Penicillin Binding Protein (PBP) Inhibitor Program

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.

Antibiotics to treat multi-drug resistant (MDR) Acinetobacter baumannii

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.

In 2020, the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services (HHS) awarded Venatorx $3.2 million, with the potential to receive up to $44.2 million, if all project milestones are met, to advance its novel series of PBP Inhibitors targeting MDR A. baumannii through Phase 1 clinical testing.

This project has 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. 75N93020C00016.

Oral Antibiotics to treat MDR gonorrhea

Venatorx is developing an oral 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, CARB-X awarded Venatorx up to US$4.1 million in non-dilutive funding, with the possibility of up to an additional US$8.9 million if certain project milestones are met. CARB-X funding will help Venatorx progress these early molecules from hit-to-lead through IND-enabling studies.

This project (04CARB-X 0652) is supported by the Cooperative Agreement Number IDSEP160030 from ASPR/BARDA and by awards from Wellcome Trust, and Germany’s Federal Ministry of Education and Research.

Countermeasure against Potential Drug-Resistant Biodefense Category A/B Respiratory Pathogens

In 2017, Venatorx was awarded up to $16 million from the Defense Threat Reduction Agency (DTRA), an agency of the U.S. Department of Defense. The funding supports discovery and preclinical development of a novel, first-in-class antibiotic for biodefense applications.

The project is supported by DTRA under Contract No. HDTRA117C0070.

Intravenous Antibiotic to Combat MDR Bacteria

In 2017, Venatorx was awarded up to $9.4 million from CARB-X to be used to support discovery and pre-clinical development of a new class of antibiotic that circumvents beta-lactam antibiotic resistance, but with the same safe and effective mechanism of action of beta-lactams.

This project (01CARB-X0109) was supported by the Cooperative Agreement Number IDSEP160030 from ASPR/BARDA and by awards from Wellcome Trust, and Germany’s Federal Ministry of Education and Research.