Benzinga | Jul 1, 2021 08:03AM EDT

Entasis Therapeutics Highlights Presentation Of ETX0462 Data At 2021 World Microbe Forum

Entasis Therapeutics Holdings Inc. (NASDAQ:ETTX), a clinical-stage biopharmaceutical company focused on the discovery and development of novel antibacterial products, today announced the presentation of preclinical data on ETX0462, a novel, first-in-class, diazabicyclooctane with antimicrobial activity against multidrug-resistant (MDR) Gram-negative and biothreat pathogens, at the 2021 World Microbe Forum. ETX0462 potentially represents the first new antibiotic class in 35 years to treat MDR Gram-negative and biothreat infections.



At the World Microbe Forum, Entasis scientists presented their approach to the discovery of ETX0462 that incorporated Structure-Porin Permeation Relationships and Structure-Based Drug Design to identify key principles for penicillin-binding protein (PBP) inhibition and corresponding antimicrobial activity against contemporary MDR Gram-negative and biothreat isolates, including P. aeruginosa, K. pneumoniae, S. maltophilia, E. coli, B. anthracis, Y. pestis, F. tularensis and Burkholderia spp. Entasis scientists further demonstrated that the activity of ETX0462 was unaffected by all four Ambler classes of ?-lactamases and has a low propensity for resistance emergence due to its ability to permeate bacterial cells through multiple porins and inhibit several PBPs.

"ETX0462 is the latest product candidate to emerge from our discovery platform and the first example of a novel class of agents targeting the established mechanism of ?-lactam antibiotics without being susceptible to the most common ?-lactam resistance mechanism, ?-lactamases," commented Ruben Tommasi, Chief Scientific Officer at Entasis. "We look forward to continuing our successful collaboration with CARB-X as we progress ETX0462 towards the clinic."

In in vivo studies, ETX0462 exhibited robust bactericidal activity reaching >3-log drop in bacterial count vs. initial inoculum in a neutropenic murine lung model against clinical isolates of P. aeruginosa. Similar in vivo efficacy was also demonstrated for the biothreat pathogens Y. pestis and B. pseudomallei. Entasis also shared that the PK/PD index of ETX0462 is driven by % Time > MIC and a ~60% target for 1-log bactericidal activity. Entasis demonstrated that ETX0462 was well tolerated in a rat 14-day GLP toxicology study reaching the limit dose of 2,000 mg/kg.

Additional details of the ETX0462 data presented can be found on the Entasis Presentations webpage.