RTW Investments (SYRE) reports 4.8% Spyre Therapeutics stake for managed funds

Rhea-AI Filing Summary

Spyre Therapeutics, Inc. received an updated Schedule 13G/A (Amendment No. 2) reporting ownership by RTW Investments, LP and its managing partner and CIO, Roderick Wong, M.D. The reporting persons collectively report beneficial ownership of 4,251,996 shares of common stock, representing 4.8% of the class.

The shares are held by certain RTW-managed funds, with RTW Investments and Dr. Wong reporting shared voting and dispositive power over all 4,251,996 shares and no sole voting or dispositive power. The ownership percentage is based on 87,936,477 shares outstanding as of June 24, 2026 as reported by the company.

Key Figures

Shares beneficially owned: 4,251,996 shares Percent of class owned: 4.8% Shares outstanding baseline: 87,936,477 shares +5 more

8 metrics

Shares beneficially owned 4,251,996 shares Common stock of Spyre Therapeutics reported by RTW Investments and Roderick Wong

Percent of class owned 4.8% Ownership percentage of Spyre Therapeutics common stock reported for each reporting person

Shares outstanding baseline 87,936,477 shares Spyre Therapeutics shares outstanding as of June 24, 2026 used to calculate 4.8%

Shared voting power 4,251,996 shares Shares over which RTW Investments and Roderick Wong have shared voting power

Shared dispositive power 4,251,996 shares Shares over which RTW Investments and Roderick Wong have shared dispositive power

Amendment number Amendment No. 2 Amendment number of the Schedule 13G filing for Spyre Therapeutics

Ownership threshold note 5 percent or less Item 5 states ownership of 5 percent or less of the class

Signature date 08/14/2026 Date Roderick Wong signed the Schedule 13G/A on behalf of the reporting persons

Key Terms

beneficial owner, shared voting power, shared dispositive power, investment adviser, +2 more

6 terms

beneficial owner financial

"the beneficial owner of the Shares reported herein"

A beneficial owner is the person who ultimately owns or controls a financial asset or property, even if their name isn't directly on official documents. Think of it like someone who secretly holds the keys to a safe deposit box—others may appear to have access, but the true owner is the one who benefits from what's inside. Identifying beneficial owners helps ensure transparency and prevent illegal activities like money laundering or fraud.

shared voting power financial

"Shared Voting Power 4,251,996.00"

Shared voting power occurs when two or more parties jointly have the right to vote or decide how a block of company shares is cast, like co-owners who must agree before moving a piece of furniture. Investors care because who controls voting rights affects board elections, major corporate decisions and takeover outcomes, and shared control can alter regulatory disclosures and the practical influence any holder has over a company’s direction and value.

shared dispositive power financial

"Shared Dispositive Power 4,251,996.00"

investment adviser financial

"the investment adviser to certain funds (the "RTW Funds")"

An investment adviser is a person or firm that professionally manages money and gives recommendations about buying, selling, or holding investments. Like a financial coach or guide, they have a legal duty to act in a client's best financial interest, so their advice, fees and potential conflicts can directly affect returns and risk — making their role important for investors who want informed, accountable help with portfolios.

percent of class financial

"The percentages set forth in Row 11 of the cover pages are calculated"

Percent of class is the portion of a specific category of securities—such as a company’s common shares, preferred shares, or a bond series—that takes part in or approves a corporate action (vote, consent, tender, etc.). Investors watch this number because it reveals how much support or opposition exists within that particular shareholder group; like counting how many members of a club back a proposal, it can determine whether a plan passes or how influence is distributed.

Registration Statement on Form S-3ASR regulatory

"as reported in the Issuer's Registration Statement on Form S-3ASR filed"

A registration statement on Form S-3ASR is a pre-approved filing used by well-established public companies to register securities they may sell over time, with the paperwork becoming effective automatically so offerings can begin quickly. For investors, it matters because it lets a company raise money or issue stock or debt on short notice — like a company keeping a ready-to-use credit line — which can dilute existing shares or change the company’s cash position rapidly.

FAQ

What stake in Spyre Therapeutics (SYRE) does RTW Investments report in this filing?

RTW Investments and Roderick Wong report beneficial ownership of 4,251,996 shares of Spyre Therapeutics common stock, representing 4.8% of the outstanding shares based on 87,936,477 shares as of June 24, 2026.

Who are the reporting persons in this Spyre Therapeutics (SYRE) Schedule 13G/A?

The reporting persons are RTW Investments, LP, a Delaware limited partnership and investment adviser to certain funds, and Roderick Wong, M.D., its Managing Partner and Chief Investment Officer, reporting with respect to shares held by RTW-managed funds.

What voting and dispositive powers over SYRE shares are reported by RTW Investments and Roderick Wong?

RTW Investments and Roderick Wong report 0 shares with sole voting or dispositive power and 4,251,996 shares with shared voting and shared dispositive power, all held through RTW-managed funds.

What percentage of Spyre Therapeutics (SYRE) does 4,251,996 shares represent in this filing?

The filing states that 4,251,996 shares of Spyre Therapeutics common stock represent 4.8% of the class, calculated using 87,936,477 shares outstanding as of June 24, 2026, from the company’s Form S-3ASR.

Who has the economic interest in the SYRE shares reported by RTW Investments?

