S-8

Large accelerated filer

Accelerated filer

Non-accelerated filer

Smaller reporting company

Emerging growth company

As filed with the Securities and Exchange Commission on August 12, 2025

Registration No. 333-

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM S-8

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

SPERO THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)


Delaware		46-4590683
(State or other jurisdiction of incorporation or organization)		(I.R.S. Employer Identification No.)

675 Massachusetts Avenue, 14th Floor Cambridge, Massachusetts		02139
(Address of Principal Executive Offices)		(Zip Code)

SPERO THERAPEUTICS, INC. 2017 STOCK INCENTIVE PLAN, AS AMENDED

(Full title of the plan)

Esther Rajavelu, President, Chief Executive Officer, Chief Financial Officer and Treasurer

Spero Therapeutics, Inc.

675 Massachusetts Avenue, 14th Floor

Cambridge, Massachusetts 02139

(Name and address of agent of service)

(857) 242-1600

(Telephone number, including area code, of agent for service)

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☐

EXPLANATORY NOTE

This registration statement registers an aggregate of 3,000,000 additional shares of common stock of Spero Therapeutics, Inc. (the “Registrant”) reserved under the Spero Therapeutics, Inc. 2017 Stock Incentive Plan, as amended (the “2017 Plan”), representing an increase of 3,000,000 shares reserved under the 2017 Plan effective June 12, 2025. This registration statement registers additional securities of the same class as other securities for which a registration statement filed on Form S-8 relating to the 2017 Plan has previously been filed and is effective. This registration statement incorporates by reference the contents of (i) the registration statement on Form S-8 (File No. 333-222060), filed with the Securities and Exchange Commission on December 14, 2017 by the Registrant, (ii) the registration statement on Form S-8 (File No. 333-230281), filed with the Securities and Exchange Commission on March 14, 2019 by the Registrant, (iii) the registration statement on Form S-8 (File No. 333-237283), filed with the Securities and Exchange Commission on March 19, 2020 by the Registrant, (iv) the registration statement on Form S-8 (File No. 333-254173), filed with the Securities and Exchange Commission on March 11, 2021 by the Registrant, (v) the registration statement on Form S-8 (File No. 333-259662), filed with the Securities and Exchange Commission on September 20, 2021 by the Registrant, (vi) the registration statement on Form S-8 (File No. 333-268344), filed with the Securities and Exchange Commission on November 14, 2022 by the Registrant, (vii) the registration statement on Form S-8 (File No. 333-275514), filed with the Securities and Exchange Commission on November 13, 2023 by the Registrant, and (viii) the registration statement on Form S-8 (File No. 333-281245), filed with the Securities and Exchange Commission on August 5, 2024 by the Registrant, in each case, except for Item 8, Exhibits.

Item 8. Exhibits.


Exhibit Number	Exhibit Description	Filed Herewith		Incorporated by Reference herein from Form or Schedule			Filing Date		SEC File/ Reg. Number

4.1	Form of Common Stock Certificate of Registrant.				Form S-1 (Exhibit 4.1	)		10/6/2017		333-220858

4.2	Amended and Restated Certificate of Incorporation of the Registrant.				Form 8-K (Exhibit 3.1	)		11/6/2017		001-38266

4.3	Certificate of Amendment to Amended and Restated Certificate of Incorporation of the Registrant.				Form 8-K (Exhibit 3.1	)		8/18/2021		001-38266

4.4	Amended and Restated Bylaws of the Registrant.				Form 10-Q (Exhibit 3.1	)		11/13/2023		001-38266

5.1	Opinion of Wilmer Cutler Pickering Hale and Dorr LLP.		X

23.1	Consent of PricewaterhouseCoopers LLP, independent registered public accounting firm.		X

23.2	Consent of Wilmer Cutler Pickering Hale and Dorr LLP (included in opinion of counsel filed as Exhibit 5.1).		X

24.1	Power of Attorney (set forth on the signature page of this registration statement).		X

99.1	2017 Stock Incentive Plan, as amended.				Form 10-Q (Exhibit 10.1	)		8/12/2025		001-38266

99.2	Form of Stock Option Agreement under the 2017 Stock Incentive Plan, as amended.				Form S-8 (Exhibit 4.6	)		9/20/2021		333-259662

99.3	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

107	Filing Fee Table.		X

SIGNATURES

Pursuant to the requirements of the Securities Act of 1933, the Registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-8 and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Cambridge, Commonwealth of Massachusetts, on August 12, 2025.


SPERO THERAPEUTICS, INC.

By:		/s/ Esther Rajavelu
		Esther Rajavelu
		President, Chief Executive Officer, Chief Financial Officer and Treasurer

POWER OF ATTORNEY AND SIGNATURES

Each person whose signature appears below constitutes and appoints Esther Rajavelu and Timothy Keutzer, and each of them singly, his or her true and lawful attorneys-in-fact and agents, with full power of substitution and resubstitution in each of them singly, for him or her and in his or her name, place and stead, and in any and all capacities, to sign any and all amendments (including post-effective amendments) to this Registration Statement on Form S-8 of Spero Therapeutics, Inc., and to file the same, with all exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, granting to the attorneys-in-fact and agents, and each of them, full power and authority to do and perform each and every act and thing requisite or necessary to be done in connection therewith, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming all that the attorneys-in-fact and agents or any of each of them or their substitute may lawfully do or cause to be done by virtue hereof.

Pursuant to the requirements of the Securities Act of 1933, this registration statement has been signed by the following persons in the capacities and on the dates indicated.


Signature	Title	Date

/s/ Esther Rajavelu Esther Rajavelu	President, Chief Executive Officer, Chief Financial Officer and Treasurer (Principal Executive Officer, Principal Financial Officer and Principal Accounting Officer)	August 12, 2025

/s/ Frank E. Thomas Frank E. Thomas	Chairman	August 12, 2025

/s/ Milind Deshpande, Ph.D. Milind Deshpande, Ph.D.	Director	August 12, 2025

/s/ Scott Jackson Scott Jackson	Director	August 12, 2025

/s/ Ankit Mahadevia, M.D. Ankit Mahadevia, M.D.	Director	August 12, 2025

/s/ John C. Pottage, M.D. John C. Pottage, M.D.	Director	August 12, 2025

/s/ Cynthia Smith Cynthia Smith	Director	August 12, 2025

/s/ Kathleen Tregoning Kathleen Tregoning	Director	August 12, 2025

/s/ Patrick Vink, M.D. Patrick Vink, M.D.	Director	August 12, 2025