What changed in this filing

/stocks — the workspaceLOADING

Item 9A. Controls and Procedures

2025-02-27 compared with 2024-02-29 · 818 added, 46 removed, 128 unchanged (87% of the section changed)

2 unchanged sentences

Our management, with the participation of our principal executive officer and our principal financial officer, evaluated, as of the end of the period covered by this Annual Report on Form 10-K, the effectiveness of our disclosure controls and procedures.

Based on that evaluation of our disclosure controls and procedures as of December 31, 2023, our principal executive officer and principal financial officer concluded that our disclosure controls and procedures as of such date were effective at the reasonable assurance level.

The term “disclosure controls and procedures,” as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), means controls and other procedures of a company that are designed to ensure that information required to be disclosed by a company in the reports that it files or submits under the Exchange Act is recorded, processed, summarized and reported, within the time periods specified in the SEC’s rules and forms.

1 unchanged sentence

Management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives and our management necessarily applies its judgment in evaluating the cost-benefit relationship of possible controls and procedures.

Our principal executive officer and principal financial officer evaluated the effectiveness of the Company’s disclosure controls and procedures and concluded that the Company’s disclosure controls and procedures were not effective as of December 31, 2024 because of the material weakness in internal control over financial reporting disclosed below in Management's Annual Report on Internal Control Over Financial Reporting.

Notwithstanding the material weakness in internal control over financial reporting, our management, including our principal executive officer and principal financial officer, have concluded that our consolidated financial statements present fairly, in all material respects, our financial position, results of our operations and our cash flows for the periods presented in this Annual Report, in conformity with U.S.

Management’s Annual Report on Internal Control Over Financial Reporting

Our management is responsible for establishing and maintaining adequate internal control over financial reporting.

Internal control over financial reporting is defined in Rules 13a-15(f) and 15d-15(f) promulgated under the Exchange Act as a process designed by, or under the supervision of, our principal executive and principal financial officers and effected by our board of directors, management and other personnel to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with U.S.

Internal control over financial reporting is defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act as a process designed by, or under the supervision of, our principal executive and principal financial officers and effected by our board of directors, management and other personnel to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting standards.

Our internal control over financial reporting includes those policies and procedures that:

4 unchanged sentences

Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements.

Also, projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.

Also, projections of any evaluation of effectiveness to future periods are subject to the risk that

controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.

Our management, with the participation of our principal executive officer and principal financial officer, assessed the effectiveness of our internal control over financial reporting as of December 31, 2024.

In making this assessment, management used the criteria set forth by the Committee of Sponsoring Organizations of the Treadway Commission (COSO) in its 2013 Internal Control – Integrated Framework.

Based on our assessment, our management has concluded that, as of December 31, 2023, our internal control over financial reporting was effective based on those criteria.

This Annual Report on Form 10-K does not include an attestation report of our independent registered public accounting firm regarding internal control over financial reporting.

For as long as we remain a “smaller reporting company” as defined by Rule 12b-2 of the Exchange Act and report less than $100 million of annual revenues in our most recent fiscal year, we intend to take advantage of the exemption permitting us not to comply with the requirement that our independent registered public accounting firm provide an attestation on the effectiveness of our internal control over financial reporting.

A material weakness is a deficiency, or a combination of deficiencies, in internal control over financial reporting, such that there is a reasonable possibility that a material misstatement of the company’s annual or interim financial statements will not be prevented or detected on a timely basis.

We did not design and maintain effective controls related to the earnings per share calculation, as there was not an effectively designed control in place to evaluate the treatment of the Series A Preferred Stock and the Series B Preferred Stock for the purpose of calculating earnings per share under the two-class method.

This material weakness resulted in the restatement of the Company’s consolidated financial statements as of and for the year ended December 31, 2023, as well as the quarterly condensed consolidated financial information for the 2024 interim periods ended March 31, 2024, June 30, 2024, and September 30, 2024 related to earnings per share.

Additionally, the material weakness could result in misstatements of the earnings per share calculation that would result in a material misstatement to the annual or interim financial statements that would not be prevented or detected.

Because of this material weakness, management concluded that the Company did not maintain effective internal control over financial reporting as of December 31, 2024.

The effectiveness of the Company’s internal control over financial reporting as of December 31, 2024 has been audited by PricewaterhouseCoopers LLP, an independent registered public accounting firm, as stated in their report which appears herein.

Remediation Plan

In order to address the material weakness described above, management, with direction from the Audit Committee, has:

• completed a comprehensive evaluation to identify the cause of the material weakness;

• completed the review and enhancement of the existing control designs relating to the calculation of the Company's net loss per share;

• implemented the identified enhancements into impacted control processes.

While the Company has implemented the needed remediating processes described above, remediation requires the demonstration of effective control operation for a sufficient period of time.

The material weakness will not be considered remediated until the applicable controls operate for a sufficient period of time, and management has concluded, through testing, that these controls are operating effectively.

Changes in Internal Control Over Financial Reporting

There were no changes in our internal control over financial reporting that occurred during the quarter ended December 31, 2023 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

In the fourth quarter of 2024, we updated the design of our controls over the earnings per share calculation to include Series A and Series B Preferred Stock, and to evaluate the substance of financing arrangements for purposes of calculating earnings per share.

We executed the newly designed control in connection with the disclosure controls and procedures for this Annual Report.

Other than the remediation efforts disclosed above, there have been no additional changes in internal control over financial reporting that materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

OTHER INFORMATION

2 unchanged sentences

DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE

The information required by this item is incorporated herein by reference from the applicable information set forth in “the Proxy Statement with respect to our 2024 Annual Meeting of Stockholders to be filed with the SEC within 120 days of the end of the fiscal year covered by this Annual Report on Form 10-K (the “2024 Proxy Statement”), including the sections titled “Information Regarding Director Nominees and Continuing Directors,” “Executive Officers,” “Corporate Governance,” and, if applicable, “Delinquent Section 16(a) Reports.”

Management and Board of Directors

The following table sets forth the names, ages as of February 27, 2025, and positions of the individuals who currently serve as directors and executive officers of Spyre Therapeutics, Inc.

Executive Officers and Employee Director

Cameron Turtle 35 Chief Executive Officer and Director

Scott Burrows 47 Chief Financial Officer

Heidy King-Jones 42 Chief Legal Officer and Corporate Secretary

Sheldon Sloan

67 Chief Medical Officer

Non-Employee Directors

Laurie Stelzer (1)(2)

Albers (2)(3)

Tomas Kiselak (3)

Peter Harwin (1)

Michael Henderson (2)

Sandra Milligan (1)(3)

(1) Member of the Nominating Committee

(2) Member of the Audit Committee

(3) Member of the Compensation Committee

Our business and affairs are managed by and under the direction of our Board, which currently consists of eight members.

Our Board is divided into three classes, with members of each class holding office for staggered three-year terms.

There are currently three Class I directors, Mark McKenna, Cameron Turtle and Laurie Stelzer, whose terms expire at the 2026 Annual Meeting of Stockholders;

two Class II directors, Jeffrey W.

Albers and Tomas Kiselak, whose terms expire at the 2027 Annual Meeting of Stockholders;

and three Class III directors, Peter Harwin, Michael Henderson and Sandra Milligan, whose terms expire at the 2025 Annual Meeting of Stockholders.

Our executive officers are elected by the Board and serve at the Board’s discretion.

The following is a biographical summary of the experience of our executive officers and directors:

Executive Officers and Employee Director

Cameron Turtle, DPhil.

Turtle joined us as Chief Operating Officer in June 2023, and was appointed as our Chief Executive Officer and a director in November 2023.

Prior to joining the Company, Dr.

Turtle was an advisor to Pre-Merger Spyre from May 2023 to June 2023.

Previously, he served as Venture Partner at Foresite Labs, a life sciences investment firm, from July 2022 to May 2023;

Chief Strategy Officer of BridgeBio Pharma (Nasdaq:

BBIO), a biopharmaceutical company, from January 2021 to April 2022;

and Chief Business Officer of Eidos Therapeutics (Nasdaq:

EIDX), a biopharmaceutical company, from November 2018 to January 2021, where he led business development, investor relations, and multiple operational functions as the company advanced an investigational medicine for a form of heart failure.

Prior to joining BridgeBio and Eidos, he was a consultant at McKinsey & Company, where he worked with pharmaceutical and medical device companies on topics including M&A, growth strategy, clinical trial strategy, and sales force optimization.

Turtle has served as a member of the board of directors of Oruka Therapeutics, Inc.

ORKA) since August 2024.

Turtle received his B.S.

with honors in Bioengineering from the University of Washington and his D.Phil.

in Cardiovascular Medicine from the University of Oxford, St.

John’s College.

He is the recipient of

several awards, including a Rhodes Scholarship, Goldwater Scholarship, Forbes 30 Under 30 and San Francisco Business Times 40 Under 40.

We believe Dr.

Turtle is qualified to serve on our Board due to his experience as a leader in building, financing, and shaping biopharma organizations from preclinical development to late-stage clinical trials and commercialization.

Scott Burrows.

Burrows joined as our Chief Financial Officer in September 2023.

Prior to Spyre, Mr.

Burrows most recently served as the Chief Financial Officer of Arcutis Biotherapeutics, Inc.

ARQT), a biopharmaceutical company, from April 2021 to August 2023 and as Vice President of Finance from May 2019 to April 2021, where he helped lead Arcutis through a successful initial public offering, several further equity and debt financings, and the transition to a fully integrated commercial-stage company.

Prior to Arcutis, Mr.

Burrows was the head of international investor relations for Shire, plc, a biotechnology company that was acquired by Takeda Pharmaceutical Company Limited in 2019, from March 2018 to May 2019.

Earlier in his career, he spent 15 years at Amgen, Inc.

in roles of increasing responsibility across financial planning and analysis, treasury and investor relations.

