X0202 SCHEDULE 13D/A 0001193125-23-180612 0001802528 XXXXXXXX LIVE 6 Common Stock, $0.0001 par value 04/16/2026 false 0001636282 00773J202 SPYRE THERAPEUTICS, INC.

221 Crescent Street Building 23, Suite 105 Waltham MA 02453

Ms. Erin O'Connor (267) 262-5300 Fairmount Funds Management LLC 200 Barr Harbor Drive, Suite 400 West Conshohocken PA 19428 0001802528 N Fairmount Funds Management LLC a AF N DE 0.00 8184941.00 0.00 8184941.00 8184941.00 N 9.09 IA The securities include (i) 4,018,101 shares of common stock, $0.0001 par value per share (the "Common Stock") and (ii) 4,166,840 shares of Common Stock issuable upon conversion of 104,171 shares of Series A Preferred Stock, par value $0.0001 per share (the "Series A Preferred Stock"), held directly by Fairmount Healthcare Fund II L.P. ("Fund II"). The securities exclude shares of Common Stock issuable upon conversion of shares of Series A Preferred Stock and Series B Preferred Stock, par value $0.0001 per share (the "Series B Preferred Stock") held directly by Fund II in excess of the beneficial ownership limitation of 9.99%. Row 13 is based on 90,060,297 shares of Common Stock outstanding as of April 16, 2026, consisting of (i) 85,664,811 shares of Common Stock outstanding as of April 16, 2026, as reported in the Company's final prospectus supplement filed pursuant to Rule 424(b)(5) dated April 14, 2026, (ii) 228,646 shares underlying options that are currently exercisable or will be exercisable within 60 days of the date of this filing by the Reporting Persons and (iii) 4,166,840 shares of Common Stock underlying the 104,171 shares of Series A Preferred Stock owned by Fund II, applying the beneficial ownership limitation. 0001769651 N Fairmount Healthcare Fund II L.P. a AF N DE 0.00 8184941.00 0.00 8184941.00 8184941.00 N 9.09 PN The securities include (i) 4,018,101 shares of Common Stock and (ii) 4,166,840 shares of Common Stock issuable upon conversion of 104,171 shares of Series A Preferred Stock held directly by Fund II. The securities exclude shares of Common Stock issuable upon conversion of shares of Series A Preferred Stock and Series B Preferred Stock held directly by Fund II in excess of the beneficial ownership limitation of 9.99%. Row 13 is based on 90,060,297 shares of Common Stock outstanding as of April 16, 2026, consisting of (i) 85,664,811 shares of Common Stock outstanding as of April 16, 2026, as reported in the Company's final prospectus supplement filed pursuant to Rule 424(b)(5) dated April 14, 2026, (ii) 228,646 shares underlying options that are currently exercisable or will be exercisable within 60 days of the date of this filing by the Reporting Persons and (iii) 4,166,840 shares of Common Stock underlying the 104,171 shares of Series A Preferred Stock owned by Fund II, applying the beneficial ownership limitation. 0001663607 N Peter Harwin a AF N X1 520361.00 8496341.00 520361.00 8496341.00 9016702.00 N 9.99 IN The securities include (a) 406,038 shares of Common Stock held directly by Mr. Harwin, (b) 114,323 shares of Common Stock issuable upon the exercise of options that are currently exercisable or will be exercisable within 60 days of the date of this filing held directly by Mr. Harwin*, and (c) Fund II's direct holdings of (i) 4,018,101 shares of Common Stock and (ii) 4,478,240 shares of Common Stock issuable upon conversion of 111,956 shares of Series A Preferred Stock held directly by Fund II. The securities exclude shares of Common Stock issuable upon conversion of shares of Series A Preferred Stock and Series B Preferred Stock held directly by Fund II in excess of the beneficial ownership limitation of 9.99%. Row 13 is based on 90,257,374 shares of Common Stock outstanding as of April 16, 2026, consisting of (i) 85,664,811 shares of Common Stock outstanding as of April 16, 2026, as reported in the Company's final prospectus supplement filed pursuant to Rule 424(b)(5) dated April 14, 2026, (ii) 114,323 shares of Common Stock underlying options that are currently exercisable or will be exercisable within 60 days of the date of this filing by Mr. Harwin and (iii) 4,478,240 shares of Common Stock underlying the 111,956 shares of Series A Preferred Stock owned by Fund II, applying the beneficial ownership limitation. * Under Mr. Harwin's arrangement with Fairmount, Mr. Harwin holds the options for one or more investment vehicles managed by Fairmount (each, a "Fairmount Fund"). Mr. Harwin is obligated to turn over to Fairmount any net cash or stock received from the option for the benefit of such Fairmount Fund. Mr. Harwin therefore disclaims beneficial ownership of the option and underlying common stock. 