ORBIMED ADVISORS LLC - 18 May 2024 Form 4 Insider Report for ALPINE IMMUNE SCIENCES, INC.

Footnote F1

This Form 4 reports securities disposed of pursuant to the Agreement and Plan of Merger (the "Merger Agreement"), dated April 10, 2024, among Alpine Immune Sciences, Inc., a Delaware corporation (the "Company"), Vertex Pharmaceuticals Incorporated, a Massachusetts corporation ("Parent"), and Adams Merger Sub, Inc., a Delaware corporation and a wholly owned subsidiary of Parent ("Merger Sub"). Pursuant to the Merger Agreement, Merger Sub completed a tender offer for shares of the Company's Common Stock, par value $0.001 per share ("Company Common Stock"), effective May 18, 2024 (the "Offer Closing"), and thereafter merged with and into the Company (the "Merger", and together with the Offer Closing, the "Transactions"), effective May 20, 2024 (the "Effective Time"), with the Company surviving the Merger as a wholly owned subsidiary of Parent.

Footnote F2

In connection with the consummation of the Transactions, each share of Company Common Stock was either (x) purchased at the Offer Closing for $65.00 in cash per share (the "Offer Price"), without interest thereon and subject to any applicable tax withholding, or (y) automatically converted in the Merger at the Effective Time into the right to receive the Offer Price in cash, without interest thereon, subject to any applicable tax withholding.

Footnote F3

These securities are held of record by OrbiMed Private Investments VI, LP ("OPI VI"). OrbiMed Capital GP VI LLC ("GP VI") is the general partner of OPI VI, and OrbiMed Advisors LLC ("OrbiMed Advisors"), a registered investment adviser under the Investment Advisers Act of 1940, as amended, is the managing member of GP VI. By virtue of such relationships, GP VI and OrbiMed Advisors may be deemed to have voting power and investment power over the securities held by OPI VI and as a result, may be deemed to have beneficial ownership over such securities. OrbiMed Advisors exercises voting and investment 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 VI.

Footnote F4

These securities are held of record by OrbiMed Genesis Master Fund, L.P. ("Genesis"). OrbiMed Genesis GP LLC ("Genesis GP") is the general partner of Genesis, and OrbiMed Advisors is the managing member of Genesis GP. By virtue of such relationships, Genesis GP and OrbiMed Advisors may be deemed to have voting power and investment power over the securities held by Genesis and as a result, may be deemed to have beneficial ownership over such securities. OrbiMed Advisors exercises voting and investment 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.

Footnote F5

This report on Form 4 is jointly filed by OrbiMed Advisors, GP VI, and Genesis GP. 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 pecuniary interest therein, if any. The Reporting Persons have designated a representative, Peter A. Thompson, a member of OrbiMed Advisors, to serve on the Company's board of directors. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for purposes of Section 16 of the Exchange Act, or for any other purpose.