Burrows began his career at Arthur Andersen as a consultant.

Burrows also serves as on the board of directors of Food Share of Ventura County, a non-profit organization.

He earned his B.A.

from the University of California, Los Angeles, and is a licensed C.P.A.

Heidy King-Jones.

King-Jones joined as our Chief Legal Officer and Corporate Secretary in September 2023.

King-Jones most recently served as the Chief Legal Officer and Corporate Secretary at Provention Bio, Inc., a biopharmaceutical company, from 2020 to 2023, including through various financings, the approval of Tzield®, the company’s successful transition from clinical-stage to commercial-stage as well as its acquisition by Sanofi in April 2023.

Prior to her leadership role at Provention Bio, she was a Senior Vice President, General Counsel and Corporate Secretary at Axcella Health Inc., a biotechnology company, from 2019 to 2020 and as Vice President, Legal and Corporate Secretary from 2018 to 2019, where she was responsible for Axcella’s corporate legal function and strategy.

From 2013 to 2018, she held positions of increasing responsibility in the legal department at Sarepta Therapeutics, Inc.

SRPT), including overseeing all Corporate Law matters as Senior Director, Corporate Law.

While at Sarepta, she served as a member of the company’s commercial readiness working group and was responsible for the development of the compliance program, contract and other legal work for the launch of its first product, Exondys 51 ® .

King-Jones began her legal career in the Securities & Public Companies Practice Group at Ropes & Gray LLP, where she represented private and publicly traded companies in the pharmaceutical, utility and technology industries.

She holds a J.D.

and LL.M in International and Comparative Law from Cornell Law School, and a B.A.

from Dartmouth College.

Sheldon Sloan, M.D., M.B.E.

Sloan has served as our Chief Medical Officer since October 2024.

Sloan most recently served as the Chief Medical Officer of Abivax S.A.

ABVX), a biopharmaceutical company, from March 2023 to August 2024, where he was responsible for leading medical strategy to support the lead Phase 3 program, develop lifecycle strategy for lead and follow on compounds, investor interface, business development support, and building a Phase 3 medical infrastructure including Clinical Development, Pharmacovigilance, Bioinformatics, Medical Affairs and Clinical Pharmacology.

From March 2022 to January 2023, Dr.

Sloan was Vice President and Program Lead for etrasimod UC at Pfizer, Inc.

PFE), a biopharmaceutical company, where he was responsible for leading the etrasimod UC cross functional team and overseeing NDA and MM submission.

From November 2019 to March 2022, Dr.

Sloan was Vice President and Program Lead for etrasimod GI at Arena Pharmaceuticals, Inc., a Nasdaq-listed biopharmaceutical company that was acquired by Pfizer in March 2022, where he was responsible for leading the cross functional etrasimod UC team for the Phase 3 program.

Between September 1997 and October 2019, Dr.

Sloan held different leadership positions at Johnson and Johnson (NYSE:

JNJ), a pharmaceutical and medical technologies company, in Medical Affairs, Research and Development, and Science Policy, including Global Medical Affairs Leader for IBD, leading the global launch strategy and execution for CD and UC for Stelara.

He holds a Doctor of Medicine from Rush Medical College, Chicago, a Master of Bioethics from the University of Pennsylvania and a Bachelor of Science from University of Illinois Urbana-Champaign.

Sloan currently serves on the Columbia University Masters of Bioethics Advisory Board, the Drexel University Dornsife School of Public Health Dean's Impact, Advancement and Learning Council, and the American Gastroenterological Association Ethics Committee.

Non-employee Directors

Mark McKenna .

McKenna has served as a director since February 2024.

McKenna is the founder of Mirador Therapeutics, Inc., a biotechnology company, and has served as its Chairman and Chief Executive Officer since March 2024.

McKenna has also served as chairman of the board of directors of Apogee Therapeutics, Inc.

APGE), a biotechnology company, since August 2023 and a director at New Amsterdam Pharma (Nasdaq:

NAMS), a clinical biopharmaceutical company, since July 2024.

In addition, Mr.

McKenna has served as a venture partner at Arch Venture Partners, an investment firm, since February 2024 and Senior Advisor at Fairmount Funds Management LLC, a healthcare investment firm, since October 2023.

Prior to Mirador, Mr.

McKenna served as the President and Chief Executive Officer and a member of the board of directors of Prometheus Biosciences, Inc., a clinical stage biotechnology company, from September 2019 to June 2023, when Prometheus was acquired by Merck & Co, Inc.

and as Chairman of the board of Prometheus from August 2021 to June 2023.

Prior to Prometheus, Mr.

McKenna was a corporate officer of Bausch Health Companies, Inc.

and served as President of its subsidiary, Salix Pharmaceuticals, Inc., a pharmaceutical company, from March 2016 through August 2019.

Prior to Salix Pharmaceuticals, Mr.

McKenna spent more than a decade in various roles with Bausch + Lomb, also a division of Bausch Health Companies, Inc., most recently as Senior Vice President and General Manager of its U.S.

Vision Care business.

McKenna holds a B.S.

in marketing from Arizona State University and an M.B.A.

from Azusa Pacific University.

McKenna was Ernst & Young's Entrepreneur of the Year in 2023.

We believe Mr.

McKenna is qualified to serve on our Board due to his extensive experience as an executive officer in the biopharmaceutical industry.

Laurie Stelzer .

Stelzer has served as a director since November 2023.

Stelzer has served as Chief Financial Officer of Kailera Therapeutics, Inc., a biotechnology company focused on developing therapies for obesity, since January 2025.

Prior to joining Kailera, Ms.

Stelzer served as Chief Financial Officer of Orna Therapeutics, Inc., a biotechnology company focused on RNA therapeutics, from May 2024 to January 2025.

Prior to joining Orna, Ms.

Stelzer served as Chief Financial Officer of ReNAgade Therapeutics, Inc., a biotechnology company focused on RNA therapeutics, from September 2023 to May 2024.

Prior to joining ReNAgade, Ms.

Stelzer served as Chief Financial Officer of Mirati Therapeutics, Inc.

MRTX), a commercial-stage targeted oncology company, from May 2022 to September 2023.

Prior to joining Mirati Therapeutics, Ms.

Stelzer served as Executive Vice President and Chief Financial Officer of Arena Pharmaceuticals, Inc.

(acquired by Pfizer Inc.), a biopharmaceutical company, from March 2020 until the completion of Pfizer’s acquisition in March 2022.

Prior to joining Arena Pharmaceuticals, Ms.

Stelzer served as Chief Financial Officer at Halozyme Therapeutics, Inc.

HALO), a biopharma technology platform company, from June 2015 to March 2020, where she led the Finance, Information Technology, Business Development, Project Management and Site Operations organizations.

Prior to joining Halozyme Therapeutics, Ms.

Stelzer held senior management roles at Shire Plc (acquired by Takeda Pharmaceutical), including Senior Vice President of Finance, Division Chief Financial Officer for the Regenerative Medicine Division and Head of Investor Relations.

Previously, she also worked at Amgen, Inc.

AMGN), a global biopharmaceutical company, for 15 years, serving in positions of increasing responsibility in the areas of Finance, Treasury, Global Accounting and International/Emerging Markets.

Stelzer has served as a member of the board of directors of Sionna Therapeutics (Nasdaq:

SION), a clinical-stage cystic fibrosis company, since 2024, PMV Pharmaceuticals, Inc.

PMVP), a precision oncology company, since 2020, Surface Oncology, Inc.

SURF), a clinical-stage immune-oncology company, from 2018 until its acquisition by Coherus in September 2023 and Longboard Pharmaceuticals, a clinical-stage neurology company from 2020 to 2021.

Stelzer received her B.S.

in Accounting from Arizona State University and her M.B.A.

from University of California, Los Angeles, Anderson School of Management.

We believe Ms.

Stelzer is qualified to serve on our Board because of her financial expertise and experience within the biopharmaceutical industry.

Jeffrey Albers.

Albers has served as a director since November 2023.

Albers has over 25 years of experience working in the biopharmaceutical industry and bringing important new medicines to patients with cancer and rare diseases.

He has served as Chairman of Blueprint Medicines Corporation (Nasdaq:

BPMC), a global precision therapy company, since June 2021, and Venture Partner at Atlas Venture, a venture capital firm focused on investment in biotechnology companies, since January 2023.

Albers served as Chief Executive Officer, President and Chairman of Blueprint Medicines from June 2021 to April 2022, Executive Chairman from

April 2022 to December 2022 and as Chief Executive Officer, President and Director from July 2014 to June 2021.

Prior to joining Blueprint Medicines in July 2014, Mr.

Albers was President of Algeta ASA, a Norwegian biotechnology company from January 2012 to April 2014, where he oversaw the U.S.

Prior to Algeta ASA, from July 2005 to November 2011, Mr.

Albers was at Genzyme Corporation, a biotechnology company that is now a wholly owned subsidiary of Sanofi S.A., most recently as Vice President of the U.S.

hematology and oncology business unit.

In addition to Blueprint Medicines, Mr.

Albers serves on the board of directors of Kymera Therapeutics, Inc.

KYMR) and several private companies, and previously served on the board of directors of Magenta Therapeutics, Inc.

(which later became Dianthus Therapeutics, Inc.

DNTH)) from July 2017 to September 2023.

Albers received a B.S.

from Indiana University and an M.B.A.

from Georgetown University.

We believe Mr.

Albers is qualified to serve on our Board due to his extensive leadership experience in the biopharmaceutical industry.

Tomas Kiselak.

Kiselak has served as a director since June 2023.

Kiselak is a Managing Member at Fairmount Funds Management LLC, a healthcare investment firm he co-founded in April 2016.

Prior to Fairmount, Mr.

