SC 13G

 UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 13G

(Rule 13d-102)

INFORMATION TO BE INCLUDED IN STATEMENTS FILED PURSUANT

TO RULES 13d-1(b), (c), AND (d) AND AMENDMENTS THERETO FILED

PURSUANT TO RULE 13d-2(b)

(Amendment No.   )¹

Alpine Immune Sciences, Inc.

 (Name of Issuer)

Common Stock, par value $0.001

 (Title of Class of Securities)

02083G100

 (CUSIP Number)

January 18, 2019

 (Date of Event Which Requires Filing of this Statement)

Check the appropriate box to designate the rule pursuant to which this Schedule is filed:

☐  Rule 13d-1(b)

☒  Rule 13d-1(c)

☐  Rule 13d-1(d)

1              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. 02083G100

	1	NAME OF REPORTING PERSON
			Biotechnology Value Fund, L.P.
	2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP				(a) ☒
						(b) ☐
	3	SEC USE ONLY
	4	CITIZENSHIP OR PLACE OF ORGANIZATION
			Delaware
NUMBER OF			5	SOLE VOTING POWER
SHARES
BENEFICIALLY					0 shares
OWNED BY			6	SHARED VOTING POWER
EACH
REPORTING					584,078(1)
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					584,078(1)
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			584,078(1)
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			3.1%(1)
	12	TYPE OF REPORTING PERSON
			PN

⁽¹⁾ Excludes 112,610 Shares (as defined herein) underlying the Warrants (as defined herein) that are not exercisable due to the Beneficial Ownership Limitation (as defined herein), which provides that the Warrants may not be exercised if, after such exercise, the Reporting Persons would beneficially own more than 4.99% of the Shares outstanding.

2

CUSIP No. 02083G100

	1	NAME OF REPORTING PERSON
			Biotechnology Value Fund II, L.P.
	2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP				(a) ☒
						(b) ☐
	3	SEC USE ONLY
	4	CITIZENSHIP OR PLACE OF ORGANIZATION
			Delaware
NUMBER OF			5	SOLE VOTING POWER
SHARES
BENEFICIALLY					0 shares
OWNED BY			6	SHARED VOTING POWER
EACH
REPORTING					460,853(1)
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					460,853(1)
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			460,853(1)
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			2.5%(1)
	12	TYPE OF REPORTING PERSON
			PN

⁽¹⁾ Excludes 92,035 Shares (as defined herein) underlying the Warrants (as defined herein) that are not exercisable due to the Beneficial Ownership Limitation (as defined herein), which provides that the Warrants may not be exercised if, after such exercise, the Reporting Persons would beneficially own more than 4.99% of the Shares outstanding.

3

CUSIP No. 02083G100

	1	NAME OF REPORTING PERSON
			Biotechnology Value Trading Fund OS LP
	2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP				(a) ☒
						(b) ☐
	3	SEC USE ONLY
	4	CITIZENSHIP OR PLACE OF ORGANIZATION
			Cayman Islands
NUMBER OF			5	SOLE VOTING POWER
SHARES
BENEFICIALLY					0 shares
OWNED BY			6	SHARED VOTING POWER
EACH
REPORTING					84,524(1)
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					84,524(1)
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			84,524(1)
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			Less than 1% (1)
	12	TYPE OF REPORTING PERSON
			PN

⁽¹⁾ Excludes 13,232 Shares (as defined herein) underlying the Warrants (as defined herein) that are not exercisable due to the Beneficial Ownership Limitation (as defined herein), which provides that the Warrants may not be exercised if, after such exercise, the Reporting Persons would beneficially own more than 4.99% of the Shares outstanding.

4

CUSIP No. 02083G100

	1	NAME OF REPORTING PERSON
			BVF Partners OS Ltd.
	2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP				(a) ☒
						(b) ☐
	3	SEC USE ONLY
	4	CITIZENSHIP OR PLACE OF ORGANIZATION
			Cayman Islands
NUMBER OF			5	SOLE VOTING POWER
SHARES
BENEFICIALLY					0 shares
OWNED BY			6	SHARED VOTING POWER
EACH
REPORTING					84,524(1)
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					84,524(1)
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			84,524(1)
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			Less than 1%(1)
	12	TYPE OF REPORTING PERSON
			CO

⁽¹⁾ Excludes 13,232 Shares (as defined herein) underlying the Warrants (as defined herein) that are not exercisable due to the Beneficial Ownership Limitation (as defined herein), which provides that the Warrants may not be exercised if, after such exercise, the Reporting Persons would beneficially own more than 4.99% of the Shares outstanding.

