Profile of Entasis Therapeutics ETX0462 Candidate Published in the Journal Nature

Publication Details the Discovery and Preclinical Profile of ETX0462, a First-in-Class Candidate Against Multidrug-Resistant Pathogens

WALTHAM, Mass., Sept. 15, 2021 (GLOBE NEWSWIRE) — Entasis Therapeutics Holdings Inc. (NASDAQ: ETTX), a clinical-stage biopharmaceutical company focused on the discovery and development of novel antibacterial products, today announced the publication of a profile of the company’s ETX0462 candidate in the prestigious scientific journal Nature (DOI: 10.1038/s41586-021-03899-0). The article, titled “Rational design of a new antibiotic class for drug-resistant infections” describes the discovery and preclinical profile of ETX0462, which could become the first of a new class of antibiotics for multidrug-resistant (MDR) Gram-negative and biothreat infections.

The manuscript details the discovery of ETX0462, highlighting the importance of concurrent optimization of biochemical potency and drug penetration into the bacterial cells to identify structural elements critical for antimicrobial activity against multiple contemporary MDR Gram-negative and biothreat bacterial pathogens, including MDR Pseudomonas. Thanks to its innovative chemical design, the activity of ETX0462 is unaffected by all four Ambler classes of β-lactamases. Furthermore, ETX0462’s ability to permeate bacterial cells through multiple porins and inhibition of multiple penicillin-binding proteins (PBP) enzyme subtypes, results in low propensity for resistance emergence.

“To our knowledge, the novel lead optimization approach which led to ETX0462 is a first in antibiotic drug discovery,” commented Ruben Tommasi, Chief Scientific Officer at Entasis. “Leveraging our platform of permeation and biochemical assays, we developed detailed knowledge of factors affecting accumulation in Gram-negative pathogens as well as PBP target potency. We’re excited to see these efforts culminate in the development of ETX0462. We continue to leverage our innovative drug discovery platform to design additional preclinical candidates against high-priority bacterial pathogens.”

“I would like to congratulate the authors on the publication of this profile of ETX0462 in the prestigious scientific journal, Nature,” stated Manos Perros, Chief Executive Officer at Entasis. “With topline data from the ongoing ATTACK pivotal trial for SUL-DUR expected in early 4th quarter, zoliflodacin in Phase 3 and ETX0282CPDP having completed an initial Phase 1, our R&D team has once again succeeded in translating excellent science to promising innovation for patients suffering from bacterial infections.”

About Entasis Therapeutics Inc.
Entasis is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel antibacterial products to treat serious infections caused by multidrug-resistant Gram-negative bacteria. Entasis’ pathogen-targeted design platform has produced a pipeline of product candidates, including SUL-DUR (targeting Acinetobacter baumannii infections), zoliflodacin (targeting Neisseria gonorrhoeae infections), ETX0282CPDP (targeting Enterobacterales infections) and ETX0462 (targeting Pseudomonas infections). For more information, visit

About ETX0462
ETX0462 is a novel, first-in-class, diazabicyclooctane with antimicrobial activity against multidrug-resistant (MDR) Gram-negative and biothreat pathogens including, P. aeruginosa, K. pneumoniae, S. maltophilia, E. coli, B. anthracis, Y. pestis, F. tularensis and Burkholderia spp. Similar to β-lactam antibiotics, ETX0462 inhibits penicillin-binding proteins which are essential for bacterial cell wall biosynthesis, however, unlike β-lactam antibiotics, ETX0462 is unaffected by β-lactamase mediated resistance. ETX0462 is supported by CARB-X.


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Source: Entasis Therapeutics Holdings Inc.