Kiselak was a managing director at RA Capital Management, LLC, a healthcare and life science investment firm.

Kiselak currently serves as the chairman of the board of directors of Viridian Therapeutics, Inc.

VRDN) and as a director for Apogee Therapeutics, Inc.

APGE), Dianthus Therapeutics, Inc.

DNTH), Zenas BioPharma, Inc.

ZBIO) as well as several private companies.

He received a B.S.

in neuroscience and economics from Amherst College.

We believe Mr.

Kiselak is qualified to serve on our Board because of his experience advising biotechnology companies and as a manager of funds specializing in the area of life sciences.

Peter Harwin.

Harwin has served as a director since June 2023.

Harwin is a Managing Member at Fairmount Funds Management LLC, a healthcare investment firm he co-founded in April 2016.

Prior to Fairmount, Mr.

Harwin was a member of the investment team at Boxer Capital, LLC, an investment fund that was part of the Tavistock Group, based in San Diego.

Harwin also serves as chairman of the board of directors of Cogent Biosciences, Inc.

COGT) and is a director of Viridian Therapeutics, Inc.

VRDN), Apogee Therapeutics, Inc.

APGE), Oruka Therapeutics, Inc.

ORKA) and Paragon Therapeutics, Inc.

Harwin holds a B.B.A.

from Emory University.

We believe Mr.

Harwin is qualified to serve on our Board because of his experience serving as a director of biotechnology companies and as a manager of funds specializing in the area of life sciences.

Michael Henderson, M.D.

Henderson has served as a director since June 2023.

Henderson has served as Chief Executive Officer of Apogee Therapeutics, Inc.

APGE), a biotechnology company, since September 2022 as well as a member of its board of directors since June 2023.

Henderson is an experienced biotechnology executive with expertise in business leadership, drug development, and commercial strategy.

He has overseen the creation of multiple companies, launched a significant number of drug development programs, and led teams to two FDA approvals, to date.

Prior to joining Apogee, Dr.

Henderson served as Chief Business Officer of BridgeBio Pharma, Inc.

BBIO), a commercial-stage biopharmaceutical company, from January 2020 to September 2022, where he was responsible for furthering the overarching strategy of BridgeBio, identifying and investing in new technologies and running business development and operations.

Prior to holding that position, he spent two years serving as BridgeBio’s Senior Vice President, Asset Acquisition, Strategy and Operations, where he was responsible for business development, strategy and operations.

Henderson joined BridgeBio as Vice President of Asset Acquisition, Strategy and Operations in April 2016.

Henderson also served as the Chief Executive Officer of a number of BridgeBio’s subsidiaries.

Prior to BridgeBio, Dr.

Henderson worked at McKinsey & Company, a global management consulting firm, from January 2015 to April 2016 and prior to that, he co-founded PellePharm, Inc., a biotechnology company, in August 2011.

Henderson previously served on the board of directors of ARYA Sciences Acquisition Corp IV (Nasdaq:

ARYD), a special purpose acquisition company focused on the healthcare industry, from February 2021 to August 2024.

Henderson received his B.A.

in global health from Harvard University and his M.D.

from Stanford University.

We believe Dr.

Henderson is qualified to serve on our Board because of his experience in business leadership, drug development and commercial strategy in the area of life sciences.

Sandra Milligan, M.D., J.D.

Milligan has served as a director since May 2024.

Milligan has served as SVP, Global Regulatory Affairs of Daiichi Sankyo, Inc.

since February 2025.

Prior to joining Daiichi, Dr.

Milligan served as Interim CEO of Aspira Women's Health (Nasdaq:

AWH), a biotechnology company focused on the development of gynecologic disease diagnostic tools, from December 2024 to January 2025, and as President from April 2024 to February 2025.

Previously, from 2020 to 2024, Dr.

Milligan served as the Head of Research and Development of Organon & Co.

OGN), a global healthcare company, and, from 2015 to 2020, as Senior Vice President and Head of Global Regulatory Affairs and Clinical Safety of Merck & Co.

MRK), a global healthcare company.

Previously, from 2012 to 2015, she served as Vice President of Product Development Regulatory for Genentech, Inc., a biotechnology company, and, from 2002 to 2012, she was at Amgen Inc.

AMGN), a biotechnology company, in positions of increasing responsibility across legal and regulatory affairs functions.

Milligan served in the United States Army Medical Corps from 1987 to 1994.

Milligan has served as a member of the board of directors of Gossamer Bio, Inc.

GOSS), a biopharmaceutical company, since June 2021.

Milligan was on the board of directors of the Drug Information Association, or DIA, from 2011 to 2017, including serving as chair, and is now a DIA fellow.

Milligan received a B.S.

in Biology and a B.A.

in Psychology from the University of California, Irvine.

Additionally, she is a graduate of George Washington University School of Medicine and received a J.D.

from the Georgetown University Law Center.

We believe Dr.

Milligan is qualified to serve on our Board because of her leadership experience in the biopharmaceutical industry and her expertise in clinical development and regulatory affairs, including within Inflammatory Bowel Disease.

Code of Business Conduct and Ethics

Our Board has adopted a Code of Business Conduct and Ethics that establishes the standards of ethical conduct applicable to all our directors, officers and employees, including our principal executive officer, principal financial officer and principal accounting officer, or persons performing similar functions.

It addresses, among other matters, compliance with laws and policies, conflicts of interest, corporate opportunities, regulatory reporting, external communications, confidentiality requirements, insider trading, proper use of assets and how to report compliance concerns.

A copy of the code is available on our website located at https://ir.spyre.com/corporate-governance under “Governance Documents.” We intend to disclose any amendments to the code, or any waivers of its requirements, on our website to the extent required by applicable rules.

Our Board is responsible for applying and interpreting the code in situations where questions are presented to it.

Insider Trading Policy

We have adopted insider trading policies and procedures governing the purchase, sale and other transactions in Company securities by our directors, officers and employees, and other covered persons, as well as the Company itself, that we believe are reasonably designed to promote compliance with insider trading laws, rules and regulations, and Nasdaq Stock Market (“Nasdaq”) listing rules, as applicable.

As part of these policies and procedures, we prohibit our directors, officers, employees and consultants from engaging in (a) short-term trading;

(b) short sales;

(c) transactions involving publicly traded options or other derivatives, such as trading in puts or calls with respect to Company securities;

and (d) hedging transactions.

Audit Committee and Audit Committee Financial Expert

We have a separately designated standing Audit Committee.

The members of our Audit Committee are Laurie Stelzer (Chair), Jeffrey W.

Albers and Michael Henderson, each of whom qualifies as an “independent” director for audit committee purposes, as defined under Nasdaq listing rules and the rules and regulations established by the SEC.

Stelzer qualifies as an “audit committee financial expert,” as that term is defined in the rules and regulations established by the SEC, and all members of the Audit Committee are “financially literate” under Nasdaq listing rules.

Delinquent Section 16(a) Reports

Section 16(a) of the Exchange Act requires our directors, officers and persons who beneficially own more than 10% of a registered class of our equity securities to file with the SEC initial reports of ownership and

reports of changes in ownership of our common stock and other equity securities.

To our knowledge, based solely on our review of Forms 3, 4 and 5 filed with the SEC or written representations that no Form 5 was required, during the year ended December 31, 2024, we believe that all of our directors, officers and persons who beneficially own more than 10% of a registered class of our equity securities timely filed all reports required under Section 16(a) of the Exchange Act.

EXECUTIVE COMPENSATION

This section provides an overview of the material components of our executive compensation program each for our Chief Executive Officer, other individuals who served as a principal executive officer during any part of 2024, and each of our two other most highly compensated executive officers (collectively, our “named executive officers” or “NEOs”) during 2024.

The compensation provided to our named executive officers for 2024 is set forth in detail in the “Summary Compensation Table” and other tables that follow in this section, as well as the accompanying footnotes and narratives relating to those tables.

Our named executive officers for 2024 were:

Cameron Turtle Chief Executive Officer

Sheldon Sloan Chief Medical Officer (1)

Scott Burrows Chief Financial Officer

Sloan was appointed Chief Medical Officer of the Company effective October 1, 2024.

Investor Outreach and Response to 2024 Say-on-Pay Vote

Each year, we provide our stockholders the opportunity to cast a non-binding advisory vote on the compensation of our named executive officers (commonly known as a "Say-on-Pay" vote).

Our Board and our Compensation Committee consider the results of the Say-on-Pay vote in determining the compensation of our executive officers, including our named executive officers.

At our 2024 Annual Meeting of Stockholders, approximately 62% of the votes cast approved the compensation of our named executive officers.

Since the vote, we reached out to our top 25 institutional investors and have spoken with the investment team or corporate governance contacts at several of our major stockholders, excluding Fairmount, representing approximately 43% of our outstanding common stock based on public filings as of September 30, 2024.

The primary stockholder concerns raised during our discussions included the lack of disclosure of clear performance goals and compensation rationale, lack of outreach due to prior year low Say-on-Pay vote and the magnitude of awards granted to executives.

We believe that proxy advisor voting recommendations and the voting results for our 2024 annual meeting reflect a general misunderstanding around legacy Aeglea pay decisions and the significance of our transformation in 2023.

During 2023, the Company completed a reverse merger, which brought in an entirely new pipeline of product candidates targeting IBD, and refreshed the Board and executive team to lead development of this new pipeline and sunset legacy asset development.

The investment required to pivot the Company’s business and strategy included situation-specific compensation arrangements necessary to recruit an executive team, which are not reflective of our go-forward compensation program.

These investments drove significant value creation for stockholders in 2023, including going from a market capitalization of less than $50 million prior to the closing of the reverse merger in June 2023 to a market capitalization well over $1.0 billion by the end of 2023 and throughout 2024.

