Material Agreement (Form 8-K)

On September 9, 2025, Amylyx Pharmaceuticals, Inc. ("Amylyx" or the "Company") entered into an underwriting agreement (the "Underwriting Agreement") with Leerink Partners LLC and Guggenheim Securities, LLC, as representatives of the several underwriters named therein (the "Underwriters"), relating to the issuance and sale of an aggregate of 17,500,000 shares (the "Firm Shares") of the Company's common stock, par value $0.0001 per share ("Common Stock"), at a price to the public of $10.00 per share (the "Offering"). Pursuant to the Underwriting Agreement, the Company also granted the Underwriters a 30-dayoption to purchase up to 2,625,000 additional shares of Common Stock at the public offering price less the underwriting discounts and commissions (the "Option Shares" and together with the Firm Shares, the "Shares").

The aggregate net proceeds to the Company, after deducting underwriting discounts and commissions and other estimated offering expenses payable by the Company, will be approximately $164.0 million, or approximately $188.7 million if the option to purchase the Option Shares is exercised in full by the Underwriters. Amylyx intends to use the net proceeds from this Offering, together with existing cash, cash equivalents and marketable securities, to advance avexitide commercial readiness and for research and development, working capital and other general corporate purposes. The Offering is expected to close on September 11, 2025, subject to customary closing conditions. All of the Shares in the Offering are being sold by the Company.

The Underwriting Agreement contains customary representations and warranties, conditions to closing, market standoff provisions, termination provisions and indemnification obligations, including for liabilities under the Securities Act of 1933, as amended. The representations, warranties and covenants contained in the Underwriting Agreement were made only for purposes of such agreement and as of specific dates, and were solely for the benefit of the parties to the Underwriting Agreement.

The Offering is being made pursuant to a prospectus supplement, dated September 9, 2025 (the "Prospectus Supplement"), filed with the Securities and Exchange Commission ("SEC") on September 10, 2025, and an accompanying base prospectus that forms a part of the registration statement on Form S-3(File No. 333-285525), filed with the SEC on March 4, 2025 and declared effective by the SEC on March 26, 2025. This Current Report on Form 8-Kdoes not constitute an offer to sell or a solicitation of an offer to buy shares of Common Stock.

The foregoing description of certain terms of the Underwriting Agreement and the transactions contemplated thereby does not purport to be complete, and is subject to and qualified in its entirety by reference to the full text of the Underwriting Agreement that is filed as Exhibit 1.1 to this Current Report on Form 8-Kand is incorporated by reference herein.

The legal opinion of Goodwin Procter LLP relating to the legality of the issuance and sale of the Shares in the Offering is filed as Exhibit 5.1 to this Current Report on Form 8-K.