2 to this Statement and incorporated herein by reference.

Mona Ashiya (“Ashiya”), an employee of OrbiMed Advisors, is a member of the Board of Directors of the Issuer and, accordingly, OrbiMed Advisors and OrbiMed GP may have the ability to affect and influence control of the Issuer. From time to time, Ashiya may receive stock options or other awards of equity-based compensation pursuant to the Issuer’s compensation arrangements for non-employee directors. Pursuant to an agreement with OrbiMed Advisors and OrbiMed GP, Ashiya is obligated to transfer any securities issued under any such stock options or other awards, or the economic benefit thereof, to OrbiMed Advisors and OrbiMed GP, which will in turn ensure that such securities or economic benefits are provided to OPI VII.

Lock-up Agreement

In connection with the Offering, OPI VII, Genesis, OPM and Ashiya entered into a lockup agreement (the “Lock-up Agreement”) with the Issuer’s underwriters pursuant to which, among other things, each of these stockholders agreed not to, except in limited circumstances, directly or indirectly (i) sell, offer to sell, contract to lend, pledge, hypothecate, grant any security interest in, transfer or dispose of any Shares, and (ii) effect any short sale, establish or increase any “put equivalent position” or liquidate or decrease any “call equivalent position” with respect to any Shares, or otherwise enter into any swap, derivative or other transaction or arrangement that transfers to another, in whole or in part, any economic risk of ownership of a Share, whether or not such transaction is to be settled by delivery of Shares, other securities, cash or other consideration, from the date of the final prospectus supplement for the Offering until 90 days from the date of the final prospectus supplement for the Offering.

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 Form of Lock-up Agreement, a copy of which is filed as Exhibit 3 and incorporated herein by reference.

Item 7.  Material to Be Filed as Exhibits

Exhibit	Description
1.	Joint Filing Agreement among OrbiMed Advisors LLC, OrbiMed Capital GP VI LLC, OrbiMed Genesis GP LLC, and OrbiMed Capital LLC.
2.	Form Series A Warrant to Purchase Common Stock (filed as Exhibit 4.1 to the Issuer’s current report on Form 8-K as filed with the Commission on November 7, 2019 (SEC File No. 333-225650) and incorporated herein by reference).
3	Form of Lock-Up Agreement

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: February 2, 2022	ORBIMED ADVISORS LLC
	By:	/s/ Carl L. Gordon
		Name: Carl L. Gordon
		Title: Member
	ORBIMED CAPITAL GP VII LLC
	By:	ORBIMED ADVISORS LLC, its managing member
	By:	/s/ Carl L. Gordon
		Carl L. Gordon
		Title: Member of OrbiMed Advisors LLC
	ORBIMED GENESIS GP LLC
	By: / ORBIMED ADVISORS LLC, its managing member
	By:	/s/ Carl L. Gordon
		Carl L. Gordon
		Title: Member of OrbiMed Advisors LLC
	ORBIMED CAPITAL LLC
	By:	/s/ Carl L. Gordon
		Carl L. Gordon
		Title: Member

SCHEDULE I

The names and present principal occupations of each of the executive officers and directors of OrbiMed Advisors LLC are set forth below. Unless otherwise noted, each of these persons is a United States citizen and has a business address of 601 Lexington Avenue, 54th Floor, New York, NY 10022.

Name	Position with Reporting Person	Principal Occupation
Carl L. Gordon	Member	Member OrbiMed Advisors LLC
Sven H. Borho German and Swedish Citizen	Member	Member OrbiMed Advisors LLC
W. Carter Neild	Member	Member OrbiMed Advisors LLC
Geoffrey C. Hsu	Member	Member OrbiMed Advisors LLC
C. Scotland Stevens	Member	Member OrbiMed Advisors LLC
David P. Bonita	Member	Member OrbiMed Advisors LLC
Peter A. Thompson	Member	Member OrbiMed Advisors LLC
Matthew S. Rizzo	Member	Member OrbiMed Advisors LLC
Trey Block	Chief Financial Officer	Chief Financial Officer OrbiMed Advisors LLC

SCHEDULE II

The names and present principal occupations of each of the executive officers and directors of OrbiMed Capital LLC are set forth below. Unless otherwise noted, each of these persons is a United States citizen and has a business address of 601 Lexington Avenue, 54th Floor, New York, NY 10022.