Our current Board, the Compensation Committee and our management team are committed to implementing a robust compensation program aligned with stockholder interests and supported by peer group and market data, which we believe is reflected in our 2024 compensation program.

We value the opinion of our stockholders.

Our Board and our Compensation Committee will continue to consider the result of the Say-on-Pay vote, as well as feedback received throughout the year, when making compensation decisions for our executive officers.

Summary Compensation Table

The following table provides information regarding all plan and non-plan compensation awarded to, earned by or paid to each of our named executive officers for the years ended December 31, 2024 and 2023.

Name and Principal Position Year Salary

Awards ($) (2)

Incentive Plan

Cameron Turtle

2024 625,000 — — 5,914,353 412,500 8,333 6,960,186

Chief Executive Officer 2023 272,850 141,000 — 15,500,492 — 5,203 15,919,545

Sheldon Sloan

2024 124,000 120,000 — 9,075,480 59,500 9,760 9,388,740

Chief Medical Officer

Scott Burrows

2024 475,000 — — 1,490,566 228,000 13,800 2,207,366

Chief Financial Officer 2023 154,589 175,700 2,452,096 4,767,637 — 1,517 7,551,539

(1) For 2024, the amount reported in this column reflects a sign-on bonus for Dr.

Sloan in connection with the commencement of his employment with the Company during 2024, as described in more detail under “Narrative Disclosure to Summary Compensation Table—Offer Letters” below.

(2) Amounts reported in this column for 2024 represent the aggregate grant date fair value of stock options granted to our NEOs, as computed in accordance with ASC 718.

See Note 15 to our consolidated financial statements in this Annual Report for more information regarding the assumptions used in calculating the grant date fair value of stock options.

(3) Amounts reported in this column for 2024 represent the annual bonuses earned under the 2024 annual bonus program, as described in more detail under “Narrative Disclosure to Summary Compensation Table—Elements of Compensation—Annual Bonus Program” below.

(4) Amounts reported in this column for 2024 include matching contributions under our 401(k) plan made during 2024.

Narrative Disclosure to Summary Compensation Table

Under the Compensation Committee's compensation philosophy, compensation positioning is used to attract and retain key employees for the Company’s continued success and growth.

While market data is helpful to the Compensation Committee in setting compensation framework and guiding decisions, other factors such as general market practices, Company strategy, tenure, performance and criticality are also considered.

The compensation philosophy serves as the foundation to reinforce the Company’s business strategy and desired culture, while balancing internal and external alignment.

In October 2023, our Compensation Committee, in consultation with Alpine, its independent compensation consultant, established a peer group that focuses on U.S.-based, pre-clinical or early clinical biotechnology/pharmaceutical companies (with priority placed on companies with a similar therapeutic focus) with a market capitalization ranging from $250 million to $2 billion and less than 100 employees.

group, which was approved by the Board and used in establishing executive compensation for 2024, includes the following companies:

ACELYRIN Arcellx, Inc.

Kymera Therapeutics, Inc.

Aclaris Therapeutics, Inc.

Astria Therapeutics, Inc.

Morphic Holding, Inc.

Cabaletta Bio, Inc.

Pliant Therapeutics, Inc.

Alpine Immune Sciences, Inc.

Celldex Therapeutics, Inc.

RAPT Therapeutics, Inc.

AnaptysBio, Inc.

IGM Biosciences, Inc.

Ventyx Biosciences, Inc.

Apogee Therapeutics, Inc.

Janux Therapeutics, Inc.

Vera Therapeutics, Inc.

In September 2024, our Compensation Committee, in consultation with Alpine, evaluated our peer group and approved updates to the peer group used in establishing executive compensation for 2025 based on market capitalization, pipeline stage, employee population and other relevant factors.

Elements of Compensation

Each NEO’s base salary is a fixed annual amount that is intended to compensate the NEO for performing specific job responsibilities and is based on the NEO’s level of experience and requisite skills.

Our Compensation Committee annually evaluates and approves (or recommends to the Board for approval for our Chief Executive Officer) each NEO’s base salary.

As part of this annual evaluation in 2024, the Compensation Committee determined to increase the base salary for Mr.

Burrows by $20,000 in consideration of peer group data and recommendations from the Company's independent compensation consultant.

In connection with his appointment, the Compensation Committee established Dr.

Sloan's base salary of $496,000.

The table below sets forth the base salary as of December 31, 2024 for each NEO:

Named Executive Officer Base Salary

as of 12/31/2024

Cameron Turtle $ 625,000

Sheldon Sloan $ 496,000

Scott Burrows $ 475,000

Annual Bonus Program

We provide our executive officers, including our NEOs, with the opportunity to earn annual cash incentives to encourage the achievement of corporate objectives.

We established our annual bonus program to motivate our executives to achieve short-term financial and business objectives, reflecting our “pay for performance” culture, resulting in a significant portion of NEO compensation tying directly to Company achievements.

For each NEO, the target annual bonus opportunity is determined as a percentage of his or her base salary (as indicated in the table below), which was established for 2024 by the Compensation Committee in consultation with Alpine, based on market data from companies in our peer group.

Named Executive Officer 2024 Annual Bonus Target

Cameron Turtle 55 %

Sheldon Sloan 40 %

Scott Burrows 40 %

The Board approved the objectives and key targeted results and stretch goals applicable to 2024 annual bonus program for our executives in December 2023.

These milestones were intended to measure our

performance in the following categories:

Portfolio, Platform, and Corporate, as further described below.

The level of attainment of these performance milestones determines our NEOs’ earned annual bonuses.

Objective Weight Summary of Key Result

Timing Achieved

Advance Spyre Programs

60% Prepare protocols and regulatory filings to enable SPY001 and SPY002 FIH initiations, SPY001 FIH data release in 2024, and Phase 2 UC initiation in 2025

Nominate SPY003 development candidate

Advance Strategic Pillars

25% Initiate preclinical studies to support advancement of combination drug candidates into clinical trials Q2-Q4

Assess precision medicine approaches in IBD clinical trials

Develop and establish delivery device strategy and partners

Establish and Resource Spyre as an IBD Leader

15% Continued development and execution of plans across Investor Relations, Finance, Human Resources, Compliance, Legal and Intellectual Property functions to support Spyre’s growth and business plans

Phase 2 readiness

Stretch 10% Complete preclinical and regulatory activities, including early submission of SPY002 IND, to support FIH initiations and 2025 Phase 2 UC initiation Q3-Q4

Additional support

Stretch 10% Validating partnership, collaboration, or company investment

At the end of 2024, the Board and the Compensation Committee reviewed the Company’s performance against these performance measures and determined that performance was achieved at 120% of target, as each target result and all stretch goals were timely achieved.

As a result, each NEO received an annual bonus for 2024 equal to 120% of target;

Sloan’s annual bonus was pro-rated based on the date he commenced employment with the Company.

Named Executive Officer 2024 Annual Bonus

Cameron Turtle $ 412,500

Sheldon Sloan $ 59,500

Scott Burrows $ 228,000

Long-Term Incentive Compensation

For 2024, after taking into account the results of Alpine's market assessment, reviewing the practices of companies in our peer group and considering the important retentive value and performance alignment of our long-term incentive strategy, our Compensation Committee determined that it was appropriate to use stock options as 100% of the annual long-term incentive awards granted to our employees, including the NEOs.

On February 1, 2024, Dr.

Turtle and Mr.

Burrows received annual grants of stock options to purchase 277,750 shares of our common stock and 70,000 shares of our common stock, respectively, which vest in equal monthly installments through the fourth anniversary of the grant date.

In connection with his appointment as Chief Medical Officer of the Company, Dr.

Sloan received an initial grant of stock options to purchase 400,000 shares of our common stock, which vest as to 25% on October 1, 2025 (the first anniversary of the grant date) and in equal monthly installments thereafter through October 1, 2028.

Offer Letters

We have entered into offer letters with each of our NEOs in connection with their appointments (and, for Dr.

Turtle, his promotion to Chief Executive Officer), which for Dr.

Turtle was further amended in February 2024

(collectively, the “Offer Letters”).

Each Offer Letter provides for an initial base salary, target bonus opportunity and stock option grant.

Under the Offer Letters, the NEOs are eligible for certain payments or benefits upon certain terminations of employment, as described under “Additional Narrative Disclosure-Potential Payments Upon Termination of Change in Control” below.

Burrows’ Offer Letter also provided for a sign-on bonus of $115,000, which was subject to repayment in the event of a termination for cause or resignation without good reason prior to September 1, 2024, and Dr.

Sloan’s Offer Letter also provided for a sign-on bonus of $120,000, which is subject to repayment in the event of a termination for cause or resignation without good reason prior to October 1, 2025.

Each of our NEOs is also party to our standard employee invention assignment, confidentiality and non-competition agreement, which, among other things, provides standard protections regarding our ownership of intellectual property, the confidentiality of our proprietary information, non-competition and non-solicitation.

Outstanding Equity Awards at December 31, 2024

The following table presents information regarding outstanding stock options, RSUs and restricted stock held by each named executive officers as of December 31, 2024.

Name Grant Date Option Awards Stock Awards

Unexercisable

Units of Stock

Cameron Turtle 6/22/2023 709,457 1,182,430 (2)

$7.50 6/22/2033

11/22/2023 101,291 272,709 (3)

$10.39 11/22/2033

2/1/2024 57,864 219,886 (2)

$25.86 2/1/2034

Sheldon Sloan 10/1/2024 — 400,000 (3)

$27.46 10/1/2034

Scott Burrows 9/1/2023 126,517 287,340 (3)

$14.50 9/1/2033

2/1/2024 14,583 55,417 (2)

$25.86 2/1/2024

12/22/2023 101,214 (6)

(1) The market value was determined by multiplying the number of shares by $23.28, the closing price of our common stock as reported on the Nasdaq Global Select Market on December 31, 2024.

