Ledaborbactam

Cefepime-Taniborbactam Superior to Meropenem for the Composite Efficacy Endpoint Composite Efficacy Sustained at Late Follow-up Visit Safety Pro with Meropenem MALVERN, Pa. & PARSIPPANY, N.J. & FLORENCE, Italy--(BUSINESS WIRE)-- Venatorx Pharmaceuticals, Melinta Therapeutics LLC (“Melinta”), and Menarini Group today announced that The New England Journal of Medicine (NEJM) published the results of the CERTAIN-1 Phase 3 clinical study of the investigational agent cefepime-taniborbactam for the treatment of adult patients with complicated urinary tract infections (cUTI) and acute pyelonephritis (AP), including those with bacteremia. The results showed that cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a similar safety pro meropenem. This press release features multimedia. View the full release here: “Gram-negative infections such as cUTI have become increasingly difficult to treat due to acquired bacterial resistance to multiple classes of antibiotics. Cefepime-taniborbactam has the potential to treat a broad range of patients with cUTI due to suspected or confirmed multidrug-resistant (MDR) pathogens including Enterobacterales and Pseudomonas aeruginosa,” said Paul C. McGovern, MD, Senior Vice President at Venatorx and co-author of the publication. “This Phase 3 study is the culmination of a long journey of discovery and development, and we look forward to progressing this agent through the next regulatory stages so that the drug may reach patients world-wide as expeditiously as possible.” Christine Ann Miller, President and Chief Executive Officer of Melinta Therapeutics added, “We are pleased to see these results published in the New England Journal of Medicine. We look forward to leveraging our experience in marketing infectious disease products and our established commercial infrastructure, especially within the hospital and acute care settings, to make cefepime-taniborbactam available to physicians and their patients with complicated urinary tract infections if approved.” “E.coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are largely involved in cUTI Gram-negative pathogens infections reaching nearly 75% in Europe. We believe that the NEJM published CERTAIN-1 Phase 3 data indicating cefepime-taniborbactam's superiority on the composite endpoint of microbiological and clinical response alongside its comparable safety pro meropenem provides useful insight as to its expected contribution, upon approval by relevant regulatory authorities, in the treatment of hospitalized patients with cUTI starting in Europe,” said Najy Alsayed, Global Therapeutic Area Head-Infectious Diseases at Menarini Group. About CERTAIN-1 CERTAIN-1 was a randomized, multicenter, double-blind, active-controlled, non-inferiority study of hospitalized patients (N=661) with complicated urinary tract infections (cUTI), including acute pyelonephritis (AP), comparing cefepime-taniborbactam (2.5 g every 8 hours) to meropenem (1 g every 8 hours). The primary endpoint was the composite microbiologic and clinical response at the Test of Cure (TOC) visit (Day 19-23) in the microbiological intention-to-treat (microITT) population. The non-inferiority margin was -15% and there was a prespecified superiority analysis if non-inferiority was concluded. Efficacy Data Cefepime-taniborbactam met the prospectively defined non-inferiority primary endpoint of composite microbiologic and clinical response versus meropenem at the TOC visit (70.6% response rate for cefepime-taniborbactam versus 58.0% for meropenem). The prespecified superiority analysis at the TOC visit demonstrated that cefepime-taniborbactam was statistically superior to meropenem for the composite endpoint (response rate difference: 12.6% [95% confidence interval (CI): 3.1, 22.2]; p=0.009) and for the microbiologic endpoint (response rate difference: 11.7% [CI: 2.9, 21.0]); the clinical endpoint response rate difference was 4.5% [CI: -2.6, 12.6]. At the Late Follow-up (LFU) visit (Day 28-35), cefepime-taniborbactam demonstrated sustained statistical superiority to meropenem for the composite endpoint (63.8% response rate for cefepime-taniborbactam versus 51.7% for meropenem (response rate difference: 12.1% [CI: 2.2, 21.9]) and for the clinical response endpoint (response rate difference: 9.9% [CI: 1.5, 18.8); the microbiologic endpoint response rate difference was 7.7% [CI: -1.6, 17.3]. Additionally, cefepime-taniborbactam maintained a numerical advantage to meropenem against resistant pathogens: cefepime-resistant (71% response rate for cefepime-taniborbactam versus 53% for meropenem), ESBL-producing (71% response rate for cefepime-taniborbactam versus 55% for meropenem) and MDR (68% response rate for cefepime-taniborbactam versus 60% for meropenem). Safety Data Cefepime-taniborbactam demonstrated a safety pro with meropenem. Treatment-emergent adverse events occurred in 35.5% and 29.0% of cefepime-taniborbactam and meropenem treated patients respectively. Serious adverse events occurred in 2.0% of cefepime-taniborbactam patients and 1.8% of meropenem treated patients. The most