The reported positions include stock directly held by the Fund and separately managed accounts, with other reporting persons attributed beneficial ownership.
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Spyre Therapeutics, Inc. (SYRE) received a Schedule 13G reporting that, as of September 24, 2026, Paradigm BioCapital Advisors LP, its general partner Paradigm BioCapital Advisors GP LLC, and managing member Senai Asefaw, M.D. each reported beneficial ownership of 4,457,450 shares, or 5.1%. Paradigm BioCapital International Fund Ltd. reported beneficial ownership of 3,928,646 shares, or 4.5%. The Fund and separately managed accounts managed by the adviser directly beneficially own the reported common stock; the adviser, its general partner, and Asefaw may be deemed to beneficially own those direct holdings. The percentages are based on 88,173,762 shares outstanding as of July 28, 2026.
Key Figures
Reported beneficial ownership:4,457,450 sharesReported ownership percentage:5.1%Fund beneficial ownership:3,928,646 shares+2 more
5 metrics
Reported beneficial ownership4,457,450 sharesReported by Paradigm BioCapital Advisors LP, Paradigm BioCapital Advisors GP LLC, and Senai Asefaw, M.D. as of September 24, 2026
Reported ownership percentage5.1%Reported by Paradigm BioCapital Advisors LP, Paradigm BioCapital Advisors GP LLC, and Senai Asefaw, M.D.
Fund beneficial ownership3,928,646 sharesParadigm BioCapital International Fund Ltd., as of September 24, 2026
Fund ownership percentage4.5%Paradigm BioCapital International Fund Ltd.
Shares outstanding88,173,762 sharesAs of July 28, 2026; basis for the reported ownership percentages
Key Terms
beneficial ownership, Sole Voting Power, Sole Dispositive Power
3 terms
beneficial ownershipregulatory
"may be deemed to beneficially own the Common Stock"
Beneficial ownership means the person or entity that actually enjoys the benefits of owning shares or other assets — such as receiving dividends, voting rights, or price gains — even if the legal title is held in another name. For investors it matters because knowing who truly controls and profits from a company reveals who can influence decisions, exposes potential conflicts of interest or hidden concentration of power, and affects transparency and risk in the stock.
Sole Voting Powerregulatory
"Sole Voting Power 4,457,450.00"
Sole voting power is the exclusive right to cast votes attached to a shareholder’s stock without needing approval from anyone else. Like holding the only remote control for a TV, it lets that holder decide corporate matters such as board members, mergers, and policy changes, making it important to investors because it concentrates control and can strongly influence a company’s strategy and the value of its shares.
Sole Dispositive Powerregulatory
"Sole Dispositive Power 4,457,450.00"
Sole dispositive power is the exclusive legal authority to decide what happens to a security — for example, whether to sell, transfer, or retain shares — without needing anyone else’s permission. Investors care because it signals who truly controls the economic outcome of an investment: like holding the only key to a safe, the holder can realize gains or losses and may trigger regulatory reporting, insider rules, or influence over corporate ownership.
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
How many SYRE shares did Paradigm report owning?
Paradigm BioCapital Advisors LP, its general partner Paradigm BioCapital Advisors GP LLC, and Senai Asefaw, M.D. each reported beneficial ownership of 4,457,450 shares (5.1%); Paradigm BioCapital International Fund Ltd. reported 3,928,646 shares (4.5%), as of September 24, 2026.
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
SCHEDULE 13G
UNDER THE SECURITIES EXCHANGE ACT OF 1934
Spyre Therapeutics, Inc.
(Name of Issuer)
Common Stock, $0.0001 par value per share
(Title of Class of Securities)
00773J202
(CUSIP Number)
09/24/2026
(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)
schemaVersion:
SCHEDULE 13G
CUSIP Number(s):
00773J202
1
Names of Reporting Persons
Paradigm BioCapital Advisors LP
2
Check the appropriate box if a member of a Group (see instructions)
(a)
(b)
3
Sec Use Only
4
Citizenship or Place of Organization
DELAWARE
Number of Shares Beneficially Owned by Each Reporting Person With:
5
Sole Voting Power
4,457,450.00
6
Shared Voting Power
0.00
7
Sole Dispositive Power
4,457,450.00
8
Shared Dispositive Power
0.00
9
Aggregate Amount Beneficially Owned by Each Reporting Person
4,457,450.00
10
Check box if the aggregate amount in row (9) excludes certain shares (See Instructions)
11
Percent of class represented by amount in row (9)
5.1 %
12
Type of Reporting Person (See Instructions)
PN
SCHEDULE 13G
CUSIP Number(s):
00773J202
1
Names of Reporting Persons
Paradigm BioCapital Advisors GP LLC
2
Check the appropriate box if a member of a Group (see instructions)
(a)
(b)
3
Sec Use Only
4
Citizenship or Place of Organization
DELAWARE
Number of Shares Beneficially Owned by Each Reporting Person With:
5
Sole Voting Power
4,457,450.00
6
Shared Voting Power
0.00
7
Sole Dispositive Power
4,457,450.00
8
Shared Dispositive Power
0.00
9
Aggregate Amount Beneficially Owned by Each Reporting Person
4,457,450.00
10
Check box if the aggregate amount in row (9) excludes certain shares (See Instructions)
11
Percent of class represented by amount in row (9)
5.1 %
12
Type of Reporting Person (See Instructions)
OO
Comment for Type of Reporting Person: limited liability company
SCHEDULE 13G
CUSIP Number(s):
00773J202
1
Names of Reporting Persons
Senai Asefaw, M.D.
