AGLE / Aeglea BioTherapeutics Inc - تصريحات هيئة الأوراق المالية والبورصات، التقرير السنوي، بيان الوكيل

orm of Warrant to Purchase Common Stock (Parapyre Warrant 2024)

Exhibit 4.2 SPYRE THERAPEUTICS, INC. WARRANT TO PURCHASE COMMON STOCK Number of Warrant Shares: 848,184 (subject to adjustment) Warrant No. SYRE-002 Original Issue Date: December 31, 2024 THIS WARRANT TO PURCHASE COMMON STOCK (the “Warrant”) certifies that, for value received, Parapyre Holding LLC or its assigns (the “Holder”) is entitled, upon the terms and subject to the limitations on exercise

As filed with the Securities and Exchange Commission on August 5, 2025

As filed with the Securities and Exchange Commission on August 5, 2025 Registration No.

Filing Fee Table

Exhibit 107 Calculation of Filing Fee Tables FORM S-8 (Form Type) Spyre Therapeutics, Inc.

Spyre Therapeutics, Inc. 2018 Equity Inducement Plan and the First Amendment, Second Amendment, Third Amendment, Fourth Amendment, Fifth Amendment and Sixth Amendment thereto

EXHIBIT 10.1 AEGLEA BIOTHERAPEUTICS, INC. 2018 EQUITY INDUCEMENT PLAN 1. PURPOSE. The purpose of this Plan is to provide incentives to attract eligible persons whose potential contributions are important to the success of the Company, and any Parents, Subsidiaries and Affiliates that exist now or in the future, by offering them an opportunity to participate in the Company’s future performance thro

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 5, 2025 SPYRE THERAPEUTICS

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 5, 2025 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commission

Form of Warrant to Purchase Common Stock (Parapyre Warrant 2023)

Exhibit 4.1 SPYRE THERAPEUTICS, INC. WARRANT TO PURCHASE COMMON STOCK Number of Warrant Shares: 684,407 (subject to adjustment) Warrant No. SYRE-001R Original Issue Date: December 29, 2023 THIS WARRANT TO PURCHASE COMMON STOCK (the “Warrant”) certifies that, for value received, Parapyre Holding LLC or its assigns (the “Holder”) is entitled, upon the terms and subject to the limitations on exercise

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) x QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 OR o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-37722 SPYRE THERAPEUTICS, INC.

Spyre Therapeutics Reports Second Quarter 2025 Financial Results and Provides Corporate Update Initiated Phase 2 SKYLINE-UC platform study, evaluating three optimized monotherapies and three potentially paradigm-changing combinations in ulcerative co

Exhibit 99.1 Spyre Therapeutics Reports Second Quarter 2025 Financial Results and Provides Corporate Update Reported positive interim Phase 1 results for two next-generation TL1A antibodies, demonstrating both were well-tolerated, exhibited pharmacokinetic ("PK") profiles supporting quarterly or biannual dosing, and full TL1A engagement through up to 20 weeks of follow-up Initiated Phase 2 SKYLINE

Spyre Therapeutics Announces Positive Interim Phase 1 Results for Two Next- Generation TL1A Antibody Programs, and Provides Clinical Development Updates Expected to Deliver 9 Phase 2 Readouts dosing, and fully engaged TL1A through up to 20 weeks of f

Exhibit 99.1 Spyre Therapeutics Announces Positive Interim Phase 1 Results for Two Next- Generation TL1A Antibody Programs, and Provides Clinical Development Updates Expected to Deliver 9 Phase 2 Readouts SPY002 and SPY072 were well tolerated, exhibited PK that supports quarterly or less frequent dosing, and fully engaged TL1A through up to 20 weeks of follow-up; ~75 day half-life demonstrated, mo

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 17, 2025 SPYRE THERAPEUTICS,

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 17, 2025 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commission

Disclosures The information contained in this presentation has been prepared by Spyre Therapeutics, Inc. and its affiliates (“Spyre” or the “Company”) and contains information pertaining to the business and operations of the Company. The information

EX-99.2 Exhibit 99.2 Anti-TL1A Phase 1 Results and Phase 2 Development Updates June 2025 Disclosures The information contained in this presentation has been prepared by Spyre Therapeutics, Inc. and its affiliates (“Spyre” or the “Company”) and contains information pertaining to the business and operations of the Company. The information contained in this presentation: (a) is provided as at the dat

Submission of Matters to a Vote of Security Holders

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 29, 2025 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commission F

Securities and Exchange Commission

May 21, 2025 Securities and Exchange Commission Division of Corporation Finance Office of Life Sciences 100 F Street, N.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) x QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2025 OR o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-37722 SPYRE THERAPEUTICS, INC.

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 8, 2025 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commission Fi

Spyre Therapeutics Reports First Quarter 2025 Financial Results and Provides Corporate Update On track for mid-year initiations of planned Phase 2 studies in ulcerative colitis ("UC") and rheumatoid arthritis ("RA"), providing for 7+ proof-of-concept

Exhibit 99.1 Spyre Therapeutics Reports First Quarter 2025 Financial Results and Provides Corporate Update On track for mid-year initiations of planned Phase 2 studies in ulcerative colitis ("UC") and rheumatoid arthritis ("RA"), providing for 7+ proof-of-concept readouts in 2026 & 2027 Reported extended follow-up Phase 1 data for SPY001, supporting that the molecule is well tolerated, has a pharm

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. )

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. ) Filed by the Registrant x Filed by a Party other than the Registrant ¨ Check the appropriate box: ¨ Preliminary Proxy Statement ¨ Confidential, for Use of the Commission Only (as permitted by Rule 14a-6(e)(2)) ¨ Defin

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. )

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. ) Filed by the Registrant x Filed by a Party other than the Registrant ¨ Check the appropriate box: ¨ Preliminary Proxy Statement ¨ Confidential, for Use of the Commission Only (as permitted by Rule 14a-6(e)(2)) x Defin

As filed with the Securities and Exchange Commission on March 7, 2025.

As filed with the Securities and Exchange Commission on March 7, 2025. Registration No. 333-281975 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-3 (Post-Effective Amendment No. 1) REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Spyre Therapeutics, Inc. (Exact name of registrant as specified in its charter) Delaware 46-4312787 (State or other jurisdiction of

Changes in Registrant's Certifying Accountant

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): February 28, 2025 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commiss

Letter from PricewaterhouseCoopers LLP, dated March 6, 2025

Exhibit 16.1 March 6, 2025 Securities and Exchange Commission 100 F Street, N.E. Washington, DC 20549 Commissioners: We have read the statements made by Spyre Therapeutics, Inc. (copy attached), which we understand will be filed with the Securities and Exchange Commission, pursuant to Item 4.01 of Form 8-K of Spyre Therapeutics, Inc. dated March 6, 2025. We agree with the statements concerning our

March 5, 2025

March 5, 2025 VIA EDGAR AND EMAIL United States Securities and Exchange Commission Division of Corporation Finance 100 F Street, N.

As filed with the Securities and Exchange Commission on February 27, 2025

As filed with the Securities and Exchange Commission on February 27, 2025 Registration No.

Spyre Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Corporate Update Reported positive interim pharmacokinetic ("PK") and safety data in Phase 1 trial of SPY001 in November 2024 and strengthened the balance she

Exhibit 99.1 Spyre Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Corporate Update Reported positive interim pharmacokinetic ("PK") and safety data in Phase 1 trial of SPY001 in November 2024 and strengthened the balance sheet with a $230 million public offering Continued execution towards expected milestones across portfolio, with interim Phase 1 data readou

As filed with the Securities and Exchange Commission on February 27, 2025.

As filed with the Securities and Exchange Commission on February 27, 2025. Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-3 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Spyre Therapeutics, Inc. (Exact name of registrant as specified in its charter) Delaware 46-4312787 (State or other jurisdiction of incorporation or organization) (I.

Spyre Therapeutics, Inc. Insider Trading Policy

Exhibit 19.1 SPYRE THERAPEUTICS, INC. INSIDER TRADING POLICY (dated February 1, 2024) I. INTRODUCTION Federal and state laws prohibit buying, selling or making other transfers of securities by persons who have material information that is not generally known or available to the public. These laws also prohibit persons with such material nonpublic information (“MNPI”) from disclosing this informati

Subsidiaries of the Registrant

Exhibit 21.1 Subsidiaries of Spyre Therapeutics, Inc. Name of Subsidiary Jurisdiction Aeglea Biotherapeutics UK Limited England and Wales Aeglea Ireland Limited Ireland

Filing Fee Table

Calculation of Filing Fee Tables FORM S-8 (Form Type) Spyre Therapeutics, Inc. (Exact Name of Registrant as Specified in its Charter) Table 1: Newly Registered Securities Security Type Security Class Title (1) Fee Calculation Rule Amount Registered Proposed Maximum Offering Price Per Unit Maximum Aggregate Offering Price Fee Rate Amount of Registration Fee Equity Common stock, par value $0.0001 pe

Filing Fee Table.

Calculation of Filing Fee Tables S-3 Spyre Therapeutics, Inc. Table 1: Newly Registered and Carry Forward Securities Security Type Security Class Title Fee Calculation or Carry Forward Rule Amount Registered Proposed Maximum Offering Price Per Unit Maximum Aggregate Offering Price Fee Rate Amount of Registration Fee Carry Forward Form Type Carry Forward File Number Carry Forward Initial Effective

re UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 FORM 10-K

Table of Contents re UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 FORM 10-K x ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2024 o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number 001-37722 SPYRE THERAPEUTICS, INC.

Form of Debt Indenture.

Exhibit 4.2 SPYRE THERAPEUTICS, INC. Debt Securities Indenture Dated as of , 202 [ ], as Trustee CROSS-REFERENCE TABLE This Cross-Reference Table is not a part of the Indenture TIA Section Indenture Section 310(a)(1) 7.10 (a)(2) 7.10 (a)(3) N.A. (a)(4) N.A. (b) 7.08; 7.10; 12.02 311(a) 7.11 (b) 7.11 (c) N.A. 312(a) 2.05 (b) 12.03 (c) 12.03 313(a) 7.06 (b)(1) N.A. (b)(2) 7.06 (c) 12.02 (d) 7.06 314

Sales Agreement, dated September 6, 2024, between Spyre Therapeutics, Inc. and TD Securities (USA) LLC.

Exhibit 1.2 SPYRE THERAPEUTICS, INC. $200,000,000 COMMON STOCK SALES AGREEMENT September 6, 2024 TD Securities (USA) LLC 1 Vanderbilt Avenue New York, New York 10017 Ladies and Gentlemen: Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), confirms its agreement (this “Agreement”) with TD Securities (USA) LLC (“TD Cowen”), as follows: 1. Issuance and Sale of Shares. The Company agree

Amended and Restated IL-23 (SPY003) License Agreement, dated February 24, 2025, by and between the Company and Paragon Therapeutics, Inc

Exhibit 10.25 [***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE THE INFORMATION (I) IS NOT MATERIAL AND (II) IS THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL. Execution Version AMENDED AND RESTATED LICENSE AGREEMENT This Amended and Restated License Agreement (“Agreement”) is executed as of February 24, 2025 (the “Res

Description of the Registrant's securities

Exhibit 4.4 DESCRIPTION OF CAPITAL STOCK General The following description summarizes the material terms of the capital stock of Spyre Therapeutics, Inc. (“we,” “us,” “our” or the “company”), as well as other material terms of our second amended and restated certificate of incorporation (“Certificate of Incorporation”) and amended and restated bylaws (“Bylaws”) and certain provisions of Delaware l

Form of Warrant to Purchase Common Stock (Parapyre Warrant 202

Exhibit 4.6 SPYRE THERAPEUTICS, INC. WARRANT TO PURCHASE COMMON STOCK Number of Warrant Shares: 848,184 (subject to adjustment) Original Issue Date: December 31, 2024 Warrant No. SYRE-002 THIS WARRANT TO PURCHASE COMMON STOCK (the “Warrant”) certifies that, for value received, Parapyre Holding LLC or its assigns (the “Holder”) is entitled, upon the terms and subject to the limitations on exercise

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): February 27, 2025 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commiss