(2) These stock options vest in equal monthly installments through the fourth anniversary of the grant date, subject to the NEO’s continued service.

(3) These stock options vest as to 25% on the first anniversary of the grant date and in equal monthly installments thereafter through the fourth anniversary of the grant date, subject to the NEO’s continued service.

(4) In connection with the Asset Acquisition, outstanding shares of restricted common stock of Pre-Merger Spyre were assumed by the Company and converted into restricted common stock and restricted Series A Preferred Stock, which were subsequently converted to restricted and unrestricted common stock on November 24, 2023.

(5) These shares of restricted common stock vest in equal monthly installments through November 22, 2026, subject to the NEO’s continued service.

(6) These RSUs vest in equal annual installments through the fourth anniversary of the grant date, subject to the NEO’s continued service.

Additional Narrative Disclosure

Retirement Benefits

We maintain a tax-qualified 401(k) defined contribution plan that provides eligible U.S.

employees, including our NEOs, with an opportunity to save for retirement on a tax-advantaged basis.

Eligible employees may make voluntary contributions from their eligible pay, up to certain applicable annual limits set by the Internal Revenue Code of 1986, as amended.

We provide matching contributions equal to 100% of the first 3% of eligible compensation contributed by each employee, and 50% of the next 2% of eligible compensation contributed by each employee.

All company matching contributions are immediately and fully vested.

We do not maintain, and have not historically maintained, any non-qualified deferred compensation or defined benefit pension plan.

Potential Payments Upon Termination or Change in Control

Pursuant to the terms of the Offer Letters, in the event each NEO (other than Dr.

Sloan) that is a current executive officer is terminated by the Company without “cause” or as a result of a resignation for “good reason” (collectively, an “Involuntary Termination”), such NEO will, subject to the execution of a release in favor of the Company, receive:

(i) severance payments equal to 12 months of base salary and any earned but unpaid annual bonus for the preceding year;

(ii) up to 12 months of partially subsidized COBRA coverage;

and (iii) accelerated vesting of any time-based equity awards scheduled to vest in the 12 months following such termination.

However, if the Involuntary Termination is within three months before or 12 months after a change in control of the Company, the NEO will instead receive:

(A) severance payments equal to 18 months of base salary, any earned but unpaid annual bonus for the preceding year, and the target annual bonus for the year of termination (or, for Dr.

Turtle, 1.5 times the target annual bonus for the year of termination);

(B) up to 18 months of fully subsidized COBRA continuation coverage;

and (C) full acceleration of all equity awards (with performance-based awards determined in accordance with the terms of the applicable award agreement or, if not specified in such award agreement, based on the greater of target or, if determinable, actual performance).

Pursuant to the terms of Dr.

Sloan’s Offer Letter, in the event of his Involuntary Termination, Dr.

Sloan will, subject to the execution of a release in favor of the Company, receive:

(i) severance payments equal to nine months of base salary and (ii) up to nine months of partially subsidized COBRA coverage.

However, if the Involuntary Termination is within three months before or 12 months after a change in control of the Company, the NEO will instead receive:

(A) severance payments equal to 12 months of base salary and the target annual bonus for the year of termination;

(B) up to 12 months of fully subsidized COBRA continuation coverage;

As used in the Offer Letters:

• “Cause” generally means (i) the NEO’s dishonest statements or acts with respect to the Company or any affiliate of the Company, or any current or prospective customers, suppliers, vendors or other third parties with which such entity does business that results in or is reasonably anticipated to result in material harm to the Company;

(ii) the NEO’s conviction or plea of no contest to a felony or misdemeanor involving moral turpitude, deceit, dishonesty or fraud;

(iii) the NEO’s failure to perform his or her duties or responsibilities, subject to a 30-day cure period;

(iv) the NEO’s gross negligence, willful misconduct that results in or is reasonably anticipated to result in material harm to the Company;

or (v) the NEO’s violation of any material provision of any agreement with the Company or any written Company policies.

• “Good Reason” generally means (i) a material diminution in the NEO’s base salary or target bonus (excluding across-the-board reductions of less than 10%);

(ii) a material geographic relocation or requirement to change the NEO’s remote work location;

(iii) a material reduction in the NEO’s duties, authority or responsibilities;

Sloan, a requirement that he report to any person other than the Chief Executive Officer);

(iv) the failure of the Company to obtain the assumption of the Offer Letter by a successor;

or (v) the material breach of any agreement between the NEO and the Company, in each case, subject to standard notice and cure periods.

Clawback Policy and Restatement Analysis

We have a Compensation Recoupment (Clawback) Policy (the "Clawback Policy"), which is intended to comply with the requirements of Nasdaq Listing Standard 5608 implementing Rule 10D-1 under the Exchange Act.

In the event the Company is required to prepare an accounting restatement of the Company’s financial statements due to material non-compliance with any financial reporting requirement under the federal securities laws, the Company will recover, on a reasonably prompt basis, the excess incentive-based compensation received by any covered executive after October 2, 2023 and during the prior three fiscal years that exceeds the amount that the executive otherwise would have received had the incentive-based compensation been determined based on the restated financial statements.

During 2024, the Company was required to prepare an accounting restatement of the Company’s consolidated financial statements as of and for the year ended December 31, 2023, as well as the quarterly condensed consolidated financial information for the 2024 interim periods ended March 31, 2024, June 30, 2024, and September 30, 2024, as described under Part II, Item 9A of this Annual Report titled “Controls and Procedures.” In accordance with the Clawback Policy, our Compensation Committee reviewed the restated financials and concluded that there was no recovery of erroneously awarded compensation required under the Clawback Policy because the restated financials did not impact any incentive-based compensation received on or after October 2, 2023.

Equity Grant Timing Policy and Practices

In December 2024, our Compensation Committee adopted an Equity Grant Timing Policy (the “Equity Grant Timing Policy”), which provides that it is the Company’s policy to generally grant equity awards, including stock options, outside of blackout periods under our insider trading policy.

With respect to grants of stock options to our named executive officers and to the extent a grant during a close window is deemed necessary or appropriate by the Compensation Committee, awards typically may not occur during the period beginning four business days before and ending one business day after the filing of a Form 10-K or Form 10-Q or the filing or furnishing of a Form 8-K that contains material non-public information (“MNPI”).

Under the Equity Grant Timing Policy, annual equity grants to the Company’s employees are typically granted within one week following the first regularly scheduled Compensation Committee meeting each year (or, with respect to grants to the Chief Executive Officer, within one week following the first regularly scheduled Board meeting each year).

Grants to new hires generally occur on the first business day of each month for new hires who commenced employment during the previous month.

Employees, including the named executive officers, may enroll to purchase shares under the terms of our 2016 Employee Stock Purchase Plan, as amended (the “ESPP”), with purchase dates generally in February and August of each year using payroll deductions accumulated during the prior six-month period.

During 2024, we did not time the disclosure of MNPI for the purpose of affecting the value of executive compensation.

The following table sets forth information regarding stock options issued to our named executive officers during 2024 during any period beginning four business days before and ending one business day after the filing of a Form 10-K or Form 10-Q or the filing or furnishing of a Form 8-K that contains MNPI.

Sloan did not receive any stock options during any such period in 2024.

The awards set forth in the following table were granted prior to the Company's adoption of the Equity Grant Timing Policy.

Grant Date Number of Securities Underlying the Award Exercise Price of the Award ($/Sh)

Grant Date Fair Value of the Award

Percentage Change in the Closing Market Price of the Securities Underlying the Award Between the Trading Day Ending Immediately Prior to the Disclosure of MNPI and the Trading Day Beginning Immediately Following the Disclosure of MNPI (1)

Cameron Turtle

2/1/2024 277,750 $ 25.86 $ 5,914,353 ( 0.8 ) %

Scott Burrows

2/1/2024 70,000 $ 25.86 $ 1,490,566 ( 0.8 ) %

(1) Reflects the percentage change in the closing market price of our common stock between the trading day ending immediately prior to the disclosure of MNPI ($25.74 on February 2, 2024) and the trading day beginning immediately following the disclosure of MNPI ($25.53 on February 6, 2024).

Director Compensation

Each of our non-employee directors receives compensation pursuant to the non-employee director cash and equity compensation program adopted by our Board.

This program provides for the following annual cash retainers:

Annual Cash Retainer

Annual Board Chair Retainer

Audit Committee Retainers:

Chair $ 20,000

Non-Chair Member $ 10,000

Compensation Committee Retainers:

Chair $ 15,000

Non-Chair Member $ 7,500

Nominating and Corporate Governance Committee Retainers:

Chair $ 10,000

Non-Chair Member

Each non-employee director who initially joins our Board receives an initial grant of stock options that vests in equal monthly installments over three years.

Prior to May 9, 2024, new directors received stock options to purchase 40,000 shares, and following May 9, 2024, new directors received stock options with an aggregate grant date value approximating $700,000.

In accordance with this program, Mr.

McKenna received a stock option to purchase 40,000 shares on February 1, 2024, and Dr.

Milligan received a stock option to purchase 21,980 shares on May 14, 2024.

Each non-employee director who is serving as of the date of the Annual Meeting will receive a grant of stock options with an aggregate grant date value approximately $350,000.

Annual stock option grants vest in equal monthly installments over one year or, if earlier, upon the next Annual Meeting of Stockholders.

For directors appointed on or after January 1, 2024, a director is only eligible to receive an annual stock option grant if the Annual Meeting of Stockholders is more than six months following the director’s appointment to the Board.

As such, each of Messrs.

Albers, Harwin, and Kiselak, Dr.

Henderson and Ms.

Stelzer received a stock option to purchase 11,323 shares on May 14, 2024.

In addition, all non-employee directors are reimbursed their reasonable travel expenses incurred in attending board and committee meetings.

