Material Agreement (Form 8-K)

Item 1.01. Entry into a Material Definitive Agreement.

On September 24, 2025, Hyperion DeFi, Inc. (the "Company") entered into Amendment No. 1 (the "Amendment") to the Amended and Restated Sales Agreement (the "A&R Sales Agreement") with Chardan Capital Markets, LLC, with respect to the Company's existing at-the-market offering program. The Amendment, among other things, increases the aggregate offering price under the A&R Sales Agreement from $50 million to $100 million.

The issuance and sale of shares of the Company's common stock, par value $0.0001 per share (the "Common Stock"), by the Company under the A&R Sales Agreement have been, and the future issuance and sale of shares, if any, will be, pursuant to the Company's Registration Statement on Form S-3 (File No. 333-282458) filed with the U.S. Securities and Exchange Commission (the "SEC") on October 1, 2024 (the "Registration Statement"), and the prospectus supplement relating to the at-the-market offering program dated October 8, 2024, as further supplemented from time to time. As of September 24, 2025, the Company has offered and sold 4,176,196 shares of Common Stock pursuant to the A&R Sales Agreement for net proceeds of approximately $29.0 million, after deducting commissions and offering expenses.

The foregoing description of the Amendment does not purport to be complete and is qualified in its entirety by reference to the complete text of the Amendment, a copy of which is incorporated herein by reference as Exhibit 1.1.

The legal opinion of Covington & Burling LLP relating to the additional shares of Common Stock that may be sold under the Company's at-the-market offering program is filed herewith as Exhibit 5.1.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the Common Stock discussed herein, nor shall there be any offer, solicitation, or sale of the Common Stock in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.