JOINT FILING AGREEMENT

EX-99.1 2 ex-99-02142025110249.htm JOINT FILING AGREEMENT EXHIBIT 99.1 JOINT FILING AGREEMENT In accordance with Rule 13d-1(k) under the Securities Exchange Act of 1934, as amended, the undersigned agree to the joint filing on behalf of each of them of a statement on Schedule 13G (including amendments thereto) with respect to the Common Stock of Spyre Therapeutics, Inc. and further agree that this

Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): January 13, 2025 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commissi

Spyre Therapeutics Highlights 2025 Priorities and Robust Pipeline of Upcoming Clinical Readouts Phase 1 interim results expected for SPY002, two distinct extended half-life TL1A antibodies, in 2Q2025 Phase 1 interim results expected for SPY003, an ex

Exhibit 99.1 Spyre Therapeutics Highlights 2025 Priorities and Robust Pipeline of Upcoming Clinical Readouts Phase 1 interim results expected for SPY002, two distinct extended half-life TL1A antibodies, in 2Q2025 Phase 1 interim results expected for SPY003, an extended half-life IL-23 antibody, in 2H2025 Phase 2 platform trial in ulcerative colitis (UC) remains on track for initiation in mid-2025

Disclosures The information contained in this presentation has been prepared by Spyre Therapeutics, Inc. and its affiliates (“Spyre” or the “Company”) and contains information pertaining to the business and operations of the Company. The information

Exhibit 99.2 Corporate overview January 2025 Disclosures The information contained in this presentation has been prepared by Spyre Therapeutics, Inc. and its affiliates (“Spyre” or the “Company”) and contains information pertaining to the business and operations of the Company. The information contained in this presentation: (a) is provided as at the date hereof, is subject to change without notic

Jefferies LLC, Goldman Sachs & Co. LLC, Evercore Group L.L.C. and Guggenheim Securities, LLC

Exhibit 1.1 Spyre Therapeutics, Inc. 7,275,000 Shares of Common Stock, Par Value $0.0001 UNDERWRITING AGREEMENT November 18, 2024 JEFFERIES LLC GOLDMAN SACHS & CO. LLC EVERCORE GROUP L.L.C. GUGGENHEIM SECURITIES, LLC As Representatives of the several Underwriters c/o JEFFERIES LLC 520 Madison Avenue New York, New York 10022 c/o GOLDMAN SACHS & CO. LLC 200 West Street New York, New York 10282 c/o E

7,275,000 Shares Common Stock

Filed Pursuant to Rule 424(b)(5) Registration Statement No. 333-281975 PROSPECTUS SUPPLEMENT (To Prospectus dated September 18, 2024) 7,275,000 Shares Common Stock We are offering 7,275,000 shares of our common stock, par value $0.0001 per share (“common stock”). The public offering price for each share of common stock is $27.50. Our common stock is traded on the Nasdaq Global Select Market under

Entry into a Material Definitive Agreement, Financial Statements and Exhibits

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 18, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commiss

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q/A (Amendment No. 1)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q/A (Amendment No.

re UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 FORM 10-K/A (Amendment No. 2)

Table of Contents re UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 FORM 10-K/A (Amendment No.

Non-Reliance on Previously Issued Financial Statements or a Related Audit Report or Completed Interim Review, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 18, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commiss

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q/A (Amendment No. 1)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q/A (Amendment No.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q/A (Amendment No. 1)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q/A (Amendment No.

SUBJECT TO COMPLETION, DATED NOVEMBER 18, 2024

Filed Pursuant to Rule 424(b)(5) Registration Statement No. 333-281975 The information in this preliminary prospectus supplement is not complete and may be changed. This preliminary prospectus supplement and the accompanying prospectus do not constitute an offer to sell these securities, and we are not soliciting offers to buy these securities in any jurisdiction where the offer or sale is not per

SYRE / Spyre Therapeutics, Inc. / Venrock Healthcare Capital Partners III, L.P. - SC 13G/A Passive Investment

SC 13G/A 1 tm2428137d15sc13ga.htm SC 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No. 2)* Spyre Therapeutics, Inc. (Name of Issuer) Common Stock, $0.0001 Par Value Per Share (Title of Class of Securities) 00773J202 (CUSIP Number) September 30, 2024 (Date of Event Which Requires Filing of this State

AGLE / Aeglea BioTherapeutics Inc / Deep Track Capital, LP Passive Investment

SC 13G/A 1 deeptrack-syre093024a2.htm UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No. 2)* Spyre Therapeutics Inc. (Name of Issuer) Common Stock, $0.0001 Par Value Per Share (Title of Class of Securities) 00773J103 (CUSIP Number) September 30, 2024 (Date of Event Which Requires Filing of this Statement) Ch

SYRE / Spyre Therapeutics, Inc. / PERCEPTIVE ADVISORS LLC - SC 13G/A Passive Investment

SC 13G/A 1 d912069dsc13ga.htm SC 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No. 2)* Spyre Therapeutics, Inc. (Name of Issuer) Common Stock, $0.0001 par value per share (Title of Class of Securities) 00773J202 (CUSIP Number) September 30, 2024 (Date of Event Which Requires Filing of this Statement

SYRE / Spyre Therapeutics, Inc. / Avoro Capital Advisors LLC - SPYRE THERAPEUTICS, INC. Passive Investment

SC 13G/A 1 p24-3032sc13ga.htm SPYRE THERAPEUTICS, INC. SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G/A 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) September 30, 2024 (Date of Event Which Requires Filing of This Statement) Check t

SYRE / Spyre Therapeutics, Inc. / COMMODORE CAPITAL LP Passive Investment

SC 13G/A 1 formsc13ga.htm UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 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 per share (Title of Class of Securities) 00773J202 (CUSIP Number) September 30, 2024 (Date of Event Which Requires Filing of this Statement) Check the appro

SPY001 Phase 1 Results & Corporate Updates November 2024 2 Disclosures The information contained in this presentation has been prepared by Spyre Therapeutics, Inc. and its affiliates (“Spyre” or the “Company”) and contains information pertaining to t

SPY001 Phase 1 Results & Corporate Updates November 2024 2 Disclosures The information contained in this presentation has been prepared by Spyre Therapeutics, Inc.

Regulation FD Disclosure, Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 12, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commiss

Spyre Therapeutics Announces Positive Interim Results from Phase 1 Healthy Volunteer Trial for SPY001, Its Novel Half-Life Extended anti-α4β7 Antibody for the Treatment of Inflammatory Bowel Disease, with a Half-Life of >90 Days Supporting the Potent

Exhibit 99.1 Spyre Therapeutics Announces Positive Interim Results from Phase 1 Healthy Volunteer Trial for SPY001, Its Novel Half-Life Extended anti-α4β7 Antibody for the Treatment of Inflammatory Bowel Disease, with a Half-Life of >90 Days Supporting the Potential for Both Q3M & Q6M Maintenance Dosing SPY001 was well tolerated with a favorable safety profile consistent with the anti-α4β7 class S

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 7, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commissi

Spyre Therapeutics, Inc. 2018 Equity Inducement Plan and the First Amendment, Second Amendment, Third Amendment, Fourth Amendment and Fifth Amendment thereto.

EXHIBIT 99.1 AEGLEA BIOTHERAPEUTICS, INC. 2018 EQUITY INDUCEMENT PLAN 1. PURPOSE. The purpose of this Plan is to provide incentives to attract eligible persons whose potential contributions are important to the success of the Company, and any Parents, Subsidiaries and Affiliates that exist now or in the future, by offering them an opportunity to participate in the Company’s future performance thro

Spyre Therapeutics Reports Third Quarter 2024 Financial Results and Provides Corporate Update Continued execution towards expected milestones across portfolio, with SPY001 on-track for interim Phase 1 data by year-end 2024, and SPY002 on-track for in

Exhibit 99.1 Spyre Therapeutics Reports Third Quarter 2024 Financial Results and Provides Corporate Update Continued execution towards expected milestones across portfolio, with SPY001 on-track for interim Phase 1 data by year-end 2024, and SPY002 on-track for initiation of first-in-human trials in the fourth quarter of 2024 Presented new data on SPY003, a potential best-in-class half-life extende

Fifth Amendment to the Spyre Therapeutics, Inc. 2018 Equity Inducement Plan

Exhibit 10.4 FIFTH AMENDMENT TO THE SPYRE THERAPEUTICS, INC. 2018 EQUITY INDUCEMENT PLAN WHEREAS, Spyre Therapeutics, Inc., a Delaware corporation (the “Company”) maintains the Spyre Therapeutics, Inc. 2018 Equity Inducement Plan, as amended on June 22, 2023, August 30, 2023, October 30, 2023 and November 28, 2023 (the “Plan”); and WHEREAS, pursuant to Section 17 of the Plan, the Board of Director

Filing Fee Table

Exhibit 107 Calculation of Filing Fee Tables FORM S-8 (Form Type) Spyre Therapeutics, Inc.

As filed with the Securities and Exchange Commission on November 7, 2024

As filed with the Securities and Exchange Commission on November 7, 2024 Registration No.

, 2024, by and between the Company and Sheldon Sloan

Exhibit 10.5 September 20, 2024 Dr. Sheldon Sloan, M.D. Re: Offer of Employment Dear Sheldon: On behalf of Spyre Therapeutics, Inc. (the “Company”), I am very pleased to offer you a position as Chief Medical Officer (the “Role”) pursuant to this letter agreement (the “Agreement”), provided you accept such offer as indicated by your signature below. Your employment with the Company in the Role will

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) x QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2024 OR o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-37722 SPYRE THERAPEUTICS, INC.

SYRE / Spyre Therapeutics, Inc. / Deutsch Peter E. - SCHEDULE 13G Passive Investment

SC 13G 1 deutsch13g.htm SCHEDULE 13G UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. )* Spyre Therapeutics, Inc. (Name of Issuer) Common stock, par value $0.0001 (Title of Class of Securities) 00773J202 (CUSIP Number) October 14, 2024 (Date of Event which Requires Filing of this Statement) Check the appro

Amended and Restated Cell Line License Agreement, dated October 14, 2024, by and between the Company and WuXi Biologics (Hong Kong) Limited.

Exhibit 10.3 [***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE THE INFORMATION (I) IS NOT MATERIAL AND (II) IS THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL. AMENDED AND RESTATED CELL LINE LICENSE AGREEMENT This Amended and Restated Cell Line License Agreement (“Agreement”), effective as of the latest date of signatur

IL-23 (SPY003) License Agreement, dated October 11, 2024, by and between the Company and Paragon Therapeutics, Inc.

Exhibit 10.1 [***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE THE INFORMATION (I) IS NOT MATERIAL AND (II) IS THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL. EXECUTION VERSION LICENSE AGREEMENT THIS LICENSE AGREEMENT (“Agreement”) is entered into and effective as of October 11, 2024 (the “Effective Date”), by and betw

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): October 11, 2024 SPYRE THERAPEUTI

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): October 11, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commissi

Spyre Therapeutics Announces Expected Acceleration of SPY003 (IL-23p19) Clinical Timelines and Presentations at UEGW supporting Spyre’s Portfolio of Potentially Best-in-Class Antibodies and Combinations SPY003, a novel half-life extended IL-23p19 mon

Exhibit 99.1 Spyre Therapeutics Announces Expected Acceleration of SPY003 (IL-23p19) Clinical Timelines and Presentations at UEGW supporting Spyre’s Portfolio of Potentially Best-in-Class Antibodies and Combinations SPY003, a novel half-life extended IL-23p19 monoclonal antibody (mAb), with first-in-human dosing now expected first quarter 2025 New data on SPY003 presented at UEGW demonstrating rob

Disclosures The information contained in this presentation has been prepared by Spyre Therapeutics, Inc. and its affiliates (“Spyre” or the “Company”) and contains information pertaining to the business and operations of the Company. The information

Exhibit 99.2 Corporate overview October 2024 Disclosures The information contained in this presentation has been prepared by Spyre Therapeutics, Inc. and its affiliates (“Spyre” or the “Company”) and contains information pertaining to the business and operations of the Company. The information contained in this presentation: (a) is provided as at the date hereof, is subject to change without notic

Amended and Restated Biologics Master Services Agreement, dated October 14, 2024, by and between the Company and WuXi Biologics (Hong Kong) Limited.

