In vitro data on SPR719 show low propensity for resistance development in NTM-PD MAC strains when administered as a single agent and in combination with standard of care agents Study highlighting SPR720 potential benefits for prolonged combination regimens typical to NTM-PD treatment CAMBRIDGE, Mass., Oct. 16, 2024 (GLOBE NEWSWIRE) — 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 a poster presentation at IDWeek 2024, entitled “Evaluation of the Spontaneous Mutation Frequencies of SPR719 Alone and in Combination with Other Agents Used to Treat Mycobacterium avium Complex Pulmonary Disease.” The poster will be presented on Friday, October 18, 2024, in Hall J & K, at 12:15 PM – 1:30 PM Pacific Time. A copy of the poster will be available on the Spero corporate website here. SPR720 is an oral, chemically stable phosphate ester prodrug that is converted rapidly in vivo to SPR719, the active moiety. 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). The study was conducted in collaboration with Microbiologics, a leading contract research and manufacturing organization (CRMO), partnering with pharmaceutical and diagnostic companies to bring new lifesaving technology, anti-infective drugs, vaccines and therapeutics to market. “These in vitro results present an important aspect of SPR719’s activity against MAC NTM-PD,” said Chris Pillar, Ph.D., Director of Science and Operations, Microbiologics. “Resistance to antibiotics is a major health problem, particularly in diseases such as NTM-PD with long courses of treatment where resistance mechanisms can spontaneously manifest. The data presented at ID Week 2024 confirm the high potency of SPR719 against both macrolide susceptible and resistant MAC strains, with a low propensity for the spontaneous development of resistance mechanisms. Importantly, these characteristics were maintained in the combination with current standard of care (SOC) antibiotics used in the treatment of NTM-PD, and presented lower resistance compared to SOC antibiotics alone.” Poster Presentation Highlights Activity of SPR719 and current standard of care antibiotics (clarithromycin, ethambutol and rifampin) were evaluated for potency (MIC concentration testing), propensity for the spontaneous development of drug-resistance (spontaneous mutation frequency [SMF] assay) and potential interactions for combination treatment (antibacterial synergy testing) against both macrolide susceptible and macrolide resistant mycobacterium avian complex (MAC) strains.SPR719 selection concentrations as low as 2-fold the MIC suppressed the emergence of resistance against both tested MAC isolates. Mutation frequencies for SPR719 against MAC observed in this study were about 3 orders of magnitude lower than those for SOC comparators tested in this study.In-line with previous reports, SPR719 demonstrated a high degree of potency with MIC values of 2 ug/mL for both macrolide susceptible and resistant strains. No resistant colonies were isolated when SPR719 was combined with clarithromycin or ethambutol in the SMF assay.In summary, SPR719 had a low propensity for resistance development in this study and showed no instances of antagonism when combined with clarithromycin or ethambutol, highlighting its potential for use in prolonged combination regimens typically required to treat NTM-PD. About Nontuberculous Mycobacterium Pulmonary Disease (NTM-PD) NTM-PD, also known as NTM lung disease, is caused by bacteria naturally found in soil, dust, and water. These bacteria are members of the Mycobacterium family and are distinct from tuberculosis and leprosy. The most common bacteria that cause of NTM infections is the Mycobacterium avium complex (MAC). NTM is a growing global health concern with significant unmet medical needs. Although rare, the incidence of NTM pulmonary disease is increasing worldwide. It is estimated that approximately 130,000 patients suffer from NTM in the U.S. and Europe, a figure that is growing at a rate of 8% annually. Patients with NTM lung disease experience progressive symptoms, lung damage, and reduced quality of life due to chronic symptoms and impaired lung function. NTM infections can occur after surgery, trauma, injections, or exposure to contaminated water. Prevention involves effective water management programs in healthcare facilities, and treatment typically requires consultation with infectious disease or pulmonary specialists. Patients currently have limited treatment options for NTM lung disease. 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 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 potential benefits of any of Spero’s current or future product candidates in treating patients; and Spero’s strategy, goals and anticipated financial performance, milestones, business plans and focus. . 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, 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 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:Shai Biran, PhDSpero Therapeutics IR@Sperotherapeutics.com Media Inquiries: media@sperotherapeutics.com