Name	Position with Reporting Person	Principal Occupation
Carl L. Gordon	Member	Member OrbiMed Capital LLC
Sven H. Borho German and Swedish Citizen	Member	Member OrbiMed Capital LLC
W. Carter Neild	Member	Member OrbiMed Capital LLC
Geoffrey C. Hsu	Member	Member OrbiMed Capital LLC
C. Scotland Stevens David P. Bonita	Member Member	Member OrbiMed Capital LLC Member OrbiMed Capital LLC
Peter A. Thompson	Member	Member OrbiMed Capital LLC
Matthew S. Rizzo	Member	Member OrbiMed Capital LLC
Trey Block	Chief Financial Officer	Chief Financial Officer OrbiMed Capital LLC

SCHEDULE III

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

SCHEDULE IV

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

EXHIBIT INDEX

Exhibit	Description
1.	Joint Filing Agreement among  OrbiMed Advisors LLC, OrbiMed Capital GP VI LLC, OrbiMed Genesis GP LLC, and OrbiMed Capital LLC.
2.	Form Series A Warrant to Purchase Common Stock (filed as Exhibit 4.1 to the Issuer’s current report on Form 8-K as filed with the Commission on November 7, 2019 (SEC File No. 333-225650) and incorporated herein by reference).
3	Form of Lock-Up Agreement

EX-99.1

Exhibit 1

JOINT FILING AGREEMENT

 The undersigned hereby agree that the Statement on Schedule 13D, dated February 2, 2022, with respect to the ordinary shares of Sierra Oncology, Inc. is 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. Each of the undersigned agrees to be responsible for the timely filing of this Statement, 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.

Dated: February 2, 2022	ORBIMED ADVISORS LLC
	By:	/s/ Carl L. Gordon
		Name: Carl L. Gordon
		Title: Member
	ORBIMED CAPITAL GP VII LLC
	By:	ORBIMED ADVISORS LLC, its managing member
	By:	/s/ Carl L. Gordon
		Carl L. Gordon
		Title: Member of OrbiMed Advisors LLC
	ORBIMED GENESIS GP LLC
	By: / ORBIMED ADVISORS LLC, its managing member
	By:	/s/ Carl L. Gordon
		Carl L. Gordon
		Title: Member of OrbiMed Advisors LLC
	ORBIMED CAPITAL LLC
	By:	/s/ Carl L. Gordon
		Carl L. Gordon
		Title: Member

EX-99.3

Exhibit 3

Form of Lock-up Agreement

January 24, 2022

Jefferies LLC

Cantor Fitzgerald & Co.

As Representatives of the Several Underwriters

c/o        Jefferies LLC

520 Madison Avenue

New York, New York 10022

c/o        Cantor Fitzgerald & Co.

499 Park Avenue

New York, New York 10022

RE:       Sierra Oncology, Inc. (the “Company”)

Ladies & Gentlemen:

The undersigned is an owner of shares of common stock, par value $0.001 per share, of the Company (the “Shares”) or of securities convertible into or exchangeable or exercisable for Shares. The Company proposes to conduct a public offering of Shares (the “Offering”) for which Jefferies LLC and Cantor Fitzgerald & Co. will act as the representatives (the “Representatives”) of the underwriters. The undersigned recognizes that the Offering will benefit each of the Company and the undersigned. The undersigned acknowledges that the underwriters are relying on the representations and agreements of the undersigned contained in this letter agreement in conducting the Offering and, at a subsequent date, in entering into an underwriting agreement (the “Underwriting Agreement”) and other underwriting arrangements with the Company with respect to the Offering.

Annex A sets forth definitions for capitalized terms used in this letter agreement that are not defined in the body of this letter agreement. Those definitions are a part of this letter agreement.

In consideration of the foregoing, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the undersigned hereby agrees that, during the Lock-up Period, the undersigned will not (and will cause any Family Member not to), subject to the exceptions set forth in this letter agreement, without the prior written consent of Jefferies LLC, which may withhold its consent in its sole discretion:

· Sell or Offer to Sell any Shares or Related Securities currently or hereafter owned either of record or beneficially (as defined in Rule 13d-3 under the Exchange Act) by the undersigned or such Family Member,

· enter into any Swap,

· make any demand for, or exercise any right with respect to, the registration under the Securities Act of the offer and sale of any Shares or Related Securities, or cause to be filed a registration statement, prospectus or prospectus supplement (or an amendment or supplement thereto) with respect to any such registration, or

· publicly announce any intention to do any of the foregoing.

