Tebipenem Pivoxil

Phase 3 PIVOT-PO trial of tebipenem HBr remains on track to complete enrollment in 2H 2025 Reiterate cash runway into mid-2026; Q3 2024 ending cash balance of $76.3M CAMBRIDGE, Mass., Nov. 14, 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 financial results for the third quarter ended September 30, 2024, and provided a business update. “Enrollment in the Phase 3 tebipenem HBr trial is progressing well, and we are on track to complete enrollment in the second half of 2025. Further, our work on the Phase 2 ready SPR206 program continues, contingent on availability of non-dilutive funding,” said Sath Shukla, President and Chief Executive Officer of Spero. “With SPR720 development plans now suspended while we complete a review of the full dataset from the Phase 2a trial, our extended cash runway into mid-2026 and streamlined operations position us well to achieve our ultimate goal of delivering new therapies to patients in need.” Pipeline Update Tebipenem HBr Tebipenem HBr is an investigational oral carbapenem antibiotic being developed for the treatment of complicated urinary tract infections (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. Enrollment on track in PIVOT-PO, the global Phase 3 clinical trial of tebipenem HBr in patients with cUTI. This randomized, double-blinded trial compares oral tebipenem HBr with intravenous imipenem cilastatin, in hospitalized adult patients with cUTI/AP. The primary endpoint is overall response (a combination of clinical cure and favorable microbiological response) at the Test-of-Cure (TOC) visit. Target enrollment for the trial is approximately 2,648 patients, with enrollment completion expected in the second half of 2025. For more information on PIVOT-PO, refer to ClinicalTrials.gov ID NCT06059846. SPR206 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 U.S. Food and Drug Administration (FDA) has cleared the Company's IND for a Phase 2 trial in patients with hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP). The Company maintains its guidance to initiate the trial contingent on availability of non-dilutive funding. SPR720 SPR720 is an investigational 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. In October 2024, a planned interim analysis of the Phase 2a proof-of-concept study of SPR720 for the treatment of nontuberculous mycobacterial pulmonary disease (NTM-PD) demonstrated that the study did not meet its primary endpoint. While the data showed antimicrobial activity associated with SPR720, the interim analysis did not show sufficient separation from placebo and highlighted potential dose limiting safety issues in patients dosed at 1,000 mg orally once daily, including three cases of reversible grade 3 hepatotoxicity. In evaluating the totality of both the efficacy and safety data, the Company suspended its development program for SPR720 and will evaluate other potential paths forward as the remaining data are collected and analyzed. Corporate Update In October 2024, following suspension of the current SPR720 development plans, Spero underwent a restructuring and reduction in force of approximately 39%, which extended the Company’s cash runway into mid-2026. Third quarter 2024 Financial Results Spero reported a net loss of $17.1 million, or ($0.32) per share of common stock, basic and diluted, for the third quarter ended September 30, 2024, compared with a net loss of $3.2 million, or ($0.06) per share of common stock, basic and diluted, for the third quarter ending September 30, 2023.Total revenue for the third quarter of 2024 was $13.5 million, compared with total revenue of $25.5 million for the third quarter of 2023. The revenue decrease for the third quarter of 2024 was primarily due to lower revenues related to ongoing collaborations.Research and development expenses for the third quarter of 2024 were $26.9 million, compared to $16.4 million of research and development expenses for the same period in 2023. The increase in research and development expenses year-over-year was primarily due to increased clinical trial expenses for PIVOT-PO.General and administrative expenses for the third quarter of 2024 were $5.2 million, compared to $5.7 million of general and administrative expenses for the same period in 2023. This year-over-year decrease was primarily due to decreased consulting and professional expenses.As of September 30, 2024, Spero had cash and cash equivalents of $76.3 million. Following the reduction in force and restructuring described above, Spero estimates that its existing cash and cash equivalents, together with earned and non-contingent development milestone payments from GSK, as well as other non-dilutive funding commitments, will be sufficient to fund its operating expenses and capital expenditures into mid-2026. 