Spero Therapeutics Announces First Quarter 2024 Operating Results and Provides a Business Update On track for topline data from SPR720 Phase 2a proof-of-concept trial in treatment-naive and treatment-experienced non-refr

Spero Therapeutics Announces First Quarter 2024 Operating Results and Provides a Business Update

CAMBRIDGE, Mass., May 15, 2024 Spero

Therapeutics, Inc. (Nasdaq: SPRO), a multi-asset clinical-stage biopharmaceutical company, focused on identifying and developing novel treatments for rare diseases and multi-drug resistant (MDR) bacterial infections, today

announced financial and operational results for the quarter ended March 31, 2024.

We continued to make progress towards our stated goals

across our clinical pipeline, in both our wholly-owned and partnered programs, stated Sath Shukla, President and Chief Executive Officer of Spero. Anticipated top-line data from the Phase 2a

clinical trial of SPR720 in the second half of 2024 continues to present an exciting potential opportunity to redefine the standard of care in nontuberculous mycobacterial pulmonary disease (NTM-PD).

Additionally, tebipenem HBr as the potential first oral carbapenem for complicated urinary tract infection (cUTI) continues to enroll patients globally in our Phase 3 PIVOT-PO clinical trial, with enrollment

completion anticipated in the second half of 2025. Supported by a strong balance sheet, Spero remains well capitalized with expected cash runway into late 2025.

SPR720 is an investigational, novel, oral, first-line treatment for NTM-PD.

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

potentially avoid hospitalizations or reduce duration of in-patient therapy. Spero granted GSK an exclusive license to commercialize tebipenem HBr in all territories, except certain Asian territories.

SPR206 is an innovative, investigational,

intravenously administered direct-acting 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.

First Quarter 2024 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.

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; Biomedical Advanced Research and Development Authority, under contract number HHSO100201800015C.

Government Agency Research

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.

Department of Defense

Select SPR206 studies are 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 Disease

Select SPR206 studies have been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National

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

About Spero Therapeutics

Spero Therapeutics, headquartered in Cambridge, Massachusetts, is a multi-asset 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. These statements include, but are not limited to, statements about the design, initiation, timing,

progress and results of Spero s preclinical studies and clinical trials and its research and development programs, as well as the regulatory path forward for tebipenem HBr and potential FDA approval, the potential commercialization of tebipenem

HBr, the potential receipt under the GSK license agreement of milestone payments and royalties on future sales of tebipenem HBr, and Spero s cash runway. In some cases, forward-looking statements can be identified by terms such as

may, will, should, expect, plan, aim, anticipate, could, intent, target, project, contemplate,

believe, estimate, predict, potential or continue or the negative of these terms or other similar expressions. Actual results may differ materially from those indicated by such forward

looking statements as a result of various important factors, including whether tebipenem HBr, SPR720 and SPR206 will advance through the clinical trial process on a timely basis, 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; 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 ongoing 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 as of the date of this press release. Spero anticipates that subsequent events and developments will cause its views to change. However, while Spero may elect to update these forward-looking statements at some point in the future, it

specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Spero s views as of any date subsequent to the date of this press release.

Investor Relations Contact:

Managing Director, LifeSci Advisors, LLC

Spero Therapeutics, Inc.

Condensed Consolidated Balance Sheet Data

Spero Therapeutics, Inc.

Condensed Consolidated Statements of Operations

(in thousands, except share and per share data)