frequently reported treatment-emergent adverse events were headache (6.1% with cefepime-taniborbactam versus 3.7% for meropenem), diarrhea (4.1% versus 2.3%), and constipation (3.2% versus 1.4%). Three percent of patients treated with cefepime-taniborbactam discontinued therapy due to a treatment-emergent adverse event versus 0.9% of patients treated with meropenem. The safety data for cefepime-taniborbactam was consistent with the historical safety data for cefepime. About Cefepime-Taniborbactam Cefepime-taniborbactam is an investigational agent that is a combination of cefepime, a fourth-generation cephalosporin, and the novel beta-lactamase inhibitor (BLI), taniborbactam, that exhibits broad coverage of both serine- and metallo-beta-lactamases. In combination with cefepime, taniborbactam is under development as a new treatment option for patients with serious bacterial infections caused by difficult-to-treat drug resistant gram-negative pathogens, including carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant or multidrug-resistant Pseudomonas aeruginosa (CRPA/MDR-PA). Funding Partners and Collaborators for Cefepime-Taniborbactam This project has been funded 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 number HHSN272201300019C, and Wellcome Trust under Award No. 360G-Wellcome-101999/Z/13/Z, and has continued 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 numbers HHSO100201900007C and 75A50122C00080. In September 2018, Venatorx entered into an exclusive license agreement with Everest Medicines to support the development, registration, and commercialization of cefepime-taniborbactam in Greater China, South Korea, and select countries in Southeast Asia. Everest will be solely responsible for the commercialization of cefepime-taniborbactam in its territory and Venatorx will be eligible to receive royalties on net sales. In April 2020, Venatorx and the GARDP Foundation (GARDP) announced a collaboration to accelerate the development of, and access to, cefepime-taniborbactam for adult and pediatric populations. Venatorx has granted GARDP exclusive rights to distribute and sub-distribute cefepime-taniborbactam, once it is approved for clinical use, in low- and lower-middle-income countries. In November 2023, Venatorx and Melinta entered into an exclusive License Agreement to facilitate a strategic partnership in the U.S. to commercialize cefepime-taniborbactam, a beta-lactam / beta-lactamase inhibitor (BL/BLI) combination antibiotic being developed for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults. In December 2023, Venatorx entered into an agreement with Menarini Group, who acquired the exclusive rights to commercialize, upon approval of relevant health authorities, cefepime-taniborbactam in 96 countries in Europe, Latin America, Middle East, Turkey and North Africa and the Commonwealth of Independent States (CIS). About Venatorx Pharmaceuticals Venatorx is a private, late-stage clinical pharmaceutical company focused on improving health outcomes for patients with multidrug-resistant bacterial infections and hard-to-treat viral infections. Venatorx’s lead program, cefepime-taniborbactam, is a clinical-stage antibiotic that completed a Phase 3 study in adults with complicated urinary tract infections (cUTI), including pyelonephritis. In October 2022, BARDA awarded a contract of up to $318M for development and procurement of cefepime-taniborbactam for the treatment of melioidosis and multi-drug resistant infections. Cefepime-taniborbactam is currently under review by the FDA for the treatment of cUTI, including acute pyelonephritis. Venatorx is also developing an oral antibacterial, ceftibuten-ledaborbactam (formerly known as VNRX-7145), for the treatment of cUTI, including pyelonephritis, caused by certain bacteria in adult patients with limited treatment options; this product is completing Phase 1 and will advance directly to a global Phase 3 cUTI clinical trial.. For more information about Venatorx and its anti-infectives portfolio, please visit . About Melinta Therapeutics LLC Melinta Therapeutics is a biopharmaceutical company dedicated to providing innovative therapies to people impacted by acute and life-threatening illnesses. We focus our expanding portfolio on serving patients with an unmet need because that’s how we make the most meaningful impact. At Melinta, we’re visionaries dedicated to innovation while staying grounded in what matters most: patients. Our portfolio currently includes seven commercial-stage products: BAXDELA® (delafloxacin), KIMYRSA® (oritavancin), MINOCIN® (minocycline) for Injection, ORBACTIV® (oritavancin), REZZAYO® (rezafungin for injection), TOPROL-XL® (metoprolol succinate) and VABOMERE® (meropenem and vaborbactam). For more information about Melinta Therapeutics, our commitment to patients, and to learn about our portfolio of therapies, visit . About Menarini Group The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4.4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini’s products are available in 140 countries worldwide. For further information, please visit .