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. 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 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, 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; Biomedical Advanced Research and Development Authority, under contract number HHSO100201800015C. 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. 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 Spero Therapeutics, Inc.Condensed Consolidated Balance Sheet Data(in thousands)(Unaudited) September 30, December 31, 2024 2023Cash and cash equivalents$76,290 $76,333Other assets 58,871 106,057Total assets$ 135,161 $ 182,390 Total liabilities 69,654 75,496Total stockholder's equity 65,507 106,894Total liabilities and stockholders' equity$ 135,161 $ 182,390 Spero Therapeutics, Inc.Condensed Consolidated Statements of Operations(in thousands, except share and per share data) (unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Revenues: Grant revenue$5,650 $2,091 $14,893 $5,349 Collaboration revenue - related party 7,754 23,164 17,721 24,200 Collaboration revenue 65 218 319 710 Total revenues 13,469 25,473 32,933 30,259 Operating expenses: Research and development 26,864 16,393 67,921 34,883 General and administrative 5,198 5,708 16,648 19,121 Impairment of long-term asset — 5,306 — 5,306 Total operating expenses 32,062 27,407 84,569 59,310 Loss from operations (18,593) (1,934) (51,636) (29,051)Other income (expense) 1,156 940 3,668 2,877 Net loss (17,437) (994) (47,968) (26,174)Income tax expense 290 (2,211) 290 (2,211)Net loss$(17,147) $(3,205) $(47,678) $(28,385) Net loss per share attributable to common shareholders per share, basic and diluted$(0.32) $(0.06) $(0.89) $(0.54) Weighted average shares outstanding, basic and diluted: 54,124,862 52,710,280 53,869,824 52,603,709

iStock, simplehappyart Following disappointing results for an antibiotic candidate whose development program is now being suspended, Spero Therapeutics is looking to extend its cash runway while it focuses on other assets in its pipeline. As part of a restructuring following the suspension of its development program for an antibiotic candidate, Spero Therapeutics will lay off about 39% of its workforce, the company announced Oct. 29. The clinical-stage biopharma expects to mostly complete the cuts by end of the year, according to an Oct. 29 SEC filing . As of Dec. 31, Spero had 46 employees, 30 of whom were mostly handling R&D activities, as noted in a March 13 SEC filing . If the Cambridge, Massachusetts, business has the same number of employees now, the cuts could affect about 18 people. Regarding its antibiotic candidate, Spero shared that an interim analysis of the Phase IIa study of SPR720, a treatment being investigated for nontuberculous mycobacterial pulmonary disease, did not meet the primary endpoint. The company noted that while there was antimicrobial activity associated with SPR720, the analysis did not show sufficient separation from placebo. In addition, the data highlighted potential dose-limiting safety issues in subjects dosed at 1,000 milligrams orally once daily, including three cases of reversible grade 3 hepatotoxicity. Spero’s restructuring is expected to extend the company’s cash runway and support operations into mid-2026, according to the announcement. During this time, the biopharma will focus on advancing tebipenem HBr in an ongoing global Phase III trial and preparing for a Phase II trial for SPR206, contingent on continued nondilutive funding. Tebipenem HBr is an oral carbapenem antibiotic meant to treat complicated urinary tract infections. SPR206 is an intravenously administered next-generation polymyxin that has shown antibiotic activity against multidrug-resistant Gram-negative pathogens, according to the company. Tebipenem HBr is tied to a previous layoff at Spero. In 2022, the company cut about 75% of its workforce as part of a restructuring ahead of an expected FDA rejection of the antibiotic. According to a May 3, 2022, SEC filing , those layoffs reduced Spero’s full-time staff from 146 to 35 employees. The FDA did reject the drug , and in September 2022, GlaxoSmithKline announced it would license tebipenem HBr as part of a $66 million licensing deal .