Spero Therapeutics Announces Second Quarter 2025 Operating Results and Provides a Business Update PIVOT-PO Phase 3 trial evaluating tebipenem Hbr in complicated urinary tract infection (cUTI) patients stopped early for e

Spero Therapeutics Announces Second Quarter 2025 Operating Results and Provides a Business Update

CAMBRIDGE, Mass., Aug 12, 2025 Spero Therapeutics, Inc. (Nasdaq: SPRO), a clinical-stage

biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and multi-drug resistant (MDR) bacterial infections, today announced financial results for the second quarter ended June 30, 2025, and provided a

During the second quarter, we announced that the tebipenem Phase 3 PIVOT-PO trial met its

primary endpoint, marking a significant milestone for this program. We look forward to working with GSK on next steps for this program which include completion of the Phase 3 data analysis and submission of the data package to the FDA, said

Esther Rajavelu, Chief Executive Officer and Chief Financial Officer of Spero. There remains a critical unmet need for an oral carbapenem to treat complicated urinary tract infections, including pyelonephritis. If approved, we believe

tebipenem HBr could set a new standard of care for these infections, with the potential to shorten hospital stays, improve patient outcomes, and reduce pressure on healthcare resources.

Tebipenem HBr is an investigational oral carbapenem antibiotic being developed for the treatment of cUTI, including pyelonephritis, to help patients

potentially reduce the duration of in-patient therapy. Spero granted GSK an exclusive license to commercialize tebipenem HBr in all territories, except certain Asian territories where Meiji holds development

and commercialization rights.

SPR720 is an investigational, chemically stable phosphate ester prodrug that is converted rapidly in vivo to SPR719, the active moiety, after oral

administration. SPR719 targets the ATPase site of DNA gyrase B in mycobacteria, a mechanism that is distinct from that of other antibiotics in use for nontuberculous mycobacterium pulmonary disease (NTM-PD).

Second Quarter 2025 Financial Results

For further details on Spero s financials, refer to Spero s Quarterly Report on Form 10-Q, filed with the

U.S. Securities and Exchange Commission (SEC) today.

Conference Call and Live Webcast

Spero management will host a conference call and live audio webcast at 4:30 p.m. ET today, August 12, 2025, to discuss the second quarter financial

results and provide a business update.

To access the call, please dial 1-844-825-9789 (domestic) or 1-412-317-5180 (international) and refer to

conference ID 10200686, or click on this link and request a return call with passcode 0605709. The audio webcast can be accessed live on this link and also on the Investor Relations page of the

Spero Corporate Website at https://www.sperotherapeutics.com/. The archived webcast will also be available on Spero s website for 30 days following the call.

Government Agency Research Support

in this press release are those of the authors and may not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.

Tebipenem HBr Research Support

Select tebipenem HBr

studies have been funded in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; and Biomedical Advanced Research and Development Authority, under contract number

About Spero Therapeutics

Therapeutics, headquartered in Cambridge, Massachusetts, is a clinical-stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and MDR bacterial infections with high unmet need. For more information,

visit www.sperotherapeutics.com.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including,

without limitation, statements regarding the timing, progress and results of Spero s Phase 3 PIVOT-PO trial; the timing of a planned FDA filing in 2H 2025 for tebipenem HBr; the potential of tebipenem HBr

to be the first oral carbapenem antibiotic for US patients with cUTI, including pyelonephritis, and to set a new standard of care; the potential receipt of milestone payments under Spero s license and collaboration agreements; Spero s

anticipated cash runway; and the potential benefits of any of Spero s current or future product candidates in treating patients. In some cases, forward-looking statements may be identified by terms such as may, will,

should, expect, plan, aim, anticipate, could, intent, target, project, contemplate, believe, estimate,

predict, potential or continue, the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management s current expectations and beliefs and

are subject to a number of important risks, uncertainties and other factors that may cause actual results to differ materially from those indicated by such forward looking statements, including whether tebipenem HBr will advance through the clinical

development process, or at all, taking into account the effects of possible regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, clinical trial design and clinical outcomes; whether the results of such trials will

warrant submission for approval from the FDA or equivalent foreign regulatory agencies; whether the FDA will ultimately approve tebipenem HBr and, if so, the timing of any such approval; whether the FDA will require any additional clinical data or

place labeling restrictions on the use of tebipenem HBr that would delay approval and/or reduce the commercial prospects of tebipenem HBr; whether a successful commercial launch can be achieved and market acceptance of tebipenem HBr can be

established; whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; Spero s reliance on third parties to manufacture, develop, and commercialize its product

candidates, if approved, including, in the case of tebipenem HBr, Spero s reliance on GSK pursuant to the exclusive GSK License Agreement to develop tebipenem HBr and GSK s right thereunder to determine, in its sole discretion, whether to

continue the PIVOT-PO trial or

otherwise further develop tebipenem HBr; Spero s need for additional funding; the ability to commercialize Spero s product candidates, if approved; Spero s ability to retain key

personnel; Spero s leadership transitions; whether Spero s cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; and other factors discussed in the Risk Factors set forth

in filings that Spero periodically makes with the SEC. The forward-looking statements included in this press release represent Spero s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent

date. Except as required by law, Spero explicitly disclaims any obligation to update any forward-looking statements.

Investor Relations Contact:

Spero Therapeutics, Inc.

Condensed Consolidated Balance Sheet Data

Spero Therapeutics, Inc.

Condensed Consolidated Statements of Operations

(in thousands, except share and per share data)