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SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

SCHEDULE 13G

UNDER THE SECURITIES EXCHANGE ACT OF 1934

(Name of Issuer)

(Title of Class of Securities)

(CUSIP Number)

(Date of Event Which Requires Filing of this Statement)

Check the appropriate box to designate the rule pursuant to which this Schedule is filed:

Rule 13d-1(b)

Rule 13d-1(c)

Rule 13d-1(d)

SCHEDULE 13D/A 0001829126-25-004860 0001792691 XXXXXXXX LIVE 5 COMMON STOCK, par value $0.0001 per share 09/12/2025 false 0001682639 30234E203 HYPERION DEFI, INC. 23461 South Pointe Drive Suite 390 Laguna Hills CA 92653 Andrew Schinder (212) 878-3520 Avenue Capital Group, 11 West 42nd Street, 9th Floor New York NY 10036 0001792691 N Avenue Venture Opportunities Fund, L.P. OO N DE 0.00 0.00 0.00 0.00 141716.00 Y 2.5 OO (1) Aggregate amount owned includes 141,716 shares of common stock held directly by Avenue Venture Opportunities Fund, L.P ("Fund"), but excludes 140,000 shares of common stock issuable upon exercise of a warrant to purchase shares of Issuer's common stock. Such warrant is exercisable at any time at Fund's option at a per share exercise price of $4.00. As more fully described in Item 5, aggregate beneficial ownership by the Reporting Persons is limited to a 9.99% blocker, and the aggregate amount beneficially owned in row 11 and the percentage set forth in row 13 give effect to such blocker for each Reporting Person. (2) Percent of class is based on 5,694,659 shares of Issuer's common stock outstanding as of August 11, 2025, as reported on Issuer's Form 10-Q for the quarter ending June 30, 2025. 0001886343 N Avenue Venture Opportunities Fund II, L.P. OO N DE 0.00 0.00 0.00 0.00 212575.00 Y 3.7 OO (1) Aggregate amount owned includes 212,575 shares of common stock held directly by Avenue Venture Opportunities Fund II, L.P. ("Fund II"), but excludes 210,000 shares of common stock issuable upon exercise of a warrant to purchase shares of common stock. Such warrant is exercisable at any time at Fund II's option at a per share exercise price of $4.00. As more fully described in Item 5, aggregate beneficial ownership by the Reporting Persons is limited to a 9.99% blocker, and the aggregate amount beneficially owned in row 11 and the percentage set forth in row 13 give effect to such blocker for each Reporting Person. (2) Percent of class is based on 5,694,659 shares of Issuer's common stock outstanding as of August 11, 2025, as reported on Issuer's Form 10-Q for the quarter ending June 30, 2025. 0001317338 N Avenue Capital Management II, L.P. OO N DE 354291.00 0.00 354291.00 0.00 354291.00 Y 6.2 IA (1) Avenue Capital Management II, L.P. is a registered investment adviser and is the manager ("Manager") of each of Fund and Fund II, (the "Funds"). The general partner of each of Fund and Fund II has delegated all management authority to Manager and therefore, Manager has sole voting and dispositive power over all securities of Issuer held by the Funds but disclaims beneficial ownership thereof except to the extent of its pecuniary interest, if any, therein. As more fully described in Item 5, aggregate beneficial ownership by the Reporting Persons is limited to a 9.99% blocker, and the aggregate amount beneficially owned in row 11 and the percentage set forth in row 13 give effect to such blocker for each Reporting Person. (2) Aggregate amount beneficially owned excludes Warrants to purchase an aggregate of 250,000 shares of common stock held by the Funds. (3) Percent of class is based on 5,694,659 shares of Common Stock of Issuer outstanding as of August 11, 2025, as reported on Issuer's Form 10-Q for the quarter ending June 30, 2025. Y Avenue Venture Opportunities Partners, LLC OO N DE 0.00 0.00 0.00 0.00 141716.00 N 2.5 OO (1) Avenue Venture Opportunities Partners, LLC ("AVOP") is the general partner of Fund. AVOP has delegated voting and dispositive power over securities held by Fund to Manager and disclaims beneficial ownership of securities held by Fund, except to the extent of its pecuniary interest, if any, therein. As more fully described in Item 5, aggregate beneficial ownership by the Reporting Persons is