Spero Therapeutics Announces First Quarter 2025 Operating Results and Provides a Business Update Pre-specified interim analysis of the ongoing Phase 3 PIVOT-PO clinical trial of tebipenem HBr in complicated urinary tract

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

CAMBRIDGE, Mass., May 13, 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 first quarter ended March 31, 2025, and provided a business update.

At Spero, our top priority remains the successful execution of the

tebipenem HBr clinical program as we prepare for the pre-specified interim analysis of the PIVOT-PO trial during the second quarter, said Esther Rajavelu,

President and Chief Executive Officer. We are developing tebipenem HBr to address the significant unmet need for an oral carbapenem option in the treatment of complicated urinary tract infections. We believe that, if approved, tebipenem HBr

could deliver meaningful clinical and economic benefits, by improving patient outcomes and reducing the need for hospital stays.

investigational oral carbapenem antibiotic being developed for the treatment of cUTI, including AP, to help patients potentially reduce 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 NTM-PD.

First 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.

Government Agency Research Support

The views expressed 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 HHSO100201800015C.

Spero 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 may

contain 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 preclinical studies,

clinical trials and research and development programs; Spero s strategy, goals and anticipated financial performance, milestones, business plans and focus; and Spero s cash runway. 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 statements related to tebipenem HBr s future clinical development process, 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 U.S. Food and Drug Administration (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 License Agreement to develop

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)