Total award of up to $167 million for development of novel oral antibiotic ceftibuten-ledaborbactam etzadroxil for treatment of complicated urinary tract infection (cUTI), including pyelonephritis MALVERN, Pa.--(BUSINESS WIRE)-- Venatorx Pharmaceuticals, a private, pre-commercial pharmaceutical company focused on improving health outcomes for patients with multidrug-resistant bacterial infections and hard-to-treat viral infections, today announced the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS), has awarded the company a contract to support the development of oral ceftibuten-ledaborbactam etzadroxil for the treatment of complicated urinary tract infection (cUTI), including pyelonephritis. Venatorx has recently completed multiple Phase 1 clinical studies with ceftibuten-ledaborbactam etzadroxil and will advance directly to global Phase 3 clinical trial testing under this contract. The contract will provide funding and technical support for the development activities required for submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for marketing authorization of ceftibuten-ledaborbactam etzadroxil for the treatment of cUTI, including pyelonephritis. The contract will also cover a pediatric program as a post-marketing commitment. “We thank BARDA, ASPR, and HHS for their dedication to scientific innovation and commitment to this private-public partnership. This contract supports Venatorx’s mission to address the devastating impact on patient lives from the growing number of bacterial infections in the U.S. and the urgent need for oral antibiotics to combat drug-resistant gram-negative pathogens,” said Christopher J. Burns, Ph.D., President and CEO of Venatorx. “Currently, there are no approved oral antibiotics that are effective in the treatment of drug-resistant gram-negative bacterial infections to help address increasing drug-resistant bacterial infections globally. We believe that oral ceftibuten-ledaborbactam etzadroxil could play an important role in treating drug-resistant gram-negative infections, preventing unnecessary hospitalizations, and saving lives.” Terms of the Award BARDA will provide a firm initial commitment of up to $20.3 million with options to provide up to a total of $167 million over six years. BARDA and Venatorx will share the costs of all studies needed to bring the drug to market, including a planned pivotal global Phase 3 clinical trial to treat cUTI. Venatorx will lead all regulatory activities necessary to seek FDA approval of ceftibuten-ledaborbactam etzadroxil under the contract. This project has been funded in whole or 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 75A50123C00050. About Complicated Urinary Tract Infections (cUTI) and Antimicrobial Resistance (AMR) Complicated UTIs, which include pyelonephritis, are defined as urinary tract infections ascending from the bladder accompanied by local and systemic signs and symptoms and are one of the most common bacterial infections in hospital and community settings. Bacteremia can arise secondary to infections like cUTI and can result in substantial morbidity and mortality.[1] Annually in the U.S., it is estimated that more than 2.8 million cUTI patients will be diagnosed and require antibiotic therapy leading to over $6 billion in annualized 30-day costs.[2] Between 1998 and 2011, incidence of US UTI hospitalizations increased 52%, while severity of UTI admissions decreased, indicating that patients previously treated with oral agents as outpatients in the community may now be admitted to the hospital due to increasing antimicrobial resistance to oral agents.[3] In a study of US patients hospitalized with an infection between 2012 and 2017, 83% of infections in the hospital cohort originated in the community with 32% of those infections caused by bacterial pathogens carrying extended spectrum beta-lactamases (ESBLs). During that time, the incidence of ESBL-associated infections increased by ~53%, a change that investigators believed was driven by an increase in community-onset cases.[4] Treatment of cUTIs in the community has been compromised by increasing drug resistance to commonly used oral antibiotics such as fluoroquinolones, cephalosporins and trimethoprim-sulfamethoxazole.