Exhibit 10.2 [***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) IS THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL. AMENDED AND RESTATED BIOLOGICS MASTER SERVICES AGREEMENT This Amended and Restated Biologics Master Services Agreement (this “Agreement”) is effective as of the latest d

September 30, 2024

September 30, 2024 VIA EDGAR AND EMAIL United States Securities and Exchange Commission Division of Corporation Finance 100 F Street, N.

Filing Fee Table.

Exhibit 107 Calculation of Filing Fee Tables Form S-3 (Form Type) Spyre Therapeutics, Inc.

As filed with the Securities and Exchange Commission on September 20, 2024.

As filed with the Securities and Exchange Commission on September 20, 2024. Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-3 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Spyre Therapeutics, Inc. (Exact name of registrant as specified in its charter) Delaware 46-4312787 (State or other jurisdiction of incorporation or organization) (I

September 13, 2024

September 13, 2024 VIA EDGAR AND EMAIL United States Securities and Exchange Commission Division of Corporation Finance 100 F Street, N.

Sales Agreement, dated September 6, 2024, between Spyre Therapeutics, Inc. and TD Securities (USA) LLC

Exhibit 1.2 SPYRE THERAPEUTICS, INC. $200,000,000 COMMON STOCK SALES AGREEMENT September 6, 2024 TD Securities (USA) LLC 1 Vanderbilt Avenue New York, New York 10017 Ladies and Gentlemen: Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), confirms its agreement (this “Agreement”) with TD Securities (USA) LLC (“TD Cowen”), as follows: 1. Issuance and Sale of Shares. The Company agree

Form of Debt Indenture.

Exhibit 4.2 SPYRE THERAPEUTICS, INC. Debt Securities Indenture Dated as of , 202 [ ], as Trustee CROSS-REFERENCE TABLE This Cross-Reference Table is not a part of the Indenture TIA Section Indenture Section 310(a)(1) 7.10 (a)(2) 7.10 (a)(3) N.A. (a)(4) N.A. (b) 7.08; 7.10; 12.02 311(a) 7.11 (b) 7.11 (c) N.A. 312(a) 2.05 (b) 12.03 (c) 12.03 313(a) 7.06 (b)(1) N.A. (b)(2) 7.06 (c) 12.02 (d) 7.06 314

Filing Fee Table.

Exhibit 107 Calculation of Filing Fee Tables Form S-3 (Form Type) Spyre Therapeutics, Inc.

As filed with the Securities and Exchange Commission on September 6, 2024.

As filed with the Securities and Exchange Commission on September 6, 2024. Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-3 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Spyre Therapeutics, Inc. (Exact name of registrant as specified in its charter) Delaware 46-4312787 (State or other jurisdiction of incorporation or organization) (I.

Current Report

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K/A (Amendment No. 1) CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 7, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorp

SPYRE THERAPEUTICS, INC. 33,361,402 Shares Common Stock Offered by the Selling Stockholders

Table of Contents Prospectus Supplement No. 2 Filed Pursuant to Rule 424(b)(3) (to prospectus dated April 29, 2024) Registration No. 333-278810 SPYRE THERAPEUTICS, INC. 33,361,402 Shares Common Stock Offered by the Selling Stockholders This prospectus supplement no. 2 is being filed to update and supplement information contained in the prospectus dated April 18, 2024 (the “Prospectus”), which form

TL1A (SPY002) License Agreement, dated May 14 2024, by and between the Company and Paragon Therapeutics, Inc.

Exhibit 10.4 [***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED. LICENSE AGREEMENT This License Agreement (“Agreement”) is entered into and effective as of May 14, 2024 (the “Effective Date”), by and between Paragon Therapeutics, Inc., a c

Form of Restricted Stock Unit Award Agreement under the Amended Spyre Therapeutics, Inc. 2018 Equity Inducement Plan

Exhibit 10.7 NOTICE OF RESTRICTED STOCK UNIT AWARD SPYRE THERAPEUTICS, INC. 2018 EQUITY INDUCEMENT PLAN Unless otherwise defined herein, the terms defined in the Spyre Therapeutics, Inc. (the “Company”) 2018 Equity Inducement Plan (the “Plan”) shall have the same meanings in this Notice of Restricted Stock Unit Award (the “Notice”) and the attached Restricted Stock Unit Agreement (the “RSU Agreeme

α4ß7 (SPY001) License Agreement, dated May 14, 2024, by and between the Company and Paragon Therapeutics, Inc.

Exhibit 10.3 [***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED. LICENSE AGREEMENT This License Agreement (“Agreement”) is entered into and effective as of May 14, 2024 (the “Effective Date”), by and between Paragon Therapeutics, Inc., a c

Second Amended and Restated Antibody Discovery and Option Agreement, dated May 14, 2024, by and between the Company, Paragon Therapeutics, Inc. and Parapyre Holding LLC

Exhibit 10.5 [***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED. SECOND AMENDED AND RESTATED ANTIBODY DISCOVERY AND OPTION AGREEMENT This Second Amended and Restated Antibody Discovery and Option Agreement (“Agreement”) is entered into and

Form of Stock Option Agreement under the Amended and Restated Spyre Therapeutics, Inc. 2016 Equity Incentive Plan

Exhibit 10.6 NOTICE OF STOCK OPTION GRANT SPYRE THERAPEUTICS, INC. 2016 EQUITY INCENTIVE PLAN Unless otherwise defined herein, the terms defined in the Spyre Therapeutics, Inc. (the “Company”) 2016 Equity Incentive Plan (as amended and restated, the “Plan”) shall have the same meanings in this Notice of Stock Option Grant (the “Notice of Grant”) and the attached Stock Option Agreement (the “Option

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) x QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2024 OR o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-37722 SPYRE THERAPEUTICS, INC.

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported):May 9, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commission Fil

Spyre Therapeutics Reports Second Quarter 2024 Financial Results and Provides Corporate Update Initiated dosing in Phase 1 trial of SPY001, an anti-α4β7 antibody engineered for infrequent, subcutaneous maintenance dosing, with interim proof-of-concep

Exhibit 99.1 Spyre Therapeutics Reports Second Quarter 2024 Financial Results and Provides Corporate Update Initiated dosing in Phase 1 trial of SPY001, an anti-α4β7 antibody engineered for infrequent, subcutaneous maintenance dosing, with interim proof-of-concept data on track for year-end 2024 SPY002, an anti-TL1A antibody program designed for enhanced potency to both TL1A monomers and trimers,

Current Report

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of Earliest Event Reported): May 30, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commission F

Second Amended and Restated Certificate of Incorporation of the Company, effective as of May 14, 2024

Exhibit 3.2 SPYRE THERAPEUTICS, INC. SECOND AMENDED AND RESTATED CERTIFICATE OF INCORPORATION Spyre Therapeutics, Inc. (the “Corporation”), a corporation organized and existing under and by virtue of the provisions of the General Corporation Law of the State of Delaware (the “General Corporation Law”), does hereby certify as follows: 1. The current name of the Corporation is Spyre Therapeutics, In

SPYRE THERAPEUTICS, INC. 33,361,402 Shares Common Stock Offered by the Selling Stockholders

Table of Contents Filed Pursuant to Rule 424(b)(3) Registration No. 333-278810 Prospectus Supplement No. 1 (to prospectus dated April 29, 2024) SPYRE THERAPEUTICS, INC. 33,361,402 Shares Common Stock Offered by the Selling Stockholders This prospectus supplement no. 1 is being filed to update and supplement information contained in the prospectus dated April 18, 2024 (the “Prospectus”), which form

Spyre Therapeutics Appoints Accomplished Biopharma Leader Dr. Sandra Milligan to its Board of Directors

Exhibit 99.1 Spyre Therapeutics Appoints Accomplished Biopharma Leader Dr. Sandra Milligan to its Board of Directors WALTHAM, Mass., May 15, 2024 (PR NEWSWIRE)—Spyre Therapeutics, Inc. (NASDAQ: SYRE) (the “Company” or “Spyre”), a development-stage biotechnology company advancing best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches for the treatme

Regulation FD Disclosure

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of Earliest Event Reported): May 13, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commission F

Certificate of Amendment to the Amended and Restated Certificate of Incorporation of the Company, effective as of May 14, 2024.

Exhibit 3.1 CERTIFICATE OF AMENDMENT TO THE AMENDED AND RESTATED CERTIFICATE OF INCORPORATION OF SPYRE THERAPEUTICS, INC. Spyre Therapeutics, Inc. (the “Corporation”), a corporation organized and existing under and by virtue of the provisions of the General Corporation Law of the State of Delaware (the “General Corporation Law”), does hereby certify: 1. The current name of the Corporation is Spyre

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 9, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commission Fi

Spyre Therapeutics Reports First Quarter 2024 Financial Results and Provides Corporate Update SPY001, an anti-α4β7 antibody engineered for infrequent, subcutaneous dosing successfully completed a 28-day GLP toxicity study and remains on track to begi

Exhibit 99.1 Spyre Therapeutics Reports First Quarter 2024 Financial Results and Provides Corporate Update SPY001, an anti-α4β7 antibody engineered for infrequent, subcutaneous dosing successfully completed a 28-day GLP toxicity study and remains on track to begin first-in-human studies in the second quarter of 2024, with interim proof-of-concept data expected year-end 2024 SPY002, an anti-TL1A an

Form of Warrant to Purchase Common Stock (Parapyre Warrant 2023)

E Exhibit 4.2 SPYRE THERAPEUTICS, INC. WARRANT TO PURCHASE COMMON STOCK Number of Warrant Shares: 684,407 (subject to adjustment) Original Issue Date: December 29, 2023 Warrant No. SYRE-001R THIS WARRANT TO PURCHASE COMMON STOCK (the “Warrant”) certifies that, for value received, Parapyre Holding LLC or its assigns (the “Holder”) is entitled, upon the terms and subject to the limitations on exerci

Amendment No. 1 to Novation Agreement, dated April 25, 2024, by and between Paragon Therapeutics, Inc., the Company and WuXi Biologics (Hong Kong) Limited

Exhibit 10.6 AMENDMENT NO. 1 TO THE NOVATION AGREEMENT This Amendment No. 1 (the “Amendment”), effective as of April 25, 2024 (the “Amendment Effective Date”) to the Novation Agreement effective as of July 21, 2023 and executed on September 19, 2023 (the “Novation Agreement”) is entered into by and among (i) Paragon Therapeutics, Inc., a Delaware corporation with an office at 221 Crescent Street,

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) x QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2024 OR o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-37722 SPYRE THERAPEUTICS, INC.

SYRE / Spyre Therapeutics, Inc. / Fairmount Funds Management LLC - SC 13D/A Activist Investment

SC 13D/A 1 d820181dsc13da.htm SC 13D/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13D Under the Securities Exchange Act of 1934 (Amendment No. 4) SPYRE THERAPEUTICS, INC. (Name of Issuer) Common Stock, $0.0001 par value (Title of Class of Securities) 00773J 202 (CUSIP Number) Ms. Erin O’Connor Fairmount Funds Management LLC 200 Barr Harbor Drive, Suite 400 Wes

Exchange Agreement, dated April 23, 2024, by and between the Company and Fairmount Healthcare Fund II L.P.

Exhibit 10.1 April 23, 2024 Spyre Therapeutics, Inc. 221 Crescent St., Building 23, Unit 105 Waltham, MA 02453 Attention: Scott Burrows Re: 3(a)(9) Exchange Agreement Ladies and Gentlemen: This letter agreement (the “Agreement”) confirms the agreement of Spyre Therapeutics, Inc. (the “Company”), and the holder of the Series A Non-Voting Convertible Preferred Stock, par value $0.0001 per share, of

Current Report

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of Earliest Event Reported): April 23, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commission

April 25, 2024

April 25, 2024 VIA EDGAR AND EMAIL United States Securities and Exchange Commission Division of Corporation Finance 100 F Street, N.

SYRE / Spyre Therapeutics, Inc. / Avoro Capital Advisors LLC - SPYRE THERAPEUTICS INC. Passive Investment

SC 13G/A 1 p24-1535sc13ga.htm SPYRE THERAPEUTICS INC. SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. 1)* Spyre Therapeutics Inc. (Name of Issuer) Common Stock, $0.0001 par value (Title of Class of Securities) 00773J202 (CUSIP Number) December 31, 2023** (Date of Event Which Requires Filing of This Statement) Check the

As filed with the Securities and Exchange Commission on April 18, 2024 Registration No. 333-     UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Spyre Therapeuti

Table of Contents As filed with the Securities and Exchange Commission on April 18, 2024 Registration No.

