Spero Therapeutics, Inc. 10-K

Item 9A. Controls and Procedures. Evaluation of Disclosure Controls and Procedures Our management, with the participation of our Chief Executive Officer and Chief Financial Officer (our principal executive officer and principal financial officer) evaluated the effectiveness of our disclosure controls and procedures as of December 31, 2025. 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. Disclosure controls and procedures include, without limitation, controls and procedures 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 accumulated and communicated to the company’s management, including its principal executive and principal financial officers, as appropriate to allow timely decisions regarding required disclosure. Management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives and management necessarily applies its judgment in evaluating the cost-benefit relationship of possible controls and procedures. Based on the evaluation of our disclosure controls and procedures as of December 31, 2025, our Chief Executive Officer and Chief Financial Officer concluded that, as of such date, our disclosure controls and procedures were effective at the reasonable assurance level. Management’s Annual Report on Internal Controls Over Financial Reporting Our management is responsible for establishing and maintaining adequate internal control over financial reporting as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act. Our internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with general accepted accounting principles. Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. 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. Under the supervision and with the participation of our management, including our principal executive officer and principal financial officer, we conducted an evaluation of the effectiveness of our internal control over financial reporting based on the Internal Control – Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission. Based on our evaluation under that framework, our management concluded that our internal control over financial reporting was effective as of December 31, 2025. Changes in Internal Control Over Financial Reporting No change in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act) occurred during the three months ended December 31, 2025 that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting. Item 9B. Other Information. Trading Arrangements On December 17, 2025 , Esther Rajavelu , President, Chief Executive Officer, Chief Financial Officer, Chief Business Officer and Treasurer , adopted a Rule 10b5-1 trading arrangement (as defined in Item 408(a) of Regulation S-K) (the “Trading Agreement”). The Trading Agreement will terminate on December 17, 2026 unless terminated earlier pursuant to the terms of the Trading Agreement. The aggregate number of shares to be sold under the Trading Agreement is 78,412 . None of our other directors or officers adopted or terminated a Rule 10b5-1 trading arrangement or a non-Rule 10b5-1 trading arrangement (as defined in Item 408(c) of Regulation S-K) during the three months ended December 31, 2025. Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections. Not applicable. 125 PART III Item 10. Directors, Executive Officers and Corporate Governance. The response to this item is incorporated by reference from the discussion responsive thereto under the captions “Management and Corporate Governance Matters” and “Code of Conduct and Ethics” in the Company’s proxy statement for the 2026 Annual Meeting of Stockholders to be filed with the SEC within 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K. Item 11. Executive Compensation. The response to this item is incorporated by reference from the discussion responsive thereto under the captions “Executive Officer and Director Compensation” and “Management and Corporate Governance Matters - Compensation Committee Interlocks and Insider Participation” in our proxy statement for the 2026 Annual Meeting of Stockholders to be filed with the SEC within 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K. Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters. The response to this item is incorporated by reference from the discussion responsive thereto under the captions “Security Ownership of Certain Beneficial Owners and Management” and “Equity Compensation Plan Information” in our proxy statement for the 2026 Annual Meeting of Stockholders to be filed with the SEC within 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K. Item 13. Certain Relationships and Related Transactions, and Director Independence. The response to this item is incorporated by reference from the discussion responsive thereto under the captions “Certain Relationships and Related Person Transactions” and “Management and Corporate Governance Matters” in our proxy statement for the 2026 Annual Meeting of Stockholders to be filed with the SEC within 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K. Item 14. Principal Accountant Fees and Services. The response to this item is incorporated by reference from the discussion responsive thereto under the caption “Independent Public Accounting Firm” in our proxy statement for the 2026 Annual Meeting of Stockholders to be filed with the SEC within 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K. 126 PART IV Item 15. Exhibits, Financ ial Statement Schedules. (1) Consolidated Financial Statements See Index to Consolidated Financial Statements at Item 8 herein. (2) Financial Statement Schedules All schedules are omitted because they are not applicable or the required information is shown in the consolidated financial statements or notes thereto. (3) Exhibits The following is a list of exhibits filed as part of this Annual Report on Form 10-K. Exhibit Number Exhibit Description Filed with this Report Incorporated by Reference herein from Form or Schedule Filing Date SEC File / Registration Number 3.1 Amended and Restated Certificate of Incorporation of the Registrant Form 8-K (Exhibit 3.1) 11/6/2017 001-38266 3.2 Certificate of Amendment to the Amended and Restated Certificate of Incorporation of the Registrant Form 8-K (Exhibit 3.1) 8/18/2021 001-38266 3.3 Amended and Restated Bylaws of the Registrant Form 10-Q (Exhibit 3.1) 11/13/2023 001-38266 3.4 Certificate of Designation of Preferences, Rights and Limitations of Series A Convertible Preferred Stock Form 8-K (Exhibit 3.1) 7/17/2018 001-38266 3.5 Certificate of Designation of Preferences, Rights and Limitations of Series B Convertible Preferred Stock Form 8-K (Exhibit 3.1) 11/16/2018 001-38266 3.6 Certificate of Designation of Preferences, Rights and Limitations of Series C Convertible Preferred Stock Form 8-K (Exhibit 3.1) 2/28/2020 001-38266 3.7 Certificate of Designation of Preferences, Rights and Limitations of Series D Convertible Preferred Stock Form 8-K (Exhibit 3.1) 9/14/2020 001-38266 4.1 Form of Common Stock Certificate Form S-1 (Exhibit 4.1) 10/6/2017 333-220858 4.2 Description of Registrant’s Securities Form 10-K (Exhibit 4.2) 3/30/2023 001-38266 10.1# 2017 Stock Incentive Plan, as amended Form 10-Q (Exhibit 10.1) 8/12/2025 001-38266 10.2# Form of Stock Option Agreement under the 2017 Stock Incentive Plan, as amended Form S-8 (Exhibit 4.6) 9/20/2021 333-259662 10.3# Form of Restricted Stock Unit Agreement under the 2017 Stock Incentive Plan, as amended Form 8-K (Exhibit 10.1) 8/30/2021 001-38266 10.4# 2019 Inducement Equity Incentive Plan, as amended Form 10-K (Exhibit 10.4) 3/13/2024 001-38266 10.5# Form of Stock Option Agreement under the 2019 Inducement Equity Incentive Plan, as amended Form S-8 (Exhibit 4.6) 8/10/2023 333-273880 10.6# Form of Restricted Stock Unit Agreement under the 2019 Inducement Equity Incentive Plan, as amended Form S-8 (Exhibit 4.7) 8/10/2023 333-273880 127 10.7# Form of Director and Officer Indemnification Agreement Form S-1 (Exhibit 10.4) 10/6/2017 333-220858 10.8# Non-Employee Director Compensation Policy, as amended Form 10-K (Exhibit 10.8) 3/13/2024 001-38266 10.9# Employment Agreement, dated January 1, 2020, by and between the Registrant and Timothy Keutzer. Form 10-K (Exhibit 10.12) 3/16/2020 001-38266 10.10# Amendment to Employment Agreement, dated November 10, 2022, by and