13G Filing: Biotechnology Value Fund LP and Alpine Immune Sciences Inc. (ALPN)

 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. 3)¹

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

Alpine Immune Sciences, Inc., a Delaware corporation (the
“Issuer”) (formerly known as Nivalis Therapeutics, Inc.).

201 Elliot Ave. West, Suite 230

Seattle, Washington 98119

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

1 Sansome Street, 30^th Floor

San Francisco, California 94104

Citizenship: Delaware

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

1 Sansome Street, 30^th 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”)

1 Sansome Street, 30th Floor

San Francisco, California 94104

Citizenship: Delaware

BVF Inc.

1 Sansome Street, 30^th Floor

San Francisco, California 94104

Citizenship: Delaware

Mark N. Lampert (“Mr. Lampert”)

1 Sansome Street, 30^th 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.”

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

02083G100

On July 24, 2017, the Issuer completed
a business combination with what was then known as “Alpine Immune Sciences, Inc.” (“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 Issuer, Nautilus
Merger Sub, Inc. (“Merger Sub”), and Alpine, pursuant to which Merger Sub merged with and into Alpine, with Alpine
surviving as a wholly owned subsidiary of the Issuer (the “Merger”). On the same date, in connection with, and prior
to the completion of, the Merger, the Issuer effected a 1:4 reverse stock split of its Common Stock, and on the same date, immediately
after the completion of the Merger, the Issuer changed its name to “Alpine Immune Sciences, Inc.” Immediately after
the Merger, the Issuer’s stockholders, warrantholders and optionholders immediately prior to the Merger owned, or held rights
to acquire, approximately 26% of the fully-diluted Common Stock of the Issuer.

As of the close of business on July
25, 2017 (i) BVF beneficially owned 277,314 shares of Common Stock, (ii) BVF2 beneficially owned 179,272 shares of Common Stock,
and (iii) Trading Fund OS beneficially owned 50,452 shares of Common Stock.

Partners OS as the general partner
of Trading Fund OS may be deemed to beneficially own the 50,452 shares of Common Stock 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
661,200 shares of Common Stock beneficially owned in the aggregate by BVF, BVF2, Trading Fund OS, and certain Partners managed
accounts (the “Partners Managed Accounts”), including 154,162 shares of Common Stock held in the Partners Managed Accounts.

BVF Inc., as the general partner of
Partners, may be deemed to beneficially own the 661,200 shares of Common Stock beneficially owned by Partners.

Mr. Lampert, as a director and officer
of BVF Inc., may be deemed to beneficially own the 661,200 shares of Common Stock 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 of Common Stock owned by another
Reporting Person. Partners OS disclaims beneficial ownership of the shares of Common Stock beneficially owned by Trading Fund OS.
Each of Partners, BVF Inc. and Mr. Lampert disclaims beneficial ownership of the shares of Common Stock beneficially owned by BVF,
BVF2, Trading Fund OS, and the Partners Managed Accounts, 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.

The following percentages are based
on 13,881,645 shares of Common Stock outstanding as of July 24, 2017, as disclosed in the Issuer’s Current Report filed on
Form 8-K with the Securities and Exchange Commission on July 25, 2017.

As of the close of business on July
25, 2017 (i) BVF beneficially owned approximately 2.0% of the outstanding shares of Common Stock, (ii) BVF2 beneficially owned
approximately 1.3% of the outstanding shares of Common Stock, (iii) Trading Fund OS beneficially owned less than 1% of the outstanding
shares of Common Stock (iv) Partners OS may be deemed to beneficially own less than 1% of the outstanding shares of Common Stock,
and (v) each of Partners, BVF Inc. and Mr. Lampert may be deemed to beneficially own approximately 4.8% of the outstanding shares
of Common Stock (approximately 1.1% of which is held in the Partners Managed Accounts).

See Cover Pages Items 5-9.

See Cover Pages Items 5-9.

See Cover Pages Items 5-9.

See Cover Pages Items 5-9.

If this statement is being filed to
report the fact that as of the date hereof the reporting person has ceased to be the beneficial owner of more than five percent
of the class of securities, check the following [X].

Partners, BVF Inc. and Mr. Lampert
share voting and dispositive power over the shares of Common Stock beneficially owned by BVF, BVF2, Trading Fund OS, and the Partners
Managed Accounts.

Not Applicable.

See Exhibit 99.1 to the Schedule 13G
filed by the Reporting Persons with the Securities and Exchange Commission on December 21, 2015.

Not Applicable.

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.

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: July 27, 2017