Venatorx Pharmaceuticals is developing a novel class of non-beta-lactam molecules that kill bacteria by the same selective mechanism as beta-lactams — blocking cell wall synthesis via binding to the bacterial penicillin binding proteins (PBPs). Chemically distinct from the beta-lactams, these new molecules have been designed to be impervious to degradation by any beta-lactamases. By circumventing over seventy years of beta-lactamase-driven resistance, this new class of PBP inhibitors has the potential to usher in a new wave of antibacterial therapeutics.
In November 2021, Venatorx entered into a Research Collaboration and License Agreement with Roche to discover, characterize and develop new small molecule inhibitors of the Penicillin Binding Proteins in Gram-negative bacteria focused on agents active against carbapenem-resistant Enterobacterales (CRE). Enterobacterales ranks among the “Priority 1: Critical” antibiotic resistant pathogens on the World Health Organization’s list of bacteria for which new antibiotics are urgently needed. In particular, these multidrug resistant pathogens pose a particular threat in hospitals and nursing homes, as well as among patients whose care requires devices such as ventilators and catheters. These bacteria have become resistant to a large number of antibiotics, including carbapenems and third generation cephalosporins.
In July 2020, Venatorx was awarded a contract by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services (HHS) to advance its novel series of Penicillin Binding Protein (PBP) Inhibitors targeting multi-drug resistant (MDR) Acinetobacter baumannii through Phase 1 clinical testing. A. baumannii is ranked as a “Priority 1: Critical” carbapenem resistant pathogen on the World Health Organization’s list of bacteria for which new antibiotics are urgently needed. A. baumannii is primarily associated with hospital-acquired infections and has become resistant to a large number of antibiotics, including carbapenems and third generation cephalosporins – the best-known available antibiotics for treating MDR bacteria.
Under Contract No. 75N93020C00016, the total estimated support through Option 1 for this contract is approximately $6.2 million. Venatorx has the potential to receive funding of up to $44.2 million, if all project milestones are met.
Venatorx is developing an intramuscularly-administered penicillin-binding protein inhibitor (PBPi) to address the growing problem of resistance in Neisseria gonorrhoeae to the last resort antibiotic for outpatient use, ceftriaxone. Venatorx has identified non-beta-lactam transpeptidase inhibitors that are rapidly bactericidal, impervious to beta-lactamases, and show promising selective activity against gonococci, including both wild-type strains and isolates with PBP variants that confer ceftriaxone resistance.
In 2019, The NIH awarded Venatorx an R01 grant to progress these early molecules from hit-to-lead through IND-enabling studies.
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