Filing Fee Table.

EX-FILING FEES Exhibit 107 CALCULATION OF FILING FEE TABLES Form S-1 (Form Type) Spyre Therapeutics, Inc.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. )

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. ) Filed by the Registrant x Filed by a Party other than the Registrant ¨ Check the appropriate box: ¨ Preliminary Proxy Statement ¨ Confidential, for Use of the Commission Only (as permitted by Rule 14a-6(e)(2)) x Defin

March 28, 2024

March 28, 2024 VIA EDGAR AND EMAIL United States Securities and Exchange Commission Division of Corporation Finance 100 F Street, N.

As filed with the Securities and Exchange Commission on March 26, 2024 Registration No. 333-276251 UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 PRE-EFFECTIVE AMENDMENT NO. 4 TO FORM S-1 REGISTRATION STATEMENT UNDER THE SECU

Table of Contents As filed with the Securities and Exchange Commission on March 26, 2024 Registration No.

As filed with the Securities and Exchange Commission on March 26, 2024 Registration No. 333-273769 UNITED STATES SECURITIES AND EXCHANGE COMMISSIO N WASHINGTON, D.C. 20549 POST-EFFECTIVE AMENDMENT NO . 3 TO FORM S-1 REGISTRATION STATEMENT UNDER THE S

Table of Contents As filed with the Securities and Exchange Commission on March 26, 2024 Registration No.

Abu Dhabi • Beijing • Brussels • Century City • Dallas • Denver • Dubai • Frankfurt • Hong Kong • Houston • London • Los Angeles Munich • New York • Orange County • Palo Alto • Paris • Riyadh • San Francisco • Singapore • Washington, D.C.

Gibson, Dunn & Crutcher LLP One Embarcadero Center, Suite 2600 San Francisco, CA 94111-3715 Tel 415.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. )

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. ) Filed by the Registrant x Filed by a Party other than the Registrant ¨ Check the appropriate box: x Preliminary Proxy Statement ¨ Confidential, for Use of the Commission Only (as permitted by Rule 14a-6(e)(2)) ¨ Defin

Certificate of Amendment to Certificate of Designation of Series B Non-Voting Convertible Preferred Stock

EX-3.2 Exhibit 3.2 CERTIFICATE OF AMENDMENT TO THE CERTIFICATE OF DESIGNATION OF PREFERENCES, RIGHTS AND LIMITATIONS OF SERIES B NON-VOTING CONVERTIBLE PREFERRED STOCK OF SPYRE THERAPEUTICS, INC. Pursuant to Section 151 of the General Corporation Law of the State of Delaware Spyre Therapeutics, Inc., a Delaware corporation (the “Corporation”), hereby certifies as follows: FIRST: The Corporation’s

Securities Purchase Agreement, dated as of March 18, 2024, by and among Spyre Therapeutics, Inc. and each purchaser identified on Annex A thereto

EX-10.1 Exhibit 10.1 Execution Version SECURITIES PURCHASE AGREEMENT This SECURITIES PURCHASE AGREEMENT (this “Agreement”) is dated as of March 18, 2024, by and among SPYRE THERAPEUTICS, INC., a Delaware corporation (the “Company”), and each purchaser identified on Annex A hereto (each, including its successors and assigns, a “Purchaser” and collectively, the “Purchasers”). RECITALS A. The Company

Spyre Therapeutics Announces $180 Million Private Placement

EX-99.1 Exhibit 99.1 Spyre Therapeutics Announces $180 Million Private Placement WALTHAM, Mass., March 18, 2024 (PR NEWSWIRE)—Spyre Therapeutics, Inc. (“Spyre” or the “Company”) (NASDAQ: SYRE), a biotechnology company advancing a pipeline of investigational antibody therapeutics with the potential to transform the treatment of inflammatory bowel disease (“IBD”), today announced that it has entered

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): March 18, 2024 SPYRE THERAPEUTICS

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): March 18, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commission

SPYRE THERAPEUTICS, INC. 18,809,064 Shares Common Stock Offered by the Selling Stockholders

Prospectus Supplement No. 4 Filed Pursuant to Rule 424(b)(3) (to prospectus dated November 20, 2023) Registration No. 333-273769 SPYRE THERAPEUTICS, INC. 18,809,064 Shares Common Stock Offered by the Selling Stockholders This prospectus supplement no. 4 is being filed to update and supplement information contained in the prospectus dated November 20, 2023 (the “Prospectus”) related to the proposed

Form of Registration Rights Agreement (March 2024 PIPE)

EX-10.2 Exhibit 10.2 Execution Version REGISTRATION RIGHTS AGREEMENT This Registration Rights Agreement (this “Agreement”) is dated as of March 18, 2024, by and among Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), and the several purchasers signatory hereto (each, including its successors and assigns, a “Purchaser” and collectively, the “Purchasers”). This Agreement is made purs

As filed with the Securities and Exchange Commission on March 14 , 2024 Registration No. 333-273769 UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 POST-EFFECTIVE AMENDMENT NO . 2 TO FORM S-1 REGISTRATION STATEMENT UNDER THE S

Table of Contents As filed with the Securities and Exchange Commission on March 14 , 2024 Registration No.

As filed with the Securities and Exchange Commission on March 14, 2024 Registration No. 333-276251 UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 PRE-EFFECTIVE AMENDMENT NO. 3 TO FORM S-1 REGISTRATION STATEMENT UNDER THE SECU

Table of Contents As filed with the Securities and Exchange Commission on March 14, 2024 Registration No.

Abu Dhabi • Beijing • Brussels • Century City • Dallas • Denver • Dubai • Frankfurt • Hong Kong • Houston • London • Los Angeles Munich • New York • Orange County • Palo Alto • Paris • Riyadh • San Francisco • Singapore • Washington, D.C.

Gibson, Dunn & Crutcher LLP One Embarcadero Center, Suite 2600 San Francisco, CA 94111-3715 Tel 415.

As filed with the Securities and Exchange Commission on March 5, 2024 Registration No. 333-273769 UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 POST-EFFECTIVE AMENDMENT NO . 1 TO FORM S-1 REGISTRATION STATEMENT UNDER THE SEC

As filed with the Securities and Exchange Commission on March 5, 2024 Registration No.

Offer Letter, dated August 18, 2023, by and between the Company and Heidy King-Jones (incorporated by reference to Exhibit 10.19 to the Company’s registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 10.19 August 18, 2023 Heidy King-Jones Re: Offer of Employment Dear Heidy: On behalf of Aeglea BioTherapeutics, Inc. (the “Company”), I am very pleased to offer you a position as Chief Legal Officer and Corporate Secretary (the “Role”) pursuant to this letter agreement (the “Agreement”), provided you accept such offer as indicated by your signature below. Your employment with the Company i

re UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 FORM 10-K/A (Amendment No. 1)

re UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 FORM 10-K/A (Amendment No.

Spyre Therapeutics, Inc. 2016 Employee Stock Purchase Plan, as amended by the First Amendment on January 31, 2024 (incorporated by reference to Exhibit 10.8 to the Company’s registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 10.8 SPYRE THERAPEUTICS, INC. 2016 EMPLOYEE STOCK PURCHASE PLAN (as amended by the First Amendment on January 31, 2024) 1. PURPOSE. Spyre Therapeutics, Inc. has adopted this Plan effective as of the date of the IPO. The purpose of this Plan is to provide eligible employees of the Company and the Participating Corporations with a means of acquiring an equity interest in the Company and to e

As filed with the Securities and Exchange Commission on March 1, 2024 Registration No. 333-276251 UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 PRE-EFFECTIVE AMENDMENT NO. 2 TO FORM S-1 REGISTRATION STATEMENT UNDER THE SECUR

As filed with the Securities and Exchange Commission on March 1, 2024 Registration No.

Filing Fee Table (incorporated by reference to Exhibit 107 to the Company’ registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 107 Calculation of Filing Fee Tables FORM S-1 (Form Type) Spyre Therapeutics, Inc.

Consulting Agreement by and between the Company and Mark McKenna, effective August 1, 2023 (incorporated by reference to Exhibit 10.20 to the Company’s registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 10.20 CONSULTING AGREEMENT THIS CONSULTING AGREEMENT (together with the attached Exhibit A (the “Business Terms Exhibit”) and Exhibit B (the “EU Data Privacy Exhibit”), the “Agreement”), is made as of August 1, 2023 (the “Effective Date”) by and between Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Company”), and Mark McKenna (“Consultant”). The Company desires to have the ben

Abu Dhabi • Beijing • Brussels • Century City • Dallas • Denver • Dubai • Frankfurt • Hong Kong • Houston • London • Los Angeles Munich • New York • Orange County • Palo Alto • Paris • Riyadh • San Francisco • Singapore • Washington, D.C.

Gibson, Dunn & Crutcher LLP One Embarcadero Center, Suite 2600 San Francisco, CA 94111-3715 Tel 415.

Spyre Therapeutics, Inc. 2016 Employee Stock Purchase Plan, as amended by the First Amendment on January 31, 2024

Exhibit 10.4 SPYRE THERAPEUTICS, INC. 2016 EMPLOYEE STOCK PURCHASE PLAN (as amended by the First Amendment on January 31, 2024) 1. PURPOSE. Spyre Therapeutics, Inc. has adopted this Plan effective as of the date of the IPO. The purpose of this Plan is to provide eligible employees of the Company and the Participating Corporations with a means of acquiring an equity interest in the Company and to e

re UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 FORM 10-K

Table of Contents re UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 FORM 10-K x ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2023 o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number 001-37722 SPYRE THERAPEUTICS, INC.

Spyre Therapeutics, Inc. Compensation Recoupment (Clawback) Policy

Exhibit 97 SPYRE THERAPEUTICS, INC. COMPENSATION RECOUPMENT (CLAWBACK) POLICY (Adopted By Board on October 25, 2023) Recoupment of Incentive-Based Compensation It is the policy of Spyre Therapeutics, Inc. (the “Company”) that, in the event the Company is required to prepare an accounting restatement of the Company’s financial statements due to the Company’s material non-compliance with any financi

Subsidiaries of the Registrant

Exhibit 21.1 Subsidiaries of Spyre Therapeutics, Inc. Name of Subsidiary Jurisdiction Spyre Therapeutics LLC Delaware Aeglea Development Company, Inc. Delaware AERase, Inc. Delaware AECase, Inc. Delaware AEMase, Inc. Delaware AE4ase, Inc. Delaware AE5ase, Inc. Delaware AE6ase, Inc. Delaware Aeglea Biotherapeutics UK Limited England and Wales Aeglea Ireland Limited Ireland Aeglea BioTherapeutics US

Description of the Registrant's securities

Exhibit 4.5 DESCRIPTION OF CAPITAL STOCK General The following description summarizes the material terms of the capital stock of Spyre Therapeutics, Inc. (“we,” “us,” “our” or the “company”), as well as other material terms of our amended and restated certificate of incorporation (“Certificate of Incorporation”) and amended and restated bylaws (“Bylaws”) and certain provisions of Delaware law. Thi

Offer Letter, dated August 18, 2023, by and between the Company and Heidy King-Jones

Exhibit 10.19 August 18, 2023 Heidy King-Jones Re: Offer of Employment Dear Heidy: On behalf of Aeglea BioTherapeutics, Inc. (the “Company”), I am very pleased to offer you a position as Chief Legal Officer and Corporate Secretary (the “Role”) pursuant to this letter agreement (the “Agreement”), provided you accept such offer as indicated by your signature below. Your employment with the Company i

Filing Fee Table

Exhibit 107 Calculation of Filing Fee Tables FORM S-8 (Form Type) Spyre Therapeutics, Inc.

