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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of The Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): November 13, 2025

SPERO THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

Delaware |  | 001-38266 |  | 46-4590683
(State or other jurisdiction of incorporation) |  | (Commission File Number) |  | (I.R.S. Employer Identification No.)

675 Massachusetts Avenue, 14th Floor |  |
Cambridge, Massachusetts |  | 02139
(Address of principal executive offices) |  | (Zip Code)

Registrant’s telephone number, including area code (857) 242-1600

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class |  | Trading Symbol(s) |  | Name of each exchange on which registered
Common Stock, $0.001 par value |  | SPRO |  | The Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company☐

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 13(a) of the Exchange Act. ☐

Item 2.02 | Results of Operations and Financial Condition.

On November 13, 2025, Spero Therapeutics, Inc. (the “Company”) issued a press release announcing its results for the third quarter ended September 30, 2025. A copy of the press release issued in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K.

The information contained in this Item 2.02 and in the press release furnished as Exhibit 99.1 hereto shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that Section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended (the “Securities Act”), or incorporated by reference in any filing with the U.S. Securities and Exchange Commission made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.

Item 7.01 | Regulation FD Disclosure.

On November 13, 2025, the Company released an investor presentation (the “Investor Presentation”), which includes updates regarding the Company’s business and operations that management intends to use from time to time in investor communications and conferences. A copy of the Investor Presentation is attached and furnished hereto as Exhibit 99.2 and is also available on the “Investor Relations” portion of the Company’s website at https://www.sperotherapeutics.com/investor-relations/stock-information.

The information in this Item 7.01 and Exhibit 99.2, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section or sections 11 and 12(a)(2) of the Securities Act, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such filing.

Item 9.01 | Financial Statements and Exhibits

(d) | Exhibits

Exhibit No. |  | Description
99.1 |  | Press release issued by Spero Therapeutics, Inc. on November 13, 2025
99.2 |  | Corporate Investor Presentation of Spero Therapeutics, Inc. as of November 13, 2025
104 |  | Cover Page Interactive Data File (embedded within the Inline XBRL document and incorporated as Exhibit 101)

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

Date: November 13, 2025 |  | SPERO THERAPEUTICS, INC.
|  |  |  | By: |  | /s/ Esther Rajavelu
|  |  |  |  |  | Esther Rajavelu
|  |  |  |  |  | Chief Executive Officer, Chief Financial Officer and Chief Business Office