5

CUSIP No. 02083G100

	1	NAME OF REPORTING PERSON
			BVF Partners L.P.
	2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP				(a) ☒
						(b) ☐
	3	SEC USE ONLY
	4	CITIZENSHIP OR PLACE OF ORGANIZATION
			Delaware
NUMBER OF			5	SOLE VOTING POWER
SHARES
BENEFICIALLY					0 shares
OWNED BY			6	SHARED VOTING POWER
EACH
REPORTING					1,201,718(1)
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					1,201,718(1)
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			1,201,718(1)
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			6.5%(1)
	12	TYPE OF REPORTING PERSON
			PN, IA

⁽¹⁾ Excludes 217,877 Shares (as defined herein) underlying the Warrants (as defined herein) that are not exercisable due to the Beneficial Ownership Limitation (as defined herein), which provides that the Warrants may not be exercised if, after such exercise, the Reporting Persons would beneficially own more than 4.99% of the Shares outstanding.

6

CUSIP No. 02083G100

	1	NAME OF REPORTING PERSON
			BVF Inc.
	2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP				(a) ☒
						(b) ☐
	3	SEC USE ONLY
	4	CITIZENSHIP OR PLACE OF ORGANIZATION
			Delaware
NUMBER OF			5	SOLE VOTING POWER
SHARES
BENEFICIALLY					0 shares
OWNED BY			6	SHARED VOTING POWER
EACH
REPORTING					1,201,718(1)
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					1,201,718(1)
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			1,201,718(1)
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			6.5%(1)
	12	TYPE OF REPORTING PERSON
			CO

⁽¹⁾ Excludes 217,877 Shares (as defined herein) underlying the Warrants (as defined herein) that are not exercisable due to the Beneficial Ownership Limitation (as defined herein), which provides that the Warrants may not be exercised if, after such exercise, the Reporting Persons would beneficially own more than 4.99% of the Shares outstanding.

7

CUSIP No. 02083G100

	1	NAME OF REPORTING PERSON
			Mark N. Lampert
	2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP				(a) ☒
						(b) ☐
	3	SEC USE ONLY
	4	CITIZENSHIP OR PLACE OF ORGANIZATION
			United States
NUMBER OF			5	SOLE VOTING POWER
SHARES
BENEFICIALLY					0 shares
OWNED BY			6	SHARED VOTING POWER
EACH
REPORTING					1,201,718(1)
PERSON WITH			7	SOLE DISPOSITIVE POWER
					0 shares
			8	SHARED DISPOSITIVE POWER
					1,201,718(1)
	9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
			1,201,718(1)
	10	CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES				☐
	11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
			6.5%(1)
	12	TYPE OF REPORTING PERSON
			IN

⁽¹⁾ Excludes 217,877 Shares (as defined herein) underlying the Warrants (as defined herein) that are not exercisable due to the Beneficial Ownership Limitation (as defined herein), which provides that the Warrants may not be exercised if, after such exercise, the Reporting Persons would beneficially own more than 4.99% of the Shares outstanding.

8

CUSIP No. 02083G100

Item 1(a). Name of Issuer:

Alpine Immune Sciences, Inc., a Delaware corporation (the “Issuer”).

Item 1(b). Address of Issuer's Principal Executive Offices:

201 Elliott Avenue West, Suite 230

Seattle, Washington 98119

Item 2(a). Name of Person Filing

Item 2(b). Address of Principal Business Office or, if None, Residence

Item 2(c). Citizenship

Biotechnology Value Fund, L.P. (“BVF”)

44 Montgomery St., 40th Floor

San Francisco, California 94104

Citizenship: Delaware

Biotechnology Value Fund II, L.P. (“BVF2”)

44 Montgomery St., 40th Floor

San Francisco, California 94104

Citizenship: Delaware

Biotechnology Value Trading Fund OS LP (“Trading Fund OS”)

PO Box 309 Ugland House

Grand Cayman, KY1-1104

Cayman Islands

Citizenship: Cayman Islands

BVF Partners OS Ltd. (“Partners OS”)

PO Box 309 Ugland House

Grand Cayman, KY1-1104

Cayman Islands

Citizenship: Cayman Islands

BVF Partners L.P. (“Partners”)

44 Montgomery St., 40th Floor

San Francisco, California 94104

Citizenship: Delaware

BVF Inc.

44 Montgomery St., 40th Floor

San Francisco, California 94104

Citizenship: Delaware

Mark N. Lampert (“Mr. Lampert”)

44 Montgomery St., 40th Floor

San Francisco, California 94104

Citizenship: United States

Each of the foregoing is referred to as a “Reporting Person” and collectively as the “Reporting Persons.”