limited to a 9.99% blocker, and the aggregate amount beneficially owned in row 11 and the percentage set forth in row 13 give effect to such blocker for each Reporting Person. (2) Percent of class is based on 5,694,659 shares of Issuer's common stock outstanding as of August 11, 2025, as reported on Issuer's Form 10-Q for the quarter ending June 30, 2025. Y Avenue Venture Opportunities Partners II, LLC OO N DE 0.00 0.00 0.00 0.00 212575.00 N 3.7 OO (1) Avenue Venture Opportunities Partners II, LLC ("AVOPII") is the general partner of Fund II. AVOPII has delegated voting and dispositive power over securities held by Fund II to Manager and disclaims beneficial ownership of securities held by Fund II, except to the extent of its pecuniary interest, if any, therein. As more fully described in Item 5, aggregate beneficial ownership by the Reporting Persons is limited to a 9.99% blocker, and the aggregate amount beneficially owned in row 11 and the percentage set forth in row 13 give effect to such blocker for each Reporting Person. (2) Percent of class is based on 5,694,659 shares of Issuer's common stock outstanding as of August 11, 2025, as reported on Issuer's Form 10-Q for the quarter ending June 30, 2025. Y GL Venture Opportunities Partners, LLC OO N DE 0.00 0.00 0.00 0.00 141716.00 N 2.5 OO (1) GL Venture Opportunities Partners, LLC ("GLVOP") is the managing member of AVOP, the general partner of Fund. GLVOP has no voting or dispositive power over securities held by Fund and disclaims beneficial ownership of securities held by Fund, except to the extent of its pecuniary interest, if any, therein. As more fully described in Item 5, aggregate beneficial ownership by the Reporting Persons is limited to a 9.99% blocker, and the aggregate amount beneficially owned in row 11 and the percentage set forth in row 13 give effect to such blocker for each Reporting Person. (2) Percent of class is based on 5,694,659 shares of Issuer's common stock outstanding as of August 11, 2025, as reported on Issuer's Form 10-Q for the quarter ending June 30, 2025. Y GL Venture Opportunities Partners II, LLC OO N DE 0.00 0.00 0.00 0.00 212575.00 N 3.7 OO (1) GL Venture Opportunities Partners II, LLC ("GLVOPII") is the managing member of AVOPII, the general partner of Fund II. GLVOPII has no voting or dispositive power over securities held by Fund II and disclaims beneficial ownership of securities held by Fund II, except to the extent of its pecuniary interest, if any, therein. As more fully described in Item 5, aggregate beneficial ownership by the Reporting Persons is limited to a 9.99% blocker, and the aggregate amount beneficially owned in row 11 and the percentage set forth in row 13 give effect to such blocker for each Reporting Person. (2) Percent of class is based on 5,694,659 shares of Issuer's common stock outstanding as of August 11, 2025, as reported on Issuer's Form 10-Q for the quarter ending June 30, 2025. 0001259927 N Marc Lasry OO N X1 0.00 0.00 0.00 0.00 354291.00 N 6.2 IN (1) Marc Lasry is the beneficial owner of GLVOP and GLVOPII and therefore is the ultimate beneficial owner of the Funds. Mr. Lasry does not have voting or dispositive power over securities held by the Funds. As more fully described in Item 5, aggregate beneficial ownership by the Reporting Persons is limited to a 9.99% blocker, and the aggregate amount beneficially owned in row 11 and the percentage set forth in row 13 give effect to such blocker for each Reporting Person. (2) Percent of class is based on 5,694,659 shares of Issuer's common stock outstanding as of August 11, 2025, as reported on Issuer's Form 10-Q for the quarter ending June 30, 2025. COMMON STOCK, par value $0.0001 per share HYPERION DEFI, INC. 23461 South Pointe Drive Suite 390 Laguna Hills CA 92653 This Amendment No. 5 (this "Amendment") amends the Schedule 13D, filed with the Securities and Exchange Commission (the "SEC") on May 15, 2025, as amended by Amendment No. 1, filed with the SEC on June 3, 2025, Amendment No. 2, filed with the SEC on June 13, 2025, Amendment No. 3, filed with the SEC on June 20, 2025, and Amendment No. 4, filed with the SEC on July 2, 2025 (collectively, the "Schedule 13D"), by