ETX-0462

ETX-0462 is a first-in-class diazabicyclooctane antibacterial designed to inhibit multiple penicillin-binding proteins and retain activity in the presence of all four Ambler classes of β-lactamases, providing broad-spectrum coverage against multidrug-resistant Gram-negative ESKAPE pathogens, Stenotrophomonas maltophilia, and several biothreat organisms including Yersinia pestis and Burkholderia pseudomallei[3][4][7]. It shows potent in vitro and in vivo activity, including bactericidal efficacy in neutropenic murine models of Pseudomonas aeruginosa lung infection, and has preclinical PK/PD characterized by time above MIC driving effect; it was well tolerated in a 14-day rat GLP toxicology study up to 2,000 mg/kg[3][2]. Structural biology work includes a crystal structure bound to Pseudomonas aeruginosa PBP3, supporting its PBP-targeted mechanism[7]. ETX-0462 was discovered by Entasis Therapeutics, supported by CARB-X, and as of the latest public updates remains in preclinical development[4][1].