between the Registrant and Timothy Keutzer Form 10-Q (Exhibit 10.9) 11/14/2022 001-38266 10.11# Second Amendment to Employment Agreement, dated as of February 1, 2023, by and between the Registrant and Timothy Keutzer Form 10-Q (Exhibit 10.1) 5/11/2023 001-38266 10.12# Employment Agreement, dated October 31, 2023, by and between the Registrant and Esther Rajavelu Form 10-Q (Exhibit 10.1) 5/15/2024 001-38266 10.13# Interim Period Agreement, dated January 10, 2025, by and between the Registrant and Esther Rajavelu Form 8-K (Exhibit 10.2) 1/10/2025 001-38266 10.14# Amended and Restated Employment Agreement, dated April 28, 2025, by and between the Registrant and Esther Rajavelu Form 10-Q (Exhibit 10.10) 5/13/2025 001-38266 10.15# Amended and Restated Consulting Agreement, effective as of January 29, 2025, by and between the Registrant and John C. Pottage, Jr., M.D. Form 10-K (Exhibit 10.28) 3/27/2025 001-38266 10.16 Lease Agreement, dated August 24, 2015, by and between the Registrant and U.S. REIF Central Plaza Massachusetts, LLC Form S-1 (Exhibit 10.11) 10/6/2017 333-220858 10.17 First Amendment to Lease Agreement, dated January 17, 2018, by and between the Registrant and U.S. REIF Central Plaza Massachusetts, LLC Form 8-K (Exhibit 99.1) 1/23/2018 001-38266 10.18 Second Amendment to Lease Agreement, dated December 16, 2019, by and between the Registrant and U.S. REIF Central Plaza Massachusetts, LLC Form 8-K (Exhibit 99.1) 12/19/2019 001-38266 10.19 Third Amendment to Lease Agreement, dated May 4, 2020, by and between the Registrant and U.S. REIF Central Plaza Massachusetts, LLC Form 10-Q (Exhibit 10.4) 8/6/2020 001-38266 10.20† Stock Purchase Agreement, dated June 6, 2016, by and among Spero Cantab, Inc., the Registrant, Spero Cantab UK Limited, PBB Distributions Limited, New Pharma License Holdings Limited, Cantab Anti-Infectives Ltd and Pro Bono Bio PLC, as amended by Amendment to Stock Purchase Agreement, dated July 18, 2017 Form S-1 (Exhibit 10.13) 10/6/2017 333-220858 10.21† License Agreement, dated June 14, 2017, by and between the Registrant and Meiji Seika Pharma Co., Ltd., as supplemented by Addendum to License Agreement, dated June 14, 2017 Form S-1 (Exhibit 10.15) 10/6/2017 333-220858 10.22† Contract Award, dated July 12, 2018, issued by the Biomedical Advanced Research and Development Authority of the United States Department of Health and Human Services Form 10-Q (Exhibit 10.1) 11/8/2018 001-38266 128 10.23†† Amended and Restated License Agreement, dated January 15, 2021, by and between the Registrant and Everest Medicines II Limited Form 10-K (Exhibit 10.25) 3/11/2021 001-38266 10.24† License Agreement, dated June 30, 2021, by and between the Registrant and Pfizer Inc. Form 10-Q (Exhibit 10.1) 8/5/2021 001-38266 10.25† Share Purchase Agreement, dated June 30, 2021, by and between the Registrant and Pfizer Inc. Form 10-Q (Exhibit 10.2) 8/5/2021 001-38266 10.26†† Termination Letter, dated December 31, 2025, by and between Registrant and Pfizer Inc. regarding termination of License Agreement X 10.27†† Exclusive License Agreement, dated September 21, 2022, by and between the Registrant and GlaxoSmithKline Intellectual Property (No. 3) Limited Form 10-Q (Exhibit 10.3) 11/14/2022 001-38266 10.28†† Amendment 1 to Exclusive License Agreement, dated July 4, 2023, by and between the Registrant and GlaxoSmithKline Intellectual Property (No. 3) Limited Form 10-K (Exhibit 10.34) 3/13/2024 001-38266 10.29†† Amendment 2 to Exclusive License Agreement, dated December 20, 2023, by and between the Registrant and GlaxoSmithKline Intellectual Property (No. 3) Limited Form 10-K (Exhibit 10.35) 3/13/2024 001-38266 10.30†† Amendment 3 to Exclusive License Agreement, dated March 4, 2024, by and between the Registrant and GlaxoSmithKline Intellectual Property (No. 3) Limited Form 10-Q (Exhibit 10.4) 5/15/2024 001-38266 10.31†† Amendment 4 to Exclusive License Agreement, dated October 28, 2024, by and between the Registrant and GlaxoSmithKline Intellectual Property (No. 3) Limited Form 10-Q (Exhibit 10.4) 11/14/2024 001-38266 10.32 Controlled Equity Offering Sales Agreement, dated March 11, 2021, by