Imipenem

Data presented at IDWeek 2025 after study stopped early for efficacyPrimary endpoint met, demonstrating non-inferiority of oral tebipenem HBr compared to intravenous treatment1Data will be shared with regulatory authorities to support regulatory filings CAMBRIDGE, Mass., Oct. 21, 2025 (GLOBE NEWSWIRE) -- Spero Therapeutics, Inc. (Nasdaq: SPRO) and GSK plc (LSE/NYSE: GSK) today announced efficacy and safety results of the positive pivotal phase 3 PIVOT-PO trial evaluating tebipenem HBr, an investigational oral treatment for complicated urinary tract infections (cUTIs), including pyelonephritis (NCT06059846). These results were presented on October 20, 2025, in a late-breaking oral abstract session at IDWeek 2025 in Atlanta, Georgia. Complicated UTIs represent an important health issue, with an estimated 2.9 million cases of cUTIs treated annually in the U.S. alone.2 These infections are often caused by multidrug-resistant pathogens3 and carry serious risks including organ failure, sepsis, and even death.3-5 They also result in significant emergency department visits and hospitalizations, contributing to over $6 billion per year in healthcare costs.6 Current standard of care includes carbapenem antibiotics in cases of sepsis or resistance to other antibiotics, but they are only available for intravenous administration.7, 8 The trial, which was stopped early for efficacy in May this year, demonstrated non-inferiority of tebipenem HBr compared to intravenous imipenem-cilastatin in hospitalized patients with cUTI, including pyelonephritis, based on the overall response (composite of clinical cure plus microbiological eradication of the bacteria causing the infection) at the test of cure visit. Tebipenem HBr (oral, 600 mg) achieved a 58.5% overall success rate (261/446 participants) compared to 60.2% overall success rate (291/483 participants) for imipenem-cilastatin (intravenous, 500 mg) (adjusted treatment difference: −1.3%; 95% CI: −7.5%, 4.8%). The safety profile of tebipenem HBr was generally similar to that of other carbapenem antibiotics. The most frequently reported adverse events (in ≥3% of patients who received tebipenem HBr) were diarrhea and headache; these events were all mild or moderate and non-serious. Tony Wood, Chief Scientific Officer, GSK, said: “Complicated UTIs can have serious consequences for patients, including organ failure and sepsis, and oral options for drug-resistant infections are limited. These ground-breaking data show for the first time that cUTIs, including pyelonephritis, can be treated with an oral carbapenem antibiotic as effectively as with an intravenous one. We have a long-standing commitment to delivering novel anti-infectives and are delighted to offer the potential of tebipenem HBr as an effective oral alternative that could be taken at home.” Esther Rajavelu, Chief Executive Officer, Spero Therapeutics, said: “These data presented at IDWeek represent the culmination of years of dedicated work by our team in close collaboration with GSK. We are deeply grateful to the physicians, researchers, support staff, and, most importantly, to the patients who made this study, and the ones before it, possible. Along with GSK, we are now focused on advancing tebipenem HBr toward FDA submission and bringing this important therapy to patients in need.” Dr George Sakoulas, Infectious Disease specialist, Sharp Memorial Hospital in San Diego, commented: “Increasing antibiotic resistance among community-acquired bacteria that cause complicated urinary tract infections is greatly amplifying the burden of treatment for patients, clinicians, and payers. The therapeutic flexibility of a new oral antibiotic may reduce the need for intravenous antibiotics to treat cUTI, providing benefit to patients and improving treatment options.” Secondary endpoints also show: Clinical cure (i.e. absence of symptoms) rates at test of cure visit were 93.5% in the tebipenem HBr group (417/446) compared to 95.2% in the imipenem-cilastatin group (460/483) with adjusted treatment difference: −1.6% (95% CI: −4.7%, 1.4%)Microbiological response rates at test of cure visit were 60.3% in the tebipenem HBr group (269/446) compared to 61.3% in the imipenem-cilastatin group (296/483) with adjusted treatment difference: −0.8% (95% CI: −6.9%, 5.3%)Overall, clinical and microbiological response rates at test of cure in participants with infections caused by antimicrobial-resistant Enterobacterales were consistent with the respective response rates in the primary analysis population. Spero has licensed tebipenem HBr to GSK for development and commercialization in all markets except certain Asian territories. GSK plans