9

CUSIP No. 02083G100

Item 2(d). Title of Class of Securities:

Common stock, par value $0.001 per share (the “Shares”)

Item 2(e). CUSIP Number:

02083G100

Item 3. If This Statement is Filed Pursuant to Rule 13d-1(b), or 13d-2(b) or (c), Check Whether the Person Filing is a:

	/x/	Not applicable.
(a)	/ /	Broker or dealer registered under Section 15 of the Exchange Act.
(b)	/ /	Bank as defined in Section 3(a)(6) of the Exchange Act.
(c)	/ /	Insurance company as defined in Section 3(a)(19) of the Exchange Act.
(d)	/ /	Investment company registered under Section 8 of the Investment Company Act.
(e)	/ /	An investment adviser in accordance with Rule 13d-1(b)(1)(ii)(E).
(f)	/ /	An employee benefit plan or endowment fund in accordance with Rule 13d-1(b)(1)(ii)(F).
(g)	/ /	A parent holding company or control person in accordance with Rule 13d-1(b)(1)(ii)(G).
(h)	/ /	A savings association as defined in Section 3(b) of the Federal Deposit Insurance Act.
(i)	/ /	A church plan that is excluded from the definition of an investment company under Section 3(c)(14) of the Investment Company Act.
(j)	/ /	Group, in accordance with Rule 13d-1(b)(1)(ii)(J).
(k)	/ /	Group, in accordance with Rule 240.13d-1(b)(1)(ii)(K). If filing as a non-U.S. institution in accordance with Rule 240.13d-1(b)(1)(ii)(J), please specify the type of institution: ____

Item 4. Ownership

(a) Amount beneficially owned:

As of the close of business on January 28, 2019, the Reporting Persons hold 217,877 warrants, exercisable for an aggregate of 217,877 Shares (the “Warrants”). Each Warrant entitles the holder thereof to acquire one (1) Share for an exercise price of $12.74 per Share, subject to adjustments as provided under the terms of the Warrants. The Warrants are only exercisable to the extent that the holder, together with its affiliates and any other person or entity acting as a group, would not beneficially own more than 4.99% of the outstanding Shares after giving effect to such exercise, as such percentage ownership is determined in accordance with the terms of the Warrants (the “Beneficial Ownership Limitation”). As of January 28, 2019, the Beneficial Ownership Limitation limits the aggregate exercise of the Warrants by the Reporting Persons to zero out of the 217,877 Shares underlying the Warrants owned by the Reporting Persons in the aggregate. BVF holds Warrants to purchase 112,610 additional Shares which are excluded herein as a result of the Beneficial Ownership Limitation. BVF2 holds Warrants to purchase 92,035 additional Shares which are excluded herein as a result of the Beneficial Ownership Limitation. Trading Fund OS holds Warrants to purchase 13,232 additional Shares which are excluded herein as a result of the Beneficial Ownership Limitation.

10

CUSIP No. 02083G100

As of the close of business on January 28, 2019, (i) BVF beneficially owned 584,078 Shares, (ii) BVF2 beneficially owned 460,853 Shares, and (iii) Trading Fund OS beneficially owned 84,524 Shares.

Partners OS, as the general partner of Trading Fund OS, may be deemed to beneficially own the 84,524 Shares beneficially owned by Trading Fund OS.

Partners, as the general partner of BVF, BVF2, the investment manager of Trading Fund OS, and the sole member of Partners OS, may be deemed to beneficially own the 1,201,718 Shares beneficially owned in the aggregate by BVF, BVF2, Trading Fund OS, and a certain Partners managed account (the “Partners Managed Account”), including 72,263 Shares held in the Partners Managed Account.

BVF Inc., as the general partner of Partners, may be deemed to beneficially own the 1,201,718 Shares owned by Partners.

Mr. Lampert, as a director and officer of BVF Inc., may be deemed to beneficially own the 1,201,718 Shares beneficially owned by BVF Inc.

The foregoing should not be construed in and of itself as an admission by any Reporting Person as to beneficial ownership of any Shares owned by another Reporting Person. Partners OS disclaims beneficial ownership of the Shares beneficially owned by Trading Fund OS. Each of Partners, BVF Inc. and Mr. Lampert disclaims beneficial ownership of the Shares beneficially owned by BVF, BVF2, Trading Fund OS, and the Partners Managed Account, and the filing of this statement shall not be construed as an admission that any such person or entity is the beneficial owner of any such securities.