Spyre Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Corporate Update Announced corporate name change to Spyre Therapeutics; appointment of Cameron Turtle, DPhil, as Chief Executive Officer; and began trading on

Exhibit 99.1 Spyre Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Corporate Update Announced corporate name change to Spyre Therapeutics; appointment of Cameron Turtle, DPhil, as Chief Executive Officer; and began trading on Nasdaq under the symbol "SYRE" SPY001, an anti-α4β7 antibody engineered for infrequent, subcutaneous dosing, demonstrated an updated hal

As filed with the Securities and Exchange Commission on February 29, 2024

As filed with the Securities and Exchange Commission on February 29, 2024 Registration No.

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): February 29, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commiss

Consulting Agreement by and between the Company and Mark McKenna, effective August 1, 2023

Exhibit 10.20 CONSULTING AGREEMENT THIS CONSULTING AGREEMENT (together with the attached Exhibit A (the “Business Terms Exhibit”) and Exhibit B (the “EU Data Privacy Exhibit”), the “Agreement”), is made as of August 1, 2023 (the “Effective Date”) by and between Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Company”), and Mark McKenna (“Consultant”). The Company desires to have the ben

US00773J2024 / AEGLEA BIOTHERAP / EcoR1 Capital, LLC Passive Investment

SC 13G/A 1 agle13ga.htm UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. 1) Spyre Therapeutics, Inc. (Name of Issuer) Common Stock, par value $0.0001 per share (Title of Class of Securities) 00773J202 (CUSIP Number) December 31, 2023 (Date of Event Which Requires Filing of this Statement) Check the appropr

US00773J2024 / AEGLEA BIOTHERAP / Rock Springs Capital Management LP Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 SCHEDULE 13/A Under the Securities Exchange Act of 1934 (Amendment No.

US00773J2024 / AEGLEA BIOTHERAP / Avoro Capital Advisors LLC - SPYRE THERAPEUTICS, INC. Passive Investment

SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. )* Spyre Therapeutics Inc. (Name of Issuer) Common Stock, $0.0001 par value (Title of Class of Securities) 00773J202 (CUSIP Number) December 31, 2023 (Date of Event Which Requires Filing of This Statement) Check the appropriate box to designate the rule pursuant to which

US00773J2024 / AEGLEA BIOTHERAP / Venrock Healthcare Capital Partners III, L.P. - SC 13G/A Passive Investment

SC 13G/A 1 tm246235d20sc13ga.htm SC 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No. 1)* Spyre Therapeutics, Inc. (Name of Issuer) Common Stock, $0.0001 Par Value Per Share (Title of Class of Securities) 00773J202 (CUSIP Number) December 31, 2023 (Date of Event Which Requires Filing of this Stateme

AGREEMENT

EX-99.1 2 d753218dex991.htm EX-99.1 EXHIBIT 1 AGREEMENT The persons below hereby agree that the Schedule 13G to which this agreement is attached as an exhibit, as well as all future amendments to such Schedule 13G, shall be filed on behalf of each of them. This agreement is intended to satisfy the requirements of Rule 13d-1(k)(1)(iii) under the Securities Exchange Act of 1934. Date: February 14, 2

US00773J2024 / AEGLEA BIOTHERAP / Logos Global Management LP Passive Investment

SC 13G/A 1 agle13ga.htm UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. 1) Spyre Therapeutics, Inc. (Name of Issuer) Common Stock, $0.0001 par value (Title of Class of Securities) 00773J202 (CUSIP Number) December 31, 2023 (Date of Event Which Requires Filing of this Statement) Check the appropriate box t

US00773J2024 / AEGLEA BIOTHERAP / RTW INVESTMENTS, LP - SPYRE THERAPEUTICS, INC. Passive Investment

SC 13G 1 p24-0715sc13g.htm SPYRE THERAPEUTICS, INC. SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. )* Spyre Therapeutics, Inc. (Name of Issuer) Common Stock, par value $0.0001 per share (Title of Class of Securities) 00773J202 (CUSIP Number) December 31, 2023 (Date of event which requires filing of this statement) Che

US00773J2024 / AEGLEA BIOTHERAP / BAKER BROS. ADVISORS LP - SC 13G/A Passive Investment

SC 13G/A 1 tm242424d8sc13ga.htm SC 13G/A SCHEDULE 13G SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 Under the Securities Exchange Act of 1934 (Amendment No. 1)* Spyre Therapeutics, Inc. (f/k/a Aeglea Biotherapeutics, Inc.) (Name of Issuer) Common Stock, par value $0.0001 per share (Title of Class of Securities) 00773J202** (CUSIP Number) December 31, 2023 (Date of Event which Requires Fi

US00773J2024 / AEGLEA BIOTHERAP / PERCEPTIVE ADVISORS LLC - SC 13G/A Passive Investment

SC 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No. 1)* Spyre Therapeutics, Inc. (Name of Issuer) Common Stock, $0.0001 par value per share (Title of Class of Securities) 00773J 202 (CUSIP Number) December 31, 2023 (Date of Event Which Requires Filing of this Statement) Check the appropriate box to

US00773J2024 / AEGLEA BIOTHERAP / COMMODORE CAPITAL LP Passive Investment

SC 13G/A 1 formsc13ga.htm UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. 1)* Spyre Therapeutics, Inc. (Name of Issuer) Common Stock, $0.0001 par value per share (Title of Class of Securities) 00773J202 (CUSIP Number) December 31, 2023 (Date of Event Which Requires Filing of this Statement) Check the approp

AGLE / Aeglea BioTherapeutics Inc / Deep Track Capital, LP Passive Investment

SC 13G/A 1 deeptrack-syre123123a1.htm UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No. 1)* Spyre Therapeutics Inc. (Name of Issuer) Common Stock, $0.0001 Par Value Per Share (Title of Class of Securities) 00773J103 (CUSIP Number) December 31, 2023 (Date of Event Which Requires Filing of this Statement) Che

US00773J2024 / AEGLEA BIOTHERAP / Nantahala Capital Management, LLC - SC 13G/A Passive Investment

UNITED STATES 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 per share (Title of Class of Securities) 00773J 202 (CUSIP Number) December 31, 2023 (Date of Event which Requires Filing of this Statement) Check the appropriate box to designate

US00773J2024 / AEGLEA BIOTHERAP / Affinity Asset Advisors, LLC - AMENDMENT TO FORM SC 13G Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. 1)* Spyre Therapeutics, Inc. (formerly Aeglea BioTherapeutics, Inc.) (Name of Issuer) Common Stock, par value $0.0001 per share (Title of Class of Securities) 00773J202 (CUSIP Number) Michael Hirschberg, Esq. Reitler Kailas & Rosenblatt LLP 885 Third Avenue,

US00773J2024 / AEGLEA BIOTHERAP / SUVRETTA CAPITAL MANAGEMENT, LLC Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No.

US00773J2024 / AEGLEA BIOTHERAP / Polar Capital Holdings Plc Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No.

US00773J2024 / AEGLEA BIOTHERAP / BCLS II Equity Opportunities, LP - SC 13G/A Passive Investment

SC 13G/A 1 d784098dsc13ga.htm SC 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 SCHEDULE 13G (Rule 13d-102) Information to be Included in Statements Filed Pursuant to § 240.13d-1(b), (c) and (d) and Amendments Thereto Filed Pursuant to § 240.13d-2 Under the Securities Exchange Act of 1934 (Amendment No. 3) SPYRE THERAPEUTICS, INC. (Name of Issuer) Common Stock, $0.0001

US00773J2024 / AEGLEA BIOTHERAP / INTEGRATED CORE STRATEGIES (US) LLC Passive Investment

SC 13G/A 1 SYRESC13GA2.htm UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (AMENDMENT NO. 2) SPYRE THERAPEUTICS, INC. (formerly Aeglea BioTherapeutics, Inc.) (Name of Issuer) COMMON STOCK, PAR VALUE $0.0001 PER SHARE (Title of Class of Securities) 00773J202 (CUSIP Number) DECEMBER 31, 2023 (Date of event which requires

SPYRE THERAPEUTICS, INC. 18,809,064 Shares Common Stock Offered by the Selling Stockholders

Prospectus Supplement No. 3 Filed Pursuant to Rule 424(b)(3) (to prospectus dated November 20, 2023) Registration No. 333-273769 SPYRE THERAPEUTICS, INC. 18,809,064 Shares Common Stock Offered by the Selling Stockholders This prospectus supplement no. 3 is being filed to update and supplement information contained in the prospectus dated November 20, 2023 (the “Prospectus”) related to the proposed

Form of Indemnification Agreement.

Exhibit 10.1 INDEMNIFICATION AGREEMENT This Indemnification Agreement (this “Agreement”) is entered into as of       by and between Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), and       (the “Indemnitee”) and shall be deemed effective upon the earliest date that the Indemnitee is duly elected or appointed as a director or officer of the Company. RECITALS WHEREAS, the Board of

Amended and Restated Bylaws of the Company (incorporated by reference to Exhibit 3.1 to the Company’s Current Report on Form 8-K filed on February 5, 2024).

Exhibit 3.1 AMENDED AND RESTATED BYLAWS OF SPYRE THERAPEUTICS, INC. (a Delaware corporation) ARTICLE I CORPORATE OFFICES Section 1.1 Registered Office. The registered office of Spyre Therapeutics, Inc., a Delaware corporation (the “Corporation”), shall be fixed in the Certificate of Incorporation of the Corporation (as the same may be amended and/or restated from time to time, the “Certificate of

Amended and Restated Offer Letter, dated November 22, 2023 and as amended on February 1, 2024, by and between the Company and Cameron Turtle

Exhibit 10.4 November 22, 2023 Cameron Turtle Re: Amended and Restated Employment Letter Agreement Dear Cameron: On behalf of Aeglea BioTherapeutics, Inc. (the “Company”), I am very pleased to offer you a position as Chief Executive Officer of the Company (the “Role”) pursuant to this letter agreement (the “Agreement”), provided you accept such offer as indicated by your signature below, to be eff

Code of Business Conduct and Ethics of the Company, effective as of February 1, 2024.

Exhibit 14.1 SPYRE THERAPEUTICS, INC. CODE OF BUSINESS CONDUCT AND ETHICS (dated February 1, 2024) I. INTRODUCTION This Code of Business Conduct and Ethics (this “Code”) provides a general statement of the expectations of Spyre Therapeutics, Inc. (the “Company”) regarding the ethical standards to which each director, officer and employee should adhere while acting on behalf of the Company. You are

2024 Form of Indemnification Agreement (incorporated by reference to Exhibit 10.18 to the Company’s registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 10.19 INDEMNIFICATION AGREEMENT This Indemnification Agreement (this “Agreement”) is entered into as of by and between Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), and (the “Indemnitee”) and shall be deemed effective upon the earliest date that the Indemnitee is duly elected or appointed as a director or officer of the Company. RECITALS WHEREAS, the Board of Directors

As filed with the Securities and Exchange Commission on February 2, 2024 Registration No. 333-    UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 PRE-EFFECTIVE AMENDMENT NO. 1 TO FORM S-1 REGISTRATION STATEMENT UNDER THE SECUR

As filed with the Securities and Exchange Commission on February 2, 2024 Registration No.

Entry into a Material Definitive Agreement

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of Earliest Event Reported): February 1, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commissi

Filing Fee Table

Exhibit 107 Calculation of Filing Fee Tables FORM S-1 (Form Type) Spyre Therapeutics, Inc.

Amended and Restated Bylaws

Exhibit 3.2 AMENDED AND RESTATED BYLAWS OF SPYRE THERAPEUTICS, INC. (a Delaware corporation) ARTICLE I CORPORATE OFFICES Section 1.1 Registered Office. The registered office of Spyre Therapeutics, Inc., a Delaware corporation (the “Corporation”), shall be fixed in the Certificate of Incorporation of the Corporation (as the same may be amended and/or restated from time to time, the “Certificate of

Amendment to the Amended and Restated Letter Agreement by and between the Company and Cameron Turtle, dated as of February 1, 2024.

Exhibit 10.2 February 1, 2024 Cameron Turtle Re: Amendment to Amended and Restated Employment Letter Agreement Dear Cameron: This letter, effective as of the date first set forth above (this “Amendment”), amends that certain amended and restated employment letter agreement between you and Spyre Therapeutics, Inc. (f/k/a Aeglea BioTherapeutics, Inc.) (the “Company”) dated November 22, 2023 (the “Ag

Abu Dhabi • Beijing • Brussels • Century City • Dallas • Denver • Dubai • Frankfurt • Hong Kong • Houston • London • Los Angeles Munich • New York • Orange County • Palo Alto • Paris • Riyadh • San Francisco • Singapore • Washington, D.C.