to work with US regulatory authorities to include the data as part of a filing in Q4 2025. If approved, tebipenem HBr would be the first oral carbapenem antibiotic in the US for patients who suffer from cUTIs, adding to GSK’s growing anti-infectives portfolio and helping address the challenges of antimicrobial resistance (AMR). The development of tebipenem HBr is supported in part with federal funds from the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under contract number HHSO100201800015C. About tebipenem HBrTebipenem pivoxil as hydrobromide salt (Tebipenem HBr) is a late-stage development asset developed in collaboration with Spero Therapeutics. Tebipenem HBr is being developed to treat cUTIs, including pyelonephritis. In September 2022, GSK entered into an exclusive license agreement with Spero Therapeutics for the development and commercialization of tebipenem HBr in all markets, except certain Asian territories. Under this agreement GSK has sub-licensed back to Spero Therapeutics the rights and responsibility to conduct certain development work including the PIVOT-PO Phase 3 study, after which sponsorship of the new drug application (NDA) will be transferred to GSK from Spero Therapeutics. Tebipenem HBr has received Qualified Infectious Disease Product (QIDP) and Fast Track designations from the U.S. Food and Drug Administration (FDA). About the PIVOT-PO trialPIVOT-PO was a global, randomized, double-blind, pivotal, non-inferiority (NI margin: -10%) Phase 3 clinical trial of oral tebipenem HBr compared to IV imipenem-cilastatin, in hospitalized adult patients with cUTI including pyelonephritis. Patients were randomized 1:1 to receive tebipenem pivoxil (600 mg) orally every six hours, or imipenem-cilastatin (500 mg) IV every six hours, for a total of seven to ten days. Matching placebos were used to maintain blinding. The primary efficacy endpoint was overall response (composite of clinical cure plus microbiological eradication) at the test-of-cure visit (about 17 days from first dose administration of study drug) in patients with qualifying pathogens susceptible to imipenem. The trial enrolled a total of 1,690 patients, with randomization stratified by age, baseline diagnosis (cUTI or pyelonephritis), and the presence or absence of urinary tract instrumentation. For further details on the trial, refer to clinicaltrials.gov identifier NCT06059846. About complicated urinary tract infections (cUTIs)cUTIs are broadly described as any UTI that carries an increased risk of morbidity and mortality.3 Definitions of cUTIs are not currently uniform among international societies and regulatory agencies.5, 9 cUTIs encompass a heterogeneous patient population due to the wide range of host factors, comorbidities and urological abnormalities associated with cUTIs.5, 9 Risk factors for cUTI include indwelling catheters, ureteric stents, neurogenic bladder, obstructive uropathy, urinary retention, urinary diversion, kidney stones, diabetes mellitus, immune deficiency, urinary tract modification, and UTIs in renal transplant patients.3, 10-13 About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. About Spero TherapeuticsSpero Therapeutics, headquartered in Cambridge, Massachusetts, is a clinical-stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and multi-drug resistant (MDR) bacterial infections with high unmet need. For more information, visit www.sperotherapeutics.com Forward Looking StatementsThis 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 progress and results of Spero's Phase 3 PIVOT-PO trial; the timing of a planned FDA filing in 2H 2025 for tebipenem HBr; the potential of tebipenem HBr to be the first oral carbapenem antibiotic for U.S. patients with cUTI, including pyelonephritis; the potential receipt of milestone payments under Spero’s license and collaboration agreements; and the potential benefits of any of Spero’s current or future product candidates in treating patients. 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 will advance through the clinical development process, 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, including, in the case of tebipenem HBr, Spero’s reliance on GSK pursuant to the exclusive GSK License Agreement to develop tebipenem HBr and GSK’s right thereunder to determine whether to further develop tebipenem HBr; 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 References 1. Hong D. et al, Oral Tebipenem Pivoxil Hydrobromide vs Intravenous Imipenem-Cilastatin in Patients with Complicated Urinary Tract Infections or Acute Pyelonephritis: Efficacy and Safety Results from the Phase 3 PIVOT-PO study, Oral presentation at IDWeek 2025, 20 October 2025.2. Carreno JJ, et al. Longitudinal, Nationwide, Cohort Study to Assess Incidence, Outcomes, and Costs Associated With Complicated Urinary Tract Infection. Open Forum Infect Dis. 2019;6:ofz446.3. Sabih A, Leslie SW. Complicated urinary tract infections. In: StatPearls. 