Spero Therapeutics Announces Fourth Quarter and Full Year 2024 Operating Results and Provides a Business Update Pre-specified interim analysis of Phase 3 PIVOT-PO clinical trial of tebipenem HBr in complicated urinary tr

Spero Therapeutics Announces Fourth Quarter and Full Year 2024 Operating Results and Provides a Business Update

CAMBRIDGE, Mass., March 27, 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 fourth quarter and full year ended December 31, 2024, and provided a business update.

Spero is focused on the execution of the

tebipenem HBr clinical program, including preparing for the pre-specified interim analysis next quarter, said Esther Rajavelu, Interim President and Chief Executive Officer. We believe that, if

approved, tebipenem HBr could address a critical unmet need for an oral carbapenem in the treatment of patients with complicated urinary tract infections. Tebipenem HBr has the potential to shorten hospital stays, improve patient outcomes, and

alleviate pressure on healthcare resources.

Ms. Rajavelu added: As previously announced, we are reviewing the comprehensive data

we ve gathered for SPR720 after suspending development of the oral program for NTM-PD. There remains a high unmet need for new, approved therapies for this difficult to treat disease, and a complete data

analysis would enable us to make an informed decision on the program. Further, we have decided to discontinue our SPR206 program, following a pipeline review and reprioritization. We are grateful to our partners and the government agencies who

helped finance this program and to the Spero team members who have worked diligently on its progression into a Phase 2 ready asset.

Tebipenem HBr is an investigational

oral carbapenem antibiotic being developed for the treatment of cUTI including acute pyelonephritis (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.

SPR206 is an investigational, intravenously administered next-generation polymyxin that has shown antibiotic activity against MDR Gram-negative pathogens,

including carbapenem-resistant Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa in preclinical studies. The Company announced discontinuation of the SPR206 program following a reprioritization of the pipeline in Q1

Fourth Quarter and Full Year 2024 Financial Results

For further details on Spero s financials, refer to Spero s Annual Report on Form 10-K, filed with the U.S. Securities and Exchange Commission (SEC) today.

Conference Call and Live Webcast

Spero will host a conference call and webcast today at 4:30 p.m. ET. To access the call, please dial 1-844-825-9789 (domestic) or 1-412-317-5180

(international) and refer to conference ID 10196669 or click on this Link and request a return call via Call me . The Call me

passcode is 9270590. The conference call will also be webcast live and can be accessed through this website link, and on Spero s website at www.sperotherapeutics.com on the Events and Presentations page under the

Connect tab. An archived webcast will be available on Spero s website for 30 days following the presentation.

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.

Department of Defense

Select SPR206 studies were supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Joint Warfighter Medical

Research Program under Award No. W81XWH 19 1 0295. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.

National Institute of Allergy and Infectious Diseases

Select SPR206 studies were funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases; National Institutes of

Health; and Department of Health and Human Services, under Contract No. 75N93021C00022.

About Spero Therapeutics

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 [Note to Draft: Legal to Update Once Final.]

[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 preclinical studies, clinical trials and research and development programs; the pre-planned interim analysis and timing

thereof for the Phase 3 PIVOT-PO clinical trial; the potential benefits of any of Spero s current or future product candidates in treating patients; 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 whether tebipenem HBr, and SPR720 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 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.]

Spero Therapeutics, Inc.

Condensed Consolidated Balance Sheet Data

Spero Therapeutics, Inc.

Condensed Consolidated Statements of Operations

(in thousands, except share and per share data)