the Reporting Persons with respect to the common stock, par value $0.0001 per share (the "Common Stock"), of Hyperion DeFi, Inc. ("Issuer"). Only those items that are hereby reported are amended; all other items in the Schedule 13D remain unchanged. Information given in response to each item shall be deemed incorporated by reference, as applicable. Capitalized terms not defined in this Amendment have the meanings ascribed to them in the Schedule 13D. The information set forth in Item 2(a) of the Schedule 13D is incorporated by reference. The Reporting Persons expressly disclaim status as a "group" for purposes of this Amendment. The agreement among the Reporting Persons to file jointly in accordance with the provisions of Rule 13d-1(k)(1) under the Act is attached to the Schedule 13D as Exhibit 99.1 thereto. Other than those securities reported herein as being held directly by such Reporting Person, each Reporting Person disclaims beneficial ownership of all securities reported in this Amendment except to the extent of such Reporting Person's pecuniary interest, if any, therein. The information set forth in Item 2(b) of the Schedule 13D is incorporated by reference. The information set forth in Item 2(c) of the Schedule 13D is incorporated by reference. The information set forth in Item 2(d) of the Schedule 13D is incorporated by reference. The information set forth in Item 2(e) of the Schedule 13D is incorporated by reference. The information set forth in Item 2(f) of the Schedule 13D is incorporated by reference. The information set forth in Item 3 of the Schedule 13D is incorporated herein by reference. (a) - (c) The information set forth in Item 4 of the Scheule 13D is incorporated by reference. This Amendment is being filed to report a change in Reporting Persons' beneficial ownership due to an increase in Issuer's outstanding shares of Common Stock. See Items 7-11 and Item 13 of the cover page for each Reporting Person. The Reporting Persons are subject to a blocker that limits their beneficial ownership to 9.99% of the outstanding shares of Common Stock of the Issuer (the "Blocker"). The aggregate beneficial ownership by each Reporting Person gives effect to the Blocker and therefore excludes shares of common stock issuable upon exercise of the Warrants. The Blocker of 9.99% may be changed to up to 19.99% at the Reporting Persons' election upon at least 61 days' notice to the Issuer. See Items 7 through 11 of the cover page for each Reporting Person. Not applicable. The information set for in Item 5(d) of the Schedule 13D is incorporated by reference. See Item 4. The information set forth in Item 6 of the Schedule 13D is incorporated herein by reference. Exhibit 99.1: Joint Filing Agreement by and among the Reporting Persons (filed as Exhibit 99.1 to Schedule 13D on May 15, 2025). https://www.sec.gov/Archives/edgar/data/1682639/000182912625003724/avenueventure_ex99-1.htm Avenue Venture Opportunities Fund, L.P. /s/ Andrew Schinder Andrew Schinder POA for Marc Lasry, Member, GL Venture Opportunities Partners LLC, Man. Member Avenue Venture Opportunities Partners LLC, Gen. Ptnr. 09/17/2025 Avenue Venture Opportunities Fund II, L.P. /s/ Andrew Schinder Andrew Schinder POA for Marc Lasry, Member GL Venture Opportunities Partners II LLC, Man. Mbr Avenue Venture Opportunities Partners II LLC, Gen. Ptnr. 09/17/2025 Avenue Capital Management II, L.P. /s/ Andrew Schinder Andrew Schinder POA for Marc Lasry, Member of Avenue Capital Management II GenPar, LLC, General Partner 09/17/2025 Avenue Venture Opportunities Partners, LLC /s/ Andrew Schinder Andrew Schinder POA for Marc Lasry, Member of GL Venture Opportunities Partners, LLC, Managing Member 09/17/2025 Avenue Venture Opportunities Partners II, LLC /s/ Andrew Schinder Andrew Schinder POA for Marc Lasry, Member of GL Venture Opportunities Partners II, LLC, Managing Member 09/17/2025 GL Venture Opportunities Partners, LLC /s/ Andrew Schinder Andrew Schinder POA for Marc Lasry, Member 09/17/2025 GL Venture Opportunities Partners II, LLC /s/ Andrew Schinder Andrew Schinder POA for Marc Lasry, Member 09/17/2025 Marc Lasry /s/ Andrew Schinder Andrew Schinder POA for Marc Lasry 09/17/2025