2023. StatPearls Publishing: Treasure Island, FL, USA.4. Vallejo-Torres L, et al. Cost of hospitalised patients due to complicated urinary tract infections: a retrospective observational study in countries with high prevalence of multidrug-resistant Gram-negative bacteria: the COMBACTE-MAGNET, RESCUING study. BMJ Open. 2018;8:e020251.5. Marantidis J, Sussman RD. Unmet Needs in Complicated Urinary Tract Infections: Challenges, Recommendations, and Emerging Treatment Pathways. Infect Drug Resist. 2023:16:1391-1405.6. Lodise TP, et al. Hospital admission patterns of adult patients with complicated urinary tract infections who present to the hospital by disease acuity and comorbid conditions: How many admissions are potentially avoidable? Am J Infect Control. 2021;49(12):1528-1534.7. Cotroneo, N., et al. In Vitro and In Vivo Characterization of Tebipenem, an Oral Carbapenem. Antimicrobial agents and chemotherapy. 2020. 64(8), e02240-19.8. Maeda M, et al. Efficacy of carbapenems versus alternative antimicrobials for treating complicated urinary tract infections caused by antimicrobial-resistant Gram-negative bacteria: protocol for a systematic review and meta-analysis. BMJ Open. 2023 Apr 21;13(4):e069166.9. Fernandez MM, et al. Poster presented at ESCMID Global, 27–30 April 2024, Barcelona, Spain. Poster P1023.10. Bonkat G, et al. Keep it Simple: A Proposal for a New Definition of Uncomplicated and Complicated Urinary Tract Infections from the EAU Urological Infections Guidelines Panel. Eur Urol. 2024;86(3):195-197.11. Wagenlehner FME, et al. Epidemiology, definition and treatment of complicated urinary tract infections. Nat Rev Urol. 2020;17(10):586-600.12. Gomila A, et al. Predictive factors for multidrug-resistant gram-negative bacteria among hospitalised patients with complicated urinary tract infections. Antimicrob Resist Infect Control. 2018;7:111.13. Altunal N, et al. Ureteral stent infections: a prospective study. Braz J Infect Dis. 2017;21(3):361-364.

TORONTO, July 22, 2025 (GLOBE NEWSWIRE) -- Arch Biopartners Inc. (“Arch” or the “Company”) (TSX Venture: ARCH and OTCQB: ACHFF) announced today that the investigator-led Phase II trial titled “Prevention Of NephroToxin Induced Acute Kidney Injury with Cilastatin” (PONTIAK) has commenced patient recruitment at its primary clinical sites in Alberta, Canada. The Phase II PONTIAK study aims to evaluate the efficacy of cilastatin in preventing AKI associated with nephrotoxic pharmaceuticals, which include commonly used drugs such as antibiotics, chemotherapy agents, and imaging dyes, some of which are known to cause kidney damage as a side effect. The trial plans to enrol approximately 698 patients in five hospital sites in Alberta. The PONTIAK clinical team, based at the Universities of Calgary and Alberta, secured $1.5 million in funding for the Phase II trial from the Canadian Institutes of Health Research (CIHR), along with $400,000 under the Accelerating Clinical Trials (ACT) initiative aimed at evaluating Canadian biotechnologies using randomized controlled trials. Arch Biopartners recently manufactured the first-ever, stand-alone cilastatin drug product and has provided the drug supply for the trial. While the trial is investigator-led and independently funded, the Company is also evaluating opportunities to support a complementary arm of the study in another jurisdiction, such as the United States under an application to the U.S. Food and Drug Administration. Quote from Richard Muruve, CEO, Arch Biopartners: “Congratulations to the PONTIAK team for achieving this milestone and beginning patient enrolment. This marks an important advancement in evaluating cilastatin as a potential first-in-class treatment to prevent AKI caused by exogenous toxins from several commonly used pharmaceutical products.” About AKI AKI reflects a broad spectrum of clinical presentations, ranging from mild injury to severe injury that may result in permanent and complete loss of renal function. Clinically, the causes of AKI include sepsis, ischemia-reperfusion injury, and various endogenous as well as exogenous (drug) toxins. There is no specific therapeutic treatment available on the market that prevents AKI. In the worst cases, the kidneys fail, requiring dialysis or kidney transplantation for patient survival. Drug toxins cause approximately 30% of AKI cases in hospitalized patients and include a wide range of