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Cefepime/enmetazobactam is given intravenously every eight hours. Credit: Jacob Lund / Shutterstock.com. The UK Medicines and Healthcare products Regulatory Agency (MHRA) has approved Advanz Pharma’s combined antibiotic, cefepime/enmetazobactam, to treat complicated infections. Marketed as Exblifep 2g/0.5g powder for concentrate for solution for infusion, the antibiotic treats adults suffering from complicated urinary tract infections (UTIs), certain kinds of pneumonia acquired during hospital stays, and bacteraemia that may arise from these conditions. Cefepime/enmetazobactam is administered intravenously for two hours to treat UTIs and four hours to treat pneumonia. Dosage is repeated every eight hours. Treatment length varies from seven to 14 days, based on the infection’s severity and patient response. Its active components are cefepime and enmetazobactam. Cefepime disrupts bacterial cell wall synthesis, leading to bacterial death. Enmetazobactam enhances cefepime’s efficacy by inhibiting beta-lactamases, enzymes that could degrade cefepime. See Also: Q&A: BARDA chief says agency wants to back tech that can combat multiple infections Insmed gets grant for treatment of gram-positive pulmonary bacterial infections The MHRA’s approval process for cefepime/enmetazobactam was expedited through the new International Recognition Procedure (IRP), taking only 55 days. The IRP leverages the expertise of trusted international regulatory partners, in this case acknowledging the European Medicines Agency’s Committee for Medicinal Products for Human Use’s recommendation on 26 January 2024. Clinical evidence supporting the approval includes a study in 1,041 adult patients in which the combined antibiotic demonstrated greater effectiveness than another comprising piperacillin and tazobactam in treating complicated UTIs. 79% of subjects in the cefepime/enmetazobactam arm had a favourable outcome after seven to 14 days versus 59% for those in the piperacillin and tazobactam arm. Data from another study of 19 healthy adults showed that the antibiotic effectively penetrates the lungs, supporting its use against hospital-acquired pneumonia. MHRA healthcare quality and access interim executive director Julian Beach stated: “Keeping patients safe and enabling their access to high-quality, safe and effective medical products are key priorities for us. “We’re assured that the appropriate regulatory standards for the approval of this medicine have been met. As with all products, we will keep its safety under close review.”

MEM-ANT3310 has the potential to become the next standard of care for life-threatening infections due to its unique coverage including carbapenem-resistant Enterobacterales and Acinetobacter baumannii Labège, France - May 25, 2023 Antabio SAS, a clinical stage biopharmaceutical company developing novel treatments for severe drug-resistant bacterial infections, announces dosing of the first subjects in its Phase 1 clinical trial of MEM-ANT3310. MEM-ANT3310 is a next generation antibacterial combination that has been designed to make a significant impact on the growing problem of antimicrobial resistance in serious hospital infections. MEM-ANT3310 combines the well-known carbapenem meropenem (MEM) with ANT3310, a breakthrough serine-beta-lactamase (SBL) inhibitor developed by Antabio. This combination has been designed to provide a unique coverage of priority Gram-negative pathogens including OXA-carbapenem-resistant Acinetobacter baumannii (CRAB), KPC- and OXA- carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa (PA). ANT3310 represents an important advance as its innovative structure completely inhibits the enzymes that confer resistance and as a result, restores MEM’s activity against these deadly pathogens. Magdalena Zalacain, Chief Scientific Officer of Antabio said, “MEM-ANT3310 is the culmination of a very creative and focused program aiming to develop a truly differentiated antibiotic active against both CRAB and CRE pathogens. MEM-ANT3310 is a strong addition to the clinical armamentarium to treat severe or life-threatening infections due to Gram-negative pathogens.” The Phase 1 clinical trial is designed to assess the safety, tolerability, and pharmacokinetic (PK) profile of single and multiple ascending doses (SAD/MAD) of intravenous ANT3310 administered alone, followed by an assessment of the combination of ANT3310 with MEM in healthy volunteers. Carole Sable, M.D., Infectious Disease expert and clinical advisor of Antabio commented, “There is a very clear need for safe and effective therapies to treat serious antibiotic-resistant infections in hospitalized patients, including when polymicrobial infections are suspected. Based on the preclinical profile of MEM-ANT3310, I believe it has the potential to provide a valuable broad-spectrum therapeutic option to meet unmet medical needs of this high-risk patient population.” Marc Lemonnier, CEO of Antabio added, “We are thrilled to reach this important milestone with the start of our first in man study for MEM-ANT3310. We see great promise for patients in this novel antibacterial combination addressing the highest WHO priorities for antibiotic resistance while building on a well-established regulatory path towards approval.” Initial funding for the development of MEM-ANT3310 of €5.5 million was received in 2022 from the French government through the “ARPEGE” program. *** About MEM-ANT3310 Carbapenems such as meropenem are the cornerstone of therapies for many life-threatening infections. Resistance to carbapenems is considered a critical priority by the World Health Organization (WHO) and Centre for Disease Control and Prevention (CDC) because it is a major cause of treatment failure, increased mortality, and huge economic costs. Bacteria resistant to carbapenems produce beta-lactamase enzymes that render antibiotics, such as meropenem (MEM), ineffective. Antabio has set out to resolve this major healthcare issue via its lead clinical stage program MEM-ANT3310. Its innovative serine-beta-lactamase inhibitor ANT3310 represents a significant breakthrough as it completely inhibits a broad range of beta-lactamases, including the Klebsiella pneumoniae carbapenemases (KPC) and oxacillin-hydrolyzing (OXA) type enzymes found in Carbapenem-Resistant Enterobacterales (CRE) and Carbapenem-Resistant Acinetobacter baumannii (CRAB), and restores MEM activity against these deadly pathogens. This is critical for the