The following table provides information for the year ended December 31, 2024 regarding all compensation awarded to, earned by or paid to each person who served as a non-employee director for some portion of 2024.

Employees who served on our Board during 2024 did not receive additional compensation for such service.

Awards ($) (1)

84,354 353,221 437,575

35,962 — 35,962

47,888 353,221 401,109

Michael Henderson

50,000 353,221 403,221

Tomas Kiselak

47,500 353,221 400,721

Alison Lawton (3)

4,396 — 4,396

Mark McKenna (4)

36,593 838,124 874,717

Sandra Milligan, M.D., J.D.

33,445 703,512 736,957

Laurie Stelzer

65,000 353,221 418,221

(1) The amounts reported in this column represent the aggregate grant date fair value of the awards granted to our non-employee directors during the year ended December 31, 2024, as computed in accordance with Accounting Standards Codification Topic 718 (“ASC 718”).

The assumptions used in calculating the grant date fair value of the awards reported in the Option Awards column are set forth in Note 15 to our consolidated financial statements included in this Annual Report on Form 10-K.

Note that the amounts reported in this column reflect the aggregate accounting cost for these awards, and do not necessarily correspond to the actual economic value that may be received by the non-employee directors from the awards.

As of December 31, 2024, our non-employee directors held the following number of outstanding stock options:

Albers, 61,323;

Harwin, 89,323;

Henderson, 89,323;

Kiselak, 89,323;

Lawton, 3,488;

McKenna, 517,000;

Milligan, 21,980;

Stelzer, 61,323.

Cox did not stand for reelection at the 2024 Annual Meeting of Stockholders.

Lawton resigned from the Board effective as of February 1, 2024.

McKenna was appointed to the Board effective as of February 1, 2024.

Milligan was appointed to the Board effective as of May 14, 2024.

SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS

The information required by this item is incorporated herein by reference from the applicable information set forth in our 2024 Proxy Statement, including the sections titled “Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters” and “Securities Authorized for Issuance Under Equity Compensation Plans.”

The following table sets forth information, to the extent known by us or ascertainable from public filings, with respect to the beneficial ownership of our common stock as of February 19, 2025 by:

• each of our directors;

• each of our NEOs;

• all of our directors and executive officers as a group;

• each person, or group of affiliated persons, who is known by us to beneficially owner of greater than 5% of our common stock.

The column entitled “Shares Beneficially Owned” is based on a total of 60,275,561 shares of our common stock outstanding as of February 19, 2025.

Beneficial ownership is determined in accordance with the rules and regulations of the SEC and includes voting or investment power with respect to our common stock.

Shares of our common stock subject to options that are currently exercisable or exercisable within 60 days of the date of this table or subject to conversion of preferred stock up to applicable beneficial ownership limitations are considered outstanding and beneficially owned by the person holding the options or preferred stock, as applicable, for the purpose of calculating the percentage ownership of that person but not for the purpose of calculating the percentage ownership of any other person.

Except as otherwise noted, the persons and entities in this table have sole voting and investing power with respect to all of the shares of our common stock beneficially owned by them, subject to community property laws, where applicable.

Except as otherwise indicated in the table below,

addresses of named beneficial owners are in care of Spyre Therapeutics, Inc., 221 Crescent Street, Building 23, Suite 105, Waltham, MA 02453.

Shares beneficially owned

Name of beneficial owner

Number Percentage

5% Stockholders:

7,623,881 12.65%

Fairmount Healthcare Fund II L.P.

6,243,861 9.99%

RTW Investments, LP (3)

3,621,996 6.01%

Peter Deutsch (4)

3,550,276 5.89%

Named Executive Officers and Directors:

Scott Burrows (5)

Sheldon Sloan (6)

Cameron Turtle (7)

1,804,041 2.94%

Peter Harwin (2)(9)

6,738,278 10.77%

Michael Henderson, M.D.

Tomas Kiselak (2)(11)

6,738,278 10.77%

Mark McKenna (12)

Sandra Milligan (13)

Laurie Stelzer (14)

All current executive officers and directors as a group (11 persons) (15)

9,951,143 15.43%

*Represents beneficial ownership of less than one percent.

(1) Based solely upon a Schedule 13G/A filed on November 12, 2024.

The shares of common stock listed in the table above are held by funds and accounts managed by direct or indirect subsidiaries of FMR LLC.

Johnson is a Director, the Chairman and the Chief Executive Officer of FMR LLC.

Members of the Johnson family, including Abigail P.

Johnson, are the predominant owners, directly or through trusts, of Series B voting common shares of FMR LLC, representing 49% of the voting power of FMR LLC.

The Johnson family group and all other Series B shareholders have entered into a shareholders’ voting agreement under which all Series B voting common shares will be voted in accordance with the majority vote of Series B voting common shares.

Accordingly, through their ownership of voting common shares and the execution of the shareholders’ voting agreement, members of the Johnson family may be deemed, under the Investment Company Act of 1940, to form a controlling group with respect to FMR LLC.

The address of these funds and accounts is 245 Summer Street, Boston, MA 02210.

(2) Based solely upon a Schedule 13D/A filed on April 25, 2024 and the Company's records.

Consists of (i) 4,018,101 shares of common stock and (ii) 2,225,760 shares of common stock issuable upon the conversion of 55,644 shares of Series A Preferred Stock held by Fairmount Healthcare Fund II LP (“Fund II”).

Excludes shares of common stock issuable upon the conversion of shares of Series A Preferred Stock and Series B Preferred Stock held by Fund II in excess of the beneficial ownership limitation of 9.99%, which such limitation restricts Fairmount and its affiliates from converting those shares of preferred stock that would result in Fairmount and its affiliates owning, after conversion, a number of shares of common stock in excess of the applicable ownership limitation.

Fairmount serves as investment manager for Fund II.

Fund II has delegated to Fairmount Funds Management LLC (“Fairmount”) the sole power to vote and the sole power to dispose of all securities held in Fund II’s portfolio.

Because Fund II has divested itself of voting and investment power over the securities it holds and may not revoke that delegation on less than 61 days’ notice, Fund II disclaims beneficial ownership of the securities it holds.

The general partner of Fairmount is Fairmount Funds Management GP LLC (“Fairmount GP”).

As managing members of Fairmount GP, Peter Harwin and Tomas Kiselak may be deemed to have voting and investment power over the shares held by Fund II.

Fairmount GP, Peter Harwin and Tomas Kiselak disclaim beneficial ownership of such shares, except to the extent of any pecuniary interest therein.

The address of each of these persons and entities is 200 Barr Harbor Drive, Suite 400, West Conshohocken, PA.

(3) Based solely upon a Schedule 13G/A filed on February 14, 2025.

RTW Investments, LP (“RTW”), in its capacity as the investment adviser to certain funds (the "RTW Funds"), has the power to vote and the power to direct the disposition of the shares held by the RTW Funds.

Accordingly, RTW may be deemed to be the beneficial owner of such securities.

Roderick Wong, M.D., as the Managing Partner of RTW, has the power to direct the vote and disposition of the securities held by RTW.

Wong disclaims beneficial ownership of the shares held by the RTW Funds, except to the extent of his pecuniary interest therein.

The address and principal office of RTW Investments, LP is 40 10th Avenue, Floor 7, New York, NY 10014, and the address of Dr.

Wong and each of the RTW Funds is c/o RTW Investments, LP, 40 10th Avenue, Floor 7, New York, NY 10014.

(4) Based solely upon a Schedule 13G filed on October 23, 2024.

The address of Peter E.

Deutsch is 25 East Pointe Lane, Old Greenwich, CT 06870.

(5) Consists of (i) 15,208 shares of common stock held by Mr.

Burrows and (ii) options exercisable for 186,639 shares of common stock within 60 days of the date of this table.

(6) Consists options exercisable for 5,968 shares of common stock within 60 days of the date of this table.

(7) Consists of (i) 747,540 shares of common stock held by Dr.

Turtle and (ii) options exercisable for 1,056,501 shares of common stock within 60 days of the date of this table.

(8) Consists of (i) 27,360 shares of common stock held by Sessions LLC, which may be deemed to be indirectly beneficially owned by Mr.

Albers, and (ii) options exercisable for 32,601 shares of common stock within 60 days of the date of this table.

(9) Includes (i) 406,038 shares of common stock held by Mr.

and (ii) options exercisable for 88,379 shares of common stock within 60 days of the date of this table.

(10) Consists of (i) 105,379 shares of common stock held by Dr.

and (ii) options exercisable for 88,379 shares of common stock within 60 days of the date of this table.

(11) Includes (i) 406,038 shares of common stock held by Mr.

and (ii) options exercisable for 88,379 shares of common stock within 60 days of the date of this table.

(12) Consists of options exercisable for 174,555 shares of common stock within 60 days of the date of this table.

(13) Consists of options exercisable for 6,716 shares of common stock within 60 days of the date of this table.

(14) Consists of options exercisable for 32,601 shares of common stock within 60 days of the date of this table.

(15) Consists of (i) 5,726,648 shares of common stock;

(ii) 2,225,760 shares of common stock issuable upon the exercise of Series A Preferred Stock;

and (iii) options exercisable for 1,998,735 shares of common stock within 60 days of the date of this table.

Securities Authorized for Issuance Under Equity Compensation Plans

The following table presents information as of December 31, 2024 with respect to compensation plans under which shares of our common stock may be issued.

