Spyre Therapeutics, Inc.

Issuer

Spyre Therapeutics, Inc.

Principal executive office address

221 Crescent Street, Building 23, Suite 105, Waltham, MA 02453

Citizenship

For citizenship or place of organization see Item 4 of the cover page of each Reporting Person.

Filing person

This Schedule 13G is filed by the following (the "Reporting Persons"): (1) Paradigm BioCapital Advisors LP (the "Adviser"); (2) Paradigm BioCapital Advisors GP LLC (the "Adviser GP"); (3) Senai Asefaw, M.D. ("Senai Asefaw"); and (4) Paradigm BioCapital International Fund Ltd. (the "Fund"). The Fund is a private investment vehicle. The Fund and one or more separately managed accounts managed by the Adviser (the "Account") directly beneficially own the Common Stock reported in this statement. The Adviser is the investment manager of the Fund and the Account. The Adviser GP is the general partner of the Adviser. Senai Asefaw is the managing member of the Adviser GP. The Adviser, the Adviser GP and Senai Asefaw may be deemed to beneficially own the Common Stock directly beneficially owned by the Fund and the Account. Each Reporting Person disclaims beneficial ownership with respect to any Common Stock other than the Common Stock directly beneficially owned by such Reporting Person.

Principal business or residence address

The principal business office of the Fund is c/o Walkers, 190 Elgin Avenue, George Town, Grand Cayman KY1-9001, Cayman Islands. The principal business office of the Adviser, the Adviser GP and Senai Asefaw is 520 Fifth Avenue, 23rd Floor, New York, NY 10036.

Not applicable indication

Y

Percent of class

See Item 11 on the cover page for each Reporting Person. The percentages of beneficial ownership contained herein are based on 88,173,762 shares of Common Stock outstanding as of July 28, 2026, as reported by the Issuer in its Form 10-Q filed with the SEC on August 4, 2026.

Amount beneficially owned

See Item 9 on the cover page for each Reporting Person, and Item 2, which information is given as of the close of business on September 24, 2026, the Date of Event which requires the filing of this Schedule 13G.

Sole voting power

See Item 5 on the cover page for each Reporting Person.

Shared voting power

See Item 6 on the cover page for each Reporting Person.

Sole dispositive power

See Item 7 on the cover page for each Reporting Person.

Shared dispositive power

See Item 8 on the cover page for each Reporting Person.

Not applicable indication

Y

Not applicable indication

Y

Not applicable indication

Y

Not applicable indication

Y

Not applicable indication

Y

Not applicable indication

N

Certifications

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