Gibson, Dunn & Crutcher LLP One Embarcadero Center, Suite 2600 San Francisco, CA 94111-3715 Tel 415.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of Earliest Event Reported): January 16, 2024 SPYRE THERAPEUTI

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of Earliest Event Reported): January 16, 2024 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commissi

US00773J2024 / AEGLEA BIOTHERAP / Fairmount Funds Management LLC - SC 13D/A Activist Investment

SC 13D/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13D Under the Securities Exchange Act of 1934 (Amendment No. 3) SPYRE THERAPEUTICS, INC. (Name of Issuer) Common Stock, $0.0001 par value (Title of Class of Securities) 00773J 202 (CUSIP Number) Ms. Erin O’Connor Fairmount Funds Management LLC 200 Barr Harbor Drive, Suite 400 West Conshohocken, PA 19428 (267)

Cell Line License Agreement, effective June 20, 2022, by and between Paragon Therapeutics, Inc. and WuXi Biologics (Hong Kong) Limited (incorporated by reference to Exhibit 10.2 to the Company’s registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 10.2 [***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED. CELL LINE LICENSE AGREEMENT This Cell Line License Agreement (“Agreement”), effective as of June 20, 2022 (“Effective Date”), is entered and made by and between WuXi Biologic

Securities Purchase Agreement, dated December 7, 2023, by and among Spyre Therapeutics, Inc. and each purchaser identified on Annex A thereto

Exhibit 4.3 Execution Version SECURITIES PURCHASE AGREEMENT This SECURITIES PURCHASE AGREEMENT (this “Agreement”) is dated as of December 7, 2023, by and among SPYRE THERAPEUTICS, INC., a Delaware corporation (the “Company”), and each purchaser identified on Annex A hereto (each, including its successors and assigns, a “Purchaser” and collectively, the “Purchasers”). RECITALS A. The Company and ea

Spyre Therapeutics, Inc. 2016 Equity Incentive Plan, As Amended and Restated Effective November 21, 2023

EXHIBIT 10.8 SPYRE THERAPEUTICS, INC. 2016 EQUITY INCENTIVE PLAN AS AMENDED AND RESTATED EFFECTIVE NOVEMBER 21, 2023 1. PURPOSE. The purpose of this Plan is to provide incentives to attract, retain and motivate eligible persons whose present and potential contributions are important to the success of the Company, and any Parents, Subsidiaries and Affiliates that exist now or in the future, by offe

Form of Pre-Funded Warrants 2022 (incorporated by reference to Exhibit 4.5 to the Company’s registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 4.5 AEGLEA BIOTHERAPEUTICS, INC. WARRANT TO PURCHASE COMMON STOCK Number of Shares: [ ] (subject to adjustment) Warrant No. [ ] Original Issue Date: [ ], 202[ ] Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Company”), hereby certifies that, for good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, [ ] or its registered assigns (the “Hol

Amended and Restated Offer Letter, dated November 22, 2023, by and between the Company and Cameron Turtle

Exhibit 10.4 November 22, 2023 Cameron Turtle Re: Amended and Restated Employment Letter Agreement Dear Cameron: On behalf of Aeglea BioTherapeutics, Inc. (the “Company”), I am very pleased to offer you a position as Chief Executive Officer of the Company (the “Role”) pursuant to this letter agreement (the “Agreement”), provided you accept such offer as indicated by your signature below, to be eff

Form of Stock Restriction Agreement

Exhibit 10.13 AEGLEA BIOTHERAPEUTICS, INC. STOCK RESTRICTION AGREEMENT This Stock Restriction Agreement (this “Agreement”) is made and entered into as of March 10, 2015 (the “Effective Date”) by and between Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Company”), and (“Stockholder”). R E C I T A L S A. Stockholder was the owner of Common B Shares (the “Units”) of Aeglea BioTherapeutic

Form of Registration Rights Agreement (December 2023 PIPE) (incorporated by reference to Exhibit 4.1 to the Company’s registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 4.1 Execution Version REGISTRATION RIGHTS AGREEMENT This Registration Rights Agreement (this “Agreement”) is dated as of December 7, 2023, by and among Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), and the several purchasers signatory hereto (each, including its successors and assigns, a “Purchaser” and collectively, the “Purchasers”). This Agreement is made pursuant to

Lease Termination Agreement dated August 7, 2023, between the Company and Las Cimas Owner LP (incorporated by reference to Exhibit 10.17 to the Company’s registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 10.18 LEASE TERMINATION AGREEMENT THIS LEASE TERMINATION AGREEMENT (this “Agreement”) is made as of the 7th day of August, 2023 (“Effective Date”), by and between LAS CIMAS OWNER LP, a Delaware limited partnership (“Landlord”) and AEGLEA BIOTHERAPEUTICS, INC., a Delaware corporation (“Tenant”). W I T N E S S E T H: Reference is hereby made to the following facts which constitute the backgr

Asset Purchase Agreement, dated July 27, 2023, by and between the Company and Immedica Pharma AB (incorporated by reference to Exhibit 10.16 to the Company’s registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 10.17 Execution Version ASSET PURCHASE AGREEMENT dated as of July 27, 2023 by and between AEGLEA BIOTHERAPEUTICS, INC. and IMMEDICA PHARMA AB TABLE OF CONTENTS PAGE ARTICLE I PURCHASE PRICE 1 Section 1.1 Purchase Price 1 Section 1.2 Milestone Payments 2 ARTICLE II PURCHASE AND SALE 5 Section 2.1 Acquired Assets 5 Section 2.2 Excluded Assets 6 Section 2.3 Assumption of Assumed Liabilities 7

2015 Equity Incentive Plan and forms of award agreements

Exhibit 10.7 AEGLEA BIOTHERAPEUTICS, INC. 2015 EQUITY INCENTIVE PLAN As Adopted on March 10, 2015 1. PURPOSE. The purpose of this Plan is to provide incentives to attract, retain and motivate eligible persons whose present and potential contributions are important to the success of the Company, its Parent and Subsidiaries by offering eligible persons an opportunity to participate in the Company’s

Offer Letter, dated August 10, 2023, by and between the Company and Scott Burrows

Exhibit 10.16 August 10, 2023 Scott Burrows Re: Offer of Employment Dear Scott: On behalf of Aeglea BioTherapeutics, Inc. (the “Company”), I am very pleased to offer you a position as Chief Financial Officer (the “Role”) pursuant to this letter agreement (the “Agreement”), provided you accept such offer as indicated by your signature below. Your employment with the Company in the Role will commenc

As filed with the Securities and Exchange Commission on December 22, 2023

As filed with the Securities and Exchange Commission on December 22, 2023 Registration No.

21, 2023 (incorporated by reference to Exhibit 99.1 to the Registrant’s Registration Statement on Form S-8 filed on December 22, 2023)

EXHIBIT 99.1 SPYRE THERAPEUTICS, INC. 2016 EQUITY INCENTIVE PLAN AS AMENDED AND RESTATED EFFECTIVE NOVEMBER 21, 2023 1. PURPOSE. The purpose of this Plan is to provide incentives to attract, retain and motivate eligible persons whose present and potential contributions are important to the success of the Company, and any Parents, Subsidiaries and Affiliates that exist now or in the future, by offe

Certificate of Designation of Series B Non-Voting Convertible Preferred Stock

Exhibit 3.4 SPYRE THERAPEUTICS, INC. CERTIFICATE OF DESIGNATION OF PREFERENCES, RIGHTS AND LIMITATIONS OF SERIES B NON-VOTING CONVERTIBLE PREFERRED STOCK Pursuant to Section 151 of the General Corporation Law of the State of Delaware THE UNDERSIGNED DOES HEREBY CERTIFY, on behalf of Spyre Therapeutics, Inc., a Delaware corporation (the “Corporation”), that the following resolution was duly adopted

Subsidiaries of the Registrant (incorporated by reference to Exhibit 21.1 to the Company’s registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 21.1 Subsidiaries of Aeglea BioTherapeutics, Inc. Name of Subsidiary Jurisdiction Aeglea Development Company, Inc. Delaware AERase, Inc. Delaware AECase, Inc. Delaware AEMase, Inc. Delaware AE4ase, Inc. Delaware AE5ase, Inc. Delaware AE6ase, Inc. Delaware Aeglea Biotherapeutics UK Limited England and Wales Aeglea Ireland Limited Ireland Aeglea BioTherapeutics US LLC Delaware Spyre Therapeu

Filing Fee Table

Exhibit 107 Calculation of Filing Fee Tables FORM S-8 (Form Type) Spyre Therapeutics, Inc.

Form of Stock Option Agreement under the Amended and Restated 2018 Equity Inducement Plan

Exhibit 10.11 NOTICE OF STOCK OPTION GRANT AEGLEA BIOTHERAPEUTICS, INC. 2018 EQUITY INDUCEMENT PLAN Unless otherwise defined herein, the terms defined in the Aeglea BioTherapeutics, Inc. (the “Company”) 2018 Equity Inducement Plan (the “Plan”) shall have the same meanings in this Notice of Stock Option Grant (the “Notice of Grant”) and the attached Stock Option Agreement (the “Option Agreement”).

Filing Fee Table

Exhibit 107 Calculation of Filing Fee Tables FORM S-1 (Form Type) Spyre Therapeutics, Inc.

Biologics Master Services Agreement, effective June 20, 2022, by and between Paragon Therapeutics, Inc. and WuXi Biologics (Hong Kong) Limited (incorporated by reference to Exhibit 10.1 to the Company’s registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 10.1 [***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED. BIOLOGICS MASTER SERVICES AGREEMENT This Biologics Master Services Agreement (this “Agreement”) is dated as of June 20, 2022 (the “Effective Date”) and is between Paragon The

Separation and Consulting Agreement and General Release of Claims by and between the Company and Jonathan Alspaugh, dated as of September 22, 2023 (incorporated by reference to Exhibit 10.14 to the Company’s registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 10.15 SEPARATION AND CONSULTING AGREEMENT AND GENERAL RELEASE OF CLAIMS This SEPARATION AND CONSULTING AGREEMENT AND GENERAL RELEASE OF CLAIMS (this “Agreement”) is entered into by and between Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Company”), and Jonathan Alspaugh (“Executive”). Executive and the Company are each referred to herein as a “Party” and collectively as the “

Form of Common Stock Certificate

Exhibit 4.2 Exhibit 4.2 The Corporation shall furnish without charge to each stockholder who so requests a statement of the powers, designations, preferences and relative, participating, optional or other special rights of each class of stock of the Corporation or series thereof and the qualifications, limitations or restrictions of such preferences and/or rights. Such requests shall be made to th

Certificate of Designation of Series A Non-Voting Convertible Preferred Stock

Exhibit 3.3 AEGLEA BIOTHERAPEUTICS, INC. CERTIFICATE OF DESIGNATION OF PREFERENCES, RIGHTS AND LIMITATIONS OF SERIES A NON-VOTING CONVERTIBLE PREFERRED STOCK Pursuant to Section 151 of the General Corporation Law of the State of Delaware THE UNDERSIGNED DOES HEREBY CERTIFY, on behalf of Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Corporation”), that the following resolution was duly

Form of Severance Agreement

Exhibit 10.14 SEVERANCE AGREEMENT This Severance Agreement (the “Agreement”) is entered into as of April , 2018 (the “Effective Date”) by and between (the “Executive”) and Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Company”). 1. Term of Agreement. This Agreement shall terminate on the date the Executive’s employment with the Company or its subsidiary, as applicable, terminates for

Agreement and Plan of Merger, dated June 22, 2023, by and among Aeglea BioTherapeutics, Inc. Aspen Merger Sub I, Inc., Sequoia Merger Sub II, LLC and Spyre Therapeutics, Inc.