[5] In a study tracking resistance of E. coli isolates from US UTI patients in 2017, high co-resistance among oral antibiotics was observed suggesting diminishing utility of currently available oral antibiotics due to increasing antimicrobial resistance.[6] Currently, there are no approved oral beta-lactam or beta-lactam/beta-lactamase inhibitor combinations that are effective against Enterobacterales expressing Ambler class A ESBLs, class C cephalosporinases, and class A& D serine carbapenemases (KPC and OXA-48). About Ceftibuten-Ledaborbactam etzadroxil Ceftibuten, an oral third-generation, highly bioavailable cephalosporin antibiotic, is approved in the US for the treatment of upper and lower respiratory tract infections and for urinary tract infections outside the US. Ledaborbactam etzadroxil is a novel broad-spectrum boronic acid beta-lactamase inhibitor (BLI). In vitro and in vivo studies demonstrated that ledaborbactam restores the activity of ceftibuten against strains of Enterobacterales expressing Ambler class A ESBLs, class C cephalosporinases, and class A & D serine carbapenemases (KPC and OXA-48, respectively) as well as multidrug-resistant (MDR) Enterobacterales. Ceftibuten-ledaborbactam etzadroxil may offer a new treatment option for outpatient therapy to treat serious bacterial infections caused by MDR Enterobacterales that are resistant to current standard-of-care oral and intravenous antibiotics, including fluoroquinolones, trimethoprim-sulfamethoxazole, cephalosporins and carbapenems. Ceftibuten-ledaborbactam etzadroxil has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations by the U.S. Food and Drug Administration (FDA) for cUTI and uncomplicated urinary tract infections. Venatorx has recently completed multiple Phase 1 clinical studies with ceftibuten-ledaborbactam etzadroxil and will advance directly to global Phase 3 clinical trial testing under this new BARDA contract. Funding Partners and Collaborators for Ceftibuten-Ledaborbactam etzadroxil This project has also 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. HHSN272201600029C. About Venatorx Pharmaceuticals, Inc. Venatorx is a private, pre-commercial pharmaceutical company focused on improving health outcomes for patients with difficult-to-treat drug resistant gram-negative bacterial infections and viral infections. Venatorx’s lead asset, cefepime-taniborbactam, is an investigational antibiotic that completed a Phase 3 study (NCT03840148) in adults with complicated urinary tract infections (cUTI), including pyelonephritis and an NDA is under FDA review with a PDUFA action date of February 22, 2024. In October 2022, BARDA awarded a contract of up to $318 million to Venatorx for development and procurement of cefepime-taniborbactam for the treatment of melioidosis. As part of its broader pipeline, Venatorx is also developing an oral antibacterial, ceftibuten-ledaborbactam etzadroxil, that will advance directly to a global Phase 3 cUTI clinical trial under its BARDA contract. For more information about Venatorx and its anti-infectives portfolio, please visit . Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the potential, safety, efficacy, and regulatory and clinical development of Venatorx Pharmaceuticals’ product candidates. References [1] Shields et al. Burden of illness in U.S. hospitals due to carbapenem-resistant gram-negative urinary tract infections in patients with or without bacteremia. BMC Infect Dis (2021) 21:572. [2] Carreno et al. Longitudinal, nationwide, cohort study to assess incidence, outcomes, and costs associated with complicated urinary tract infection. Open Forum Infect Dis. 8 October 2019 [3] Simmering, J.E., et al. The Increase in Hospitalizations for Urinary Tract Infections and the Associated Costs in the United States, 1998-2011 Open Forum Infect Dis. 2017 Feb 24;4(1):ofw281. [4] Jernigan et al. Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012–2017 N Engl J Med 2020;382:1309-19. [5] Zilberberg MD et al. Antimicrobial susceptibility and cross-resistance patterns among common complicated urinary tract infections in U.S. hospitals, 2013 to 2019. Antimicrob Agents Chemother 2020;64(8):e00346-20 [6] Critchley, I.A., et al. (2019) The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017. PLoS One 14(12): e0220265 (2019).