and between the Registrant and Cantor Fitzgerald & Co. Form 10-K (Exhibit 10.28) 3/11/2021 001-38266 19.1 Spero Therapeutics, Inc. Insider Trading Policy, effective as of June 5, 2023 Form 10-K (Exhibit 19.1) 3/27/2025 001-38266 21.1 List of Subsidiaries of the Registrant Form 10-K (Exhibit 21.1) 3/16/2020 001-38266 23.1 Consent of PricewaterhouseCoopers LLP, independent registered public accounting firm X 31.1 Certification of Principal Executive Officer and Principal Financial Officer pursuant to Section 302 of the Sarbanes-Oxley Act of 2002 X 32.1* Certification pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, by Principal Executive Officer and Principal Financial Officer X 97.1 Clawback Policy, effective as of November 12, 2023 Form 10-K (Exhibit 97.1) 3/13/2024 001-38266 101.INS XBRL Instance Document - the instance document does not appear in the Interactive Data File because its XBRL tags are embedded within the Inline XBRL document X 129 101.SCH Inline XBRL Taxonomy Extension Schema Document X 101.CAL Inline XBRL Taxonomy Extension Calculation Linkbase Document X 101.DEF Inline XBRL Taxonomy Extension Definition Linkbase Document X 101.LAB Inline XBRL Taxonomy Extension Label Linkbase Document X 101.PRE Inline XBRL Taxonomy Extension Presentation Linkbase Document X 104 Cover Page Interactive Data File (embedded within the Inline XBRL document) X † Confidential treatment received as to portions of the exhibit. Confidential materials omitted and filed separately with the SEC. †† Certain confidential portions of this Exhibit were omitted by means of marking such portions with brackets (“[***]”) because the identified confidential portions (i) are not material and (ii) is the type that the Registrant treats as private or confidential. # Management contract or compensatory plan. * The certification attached as Exhibit 32.1 that accompanies this Annual Report on Form 10-K is not deemed filed with the Securities and Exchange Commission and is not to be incorporated by reference into any filing of Spero Therapeutics, Inc. under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended, whether made before or after the date of this Form 10-K, irrespective of any general incorporation language contained in such filing. Item 16. Form 10-K Summary. None. 130 SIGNAT URES Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized . SPERO THERAPEUTICS, INC. Date: March 26, 2026 By: /s/ Esther Rajavelu Esther Rajavelu President, Chief Executive Officer, Chief Financial Officer, Chief Business Officer and Treasurer POWER OF ATTORNEY KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Esther Rajavelu or her true and lawful attorney-in-fact and agent, with full power of substitution, for her and in her name, place and stead, in any and all capacities, to sign any and all amendments to this Annual Report on Form 10-K, and to file the same, with all exhibits thereto, and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorney-in-fact and agent, full power and authority to do and perform each and every act and thing requisite and necessary to be done in connection therewith, as fully to all intents and purposes as she might or could do in person, hereby ratifying and confirming all that said attorney-in-fact and agent, or her substitutes or substitute, may lawfully do or cause to be done by virtue hereof. Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of the registrant in the capacities and on the dates indicated. Name Title Date /s/ Esther Rajavelu President, Chief Executive Officer, Chief Financial Officer, Chief Business Officer, Treasurer, and Director March 26, 2026 Esther Rajavelu (Principal Executive, Financial and Accounting Officer) /s/ Milind Deshpande, Ph.D. Director March 26, 2026 Milind Deshpande, Ph.D. /s/ Scott Jackson Director March 26, 2026 Scott Jackson /s/ John C. Pottage, M.D. Director March 26, 2026 John C. Pottage, M.D. /s/ Cynthia Smith Director March 26, 2026 Cynthia Smith /s/ Frank E. Thomas Director March 26, 2026 Frank E. Thomas /s/ Kathleen Tregoning Director March 26, 2026 Kathleen Tregoning /s/ Patrick Vink, M.D. Director March 26, 2026 Patrick Vink, M.D. 131