X0306 4 2017-07-24 0 0001626199 ALPINE IMMUNE SCIENCES, INC. ALPN 0001055951 ORBIMED ADVISORS LLC 601 LEXINGTON AVENUE, 54TH FLOOR NEW YORK NY 10022-4629 1 0 1 0 0001682115 OrbiMed Capital GP VI LLC 601 LEXINGTON AVENUE, 54TH FLOOR NEW YORK NY 10022 1 0 1 0 0001055949 ISALY SAMUEL D 601 LEXINGTON AVENUE, 54TH FLOOR NEW YORK NY 0022 1 0 1 0 Common Stock 2017-07-24 4 A 0 3298516 A 3298516 I See Footnotes 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"). 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. 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. /s/ Samuel D. Isaly 2017-07-26