The foregoing will not apply to the registration of the offer and sale of the Shares in the Offering by the Company, and the sale of the Shares to the underwriters, in each case as contemplated by the Underwriting Agreement. In addition, the foregoing restrictions shall not apply to (a) the transfer of Shares or Related Securities by gift, or by will or intestate succession to a Family Member or to a trust whose beneficiaries consist exclusively of one or more of the undersigned and/or a Family Member, (b) the transfer of Shares or Related Securities that occurs by operation of law pursuant to a court order or settlement agreement related to the distribution of assets in connection with the dissolution of a marriage or civil union; provided that any public disclosure or filing under the Exchange Act or otherwise that is required to be made during the Lock-up Period as a result of such transfer shall include a statement that such transfer has occurred by operation of law; (c) the distribution, sale of or offer to sell Shares or Related Securities acquired in the Offering or in open market transactions after the Offering; (d) the exercise of options, warrants or other rights to acquire Shares or Related Securities in accordance with their terms, provided that any such shares issued upon exercise, exchange or conversion of such Related Securities shall continue to be subject to the restrictions set forth herein; (e) the transfer or sale of Shares or Related Securities to the Company pursuant to agreements under which the Company, (i) upon termination of employment, has the option to repurchase such Shares or Related Securities, (ii) is required to repurchase such Shares or Related Securities or (iii) has a right of first refusal with respect to transfers of such Shares or Related Securities upon termination of service of the undersigned; (f) the “net” exercise of outstanding options or warrants in accordance with their terms pursuant to an employee benefit plan or warrant disclosed in the prospectus supplement relating to the Offering and the surrender of Shares in lieu of payment in cash of the exercise price and any tax withholding obligations due as a result of such exercise or settlement; (g) the amendment of a 10b5-1 Plan established prior to the date hereof or the establishment of a 10b5-1 Plan established after the date hereof, provided that (i) there are no sales under or public disclosure of such new or amended 10b5-1 Plan during the Lock-up Period and (ii) no public announcement or filing regarding such new or amended 10b5-1 Plan is required to be made, or is voluntarily made, during the Lock-up Period by or on behalf of the Company or the undersigned; and (h) the transfer of Shares or Related Securities pursuant to a bona fide third-party tender offer, merger, consolidation or other similar transaction made to all holders of the Shares involving a Change of Control of the Company; provided that in the event that the tender offer, merger, consolidation or other such transaction is not completed, the Shares and Related Securities owned by the undersigned shall remain subject to the restrictions contained in this letter agreement; provided further, however, that:

· in the case of (a) and (b) above, it shall be a condition to such transfer that (i) each transferee executes and delivers to the Representatives an agreement in form and substance satisfactory to the Representatives providing consent for the release or waiver stating that such transferee is receiving and holding such Shares and/or Related Securities subject to the provisions of this letter agreement and agrees not to Sell or Offer to Sell such Shares and/or Related Securities, engage in any Swap or engage in any other activities restricted under this letter agreement except in accordance with this letter agreement (as if such transferee had been an original signatory hereto) and (ii) such transfer shall not involve a disposition for value;

· in the case of (a) and (d) above, prior to the expiration of the Lock-up Period, no public disclosure or filing under the Exchange Act by any party to the transfer (donor, donee, transferor or transferee) shall be required, or made voluntarily, reporting a reduction in beneficial ownership of Shares in connection with such transfer; provided in the case of (d), to the extent any such warrants expire during the Lock-up Period, (i) any public filing or public announcement under Section 16(a) of the Exchange Act reporting a reduction in beneficial ownership of Shares, or otherwise, required to be made during the Lock-up Period shall clearly indicate in the footnotes thereto or comments section thereof that such transfer was made pursuant to the circumstances described in clause (d) and (ii) no public announcement shall be voluntarily made during the Lock-up Period; and

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· in the case of (c) above, prior to the expiration of the Lock-up Period, no public disclosure or filing reporting a change in beneficial ownership of Shares shall be made voluntarily during the Lock-up Period, and if the undersigned is required to file a report under Section 16 of the Exchange Act reporting a change in beneficial ownership of Shares during the Lock-up Period, the undersigned shall include a statement in such report to the effect that such transfer relates to the circumstances described in (c); and

· in the case of (f) above, (i) no public disclosure or filing under the Exchange Act by any party to the transfer shall be required, or made voluntarily, reporting a reduction in beneficial ownership of Shares in connection with such exercise or settlement, and (ii) the Shares received by the undersigned from the Company shall remain subject to the terms of this letter agreement.

