FORM 4
[ ] Check this box if no longer subject to Section 16. Form 4 or Form 5 obligations may continue. See Instruction 1(b).         
UNITED STATES SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

STATEMENT OF CHANGES IN BENEFICIAL OWNERSHIP OF SECURITIES
                                                                                  
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Filed pursuant to Section 16(a) of the Securities Exchange Act of 1934 or Section 30(h) of the Investment Company Act of 1940
                      

1. Name and Address of Reporting Person *

ORBIMED ADVISORS LLC
2. Issuer Name and Ticker or Trading Symbol

ALPINE IMMUNE SCIENCES, INC. [ ALPN ]
5. Relationship of Reporting Person(s) to Issuer (Check all applicable)

__ X __ Director                      __ X __ 10% Owner
_____ Officer (give title below)      _____ Other (specify below)
(Last)          (First)          (Middle)

601 LEXINGTON AVENUE, 54TH FLOOR
3. Date of Earliest Transaction (MM/DD/YYYY)

7/24/2017
(Street)

NEW YORK, NY 10022-4629
(City)        (State)        (Zip)
4. If Amendment, Date Original Filed (MM/DD/YYYY)

 
6. Individual or Joint/Group Filing (Check Applicable Line)

___ Form filed by One Reporting Person
_ X _ Form filed by More than One Reporting Person

Table I - Non-Derivative Securities Acquired, Disposed of, or Beneficially Owned
1.Title of Security
(Instr. 3)
2. Trans. Date 2A. Deemed Execution Date, if any 3. Trans. Code
(Instr. 8)
4. Securities Acquired (A) or Disposed of (D)
(Instr. 3, 4 and 5)
5. Amount of Securities Beneficially Owned Following Reported Transaction(s)
(Instr. 3 and 4)
6. Ownership Form: Direct (D) or Indirect (I) (Instr. 4) 7. Nature of Indirect Beneficial Ownership (Instr. 4)
Code V Amount (A) or (D) Price
Common Stock   7/24/2017     A    3298516   (1) A   (1) 3298516   I   See Footnotes   (2) (3)

Table II - Derivative Securities Beneficially Owned ( e.g. , puts, calls, warrants, options, convertible securities)
1. Title of Derivate Security
(Instr. 3)
2. Conversion or Exercise Price of Derivative Security 3. Trans. Date 3A. Deemed Execution Date, if any 4. Trans. Code
(Instr. 8)
5. Number of Derivative Securities Acquired (A) or Disposed of (D)
(Instr. 3, 4 and 5)
6. Date Exercisable and Expiration Date 7. Title and Amount of Securities Underlying Derivative Security
(Instr. 3 and 4)
8. Price of Derivative Security
(Instr. 5)
9. Number of derivative Securities Beneficially Owned Following Reported Transaction(s) (Instr. 4) 10. Ownership Form of Derivative Security: Direct (D) or Indirect (I) (Instr. 4) 11. Nature of Indirect Beneficial Ownership (Instr. 4)
Code V (A) (D) Date Exercisable Expiration Date Title Amount or Number of Shares

Explanation of Responses:
(1)  Pursuant to that certain Agreement and Plan of Merger and Reorganization (the "Merger Agreement"), dated as of April 18, 2017, by and among the Issuer, Nautilus Merger Sub, Inc. and the corporation then known as Alpine Immune Sciences, Inc. ("Old Alpine"), each share of Old Alpine common stock was converted into 0.4969 shares of the Issuer's common stock (the "Exchange Ratio").
(2)  These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the sole general partner of OPI VI, and OrbiMed Advisors LLC ("Advisors"), a registered adviser under the Investment Advisors Act of 1940, as amended, is the sole managing member of GP VI. Samuel D. Isaly ("Isaly"), a natural person, is the managing member of, and holder of a controlling interest in, Advisors. By virtue of such relationships, GP VI, Advisors and Isaly may be deemed to have voting and investment power with respect to the securities held by OPI VI noted above and as a result may be deemed to have beneficial ownership over such securities.
(3)  This report on Form 4 is jointly filed by GP VI, Advisors, and Isaly. Each of the Reporting Persons disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its or his pecuniary interest therein, if any. The Reporting Persons have designated a representative, currently Peter A. Thompson, an employee of Advisors, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any of the Reporting Persons is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Reporting Owners
Reporting Owner Name / Address
Relationships
Director 10% Owner Officer Other
ORBIMED ADVISORS LLC
601 LEXINGTON AVENUE, 54TH FLOOR
NEW YORK, NY 10022-4629
X X

OrbiMed Capital GP VI LLC
601 LEXINGTON AVENUE, 54TH FLOOR
NEW YORK, NY 10022
X X

ISALY SAMUEL D
601 LEXINGTON AVENUE, 54TH FLOOR
NEW YORK, NY 0022
X X


Signatures
/s/ Samuel D. Isaly 7/26/2017
** Signature of Reporting Person Date


Reminder: Report on a separate line for each class of securities beneficially owned directly or indirectly.
* If the form is filed by more than one reporting person, see Instruction 4(b)(v).
** Intentional misstatements or omissions of facts constitute Federal Criminal Violations. See 18 U.S.C. 1001 and 15 U.S.C. 78ff(a).
Note: File three copies of this Form, one of which must be manually signed. If space is insufficient, see Instruction 6 for procedure.
Persons who respond to the collection of information contained in this form are not required to respond unless the form displays a currently valid OMB control number.
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