Plan Category

to be Issued Upon

of Outstanding

Options, Warrants

and Rights (#) (1)

Weighted-Average

Exercise Price

of Outstanding

Options, Warrants

and Rights ($) (2)

Number of Securities

Remaining Available

Issuance Under

Equity Compensation

Plans (Excluding

Securities Reflected in

Column (a)) (#) (3)

Equity Compensation Plans Approved by Security Holders:

2015 Equity Incentive Plan 952 $ 320.25 ― (4)

2016 Equity Incentive Plan

3,145,248 $ 16.72 4,047,971 (5)

2023 Equity Incentive Plan 2,734 $ 0.36 ― (6)

2016 Employee Stock Purchase Plan

― N/A 416,592 (7)

Equity Compensation Plans Not Approved by Security Holders:

2018 Equity Inducement Plan 6,219,622 $ 14.19 637,513

9,368,556 $ 15.08 5,102,076

(1) This column reflects outstanding stock options and RSUs under the listed equity compensation plan.

(2) This column reflects the weighted-average exercise price of stock options granted under the listed equity compensation plan that were outstanding as of December 31, 2024.

RSUs reflected in column (a) are not reflected in this column as they do not have an exercise price.

(3) This column reflects the total shares of our common stock remaining available for issuance under the listed equity compensation plan as of December 31, 2024.

(4) No further awards may be made under the 2015 Equity Incentive Plan (the “2015 Plan”);

however, shares of common stock that are subject to outstanding awards under the 2015 Plan that expire or are forfeited for any reason without having been exercised in full will generally be available for future grant and issuance under the 2016 Plan.

(5) The 2016 Plan provides for an automatic increase in the number of shares reserved for issuance thereunder on January 1 of each year through January 1, 2028 equal to (a) 5% of the number of issued and outstanding shares of common stock on December 31 of the immediately preceding year, or (b) a lesser amount as approved by the Board each year.

Pursuant to this provision, the number of shares reserved for grant and issuance under the 2016 Plan increased by 3,814,905 shares on January 1, 2025.

(6) No further awards may be made under the 2023 Equity Incentive Plan, which was assumed in connection with the Asset Acquisition.

(7) The ESPP provides for an automatic annual increase in the number of shares reserved for issuance thereunder on January 1 of each year for through January 1, 2026 equal to (a) 1% of the number of issued and outstanding shares of common stock on December 31 of the immediately preceding year, or (2) a lesser amount as approved by the Board each year.

Pursuant to this provision, the number of shares reserved for grant and issuance under the ESPP increased by 602,570 shares on January 1, 2025.

CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE

The information required by this item is incorporated herein by reference from the applicable information set forth in our 2024 Proxy Statement, including the sections titled “Certain Relationships and Related Party Transactions and "Director Independence."

Certain Relationships and Related Transactions

Other than the executive officer and director compensation arrangements disclosed above under “Item 11.

Executive Compensation,” below we describe the transactions to which we were a party since January 1, 2024, in which the amount involved exceeded $120,000 and in which our directors, executive officers, holders of more than 5% of our common stock, or members of their immediate family had a direct or indirect material interest.

Related Party Transactions

Spyre's Relationships with Paragon, Parapyre and Fairmount

We are party to the Paragon Agreement (as defined below) with Paragon and Parapyre Holding LLC (“Parapyre”).

Paragon and Parapyre each beneficially owns less than 5% of a class of our voting securities through their respective holdings of our common stock.

Fairmount beneficially owns more than 5% of a class of our voting securities, has two seats on our Board (held by Peter Harwin and Tomas Kiselak) and beneficially owns more than 5% of Paragon.

Fairmount appointed Paragon’s board of directors and has the contractual right to approve the appointment of any executive officers of Paragon.

Parapyre is an entity formed by Paragon as a vehicle to hold equity in Spyre in order to share profits with certain employees of Paragon and will not perform any substantive role under the Paragon Agreement other than to receive warrants granted to Parapyre under the Paragon Agreement.

In connection with the Asset Acquisition, we assumed the rights and obligations of Pre-Merger Spyre under that certain antibody discovery and option agreement, dated May 25, 2023 and subsequently amended and restated on September 29, 2023 and May 14, 2024, by and among the Company, Paragon and Parapyre (the “Paragon Agreement”), pursuant to which we have exercised the option to acquire intellectual property license rights to or have the option to acquire intellectual property license rights with respect to certain research programs, including with respect to our product candidates.

Under the Paragon Agreement, we are obligated to compensate Paragon on a quarterly basis for its services performed under each research program based on the actual costs incurred with mark-up costs pursuant to the terms of the Paragon Agreement.

As of the date of the Asset Acquisition, Pre-Merger Spyre had incurred total expenses of $19.0 million under the Paragon Agreement since inception, inclusive of a $3.0 million research initiation fee that was due upon signing of the Paragon Agreement and $16.0 million of reimbursable expenses under the Paragon Agreement for historical costs incurred by Paragon.

As of the closing of the Asset Acquisition, $19.0 million was unpaid and was assumed by us through the Asset Acquisition.

As of the year ended December 31, 2024, approximately $0.6 million was unpaid and owed to Paragon under the Paragon Agreement.

Furthermore, following our amendment and restatement of the Paragon Agreement on September 29, 2023, we were obligated to provide certain equity grants to Parapyre upon the completion of each of the calendar years ending on December 31, 2023 and December 31, 2024 to purchase 1% of the then outstanding shares of our common stock, on a fully diluted basis, on the last business day of each applicable calendar year, at the fair market value determined by the Board (the "Parapyre Option Obligation").

We settled such 2023 and 2024 obligations by issuing Parapyre warrants to purchase 684,407 and 848,184 shares of common stock, respectively, less the $21.52 and $23.28 per share exercise price of each warrant, respectively.

As of December 31, 2024, none of the warrants issued to Parapyre have been exercised.

In July 2023 and December 2023, we exercised our option available under the Paragon Agreement with respect to the SPY001 and SPY002 research programs, respectively, and, in May 2024, we entered into the SPY001 License Agreement and the SPY002 License Agreement.

Under the terms of each of the SPY001 License Agreement and SPY002 License Agreement, we are obligated to pay Paragon up to $22.0 million based on specific development, regulatory and clinical milestones for the first Company product to reach such milestones for each licensed research program, including a $1.5 million fee for nomination of a development candidate, as applicable, and a further milestone payment of $2.5 million upon the first dosing of a human patient in a Phase 1 trial.

With respect to the SPY002 License Agreement only, on a product by product basis, we are obligated to pay sublicensing fees of up to approximately $20.0 million upon the achievement of certain milestones.

In June 2024, we exercised our option available under the Paragon Agreement with respect to the SPY003 research program and in October 2024, we entered into the SPY003 License Agreement, which was subsequently amended and restated in February 2025.

Under the terms of the SPY003 License Agreement, we are obligated to pay Paragon up to $22.0 million based on specific development, regulatory and clinical milestones for the first Company product to reach such milestones, including a $1.5 million fee for nomination of a development candidate, as applicable, and a further milestone payment of $2.5 million upon the first dosing of a human patient in a Phase 1 trial.

Subject to the execution of the option to acquire the intellectual property rights related to the SPY004 research program pursuant to the Paragon Agreement, we expect to be obligated to make similar payments upon and following the execution of a license agreement with respect to such research program.

Our option available under the Paragon Agreement with respect to the SPY004 program remains unexercised.

Private Placement Transactions

On March 18, 2024, we entered into a definitive agreement for a private placement (“March 2024 SPA”) with existing and new investors (the “March 2024 Investors”) for gross proceeds of approximately $180 million, pursuant to which the March 2024 Investors purchased an aggregate of 121,675 shares of Series B Preferred Stock at a price of $1,480.00 per share.

In connection with the March 2024 SPA, we issued (i) 6,755 shares of Series B Preferred Stock to Perceptive Life Sciences Master Fund, Ltd., (ii) 13,515 shares of Series B Preferred Stock to entities associated with RTW Investments, LP, and (iii) 1,350 shares of Series B Preferred Stock to Commodore Capital Master LP, at a price of $1,480.00 per share of Series B Preferred Stock.

On March 18, 2024, we also entered into a registration rights agreement with the March 2024 Investors, including the above-named investors, pursuant to which the March 2024 Investors are entitled to certain resale registration rights with respect to shares of our common stock held by such investors.

Consulting Agreement

In November 2023, we entered into a consulting agreement with Mr.

McKenna, which was effective until he joined the Board in February 2024, pursuant to which Mr.

McKenna agreed to provide consulting services to us as a senior advisor to the executive management team.

As compensation for such consulting services, Mr.

McKenna was granted non-qualified stock options to purchase up to 477,000 shares of our common stock under the 2016 Plan, vesting over four years with an exercise price of $10.39 per share.

Exchange Agreement

In April 2024, we entered into an exchange agreement with Fund II, pursuant to which Fund II exchanged 90,992 shares of Series A Preferred Stock for 3,639,680 shares of our common stock for no consideration.

Shares of our capital stock held by Fund II may be deemed to be beneficially owned by Messrs.

Harwin and Kiselak.

Related Party Transaction Policy

Our Board has a written policy regarding the review and approval or ratification by our Audit Committee of related person transactions.

For purposes of our policy only, a related person transaction is a transaction, arrangement or relationship or any series of similar transactions, arrangements or relationships between us or any of our subsidiaries and any related person in which the aggregate amount involved since the beginning of our last completed fiscal year exceeds or is expected to exceed $120,000 and such related person has or will have a direct or indirect interest.

A related person is defined to include any executive officers, directors or director nominees or beneficial owner of more than 5% of our common stock and any immediate family member of any of the foregoing persons.

In determining to approve or ratify any such transaction, our Audit Committee is expected to take into account, among other factors it deems appropriate, whether the transaction is on terms no less favorable than terms generally available to an unaffiliated third-party under the same or similar circumstances and the extent of the related person’s interest in the transaction.

Transactions involving compensation for services provided to us as an employee or director, among other limited exceptions, are deemed under the terms of the policy to have standing pre-approval by the Audit Committee but may be specifically reviewed if appropriate in light of the facts and circumstances.

Any director who is a related person

with respect to a transaction under review is not permitted to participate in the deliberations (other than to provide information concerning the transaction to the Audit Committee) or vote on approval of the transaction.