In addition, notwithstanding the foregoing, if the undersigned is a non-natural person, the undersigned may transfer the undersigned’s Shares or Related Securities to (A) any wholly-owned subsidiary of the undersigned or to the parent entity of the undersigned, (B) limited partners, members or stockholders of the undersigned and (C) any corporation, partnership, limited liability company, investment fund or other entity controlled or managed, or under common control or management by the undersigned or a Family Member of the undersigned; provided, however, that in any such case, it shall be a condition to the transfer that (X) the transferee execute an agreement stating that the transferee is receiving and holding such capital stock subject to the provisions of this letter agreement and there shall be no further transfer of such capital stock except in accordance with this letter agreement, (Y) in no case shall a filing or public disclosure under the Exchange Act by any party to the transfer (donor, donee, transferor or transferee) be required, or made voluntarily, reporting a reduction in beneficial ownership of Shares in connection with such transfer and (Z) any such transfer shall not involve a disposition for value.

The undersigned also agrees and consents to the entry of stop transfer instructions with the Company’s transfer agent and registrar against the transfer of Shares or Related Securities held by the undersigned and the undersigned’s Family Members, if any, except in compliance with the foregoing restrictions.

With respect to the Offering only, the undersigned waives any registration rights relating to registration under the Securities Act of the offer and sale of any Shares and/or any Related Securities owned either of record or beneficially by the undersigned, including any rights to receive notice of the Offering.

In the event that, during the Lock-up Period, Jefferies LLC releases or waives any prohibition set forth in this letter agreement on the transfer of shares of common stock, or any securities convertible into or exercisable for shares of common stock, held by any director, officer or Significant Holder (as defined below), the same percentage of the total number of outstanding shares of common stock held by the undersigned on the date of such release or waiver as the percentage of the total number of outstanding shares of common stock held by such director, officer or such Significant Holder on the date of such release or waiver that are the subject of such waiver shall be immediately and fully released on the same terms from the applicable prohibition(s) set forth herein. For the purposes of the foregoing, a “Significant Holder” shall mean any person or entity that (together with any investment funds affiliated with such person or entity) beneficially owns 2.5% or more of the total outstanding shares of common stock as of the date of the Underwriting Agreement. Notwithstanding the foregoing, the provisions of this paragraph shall not apply (1) if the release or waiver is effected solely to permit a transfer not involving a disposition for value and the transferee agrees in writing to be bound by the same terms described in this letter agreement to the extent and for the duration that such terms remain in effect at the time of transfer, (2) in the case of any secondary underwritten public offering of shares of common stock (including a secondary underwritten public offering with a primary component) (an “Underwritten Sale”), provided that the undersigned, to the extent the undersigned has a contractual right to demand or require the registration of the undersigned’s securities of the Company or otherwise “piggyback” on a registration statement filed by the Company for the offer and sale of its shares of common stock, is offered the opportunity to participate on a basis consistent with such contractual rights in such Underwritten Sale,

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(3) if the releases or waivers granted for all such waivers or releases by Jefferies LLC in an amount of common stock, individually or in the aggregate, less than or equal to $2,500,000, or (4) if the release or waiver is granted to a natural person due to circumstances of an emergency or hardship as determined by Jefferies LLC in its sole judgment, provided that, notwithstanding clauses (3) and (4), all releases and waivers pursuant to clauses (3) and (4) shall count towards and be included in the amount otherwise available for release pursuant to clause (3) and no releases or waivers shall be granted pursuant to clauses (3) or (4) if such release or waiver would cause the limit in clause (3) to be exceeded. Jefferies LLC shall use commercially reasonable efforts to promptly notify the Company of each such release (provided that the failure to provide such notice shall not give rise to any claim or liability against the Representatives or the Underwriters) and the Company shall use commercially reasonable efforts to promptly notify the undersigned of each such release. The undersigned further acknowledges that Jefferies LLC is under no obligation to inquire into whether, or to ensure that, the Company notifies the undersigned of the delivery by Jefferies LLC of any such notice, which is a matter between the undersigned and the Company.

The undersigned acknowledges and agrees that the underwriters have not provided any recommendation or investment advice nor have the underwriters solicited any action from the undersigned with respect to the Offering and the undersigned has consulted their own legal, accounting, financial, regulatory and tax advisors to the extent deemed appropriate.

