GlobeNewswire Inc | Jun 15, 2021 04:01PM EDT

June 15, 2021

CAMBRIDGE, Mass., June 15, 2021 (GLOBE NEWSWIRE) -- Spero Therapeutics, Inc.(Nasdaq: SPRO), a multi-asset clinical-stage biopharmaceutical company focused on identifying, developing, and commercializing treatments in high unmet need areas involving multi-drug resistant bacterial infections and rare diseases, today announced the initiation of two Phase 1 trials of SPR206, an intravenously (IV)-administered next-generation polymyxin product candidate. SPR206 was derived from Speros potentiator platform and is being developed to treat serious multi-drug resistant (MDR) Gram-negative infections in the hospital setting. These trials, which are now open for enrollment, include a bronchoalveolar lavage (BAL) clinical trial assessing the penetration of SPR206 into the pulmonary compartment and a renal impairment clinical trial.

SPR206 has the potential to treat serious infections in patients with limited therapeutic options, and the initiation of these Phase 1 trials represents an important step in its clinical development, said Ankit Mahadevia, M.D., Chief Executive Officer ofSpero Therapeutics. The preclinical and clinical data set supporting SPR206 demonstrates a favorable safety profile and potent activity against MDR and extensively drug resistant bacterial strains. We expect these newly initiated trials to build on prior results by providing crucial pharmacokinetic (PK) data. These PK data will inform the potential utility of SPR206 in specific tissue compartments and the design of future efficacy trials that will seek to address the urgent threat posed by MDR Gram-negative infections.

The Phase 1 BAL clinical trial is an open-label study designed to enroll thirty healthy volunteers into five cohorts. Subjects will receive three 100 mg doses of SPR206 infused every eight hours over one day. The objectives of the study are to evaluate the intrapulmonary PK, including epithelial lining fluid (ELF) and alveolar macrophage (AM) concentrations of SPR206 compared to plasma concentrations. These data are important to establish dose requirements for clinical efficacy of SPR206 in the setting of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP). This study is being conducted in collaboration with, and with financial support from, the United States Department of Defense (Award No. W81XWH1910295). The initiation of this clinical trial triggers the first of two milestone payments related to the study from Speros development partner, Everest Medicines.

The Phase 1 renal impairment clinical trial is an open-label study designed to enroll forty subjects into five cohorts. Cohort 1 will be healthy volunteers, cohorts 2-4 will be clinically stable subjects with various degrees of renal insufficiency, and cohort 5 will be clinically stable subjects with end stage renal disease (ESRD) on hemodialysis. Subjects will receive a single 100 mg infusion of SPR206. The objectives of the study are to evaluate the PK of SPR206 in healthy subjects and in those with various degrees of renal insufficiency, including ESRD. These data are important to establish if the concentrations of SPR206 are impacted by differences in renal function and whether dose adjustments for SPR206 would be recommended in such context. This study is being conducted in collaboration with, and with financial support from, the United States Department of Defense (Award No. W81XWH1910295).

Data from a prior Phase 1 clinical trial showed that SPR206 was generally well tolerated with a lack of nephrotoxicity at predicted therapeutic dose levels. Results from the Phase 1 BAL and renal impairment clinical trials are expected by early 2022.

About SPR206SPR206 is an IV-administered next generation polymyxin product candidate designed to act directly on Gram-negative bacterial infections through the molecules interactions with the bacterial outer membrane. SPR206 has demonstratedpotent broad-spectrum activityagainst Gram-negative bacteria, including organisms identified by theCenters for Disease Control and Prevention and theWorld Health Organization as urgent and serious threats to human health. Spero has 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. A Phase 1 bronchoalveolar lavage (BAL) clinical trial assessing the penetration of SPR206 into the pulmonary compartment and a Phase 1 renal impairment clinical trial of SPR206 were initiated in the second quarter of 2021 and remain ongoing. For more information on these trials and their design, see ClinicalTrials.gov identifiers NCT04868292 (BAL trial) and NCT04865393 (renal impairment trial). SPR206 has been granted Qualified Infectious Disease Product (QIDP) designation by the United States Food and Drug Administrationfor the treatment of complicated urinary tract infections and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).

About SperoSpero Therapeutics, Inc.is a multi-asset, clinical-stage biopharmaceutical company focused on identifying, developing and commercializing novel treatments for multi-drug-resistant (MDR) bacterial infections and rare diseases.

Speros lead product candidate, tebipenem HBr (tebipenem pivoxil hydrobromide; formerly SPR994), is being developed as the first oral carbapenem antibiotic for use in complicated urinary tract infections (cUTI) and acute pyelonephritis (AP). InSeptember 2020, Spero announced positive top-line results from its Phase 3 ADAPT-PO clinical trial of tebipenem HBr in cUTI and AP.

Spero is also developing SPR720 as a novel oral therapy product candidate for the treatment of rare, orphan pulmonary disease caused by non-tuberculous mycobacterial (NTM) infections.

Spero also has an IV-administered next generation polymyxin product candidate, SPR206, developed from its potentiator platform, which is being developed to treat MDR Gram-negative infections in the hospital setting.

For more information, visit https://sperotherapeutics.com.

Department of DefenseThe aforementioned SPR206 clinical trials are supported by theOffice of the Assistant Secretary of Defense for Health Affairs, through the Joint Warfighter Medical Research Program under Award No. W81XWH1910295. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by theDepartment of Defense. The U.S. Army Medical Research Acquisition Activity, 839 Chandler Street, Fort Detrick MD 21702- 5014 is the awarding and administering acquisition office.

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 Speros preclinical studies and clinical trials and its research and development programs, including the commencement of Speros planned Phase 1 bronchoalveolar lavage (BAL) clinical trial assessing the penetration of SPR206 into the pulmonary compartment and its renal impairment study of SPR206; managements assessment of the results of such preclinical studies and clinical trials; and Speros cash forecast and anticipated expenses, the sufficiency of its cash resources and the availability of additional non-dilutive funding from governmental agencies beyond any initially funded awards. 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 Speros ability to timely complete the NDA submission to the FDA for tebipenem HBr; Speros need for additional funding; the lengthy, expensive, and uncertain process of clinical drug development; whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; Speros reliance on third parties to manufacture, develop, and commercialize its product candidates, if approved; the ability to develop and commercialize Speros product candidates, if approved;the potential impact of the COVID-19 pandemic;Speros ability to retain key personnel and to manage its growth; whether Speros 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 theU.S. Securities and Exchange Commission. The forward-looking statements included in this press release represent Speros 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 somepoint in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Speros views as of any datesubsequent tothe date of this press release.

Investor Relations Contact:Ashley RobinsonLifeSciAdvisorsarr@lifesciadvisors.com617-430-7577

Media Contact:media@sperotherapeutics.com