May 31, 2023

Milestone Pharmaceuticals Inc.

1111 Dr. Frederik-Philips Boulevard
Montreal, Québec

H4M 2X6

Dear Sirs/Mesdames:

Re: Milestone Pharmaceuticals Inc. – Prospectus Supplement to Registration Statement on Form S-3

We have acted as Canadian counsel to Milestone Pharmaceuticals Inc. (the “Corporation”), a corporation governed by the Business Corporations Act (Québec), in connection with the preparation of a prospectus supplement May 31, 2023 (the “Prospectus Supplement”) to the Corporation’s prospectus dated November 12, 2021 (together with the Prospectus Supplement, the “Prospectus”) relating to the sale by the Corporation of common shares of the Corporation (the “Shares”) having an aggregate offering price of up to US$47,249,368 pursuant to the Open Market Sale Agreement^SM(the “Sales Agreement”) entered into between the Corporation and Jefferies LLC, as agent and/or principal thereunder. The Prospectus forms a part of the Corporation’s registration statement on Form S-3 (No. 333-261049) (the “Registration Statement”) filed with the Securities and Exchange Commission (the “SEC”) under the Securities Act of 1933, as amended (the “Securities Act”), which was declared effective under the Securities Act on February 2, 2022.

We have examined the Registration Statement, the Prospectus and the Sales Agreement and all such corporate and public records, statutes and regulations and have made such investigations and have reviewed such other documents as we have deemed relevant and necessary and have considered such questions of law as we have considered relevant and necessary in order to give the opinion hereinafter set forth. As to various questions of fact material to such opinions which were not independently established, we have relied upon a certificate of an officer of the Corporation.

In reviewing the foregoing documents and in giving this opinion, we have assumed (a) the legal capacity of all individuals, the genuineness of all signatures, the veracity of the information contained therein, the authenticity of all documents submitted to us as originals and the conformity to authentic or original documents of all documents submitted to us as certified, conformed, electronic, photostatic or facsimile copies and (b) the completeness, truth and accuracy of all facts set forth in the official public records, certificates and documents supplied by public officials or otherwise conveyed to us by public officials.

We are qualified to practice law in the Province of Québec and this opinion is rendered solely with respect to the Province of Québec and the federal laws of Canada applicable in the Province of Québec.

Where our opinion expressed herein refers to the Shares having been issued as being “fully-paid and non-assessable” common shares of the Corporation, such opinion assumes that all required consideration (in whatever form) has been paid or provided. No opinion is expressed as to the adequacy of any consideration received.