0001830177 N Tomas Kiselak a AF N 2B 520361.00 8496341.00 520361.00 8496341.00 9016702.00 N 9.99 IN The securities include (a) 406,038 shares of Common Stock held directly by Mr. Kiselak, (b) 114,323 shares of Common Stock issuable upon the exercise of options that are currently exercisable or will be exercisable within 60 days of the date of this filing held directly by Mr. Kiselak*, and (c) Fund II's direct holdings of (i) 4,018,101 shares of Common Stock and (ii) 4,478,240 shares of Common Stock issuable upon conversion of 111,956 shares of Series A Preferred Stock held directly by Fund II. The securities exclude shares of Common Stock issuable upon conversion of shares of Series A Preferred Stock and Series B Preferred Stock held directly by Fund II in excess of the beneficial ownership limitation of 9.99%. Row 13 is based on 90,257,374 shares of Common Stock outstanding as of April 16, 2026, consisting of (i) 85,664,811 shares of Common Stock outstanding as of April 16, 2026, as reported in the Company's final prospectus supplement filed pursuant to Rule 424(b)(5) dated April 14, 2026, (ii) 114,323 shares of Common Stock underlying options that are currently exercisable or will be exercisable within 60 days of the date of this filing by Mr. Kiselak and (iii) 4,478,240 shares of Common Stock underlying the 111,956 shares of Series A Preferred Stock owned by Fund II, applying the beneficial ownership limitation. * Under Mr. Kiselak's arrangement with Fairmount, Mr. Kiselak holds the options for one or more investment vehicles managed by Fairmount (each, a "Fairmount Fund"). Mr. Kiselak is obligated to turn over to Fairmount any net cash or stock received from the option for the benefit of such Fairmount Fund. Mr. Kiselak therefore disclaims beneficial ownership of the option and underlying common stock. Common Stock, $0.0001 par value SPYRE THERAPEUTICS, INC. 221 Crescent Street Building 23, Suite 105 Waltham MA 02453 This Amendment No. 6 amends and supplements the statement on Schedule 13D originally filed with the Securities and Exchange Commission (the "SEC") on June 30, 2023, Amendment No. 1 filed on November 29, 2023, Amendment No. 2 filed on December 11, 2023, Amendment No. 3 filed on December 29, 2023, Amendment No. 4 filed on April 25, 2024, and Amendment No. 5 filed on October 17, 2025 (as amended, the "Statement" or the "Schedule 13D") by the Reporting Persons with respect to the Common Stock of the Company. Unless otherwise defined herein, capitalized terms used in this Amendment No. 6 shall have the meanings ascribed to them in the Statement. Unless amended or supplemented below, the information in the Statement remains unchanged. This Amendment No. 6 is being filed solely to report the Reporting Persons' entry into a lock-agreement with the Company in connection with the Company's underwritten public offering; the number of shares of Common Stock, Series A Preferred Stock, and Series B Preferred Stock beneficially owned by the Reporting Persons has not changed since Amendment No. 5 to the Statement, filed on October 17, 2025. The information in rows 11 and 13 of each of the cover pages (including the explanatory note in the "Comments") of this Amendment No. 6 is incorporated by reference herein. Together, the Reporting Persons' securities include (i) 4,830,177 shares of Common Stock, (ii) 228,646 shares of Common Stock issuable upon the exercise of options held by the Reporting Persons that are currently exercisable or will be exercisable within 60 days of the date of this filing and, (iii) 3,912,800 shares of Common Stock issuable upon conversion of 97,820 shares of Series A Preferred Stock subject to the 9.99% beneficial ownership limitation applied to all of the securities owned by the Reporting Persons. The securities exclude shares of Common Stock issuable upon conversion of 248,225 shares of Series A Preferred Stock and 16,667 shares of Series B Preferred Stock held directly by Fund II in excess of the beneficial ownership limitation of 9.99%. The information in rows 7 through 10 of each of the cover pages of this Amendment No. 6 is incorporated by reference herein. None Lock-Up Agreement In connection with the Company's underwritten public offering of common stock that closed on April 16, 2026, the Reporting Persons entered into a customary lock-up letter agreement (the "Lock-Up Agreement") with Jefferies LLC, Goldman Sachs & Co. LLC, Evercore Group L.L.C. and Guggenheim Securities, LLC as the representatives (the "Representatives") of the underwriters to an underwriting agreement with the Company. Pursuant to the Lock-Up Agreement, the Reporting Persons agreed to refrain from selling shares of the Company's securities without the consent of the Representatives, and other customary lock-up conditions, for a period of 60 days from the date of the Company's final prospectus supplement related to the offering. The Reporting Persons did not purchase any securities of the Company or otherwise participate in the offering. The foregoing description of the Lock-Up Agreement does not purport to be complete and is qualified in its entirety by reference to the form of the Lock-Up Agreement, which is filed as Exhibit 99.2 to this Schedule 13D and incorporated herein by reference. 99.1 Joint Filing Agreement 99.1 (incorporated by reference to Exhibit 99.1 of the Reporting Persons' Schedule 13D filed with the SEC on October 17, 2025). 99.2 Lock-Up Agreement (incorporated by reference to Exhibit A to the Underwriting Agreement filed as Exhibit 1.1 of the Company's Form 8-K filed with the SEC on April 16, 2026). Fairmount Funds Management LLC /s/ Peter Harwin 04/20/2026 /s/ Tomas Kiselak 04/20/2026 Fairmount Healthcare Fund II L.P. /s/ Peter Harwin 04/20/2026 /s/ Tomas Kiselak 04/20/2026 Peter Harwin /s/ Peter Harwin 04/20/2026 Tomas Kiselak /s/ Tomas Kiselak 04/20/2026