Exhibit 2.1 Execution Version AGREEMENT AND PLAN OF MERGER by and among: AEGLEA BIOTHERAPEUTICS, INC., a Delaware corporation; ASPEN MERGER SUB I, INC., a Delaware corporation; SEQUOIA MERGER SUB II, LLC, a Delaware limited liability company; and SPYRE THERAPEUTICS, INC., a Delaware corporation Dated as of June 22, 2023 TABLE OF CONTENTS Page SECTION 1. DESCRIPTION OF TRANSACTION 3 1.1 The Merger

Form of Registration Rights Agreement, by and among the Company and certain purchasers (June 2023 PIPE)

Exhibit 4.4 Execution Version REGISTRATION RIGHTS AGREEMENT This Registration Rights Agreement (this “Agreement”) is dated as of June 22, 2023, by and among Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Company”), and the several purchasers signatory hereto (each, including its successors and assigns, a “Purchaser” and collectively, the “Purchasers”). This Agreement is made pursuant t

Novation Agreement, dated September 19, 2023, by and between Paragon Therapeutics, Inc., the Company and WuXi Biologics (Hong Kong) Limited

Exhibit 10.3 NOVATION AGREEMENT This Novation Agreement (this “Novation Agreement”) dated as of July 21, 2023 (the “Effective Date”), is entered into by and among (i) Paragon Therapeutics, Inc., a Delaware corporation with an office at 221 Crescent Street, Building 23, Suite 105, Waltham, MA 02453 (the “Transferor”), (ii) Aeglea Biotherapeutics, Inc., a Delaware corporation with an office at 221 C

Amended and Restated Antibody Discovery and Option agreement, dated September 29, 2023, by and between Paragon Therapeutics, Inc., Parapyre Holding LLC and Spyre Therapeutics, LLC (incorporated by reference to Exhibit 10.5 to the Company’s registration statement on Form S-1/A filed with the SEC on March 1, 2024).

Exhibit 10.5 [***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED. AMENDED AND RESTATED ANTIBODY DISCOVERY AND OPTION AGREEMENT THIS AMENDED AND RESTATED ANTIBODY DISCOVERY AND OPTION AGREEMENT (“Agreement”) is entered into and effective as

Amended and Restated Bylaws

Exhibit 3.2 AEGLEA BIOTHERAPEUTICS, INC., a Delaware Corporation AMENDED AND RESTATED BYLAWS As Amended and Restated on December 15, 2022 1 AEGLEA BIOTHERAPEUTICS, INC., a Delaware Corporation AMENDED AND RESTATED BYLAWS As Amended and Restated on December 15, 2022 ARTICLE I: STOCKHOLDERS Section 1.1: Annual Meetings. An annual meeting of stockholders shall be held for the election of directors at

Spyre Therapeutics, Inc. 2023 Equity Incentive Plan

Exhibit 10.12 SPYRE THERAPEUTICS, INC. 2023 EQUITY INCENTIVE PLAN AMENDED BY THE BOARD OF DIRECTORS: May 19, 2023 1. Purpose. The purpose of this 2023 Equity Incentive Plan (the “Plan”) of Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), is to advance the interests of the Company’s stockholders by enhancing the Company’s ability to attract, retain and motivate persons who are expe

Spyre Therapeutics, Inc. 2018 Equity Inducement Plan and the First Amendment, Second Amendment, Third Amendment and Fourth Amendment thereto

EXHIBIT 10.10 AEGLEA BIOTHERAPEUTICS, INC. 2018 EQUITY INDUCEMENT PLAN 1. PURPOSE. The purpose of this Plan is to provide incentives to attract eligible persons whose potential contributions are important to the success of the Company, and any Parents, Subsidiaries and Affiliates that exist now or in the future, by offering them an opportunity to participate in the Company’s future performance thr

Spyre Therapeutics, Inc. 2018 Equity Inducement Plan and the First Amendment, Second Amendment, Third Amendment and Fourth Amendment thereto.

EXHIBIT 99.2 AEGLEA BIOTHERAPEUTICS, INC. 2018 EQUITY INDUCEMENT PLAN 1. PURPOSE. The purpose of this Plan is to provide incentives to attract eligible persons whose potential contributions are important to the success of the Company, and any Parents, Subsidiaries and Affiliates that exist now or in the future, by offering them an opportunity to participate in the Company’s future performance thro

2018 Form of Amended and Restated Indemnification Agreement

Exhibit 10.6 INDEMNITY AGREEMENT This Indemnity Agreement, dated as of [•], 2018 is made by and between Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Company”), and [•], a director, officer or key employee of the Company or one of the Company’s subsidiaries or other service provider who satisfies the definition of Indemnifiable Person set forth below (“Indemnitee”). RECITALS A. The Co

Power of Attorney (included on the signature page to the registration statement)

As filed with the Securities and Exchange Commission on December 22, 2023 Registration No.

2016 Employee Stock Purchase Plan and forms of award agreements, as amended

Exhibit 10.9 AEGLEA BIOTHERAPEUTICS, INC. 2016 EMPLOYEE STOCK PURCHASE PLAN 1. PURPOSE. Aeglea BioTherapeutics, Inc. has adopted this Plan effective as of the date of the IPO. The purpose of this Plan is to provide eligible employees of the Company and the Participating Corporations with a means of acquiring an equity interest in the Company and to enhance such employees’ sense of participation in

Amended and Restated Certificate of Incorporation

Exhibit 3.1 AEGLEA BIOTHERAPEUTICS, INC. AMENDED AND RESTATED CERTIFICATE OF INCORPORATION Aeglea BioTherapeutics, Inc. (the “Corporation”), a corporation organized and existing under and by virtue of the provisions of the General Corporation Law of the State of Delaware (the “General Corporation Law”), does hereby certify as follows: 1. The current name of the Corporation is Aeglea BioTherapeutic

AGREEMENT

EX-99.1 EXHIBIT 1 AGREEMENT The persons below hereby agree that the Schedule 13G to which this agreement is attached as an exhibit, as well as all future amendments to such Schedule 13G, shall be filed on behalf of each of them. This agreement is intended to satisfy the requirements of Rule 13d-1(k)(1)(iii) under the Securities Exchange Act of 1934. Date: December 13, 2023 PERCEPTIVE ADVISORS LLC

US00773J2024 / AEGLEA BIOTHERAP / PERCEPTIVE ADVISORS LLC - SC 13G Passive Investment

SC 13G UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. )* Spyre Therapeutics, Inc. (Name of Issuer) Common Stock, $0.0001 par value per share (Title of Class of Securities) 00773J 202 (CUSIP Number) November 24, 2023 (Date of Event Which Requires Filing of this Statement) Check the appropriate box to desi

US00773J2024 / AEGLEA BIOTHERAP / Fairmount Funds Management LLC - SC 13D/A Activist Investment

SC 13D/A 1 d615568dsc13da.htm SC 13D/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13D 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) 00773J 202 (CUSIP Number) Ms. Erin O’Connor Fairmount Funds Management LLC 200 Barr Harbor Drive, Suite 400 Wes

SPYRE THERAPEUTICS, INC. 18,809,064 Shares Common Stock Offered by the Selling Stockholders

424B3 Prospectus Supplement No. 2 Filed Pursuant to Rule 424(b)(3) (to prospectus dated November 20, 2023) Registration No. 333-273769 SPYRE THERAPEUTICS, INC. 18,809,064 Shares Common Stock Offered by the Selling Stockholders This prospectus supplement no. 2 is being filed to update and supplement information contained in the prospectus dated November 20, 2023 (the “Prospectus”) related to the pr

Securities Purchase Agreement, dated as of December 7, 2023, by and among Spyre Therapeutics, Inc. and each purchaser identified on Annex A thereto

EX-10.1 Exhibit 10.1 Execution Version SECURITIES PURCHASE AGREEMENT This SECURITIES PURCHASE AGREEMENT (this “Agreement”) is dated as of December 7, 2023, by and among SPYRE THERAPEUTICS, INC., a Delaware corporation (the “Company”), and each purchaser identified on Annex A hereto (each, including its successors and assigns, a “Purchaser” and collectively, the “Purchasers”). RECITALS A. The Compa

Form of Registration Rights Agreement

Exhibit 10.2 Execution Version REGISTRATION RIGHTS AGREEMENT This Registration Rights Agreement (this “Agreement”) is dated as of December 7, 2023, by and among Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), and the several purchasers signatory hereto (each, including its successors and assigns, a “Purchaser” and collectively, the “Purchasers”). This Agreement is made pursuant t

Certificate of Designation of Series B Non-Voting Convertible Preferred Stock

Exhibit 3.1 SPYRE THERAPEUTICS, INC. CERTIFICATE OF DESIGNATION OF PREFERENCES, RIGHTS AND LIMITATIONS OF SERIES B NON-VOTING CONVERTIBLE PREFERRED STOCK Pursuant to Section 151 of the General Corporation Law of the State of Delaware THE UNDERSIGNED DOES HEREBY CERTIFY, on behalf of Spyre Therapeutics, Inc., a Delaware corporation (the “Corporation”), that the following resolution was duly adopted

Spyre Therapeutics Announces $180 Million Private Placement

EX-99.1 Exhibit 99.1 Spyre Therapeutics Announces $180 Million Private Placement WALTHAM, Mass., December 7, 2023 (PR NEWSWIRE)—Spyre Therapeutics, Inc. (“Spyre”) (NASDAQ: SYRE), a biotechnology company advancing a pipeline of antibody therapeutics with the potential to transform the treatment of inflammatory bowel disease (“IBD”), today announced that it has entered into a securities purchase agr

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of Earliest Event Reported): December 7, 2023 SPYRE THERAPEUTI

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of Earliest Event Reported): December 7, 2023 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commissi

US00773J2024 / AEGLEA BIOTHERAP / COMMODORE CAPITAL LP Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No.

SPYRE THERAPEUTICS, INC. 18,809,064 Shares Common Stock Offered by the Selling Stockholders

Filed Pursuant to Rule 424(b)(3) Registration No. 333-273769 Prospectus Supplement No. 1 (to prospectus dated November 20, 2023) SPYRE THERAPEUTICS, INC. 18,809,064 Shares Common Stock Offered by the Selling Stockholders This prospectus supplement no. 1 is being filed to update and supplement information contained in the prospectus dated November 20, 2023 (the “Prospectus”) related to the proposed

US00773J2024 / AEGLEA BIOTHERAP / Fairmount Funds Management LLC - SC 13D/A Activist Investment

SC 13D/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13D Under the Securities Exchange Act of 1934 (Amendment No. 1) SPYRE THERAPEUTICS, INC. (Name of Issuer) Common Stock, $0.0001 par value (Title of Class of Securities) 00773J 202 (CUSIP Number) Ms. Erin O’Connor Fairmount Funds Management LLC 200 Barr Harbor Drive, Suite 400 West Conshohocken, PA 19428 (267)

Aeglea BioTherapeutics Announces Name Change to Spyre Therapeutics, Appoints CEO and Additional Directors, and Expands Leadership Team to Develop Next-Generation Therapeutic Combinations for the Treatment of IBD Company will begin trading on Nasdaq u

Exhibit 99.1 Aeglea BioTherapeutics Announces Name Change to Spyre Therapeutics, Appoints CEO and Additional Directors, and Expands Leadership Team to Develop Next-Generation Therapeutic Combinations for the Treatment of IBD Company will begin trading on Nasdaq under trading symbol “SYRE” effective November 28, 2023 Biotechnology leader Cameron Turtle, DPhil, appointed as Chief Executive Officer a

Regulation FD Disclosure, Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers, Amendments to Articles of Incorporation or Bylaws; Change in Fiscal Year, Financial Statements and Exhibits

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 22, 2023 SPYRE THERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Commiss

Amended and Restated Certificate of Incorporation of the Company, effective as of November 28, 2023 (incorporated by reference to Exhibit 3.1 to the Registrant’s Current Report on Form 8-K filed on November 28, 2023).

Exhibit 3.1 AEGLEA BIOTHERAPEUTICS, INC. AMENDED AND RESTATED CERTIFICATE OF INCORPORATION Aeglea BioTherapeutics, Inc. (the “Corporation”), a corporation organized and existing under and by virtue of the provisions of the General Corporation Law of the State of Delaware (the “General Corporation Law”), does hereby certify as follows: 1. The current name of the Corporation is Aeglea BioTherapeutic

Amended and restated letter agreement by and between the Company and Cameron Turtle, dated as of November 22, 2023.