The filing explains that the RTW Funds have the right to receive or direct the receipt of dividends and sale proceeds from the 4,251,996 shares, while RTW Investments and Roderick Wong report beneficial ownership as investment adviser and managing partner.

What is the significance of Item 5 in this Spyre Therapeutics (SYRE) Schedule 13G/A?

Item 5 indicates ownership of 5 percent or less of the class. The reported holdings of 4.8% place RTW Investments and Roderick Wong below the 5% threshold for Spyre Therapeutics common stock.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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Available on EDGAR 08/14/2026 - 08:11 AM Accepted by SEC EDGAR 08/14/2026 - 08:10 AM Learn about SEC filing dates

SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

SCHEDULE 13G

UNDER THE SECURITIES EXCHANGE ACT OF 1934

(Amendment No. 2)

Spyre Therapeutics, Inc.

(Name of Issuer)

Common Stock, $0.0001 par value

(Title of Class of Securities)

00773J202

(CUSIP Number)

06/30/2026

(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

RTW Investments, 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 0.00
6	Shared Voting Power 4,251,996.00
7	Sole Dispositive Power 0.00
8	Shared Dispositive Power 4,251,996.00

9

Aggregate Amount Beneficially Owned by Each Reporting Person

4,251,996.00

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)

4.8 %

12

Type of Reporting Person (See Instructions)

IA, PN

SCHEDULE 13G

CUSIP Number(s): 00773J202

1

Names of Reporting Persons

Roderick Wong

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 0.00
6	Shared Voting Power 4,251,996.00
7	Sole Dispositive Power 0.00
8	Shared Dispositive Power 4,251,996.00

9

Aggregate Amount Beneficially Owned by Each Reporting Person

4,251,996.00

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)

4.8 %

12

Type of Reporting Person (See Instructions)

HC, IN

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 statement is filed by: (i) RTW Investments, LP ("RTW Investments"), a Delaware limited partnership and the investment adviser to certain funds (the "RTW Funds"), with respect to shares of Common Stock, par value $0.0001 per share (the "Shares") of Spyre Therapeutics, Inc. (the "Company") directly held by the RTW Funds; and (ii) Roderick Wong, M.D. ("Dr. Wong"), the Managing Partner and Chief Investment Officer of RTW Investments, with respect to the Shares directly held by the RTW Funds. The foregoing persons are hereinafter sometimes collectively referred to as the "Reporting Persons." The filing of this statement should not be construed as an admission that any of the foregoing persons or any Reporting Person is, for the purposes of Section 13 of the Securities Exchange Act of 1934, as amended, the beneficial owner of the Shares reported herein.
(b)	Address or principal business office or, if none, residence: The address of the business office of each of the Reporting Persons is 40 10th Avenue, Floor 7, New York, New York 10014.
(c)	Citizenship: RTW Investments is a Delaware limited partnership. Dr. Wong is a citizen of the United States.
(d)	Title of class of securities: Common Stock, $0.0001 par value
(e)	CUSIP No.: 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: The information required by Item 4(a) is set forth in Rows 5 - 9 of the cover page for each of the Reporting Persons and is incorporated herein by reference. The percentages set forth in Row 11 of the cover pages are calculated based upon 87,936,477 Shares outstanding as of June 24, 2026, as reported in the Issuer's Registration Statement on Form S-3ASR filed with the Securities and Exchange Commission (the "SEC") on June 26, 2026.
(b)	Percent of class: RTW Investments: 4.8% Dr. Wong: 4.8%
(c)	Number of shares as to which the person has:
	(i) Sole power to vote or to direct the vote: RTW Investments: 0 Dr. Wong: 0
	(ii) Shared power to vote or to direct the vote: RTW Investments: 4,251,996 Shares Dr. Wong: 4,251,996 Shares
	(iii) Sole power to dispose or to direct the disposition of: RTW Investments: 0 Dr. Wong: 0
	(iv) Shared power to dispose or to direct the disposition of: RTW Investments: 4,251,996 Shares Dr. Wong: 4,251,996 Shares
Item 5.	Ownership of 5 Percent or Less of a Class.
	Ownership of 5 percent or less of a class
Item 6.	Ownership of more than 5 Percent on Behalf of Another Person.
	If any other person is known to have the right to receive or the power to direct the receipt of dividends from, or the proceeds from the sale of, such securities, a statement to that effect should be included in response to this item and, if such interest relates to more than 5 percent of the class, such person should be identified. A listing of the shareholders of an investment company registered under the Investment Company Act of 1940 or the beneficiaries of employee benefit plan, pension fund or endowment fund is not required. See Item 2. The RTW Funds have the right to receive or the power to direct the receipt of dividends from, or the proceeds from the sale of, the Shares reported herein.
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 acquired and are held in the ordinary course of business and 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.

RTW Investments, LP

Signature:	/s/ Roderick Wong, M.D.
Name/Title:	Roderick Wong, M.D., Managing Partner
Date:	08/14/2026

Roderick Wong

Signature:	/s/ Roderick Wong, M.D.
Name/Title:	Roderick Wong, M.D.
Date:	08/14/2026

Exhibit Information

Exhibit 99.1 Joint Filing Agreement (incorporated by reference to Exhibit 99.1 to the Reporting Persons' Schedule 13G filed with the SEC on February 14, 2024).