Whether or not the Offering occurs as currently contemplated or at all depends on market conditions and other factors. The Offering will only be made pursuant to the Underwriting Agreement, the terms of which are subject to negotiation between the Company and the underwriters.

The undersigned hereby represents and warrants that the undersigned has full power, capacity and authority to enter into this letter agreement. This letter agreement is irrevocable and will be binding on the undersigned and the successors, heirs, personal representatives and assigns of the undersigned. This letter agreement will automatically terminate upon the earliest to occur, if any, of (a) the date the Company advises the Representatives in writing, prior to the execution of the Underwriting Agreement, that it has determined not to proceed with the Offering, (b) the date of the termination of the Underwriting Agreement if prior to the closing of the Offering and (c) March 31, 2022 if the Underwriting Agreement has not been executed and delivered by the Company by such date.

This letter agreement shall be governed by, and construed in accordance with, the laws of the State of New York.

[signature page follows]

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Very truly yours,

By: ________________________

Name: Mona Ashiya

Title: Director of the Company

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Very truly yours,

ORBIMED PRIVATE INVESTMENTS VII, LP

By: OrbiMed Capital GP VII LLC, its General Partner

By: OrbiMed Advisors LLC, its Managing Member

By: ________________________

Name:

Title:

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Very truly yours,

ORBIMED GENESIS MASTER FUND, L.P.

By: OrbiMed Genesis GP LLC, its General Partner

By: OrbiMed Advisors LLC, its Managing Member

By: ________________________

Name:

Title:

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Very truly yours,

ORBIMED PARTNERS MASTER FUND LIMITED

By: OrbiMed Capital LLC, solely in its capacity as Investment Advisor

By: ________________________

Name:

Title:

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ANNEX A

Certain Defined Terms
Used in Lock-up Agreement

For purposes of the letter agreement to which this Annex A is attached and of which it is made a part:

· “Call Equivalent Position” shall have the meaning set forth in Rule 16a-1(b) under the Exchange Act.

· “Change of Control” shall mean the consummation of any bona fide third party tender offer, merger, consolidation or other similar transaction approved by the Board of Directors of the Company, the result of which is that any “person” (as defined in Section 13(d)(3) of the Exchange Act), or group of persons, other than the Company or its subsidiaries, becomes the beneficial owner (as defined in Rules 13d-3 and 13d-5 of the Exchange Act) of 100% of the total voting power of the voting stock of the Company.

· “Exchange Act” shall mean the Securities Exchange Act of 1934, as amended.

· “Family Member” shall mean the spouse of the undersigned, an immediate family member of the undersigned or an immediate family member of the undersigned’s spouse, in each case living in the undersigned’s household or whose principal residence is the undersigned’s household (regardless of whether such spouse or family member may at the time be living elsewhere due to educational activities, health care treatment, military service, temporary internship or employment or otherwise). “Immediate family member” as used above shall have the meaning set forth in Rule 16a-1(e) under the Exchange Act.

· “Lock-up Period” shall mean the period beginning on the date hereof and continuing through the close of trading on the date that is 90 days after the date of the Prospectus (as defined in the Underwriting Agreement).

· “Put Equivalent Position” shall have the meaning set forth in Rule 16a-1(h) under the Exchange Act.

· “Related Securities” shall mean any options or warrants or other rights to acquire Shares or any securities exchangeable or exercisable for or convertible into Shares, or to acquire other securities or rights ultimately exchangeable or exercisable for or convertible into Shares.

· “Securities Act” shall mean the Securities Act of 1933, as amended.

· “Sell or Offer to Sell” shall mean to:

o sell, offer to sell, contract to sell or lend,

o effect any short sale or establish or increase a Put Equivalent Position or liquidate or decrease any Call Equivalent Position,

o pledge, hypothecate or grant any security interest in, or

o in any other way transfer or dispose of,

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in each case whether effected directly or indirectly.

· “Swap” shall mean any swap, hedge or similar arrangement or agreement that transfers or is designed to, intended to, or which could reasonably be expected to lead to or result in the transfer of, in whole or in part, the economic risk of ownership of Shares or Related Securities, regardless of whether any such transaction is to be settled in securities, in cash or otherwise.

Capitalized terms not defined in this Annex A shall have the meanings given to them in the body of this lock-up agreement.

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