X0202 SCHEDULE 13G 0001224962 XXXXXXXX LIVE Common Stock, $0.0001 Par Value Per Share 04/15/2026 0001636282 SPYRE THERAPEUTICS, INC. 00773J202 221 CRESCENT STREET BUILDING 23, SUITE 105 WALTHAM MA 02453 Rule 13d-1(c) Perceptive Advisors LLC b DE 0 4319496 0 4319496 4319496 N 5.0 IA Joseph Edelman b X1 0 4319496 0 4319496 4319496 N 5.0 IN Perceptive Life Sciences Master Fund, Ltd. b E9 0 4319496 0 4319496 4319496 N 5.0 CO SPYRE THERAPEUTICS, INC. 221 Crescent Street Building 23, Suite 105, Waltham, MA 02453 The names of the persons filing this report (collectively, the "Reporting Persons") with respect to the Common Stock, $0.0001 Par Value Per Share (the "Common Stock") of SPYRE THERAPEUTICS, INC. (the "Issuer") are: (i) Perceptive Advisors LLC ("Perceptive Advisors") (ii) Joseph Edelman ("Mr. Edelman") (iii) Perceptive Life Sciences Master Fund, Ltd. (the "Master Fund") The address of the principal business office of each of the Reporting Persons is: 51 Astor Place, 10th Floor, New York, NY 10003 Perceptive Advisors is a Delaware limited liability company. Mr. Edelman is a United States citizen. The Master Fund is a Cayman Islands corporation. Y The information required by this item with respect to each Reporting Person is set forth in Rows 5 through 9 and 11 of the cover pages to this Schedule 13G. The ownership percentages are based on 85,664,811 shares of Common Stock outstanding, as reported in the Issuer's prospectus supplement filed pursuant to Rule 424(b)(5) filed with the Securities and Exchange Commission on April 16, 2026, giving effect to the exercise of the underwriters' option as reported in the Issuer's Current Report on Form 8-K filed with the Securities and Exchange Commission on April 16, 2026. The Master Fund directly holds 4,319,496 shares of Common Stock. Perceptive Advisors serves as the investment manager to the Master Fund and may be deemed to beneficially own the shares held by the Master Fund. Mr. Edelman is the managing member of Perceptive Advisors and may be deemed to beneficially own the shares held by the Master Fund. Perceptive Advisors: 5.0% Mr. Edelman: 5.0% Master Fund: 5.0% Perceptive Advisors: 0 Mr. Edelman: 0 Master Fund: 0 Perceptive Advisors: 4,319,496 Mr. Edelman: 4,319,496 Master Fund: 4,319,496 Perceptive Advisors: 0 Mr. Edelman: 0 Master Fund: 0 Perceptive Advisors: 4,319,496 Mr. Edelman: 4,319,496 Master Fund: 4,319,496 Y Y Y Y Y N By signing below I certify that, to the best of my knowledge and belief, the securities referred to above were not acquired and are not held for the purpose of or with the effect of changing or influencing the control of the issuer of the securities and were not acquired and are not held in connection with or as a participant in any transaction having that purpose or effect, other than activities solely in connection with a nomination under ?? 240.14a-11. Exhibit 99.1 - Joint Filing Agreement Perceptive Advisors LLC /s/ Joseph Edelman 04/22/2026 Joseph Edelman /s/ Joseph Edelman 04/22/2026 Perceptive Life Sciences Master Fund, Ltd. /s/ Joseph Edelman 04/22/2026