(b) Percent of class:

This percentage is calculated based upon 18,559,164 Shares outstanding, which is the sum of: (i) 13,852,464 Shares outstanding as of November 1, 2018, as set forth in the Issuer’s quarterly report filed on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on November 8, 2018 and (ii) 4,706,700 Shares issued, as disclosed in the Issuer’s current report on Form 8-K filed with the SEC on January 16, 2019.

As of the close of business on January 28, 2019 (i) BVF beneficially owned approximately 3.1% of the outstanding Shares, (ii) BVF2 beneficially owned approximately 2.5% of the outstanding Shares, (iii) Trading Fund OS beneficially owned less than 1% of the outstanding Shares, (iv) Partners OS may be deemed to beneficially own less than 1% of the outstanding Shares, and (v) each of Partners, BVF Inc. and Mr. Lampert may be deemed to beneficially own approximately 6.5% of the outstanding Shares (less than 1% of the outstanding Shares is held in the Partners Managed Account).

(c) Number of shares as to which such person has:

(i) Sole power to vote or to direct the vote

See Cover Pages Items 5-9.

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CUSIP No. 02083G100

(ii) Shared power to vote or to direct the vote

See Cover Pages Items 5-9.

(iii) Sole power to dispose or to direct the disposition of

See Cover Pages Items 5-9.

(iv) Shared power to dispose or to direct the disposition of

See Cover Pages Items 5-9.

Item 5. Ownership of Five Percent or Less of a Class.

Not Applicable.

Item 6. Ownership of More than Five Percent on Behalf of Another Person.

Partners, BVF Inc. and Mr. Lampert share voting and dispositive power over the Shares beneficially owned by BVF, BVF2, Trading Fund OS, and the Partners Managed Account.

Item 7. Identification and Classification of the Subsidiary That Acquired the Security Being Reported on by the Parent Holding Company or Control Person.

Not Applicable.

Item 8. Identification and Classification of Members of the Group.

See Exhibit 99.1.

Item 9. Notice of Dissolution of Group.

Not Applicable.

Item 10. Certifications.

By signing below each of the undersigned certifies that, to the best of its knowledge and belief, the securities referred to above were not acquired and are not held for the purpose of or with the effect of changing or influencing the control of the issuer of the securities and were not acquired and are not held in connection with or as a participant in any transaction having that purpose or effect.

12

CUSIP No. 02083G100

SIGNATURE

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

Dated: January 28, 2019

BIOTECHNOLOGY VALUE FUND, L.P.		BVF INC.
By:	BVF Partners L.P., its general partner	By:	/s/ Mark N. Lampert
By:	BVF Inc., its general partner		Mark N. Lampert
			President
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President	/s/ Mark N. Lampert
		MARK N. LAMPERT
BIOTECHNOLOGY VALUE FUND II, L.P.
By:	BVF Partners L.P., its general partner
By:	BVF Inc., its general partner
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President
BVF PARTNERS L.P.
By:	BVF Inc., its general partner
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President
BVF PARTNERS OS LTD.
By:	BVF Partners L.P., its sole member
By:	BVF Inc., its general partner
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President
Biotechnology Value Trading Fund OS LP
By:	BVF Partners L.P., its investment manager
By:	BVF Inc., its general partner
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President

13

EX-99.1

Exhibit 99.1

Joint Filing Agreement

The undersigned hereby agree that the Statement on Schedule 13G dated January 28, 2019 with respect to the common stock, par value $0.001 per share, of Alpine Immune Sciences, Inc., and any further amendments thereto executed by each and any of the undersigned shall be filed on behalf of each of the undersigned pursuant to and in accordance with the provisions of Rule 13d-1(k)(1) under the Securities Exchange Act of 1934, as amended.

Dated: January 28, 2019

BIOTECHNOLOGY VALUE FUND, L.P.		BVF INC.
By:	BVF Partners L.P., its general partner	By:	/s/ Mark N. Lampert
By:	BVF Inc., its general partner		Mark N. Lampert
			President
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President	/s/ Mark N. Lampert
		MARK N. LAMPERT
BIOTECHNOLOGY VALUE FUND II, L.P.
By:	BVF Partners L.P., its general partner
By:	BVF Inc., its general partner
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President
BVF PARTNERS L.P.
By:	BVF Inc., its general partner
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President
BVF PARTNERS OS LTD.
By:	BVF Partners L.P., its sole member
By:	BVF Inc., its general partner
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President
Biotechnology Value Trading Fund OS LP
By:	BVF Partners L.P., its investment manager
By:	BVF Inc., its general partner
By:	/s/ Mark N. Lampert
	Mark N. Lampert
	President