pharmaceutical drugs such as antibiotics (vancomycin, aminoglycosides), chemotherapeutic agents, and radiographic contrast. Additionally, AKI related to cardiac surgery (CS-AKI) accounts for up to 20% of in-hospital AKI cases. About Cilastatin Cilastatin was originally developed in the early 1980s by Merck Sharp & Dohme Research Laboratories to limit the role of dipeptidase-1 (DPEP1) in the breakdown of imipenem, a β-lactam antibiotic used for the treatment of systemic infections. Cilastatin was approved for use as a fixed combination with imipenem to treat different types of bacterial infections. This fixed combination, approved by the FDA in 1985, is currently marketed under different names, including Primaxin® (USA, UK, Australia, Italy), Tienam® (Spain, Belgium), or Zienam® (Germany). Composition of matter patents for imipenem and cilastatin have expired, and the combination drug is currently in a generic phase. There is no commercial history of cilastatin as a stand-alone drug product. Cilastatin has a slightly different mechanism of action compared with Arch’s novel drug candidate, LSALT peptide (Metablok), a non-enzymatic DPEP1 inhibitor. Whereas LSALT peptide specifically blocks DPEP1-mediated inflammation in the kidney, lungs, and liver, cilastatin has off-target effects that prevent toxin uptake in the kidneys. As such, cilastatin is particularly effective for toxin-related AKI. Arch Biopartners owns and has exclusively licensed method-of-use patents to repurpose cilastatin as a new treatment targeting AKI. The PONTIAK Phase II clinical trial is registered on ClinicalTrials.gov under identifier NCT06886464. About Arch Biopartners Arch Biopartners Inc. is a late-stage clinical trial company focused on preventing acute kidney injury and organ damage caused by inflammation. The Company is developing a platform of novel drugs targeting the dipeptidase-1 (DPEP1) inflammation pathway prevalent in the kidneys, lungs, and liver. LSALT peptide and cilastatin are lead drug candidates in separate Phase II trials targeting acute kidney injury caused by inflammation and toxins, respectively. Both indications represent significant unmet medical needs in global kidney care. For more science details: www.archbiopartners.com/our-science For investor materials and filings: www.archbiopartners.com/investor-hub The Company has 65,906,366 common shares outstanding. For more information, please contact: Aaron BensonDirector of CommunicationsArch Biopartners, Inc. 647-428-7031Send a message using the Contact Form at: www.archbiopartners.com/contact-us Forward-Looking Statements This press release contains forward-looking statements within the meaning of applicable Canadian securities laws regarding expectations of our future performance, liquidity and capital resources, as well as the ongoing clinical development of our drug candidates targeting the dipeptidase-1 (DPEP-1) pathway, including the outcome of our clinical trials relating to LSALT peptide (Metablok) or cilastatin, the successful commercialization and marketing of our drug candidates, whether we will receive, and the timing and costs of obtaining, regulatory approvals in Canada, the United States, Europe and other countries, our ability to raise capital to fund our business plans, the efficacy of our drug candidates compared to the drug candidates developed by our competitors, our ability to retain and attract key management personnel, and the breadth of, and our ability to protect, our intellectual property portfolio. These statements are based on management’s current expectations and beliefs, including certain factors and assumptions, as described in our most recent annual audited financial statements and related management discussion and analysis under the heading “Business Risks and Uncertainties”. As a result of these risks and uncertainties, or other unknown risks and uncertainties, our actual results may differ materially from those contained in any forward-looking statements. The words “believe”, “may”, “plan”, “will”, “estimate”, “continue”, “anticipate”, “intend”, “expect” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We undertake no obligation to update forward-looking statements, except as required by law. Additional information relating to Arch Biopartners Inc., including our most recent annual audited financial statements, is available by accessing the Canadian Securities Administrators’ System for Electronic Document Analysis and Retrieval (“SEDAR”) website at www.sedarplus.ca . The scientific and medical content in this release has been approved by the Company’s Chief Science Officer Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release