Profile of Entasis Therapeutics ETX0462 Candidate Published in the Journal Nature

Rhea-AI Summary

Entasis Therapeutics has published a profile of its antibiotic candidate ETX0462 in the journal Nature, marking a significant advancement in the fight against multidrug-resistant (MDR) Gram-negative infections. This first-in-class drug showcases unique properties, being unaffected by β-lactamases and demonstrating effective penetration into bacterial cells. The discovery emphasizes optimizing drug potency and reducing resistance. CEO Manos Perros highlighted the ongoing trials for other candidates, projecting promising outcomes for patients with bacterial infections.

Positive

• ETX0462 displayed effective antimicrobial activity against various MDR pathogens.
• The candidate is unaffected by all four Ambler classes of β-lactamases.
• Innovative penetration and binding properties could lead to low resistance rates.

Negative

• None.

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 www.entasistx.com.

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.

Company Contact Kyle Dow Entasis Therapeutics (781) 810-0114 kyle.dow@entasistx.com

Investor Contact Bruce Mackle LifeSci Advisors (929) 469-3859 bmackle@lifesciadvisors.com

 

FAQ

What is ETX0462 and its significance in antibiotic development?

ETX0462 is a first-in-class antibiotic candidate developed by Entasis Therapeutics, targeting multidrug-resistant Gram-negative pathogens, and is unaffected by common resistance mechanisms.

In which journal was ETX0462's profile published?

The profile of ETX0462 was published in the prestigious scientific journal Nature.

What are the key features of ETX0462?

ETX0462 showcases effective permeability, inhibition of penicillin-binding proteins, and a low propensity for resistance emergence.

What ongoing trials is Entasis Therapeutics conducting?

Entasis is conducting the ATTACK pivotal trial for SUL-DUR and additional trials for zoliflodacin and ETX0282CPDP.