treatment of polymicrobial infections such as those causing hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). ANT3310, in combination with the antibiotic meropenem, has received qualified infectious disease product (QIDP) status from the FDA in 2019 for complicated urinary tract infections (cUTI), complicated intra-abdominal infections (cIAI) and hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). About Antabio Antabio is a clinical stage biopharmaceutical company developing novel and highly differentiated antibacterial treatments of drug-resistant infections as defined by the CDC and WHO’s critical priority pathogens, with a particular focus on life-threatening respiratory infections, including carbapenem-resistant nosocomial pneumonia and chronic pulmonary diseases. The company’s lead program, MEM-ANT3310, is being developed for the treatment of hospital-acquired infections such as nosocomial pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Enterobacterales (CRE). Antabio’s portfolio includes two further programs: 1) ANT3273, a groundbreaking, novel class, novel mode of action inhalation treatment of Pseudomonas aeruginosa (PA) infections, particularly those affecting patients with chronic pulmonary diseases (such as Bronchiectasis, Cystic Fibrosis and COPD); and 2) ANT2681, a novel and potent metallo beta-lactamase (MBL) inhibitor to be combined with meropenem for the treatment of MBL-producing carbapenem-resistant Enterobacterales (CRE), particularly New Delhi metallo-beta-lactamase (NDM) carrying strains. Antabio has built an international team, including former executives from Novexel, Merck, GSK, and AstraZeneca. The company has an impressive track-record in attracting non-dilutive funding, including multi-million-dollar awards from the Wellcome Trust, CARB-X, and ARPEGE. Media Contacts Antabio Marc Lemonnier, CEOpress@antabio.comMEDiSTRAVA ConsultingSylvie Berrebi, Frazer Hallantabio@medistrava.com

An international research team has provided valuable new information about what drives the global spread of genes responsible for antimicrobial resistance (AMR) in bacteria. The collaborative study will provide new information to combat the global challenge of AMR. An international research team has provided valuable new information about what drives the global spread of genes responsible for antimicrobial resistance (AMR) in bacteria. The collaborative study, led by researchers at the Quadram Institute and the University of East Anglia, brought together experts from France, Canada, Germany and the UK and will provide new information to combat the global challenge of AMR. By examining the whole genome sequences of around two thousand resistant bacteria, predominantly Escherichia coli collected between 2008 and 2016, the team found that different types of AMR genes varied in their temporal dynamics. For example, some were initially found in North America and spread to Europe, while for others the spread was from Europe to North America. Not only did the study look at bacteria from different geographic regions but also from diverse hosts including humans, animals, food (meat) and the environment (wastewater), to define how these separate but interconnected factors influenced the development and spread of AMR. Understanding this interconnectivity embodies the One Health approach and is vital for understanding transmission dynamics and the mechanisms by which resistance genes are transmitted. The study, published in the journal Nature Communications, was supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), a global collaboration spanning 29 countries and the European Commission that is tasked with turning the tide on AMR. Without concerted efforts on a global scale, AMR will undoubtedly make millions more people vulnerable to infections from bacteria and other microorganisms that can currently be tackled with antimicrobials. The team focussed on resistance to one particularly important group of antimicrobials, the Extended-Spectrum Cephalosporins (ESCs). These antimicrobials have been classed as critically important by the World Health Organization because they are a 'last resort' treatment for multidrug resistant bacteria; despite this, since their introduction, efficacy has declined as bacteria have developed resistance. Bacteria that are resistant to ESCs achieve this through the production of specific enzymes, called beta-lactamases, that are able to inactivate ESCs. The instructions for making these enzymes are encoded in genes, particularly two key types of genes: extended-spectrum beta-lactamases (ESBLs), and AmpC beta-lactamases (AmpCs). These genes may be found on the chromosomes of bacteria where they are passed to progeny during clonal multiplication, or in plasmids, which are small DNA molecules separate to the bacterium's main chromosome. Plasmids are mobile and can move directly between individual bacteria representing an alternative way of exchanging genetic material. This study identified how some resistance genes proliferated through clonal expansion of particularly successful bacterial subtypes while others were transferred directly on epidemic plasmids across different hosts and countries. Understanding the flow of genetic information within and between bacterial populations is key to understanding AMR transmission and the global spread of resistance. This knowledge will contribute to the design of vitally needed interventions that can halt AMR in the real world where bacteria from diverse hosts and environmental niches interact, and where international travel and trade mean that these interactions are not limited by geography. Professor Alison Mather, group leader at the Quadram Institute and the University of East Anglia, said: "By assembling such a large and diverse collection of genomes, we were able to identify the key genes conferring resistance to these critically important drugs. We were also able to show that the majority of resistance to extended spectrum cephalosporins is spread by only a limited number of predominant plasmids and bacterial lineages; understanding the mechanisms of transmission is key to the design of interventions to reduce the spread of AMR." Lead author Dr Roxana Zamudio said "Antimicrobial resistance is a global problem, and it is only by working collaboratively with partners in multiple countries that we can get a holistic understanding of where and how AMR is spreading." n; the gut and the microbiome; food innovation and population health.