Peter A. Thompson - 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 the Parent (Merger Sub). Pursuant to the Merger Agreement, Merger Sub completed a tender offer for shares of the Company 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

(Continued from Footnote 1) In connection with the consummation of the Transactions, each share of the 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 (the Merger Consideration), 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") 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

Each of the Reporting Person, GP VI, Genesis GP and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) of the Exchange Act, except to the extent of its or his pecuniary interest therein, if any. This report shall not be deemed an admission that any such entity or person, including the Reporting Person, is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Footnote F5

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 F6

The exercise price is equal to the closing price per share of Common Stock as reported on the Nasdaq Global Market on the date of grant.

Footnote F7

The option to purchase shares of Company Common Stock (the Company Option) is fully vested and exercisable.

Footnote F8

Pursuant to the Merger Agreement, as of immediately prior to the Effective Time, each option to purchase shares of Company Common Stock (a Company Option) that was then outstanding but not then vested or exercisable became immediately vested and exercisable in full. At the Effective Time, each Company Option that was then outstanding was automatically cancelled and, if such Company Option had a per share exercise price less than the Merger Consideration, the holder thereof became entitled to receive a cash payment, without interest thereon and subject to any applicable tax withholding, equal to the product obtained by multiplying (i) the total number of shares of Company Common Stock underlying such Company Option by (ii) the excess of the Merger Consideration over the exercise price per share such Company Option.

Footnote F9

(Continued from Footnote 8) Any Company Option that had an exercise price per share that was equal to or exceeded the Merger Consideration was cancelled without any cash payment or other consideration being made in respect thereof.

Footnote F10

1/12 of the shares subject to the option become vested and exercisable on February 2, 2024 and 1/12 of the shares subject to the option shall vest monthly thereafter.