Director Independence

Our Board determines the independence of our directors by applying the applicable rules, regulations and listing standards of Nasdaq.

These provide that a director is independent only if the Board affirmatively determines that the director does not have a relationship with us which, in the opinion of the Board, would interfere with the exercise of his or her independent judgment in carrying out the responsibilities of a director.

Such relationships may include employment, commercial, accounting, family and other business, professional and personal relationships.

Applying these standards, our Board reviews the independence of our directors, taking into account all relevant facts and circumstances.

Our Board has determined that the following members of our Board are currently independent under Nasdaq listing rules:

Henderson and Milligan, Ms.

Stelzer and Messrs.

Albers, Harwin and Kiselak.

Turtle is not independent as he is our CEO, and Mr.

McKenna is not independent due to his consulting arrangement with the Company.

In addition, former directors Russell J.

Cox and Alison Lawton were independent during the period each served on the Board in 2024.

All members of our Audit Committee, Compensation Committee and Nominating Committee must be independent directors under the Nasdaq listing rules.

Members of the Audit Committee and Compensation Committee also must satisfy the independence criteria set forth in Rule 10A-3 and Rule 10C, respectively, under the Exchange Act.

Our Board has determined that all members of our Audit Committee, Compensation Committee and Nominating Committee satisfy the relevant independence requirements for such committees.

PRINCIPAL ACCOUNTANT FEES AND SERVICES

The information required by this item is incorporated herein by reference from the applicable information set forth in our 2024 Proxy Statement, including the section titled “Ratification of Independent Auditor Appointment."

Our independent registered public accounting firm is PricewaterhouseCoopers LLP, Austin, Texas, Auditor Firm ID:

PricewaterhouseCoopers LLP ("PwC") served as our independent auditor since 2014.

The following table summarizes the audit fees billed and expected to be billed by PwC for the indicated fiscal years and the fees billed by PwC for all other services rendered during the indicated fiscal years.

All services associated with such fees were pre-approved by our Audit Committee in accordance with the “Pre-Approval Policies and Procedures” described below.

Audit Fees (1)

$ 1,574,031 $ 1,513,184

Audit-Related Fees (2)

67,990 70,923

All Other Fees (4)

$ 1,644,146 $ 1,586,232

(1) Consists of fees for professional services rendered for the audit of our financial statements, review of our interim condensed financial statements, professional consultations with respect to accounting matters and assistance with registration statements filed with the SEC and services that are normally provided by PwC in connection with statutory and regulatory filings or engagements.

Included in our 2024 and 2023 audit fees are fees of $218,000 and $40,000 respectively, related to comfort letter fees.

(2) Consists of fees for assurance and related services reasonably related to the performance of the audit or review of our financial statements.

(3) Consists of fees for professional services for tax compliance, tax advice and tax planning.

(4) Consists of fees for all other services.

Pre-Approval Policies and Procedures

Our Audit Committee has adopted procedures requiring the pre-approval of all audit and non-audit services performed by our independent auditor in order to assure that these services do not impair the auditor’s independence.

These procedures generally approve the performance of specific services subject to a cost limit for all such services.

This general approval is reviewed, and if necessary modified, at least annually.

Management must obtain the specific prior approval of the committee for each engagement of our auditor to perform other audit-related or non-audit services.

The committee does not delegate its responsibility to pre-approve services performed by our auditor to any member of management.

The committee has delegated authority to the committee chair to pre-approve audit and non-audit services to be provided to us by our auditor provided that the fees for such services do not exceed $100,000.

Any pre-approval of services by the committee chair pursuant to this delegated authority must be reported to the committee at its next regularly scheduled meeting.

EXHIBITS AND FINANCIAL STATEMENT SCHEDULES

8 unchanged sentences

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

3.1 Amended and Restated Certificate of Incorporation

3.2 Amended and Restated Bylaws S-1/A

12/22/2023 2.1

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

5/15/2024 3.2

3.2 Amended and Restated Bylaws

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

12/22/2023 3.3

3.4 Certificate of Designations of Series B Non-Voting Convertible Preferred Stock

12/22/2023 3.4

3.5 C ertificate of Amendment to Certificate of Designation of Series B Non-Voting Convertib le Preferred Stock

3/18/2024 3.2

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

4.2 Form of Common Stock Certificate S-1/A 333-276251

4.3 Securities Purchase Agreement, dated December 7, 2023, by and among Spyre Therapeutics, Inc.

and each purchaser identified on Annex A thereto

4.2 Form of Common Stock Certificate

12/22/2023 4.2

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

4.4 Description of the Registrant's securities

4.6 Form of Pre-Funded Warrants 2022 S-1/A

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

4.6 Form of Warrant to Purchase Common Stock (Parapyre Warrant 202 4 )

10.1 Form of Indemnification Agreement

2/5/2024 10.19

10.2‡ 2015 Equity Incentive Plan and forms of award agreements S-1/A

2/5/2024 10.7

Number Incorporate by Reference

1 unchanged sentence

Filing Exhibit

2015 Equity Incentive Plan and forms of award agreements

12/22/2023 10.7

10.3‡ Spyre Therapeutics, Inc.

1 unchanged sentence

12/22/2023 10.8

Form of Stock Option Agreement under the Amended and Restated Spyre Therapeutics, Inc.

2016 Equity Incentive Plan

8/7/2024 10.6

Spyre Therapeutics, Inc.

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

2/29/2024 10.4

Spyre Therapeutics, Inc.

1 unchanged sentence

2/5/2024 10.10

10.6‡ Form of Stock Option Agreement under the Amended and Restated 2018 Equity Inducement Plan S-1/A

2/5/2024 10.11

Spyre Therapeutics, Inc.

2023 Equity Incentive Plan S-1/A

Fifth Amendment to the Spyre Therapeutics, Inc.

2018 Equity Inducement Plan

11/7/2024 10.4

Form of Stock Restriction Agreement S-1/A

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

12/22/2023 10.11

Form of Severance Agreement S-1/A

Form of Restricted Stock Unit Award Agreement under the Amended Spyre Therapeutics, Inc.

2018 Equity Inducement Plan

8/7/2024 10.7

Biologics Master Services Agreement, effective June 20, 2022, by and between Paragon Therapeutics, Inc.

and WuXi Biologics (Hong Kong) Limited

Spyre Therapeutics, Inc.

2023 Equity Incentive Plan

12/22/2023 10.12

Cell Line License Agreement, effective June 20, 2022, by and between Paragon Therapeutics, Inc.

and WuXi Biologics (Hong Kong) Limited

Form of Stock Restriction Agreement

12/22/2023 10.13

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

Form of Severance Agreement

12/22/2023 10.14

1 unchanged sentence

2/5/2024 10.4

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

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

12/22/2023 10.16

Separation and Consulting Agreement and General Release of Claims by and between the Company and Jonathan Alspaugh, dated as of September 22, 2023

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

2/29/2024 10.19

Offer Letter, dated August 10, 2023, by and between the Company and Scott Burrows S-1/A

O ffer Letter, dated September 20, 2024, by and between the Company and Sheldon Sloan

11/7/2024 10.5

10.17 Asset Purchase Agreement, dated July 27, 2023, by and between the Company and Immedica Pharma AB

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

2/29/2024 10.20

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

10/15/2024 10.2

Number Incorporate by Reference

1 unchanged sentence

Filing Exhibit

10.18 Lease Termination Agreement dated August 7, 2023, between the Company and Las Cimas Owner LP

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

10/15/2024 10.3

Offer Letter, dated August 1 8 , 2023, by and between the Company and Heidy King- Jones

10.20 C onsulting Agreement by and between the Company and Mark McKenna, effective August 1, 2023

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

12/22/2023 10.3

10.21 Amendment No.

1 to Novation Agreement, dated April 25, 2024, by and between Paragon Therapeutics, Inc., the Company and WuXi Biologics (Hong Kong) Limited

5/9/2024 10.6

Second Amended and Restated Antibody Discovery and Option agreement, dated May 14, 2024 , by and between the C ompany, Paragon Therapeutics, Inc.

and Parapyre Holding LLC

8/7/2024 10.5

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

8/7/2024 10.3

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

8/7/2024 10.4

Amended and Restated IL-23 (SPY003) License Agreement, dated February 24 , 202 5 , by and between the Company and Paragon Therapeutics, Inc.

10.26 S ales Agreement, dated September 6, 2024, between Spyre Therapeutics, Inc.

and TD Securities (USA) LLC

19.1 Spyre Therapeutics, Inc.

Insider Trading Policy

21.1 Subsidiaries of the Registrant

1 unchanged sentence

24.1 Power of Attorney

Reference is made to the signature page hereto

31.1 Certification of the Principal Executive Officer pursuant to Rule 13a-14(a) or 15d-14(a) of the Securities Exchange Act of 1934

2 unchanged sentences

Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002

Number Incorporate by Reference

Description of Document Form File No.

Filing Exhibit

97 Spyre Therapeutics, Inc.

6 unchanged sentences

101.PRE Inline XBRL Taxonomy Extension Presentation Linkbase Document X

Number Incorporate by Reference

Description of Document Form File No.

Filing Exhibit

104 The cover page of this Annual Report on Form 10-K for the year ended December 31, 2024, formatted in Inline XBRL and contained in Exhibit 101

28 unchanged sentences

Principal Accounting Officer)

/s/ Russell J.

Cox Chairman of the Board

February 29, 2024

/s/ Jeffrey W.

Director February 29, 2024

Chairman of the Board February 27, 2025

/s/ Peter Harwin

8 unchanged sentences

Director February 27, 2025

/s/ Sandra Milligan

Director February 27, 2025

Sandra Milligan

/s/ Laurie Stelzer

2 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 9A. Controls and Procedures