SPRO Spero Therapeutics Inc

Spero Therapeutics, Inc. (Nasdaq: SPRO), a multi-asset clinical-stage biopharmaceutical company, focused on identifying and developing novel treatments in high unmet need areas involving rare diseases and multi-drug resistant (MDR) bacterial infections, today announced that it has received clearance by the U.S. Food and Drug Administration (FDA) for its investigational new drug (IND) application, to evaluate SPR206 in a Phase 2 clinical study. SPR206 is a novel, intravenously (IV) administered next-generation polymyxin antibiotic for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by MDR Gram-negative bacterial infections.

"Clearance of this IND is an important milestone in our SPR206 development program, as we prepare to advance this drug candidate into a Phase 2 trial in HABP/VABP," said Kamal Hamed, Spero’s Chief Medical Officer. "HABP/VABP are serious infections associated with high mortality and substantial morbidity, and their management has been complicated by the increasing prevalence of difficult-to-treat and MDR Gram-negative pathogens. SPR206 is being developed to address this unmet need, and if approved, we believe it could provide clinicians with a valuable new therapeutic option."

The planned Phase 2 study will be a randomized, double-blinded, controlled, multicenter study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of SPR206 in combination with select antibiotics for the treatment of patients diagnosed with HABP or VABP, caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex or carbapenem-resistant Pseudomonas aeruginosa. Approximately 60 adult hospitalized patients are expected to be enrolled. Patients will receive treatment for 7−14 days and will be evaluated through assessment of post-baseline clinical outcomes.

SPR206 is subject to a license agreement with Pfizer Inc., which was made alongside Pfizer’s $40 million equity investment in Spero, previously announced in June 2021. Pursuant to the license agreement, Pfizer was granted the rights to develop, manufacture, and commercialize SPR206 in ex-U.S. and ex-Asia territories. In exchange for these rights, Spero is eligible to receive up to $80 million in development and sales milestones, and high single digit to low double-digit royalties on net sales of SPR206 in these territories.

About SPR 206

SPR206 is an IV-administered next-generation polymyxin product candidate designed to act directly on Gram-negative bacterial infections through the molecule’s interactions with the bacterial outer membrane. In preclinical studies, SPR206 has demonstrated potent broad-spectrum activity against Gram-negative bacteria, including organisms identified by the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) as urgent and serious threats to human health. Spero completed a first-in-human Phase 1 assessment of SPR206 in which the product candidate was generally well tolerated and demonstrated no evidence of nephrotoxicity at anticipated therapeutic doses. Two other Phase 1 studies, a bronchoalveolar lavage (BAL) clinical trial assessing the intrapulmonary pharmacokinetics of SPR206 and a renal impairment clinical trial, were also completed. For more information on these trials and their designs, see ClinicalTrials.gov identifiers NCT03792308 (first-in-human trial), NCT04868292 (BAL trial) and NCT04865393 (renal impairment trial). SPR206 has been granted Qualified Infectious Disease Product (QIDP) designation by the United States FDA for the treatment of complicated urinary tract infections and HABP/VABP.

Department of DefenseSelect SPR206 studies have been 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. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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, Department of Health and Human Services or the U.S. Government.

About Spero Therapeutics, Inc.Spero Therapeutics, Inc., (Spero) headquartered in Cambridge, Massachusetts, is a multi-asset, clinical-stage biopharmaceutical company focused on identifying and developing novel treatments for bacterial infections, including multi-drug resistant bacterial infections and rare diseases.

• Spero is developing SPR720 as a novel oral therapy candidate for the treatment of a rare, orphan pulmonary disease caused by non-tuberculous mycobacterial infections.
• Tebipenem pivoxil HBr is an investigational drug in the United States being developed for the treatment of cUTI, including pyelonephritis, caused by certain bacteria, in adult patients who have limited treatment options; tebipenem pivoxil HBr is not FDA-approved.
• Spero is developing SPR206, an IV-administered next-generation polymyxin product candidate to treat MDR Gram-negative infections in the hospital setting. It was developed from its potentiator platform.

For more information, visit www.sperotherapeutics.com

Forward-Looking StatementsThis 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, including management’s assessment of such results, and the potential receipt of milestone payments and royalties on potential future sales of SPR206 under the Pfizer license agreement. 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:Ted JenkinsVice President, Investor Relations and Strategic FinanceIR@sperotherapeutics.com(617) 798-4039

Media Inquiries: Lora Grassilli, Health Media RelationsZeno Grouplora.grassilli@zenogroup.com646-932-3735