2
Check the appropriate box if a member of a Group (see instructions)
(a)
(b)
3
Sec Use Only
4
Citizenship or Place of Organization
UNITED STATES
Number of Shares Beneficially Owned by Each Reporting Person With:
5
Sole Voting Power
4,457,450.00
6
Shared Voting Power
0.00
7
Sole Dispositive Power
4,457,450.00
8
Shared Dispositive Power
0.00
9
Aggregate Amount Beneficially Owned by Each Reporting Person
4,457,450.00
10
Check box if the aggregate amount in row (9) excludes certain shares (See Instructions)
11
Percent of class represented by amount in row (9)
5.1 %
12
Type of Reporting Person (See Instructions)
IN
SCHEDULE 13G
CUSIP Number(s):
00773J202
1
Names of Reporting Persons
Paradigm BioCapital International Fund Ltd.
2
Check the appropriate box if a member of a Group (see instructions)
(a)
(b)
3
Sec Use Only
4
Citizenship or Place of Organization
CAYMAN ISLANDS
Number of Shares Beneficially Owned by Each Reporting Person With:
5
Sole Voting Power
3,928,646.00
6
Shared Voting Power
0.00
7
Sole Dispositive Power
3,928,646.00
8
Shared Dispositive Power
0.00
9
Aggregate Amount Beneficially Owned by Each Reporting Person
3,928,646.00
10
Check box if the aggregate amount in row (9) excludes certain shares (See Instructions)
11
Percent of class represented by amount in row (9)
4.5 %
12
Type of Reporting Person (See Instructions)
CO
SCHEDULE 13G
Item 1.
(a)
Name of issuer:
Spyre Therapeutics, Inc.
(b)
Address of issuer's principal executive offices:
221 Crescent Street, Building 23, Suite 105, Waltham, MA 02453
Item 2.
(a)
Name of person filing:
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.
(b)
Address or principal business office or, if none, residence:
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.
(c)
Citizenship:
For citizenship or place of organization see Item 4 of the cover page of each Reporting Person.
(d)
Title of class of securities:
Common Stock, $0.0001 par value per share
(e)
CUSIP Number(s):
00773J202
Item 3.
If this statement is filed pursuant to §§ 240.13d-1(b) or 240.13d-2(b) or (c), check whether the person filing is a:
(a)
Broker or dealer registered under section 15 of the Act (15 U.S.C. 78o);
(b)
Bank as defined in section 3(a)(6) of the Act (15 U.S.C. 78c);
(c)
Insurance company as defined in section 3(a)(19) of the Act (15 U.S.C. 78c);
(d)
Investment company registered under section 8 of the Investment Company Act of 1940 (15 U.S.C. 80a-8);
(e)
An investment adviser in accordance with § 240.13d-1(b)(1)(ii)(E);
(f)
An employee benefit plan or endowment fund in accordance with § 240.13d-1(b)(1)(ii)(F);
(g)
A parent holding company or control person in accordance with § 240.13d-1(b)(1)(ii)(G);
(h)
A savings associations as defined in Section 3(b) of the Federal Deposit Insurance Act (12 U.S.C. 1813);
(i)
A church plan that is excluded from the definition of an investment company under section 3(c)(14) of the Investment Company Act of 1940 (15 U.S.C. 80a-3);
(j)
A non-U.S. institution in accordance with § 240.13d-1(b)(1)(ii)(J). If filing as a non-U.S. institution in accordance with § 240.13d-1(b)(1)(ii)(J),
please specify the type of institution:
(k)
Group, in accordance with Rule 240.13d-1(b)(1)(ii)(K).
Item 4.
Ownership
(a)
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.
(b)
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.
(c)
Number of shares as to which the person has:
(i) Sole power to vote or to direct the vote:
See Item 5 on the cover page for each Reporting Person.
(ii) Shared power to vote or to direct the vote:
See Item 6 on the cover page for each Reporting Person.
(iii) Sole power to dispose or to direct the disposition of:
See Item 7 on the cover page for each Reporting Person.
(iv) Shared power to dispose or to direct the disposition of:
See Item 8 on the cover page for each Reporting Person.
Item 5.
Ownership of 5 Percent or Less of a Class.
Not Applicable
Item 6.
Ownership of more than 5 Percent on Behalf of Another Person.
Not Applicable
Item 7.
Identification and Classification of the Subsidiary Which Acquired the Security Being Reported on by the Parent Holding Company or Control Person.
Not Applicable
Item 8.
Identification and Classification of Members of the Group.
Not Applicable
Item 9.
Notice of Dissolution of Group.
Not Applicable
Item 10.
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.
SIGNATURE
After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct.
