Entasis’ CARB-X-backed non-beta lactam antibiotic; plus Takeda, Amyndas and more

Entasis Therapeutics Inc. (NASDAQ:ETTX) reported preclinical data in Nature suggesting its non-beta lactam antibiotic candidate ETX0462 can treat multidrug-resistant Gram-negative infections, a group for which no antibiotics have been approved in over 25 years. ETX0462, a PBP inhibitor, yielded greater inhibition in vitro against 40 multidrug-resistant Pseudomonas aeruginosa strains than four combinations of marketed antibiotics. The compound also  showed efficacy against all other Gram-negative ESKAPE pathogens, and five pathogens considered biothreats including Bacillus anthracis, the Gram-positive bacteria that causes anthrax. In mice, ETX0462 reduced bacterial burden in a model of multidrug-resistant P. aeruginosa infection and improved survival in models of Yersinia pestis and Burkholderia pseudomallei infections.

The company also detailed the rational design of the compound, which was based on diazabicyclooctanes, a recently discovered class of LACTB inhibitors whose development as monotherapy has been limited by high frequency of resistance and poor in vivo efficacy. ETX0462 is in preclinical development and partnered with Combating Antibiotic-Resistant Bacterial Biopharmaceutical Accelerator (CARB-X), a not-for-profit that funds early stage antimicrobial research projects. ...