Exhibit 10.1 November 22, 2023 Cameron Turtle Re: Amended and Restated Employment Letter Agreement Dear Cameron: On behalf of Aeglea BioTherapeutics, Inc. (the “Company”), I am very pleased to offer you a position as Chief Executive Officer of the Company (the “Role”) pursuant to this letter agreement (the “Agreement”), provided you accept such offer as indicated by your signature below, to be eff

Certificate of Amendment to the Restated Certificate of Incorporation of the Company, effective as of November 21, 2023.

EX-3.1 Exhibit 3.1 SECOND CERTIFICATE OF AMENDMENT OF THE RESTATED CERTIFICATE OF INCORPORATION OF AEGLEA BIOTHERAPEUTICS, INC. AEGLEA BIOTHERAPEUTICS, INC., a corporation organized and existing under and by virtue of the General Corporation Law of the State of Delaware (the “DGCL”), does hereby certify: FIRST: The name of the corporation is Aeglea BioTherapeutics, Inc. (the “Corporation”). SECOND

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 21, 2023 AEGLEA BIOTHERA

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 21, 2023 AEGLEA BIOTHERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Com

November 17, 2023

November 17, 2023 VIA EDGAR AND EMAIL United States Securities and Exchange Commission Division of Corporation Finance 100 F Street, N.

AEGLEA BIOTHERAPEUTICS, INC. INDEX TO CONSOLIDATED FINANCIAL STATEMENTS Page Audited Consolidated Financial Statements Report of Independent Registered Public Accounting Firm (ID 238 PricewaterhouseCoopers LLP) 2 Consolidated Balance Sheets 4 Consoli

Exhibit 99.2 ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA AEGLEA BIOTHERAPEUTICS, INC. INDEX TO CONSOLIDATED FINANCIAL STATEMENTS Page Audited Consolidated Financial Statements Report of Independent Registered Public Accounting Firm (ID 238 PricewaterhouseCoopers LLP) 2 Consolidated Balance Sheets 4 Consolidated Statements of Operations 5 Consolidated Statements of Comprehensive Loss 6 Cons

Form of Stock Option Agreement under the Aeglea BioTherapeutics, Inc. 2018 Equity Inducement Plan

Exhibit 10.15 NOTICE OF STOCK OPTION GRANT AEGLEA BIOTHERAPEUTICS, INC. 2018 EQUITY INDUCEMENT PLAN Unless otherwise defined herein, the terms defined in the Aeglea BioTherapeutics, Inc. (the “Company”) 2018 Equity Inducement Plan (the “Plan”) shall have the same meanings in this Notice of Stock Option Grant (the “Notice of Grant”) and the attached Stock Option Agreement (the “Option Agreement”).

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 15, 2023 AEGLEA BIOTHERAPEUTICS, INC. (Exact name of Registrant as Specified in Its Charter) Delaware 001-37722 46-4312787 (State or Other Jurisdiction of Incorporation) (Com

2016 Equity Incentive Plan and forms of award agreements, as amended

Exhibit 10.8 AEGLEA BIOTHERAPEUTICS, INC. 2016 EQUITY INCENTIVE PLAN (Amended on October 8, 2018) 1. PURPOSE. The purpose of this Plan is to provide incentives to attract, retain and motivate eligible persons whose present and potential contributions are important to the success of the Company, and any Parents, Subsidiaries and Affiliates that exist now or in the future, by offering them an opport

Certificate of Amendment to the Restated Certificate of Incorporation, effective September 8, 2023

Exhibit 3.2 CERTIFICATE OF AMENDMENT TO THE RESTATED CERTIFICATE OF INCORPORATION OF AEGLEA BIOTHERAPEUTICS, INC. Pursuant to Section 242 of the General Corporation Law of the State of Delaware AEGLEA BIOTHERAPEUTICS, INC., a corporation organized and existing under and by virtue of the provisions of the General Corporation Law of the State of Delaware (the “Corporation”), does hereby certify as f

Form of Pre-Funded Warrants 2022

Exhibit 4.5 AEGLEA BIOTHERAPEUTICS, INC. WARRANT TO PURCHASE COMMON STOCK Number of Shares: [ ] (subject to adjustment) Warrant No. [ ] Original Issue Date: [ ], 202[ ] Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Company”), hereby certifies that, for good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, [ ] or its registered assigns (the “Hol

2018 Equity Inducement Plan

Exhibit 10.11 AEGLEA BIOTHERAPEUTICS, INC. 2018 EQUITY INDUCEMENT PLAN 1. PURPOSE. The purpose of this Plan is to provide incentives to attract eligible persons whose potential contributions are important to the success of the Company, and any Parents, Subsidiaries and Affiliates that exist now or in the future, by offering them an opportunity to participate in the Company’s future performance thr

Certificate of Designations of Series A Non-Voting Convertible Preferred Stock

Exhibit 3.4 AEGLEA BIOTHERAPEUTICS, INC. CERTIFICATE OF DESIGNATION OF PREFERENCES, RIGHTS AND LIMITATIONS OF SERIES A NON-VOTING CONVERTIBLE PREFERRED STOCK Pursuant to Section 151 of the General Corporation Law of the State of Delaware THE UNDERSIGNED DOES HEREBY CERTIFY, on behalf of Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Corporation”), that the following resolution was duly

Asset Purchase Agreement, dated July 27, 2023, by and between Aeglea BioTherapeutics, Inc. and Immedica Pharma AB

Exhibit 10.21 Execution Version ASSET PURCHASE AGREEMENT dated as of July 27, 2023 by and between AEGLEA BIOTHERAPEUTICS, INC. and IMMEDICA PHARMA AB TABLE OF CONTENTS PAGE ARTICLE I PURCHASE PRICE 1 Section 1.1 Purchase Price 1 Section 1.2 Milestone Payments 2 ARTICLE II PURCHASE AND SALE 5 Section 2.1 Acquired Assets 5 Section 2.2 Excluded Assets 6 Section 2.3 Assumption of Assumed Liabilities 7

First Amendment to the Aeglea BioTherapeutics, Inc. 2018 Equity Inducement Plan

Exhibit 10.12 FIRST AMENDMENT TO THE AEGLEA BIOTHERAPEUTICS, INC. 2018 EQUITY INDUCEMENT PLAN WHEREAS, Aeglea Biotherapeutics, Inc., a Delaware corporation (the “Company”) maintains the Aeglea Biotherapeutics, Inc. 2018 Equity Inducement Plan (the “Plan”); and WHEREAS, pursuant to Section 17 of the Plan, the Board of Directors (the “Board”) may amend the Plan at any time and for any purpose as per

First Amendment to the Aeglea BioTherapeutics, Inc. 2016 Equity Incentive Plan

Exhibit 10.9 FIRST AMENDMENT TO THE AEGLEA BIOTHERAPEUTICS, INC. 2016 EQUITY INCENTIVE PLAN WHEREAS, Aeglea Biotherapeutics, Inc., a Delaware corporation (the “Company”) maintains the Aeglea Biotherapeutics, Inc. 2016 Equity Incentive Plan (as amended, the “Plan”); and WHEREAS, pursuant to Section 24 of the Plan, the Board of Directors (the “Board”) may amend the Plan at any time. NOW, THEREFORE,

Offer Letter, dated August 10, 2023, by and between the Company and Scott Burrows

Exhibit 10.20 August 10, 2023 Scott Burrows Re: Offer of Employment Dear Scott: On behalf of Aeglea BioTherapeutics, Inc. (the “Company”), I am very pleased to offer you a position as Chief Financial Officer (the “Role”) pursuant to this letter agreement (the “Agreement”), provided you accept such offer as indicated by your signature below. Your employment with the Company in the Role will commenc

ITEM 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

Exhibit 99.1 ITEM 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS You should read the following discussion and analysis of our financial condition and results of operations together with our financial statements and related notes appearing in this Annual Report. Some of the information contained in this discussion and analysis or set forth elsewhere in this

Form of Stock Restriction Agreement

Exhibit 10.17 AEGLEA BIOTHERAPEUTICS, INC. STOCK RESTRICTION AGREEMENT This Stock Restriction Agreement (this “Agreement”) is made and entered into as of March 10, 2015 (the “Effective Date”) by and between Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Company”), and (“Stockholder”). R E C I T A L S A. Stockholder was the owner of Common B Shares (the “Units”) of Aeglea BioTherapeutic

***

November 15, 2023 EDGAR CORRESPONDENCE U.S. Securities and Exchange Commission Division of Corporation Finance Office of Life Sciences 100 F Street, N.E. Washington, D.C. 20549 Attn: Laura Crotty and Dillon Hagius Re: Aeglea BioTherapeutics, Inc. Registration Statement on Form S-1 Filed on August 7, 2023 File No. 333-273769 Ladies and Gentlemen: On behalf of Aeglea BioTherapeutics, Inc. (the “Comp

Form of Common Stock Certificate

Exhibit 4.2 Exhibit 4.2 The Corporation shall furnish without charge to each stockholder who so requests a statement of the powers, designations, preferences and relative, participating, optional or other special rights of each class of stock of the Corporation or series thereof and the qualifications, limitations or restrictions of such preferences and/or rights. Such requests shall be made to th

Form of Registration Rights Agreement, by and among Aeglea BioTherapeutics, Inc. and certain purchasers

Exhibit 4.4 Execution Version REGISTRATION RIGHTS AGREEMENT This Registration Rights Agreement (this “Agreement”) is dated as of June 22, 2023, by and among Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Company”), and the several purchasers signatory hereto (each, including its successors and assigns, a “Purchaser” and collectively, the “Purchasers”). This Agreement is made pursuant t

2016 Employee Stock Purchase Plan and forms of award agreements, as amended

Exhibit 10.10 AEGLEA BIOTHERAPEUTICS, INC. 2016 EMPLOYEE STOCK PURCHASE PLAN 1. PURPOSE. Aeglea BioTherapeutics, Inc. has adopted this Plan effective as of the date of the IPO. The purpose of this Plan is to provide eligible employees of the Company and the Participating Corporations with a means of acquiring an equity interest in the Company and to enhance such employees’ sense of participation i

Registration Rights Agreement, dated March 16, 2021, by and among the Registrant and Baker Brothers Life Sciences, L.P. and 667, L.P.

Exhibit 4.3 REGISTRATION RIGHTS AGREEMENT This Registration Rights Agreement (this “Agreement”) is made as of March 16, 2021 by and between Aeglea BioTherapeutics, Inc., a Delaware corporation (the “Company”), and the persons listed on the attached Schedule A who are signatories to this Agreement (collectively, the “Investors”). Unless otherwise defined herein, capitalized terms used in this Agree

As filed with the Securities and Exchange Commission on November 15, 2023

Table of Contents As filed with the Securities and Exchange Commission on November 15, 2023 Registration No.

Securities Purchase Agreement, dated June 22, 2023, by and among the Registrant and the purchasers named therein

Exhibit 4.1 Execution Version SECURITIES PURCHASE AGREEMENT This SECURITIES PURCHASE AGREEMENT (this “Agreement”) is dated as of June 22, 2023, by and among AEGLEA BIOTHERAPEUTICS, INC., a Delaware corporation (the “Company”), and each purchaser identified on Annex A hereto (each, including its successors and assigns, a “Purchaser” and collectively, the “Purchasers”). RECITALS A. The Company and e

Amended and Restated Spyre 2023 Equity Incentive Plan

Exhibit 10.16 SPYRE THERAPEUTICS, INC. 2023 EQUITY INCENTIVE PLAN AMENDED BY THE BOARD OF DIRECTORS: May 19, 2023 1. Purpose. The purpose of this 2023 Equity Incentive Plan (the “Plan”) of Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), is to advance the interests of the Company’s stockholders by enhancing the Company’s ability to attract, retain and motivate persons who are expe

Amended and Restated Bylaws

Exhibit 3.3 AEGLEA BIOTHERAPEUTICS, INC., a Delaware Corporation AMENDED AND RESTATED BYLAWS As Amended and Restated on December 15, 2022 1 AEGLEA BIOTHERAPEUTICS, INC., a Delaware Corporation AMENDED AND RESTATED BYLAWS As Amended and Restated on December 15, 2022 ARTICLE I: STOCKHOLDERS Section 1.1: Annual Meetings. An annual meeting of stockholders shall be held for the election of directors at