UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

SCHEDULE 13D

Under the Securities Exchange Act of 1934

(Amendment No.     )*

Milestone Pharmaceuticals Inc.

(Name of Issuer)

Common Shares, no par value per share

(Title of Class of Securities)

59935V107

(CUSIP Number)

Peter Haahr

Novo Holdings A/S

Tuborg Havnevej 19

Hellerup, Denmark DK-2900

+45 3527 6592

Copy to:

B. Shayne Kennedy, Esq.

Latham & Watkins LLP

650 Town Center Drive, 20^th Floor

Costa Mesa, CA 92626

Telephone: (714) 540-1235

(Name, Address and Telephone Number of Person

Authorized to Receive Notices and Communications)

May 13, 2019

(Date of Event which Requires Filing of this Statement)

If the filing person has previously filed a statement on Schedule 13G to report the acquisition which is subject of this Schedule 13D, and is filing this statement because of Rule 13d-1(e), 13d-1(f) or 13d-1(g), check the following box. [    ]

Note: Schedules filed in paper format shall include a signed original and five copies of the schedule, including all exhibits. See Rule 13d-7(b) for other parties to whom copies are to be sent.

The information required on the remainder of this cover page shall not be deemed to be “filed” for the purpose of Section 18 of the Securities Exchange Act of 1934 (the “Act”) or otherwise subject to the liabilities of that section of the Act but shall be subject to all other provisions of the Act (however, see the Notes).

CUSIP No.: 59935V107

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This Schedule 13D relates to the common shares, no par value (the “Common Shares”), of Milestone Pharmaceuticals Inc., a Québec corporation (the “Issuer”). The Issuer’s principal executive office is located at 1111 Dr. Frederik-Phillips Boulevard, Suite 420, Montréal, Québec H4M 2X6.

The name of each director and executive officer of both Novo Holdings A/S and the Foundation is set forth on Schedule I to this Schedule 13D.

The residence or business address of each director and executive officer of both Novo Holdings A/S and the Foundation is set forth on Schedule I to this Schedule 13D.

The Foundation is a Danish self-governing and profit-making foundation, whose objectives are to provide a stable basis for commercial and research activities undertaken by the group of Novo companies and to support scientific, humanitarian and social purposes through grants.

Prior to the Issuer’s initial public offering (the “IPO”) and after giving effect to the Issuer’s reverse split of preferred shares effected on April 26, 2019, the Reporting Person held the following securities of the Issuer:

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The purchase price of the Preferred Stock was paid by Novo Holdings A/S from its working capital.

On May 10, 2019, the closing date of the IPO:

The acquisitions of Issuer securities made by Novo Holdings A/S, as described in this Schedule 13D, were for investment purposes. Novo Holdings A/S intends to review its investments in the Issuer on a continuing basis and any actions Novo Holdings A/S might undertake will be dependent upon its review of numerous factors from time to time, including, but not limited to: an ongoing evaluation of the Issuer’s business, financial condition, operations and prospects; price levels of the Issuer’s securities; general market, industry and economic conditions; the relative attractiveness of alternative business and investment opportunities; and other future developments. Novo Holdings A/S may, at any time and from time to time, acquire additional securities of the Issuer, or retain or sell all or a portion of the securities of the Issuer then held, in the open market or in privately negotiated transactions. Other than as described herein, Novo Holdings A/S currently does not have any plans or proposals that relate to, or would result in, any of the matters listed in Items 4(a)–(j) of Schedule 13D, although, depending on the factors discussed herein, Novo Holdings A/S may change its purpose or formulate different plans or proposals with respect thereto at any time.

(a)    Novo Holdings A/S beneficially owns 2,674,470 Common Shares (the “Novo Shares”) representing approximately 11.31% of the Issuer’s outstanding Common Shares, based upon 23,647,589 of the Issuer’s Common Shares outstanding after the Issuer’s initial public offering, as reported in the Issuer’s prospectus (Form 424B4) filed with the SEC on May 9, 2019.

(b)    Novo Holdings A/S is a Danish limited liability company wholly owned by the Novo Nordisk Foundation. Novo Holdings A/S, through its Board of Directors (the “Novo Board”), has the sole power to vote and dispose of the Novo Shares. The Novo Board may exercise voting and dispositive control over the Novo Shares with approval by a majority of the Novo Board. As such, no individual member of the Novo Board is deemed to hold any beneficial ownership or reportable pecuniary interest in the Novo Shares.

(c)    Novo Holdings A/S has not effected any transactions in the Issuer’s ordinary shares within the past 60 days and neither the Foundation nor any person listed on Schedule I has effected any transactions in the Issuer’s ordinary shares within the past 60 days.

(d)    Novo Holdings A/S does not know of any other person having the right to receive or the power to direct the receipt of dividends from, or the proceeds from the sale of the Issuer’s ordinary shares held in the name of the Novo Holdings A/S and reported herein.

(e)    Not applicable.

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Registration Rights Agreement. The Issuer is a party to a third amended and restated registration rights agreement, dated October 15, 2018, with all holders of preferred shares, including Novo Holdings A/S. This agreement provides that these holders are entitled to certain registration rights, including the right to demand that we file a registration statement or request that their shares be covered by a registration statement or on a registration statement that we otherwise file. The ability to cause the Issuer to effect a registration is subject to certain conditions and certain time frames. The registration rights will terminate upon the earliest of (i) the occurrence of certain mergers or consolidations of the Issuer, (ii) the date on which the shares that are the subject to the agreement are publicly sold, or if they may be publicly sold: (x) pursuant to Rule 144 of the Securities Act and (y) Section 2.5 of Regulation 45-102 respecting Resale of Securities, as adopted by the Canadian Securities Administrators of, (iii) five years after the completion of the IPO.

The Third Amended and Restated Registration Rights Agreement, dated October 15, 2018, was filed by the Issuer as exhibit 4.2 to the Issuer’s Registration Statement on Form S-1 filed with the SEC on April 12, 2019.

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SIGNATURE

After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct.

Schedule I

Information regarding each director and executive officer of both Novo Holdings A/S and the Novo Nordisk Foundation is set forth below.

Novo Holdings A/S

Novo Nordisk Foundation