Entasis Presents Data On Third Drug Candidate, Etx0282, An Orally Available, Extended-Spectrum ?eta-Lactamase Inhibitor, At AAM Microbe 2017

WALTHAM, Mass.--(BUSINESS WIRE)--Entasis Therapeutics, a leader in the discovery and development of breakthrough anti-infective products, delivered multiple presentations at the American Society of Microbiology (ASM) Microbe 2017 Conference, June 1-5 in New Orleans, Louisiana. The presentations featured ETX0282, Entasis’ next-generation oral beta-lactamase inhibitor with activity against an extended spectrum of Class A and C beta-lactamases, and ETX2514, Entasis’ I.V. broad-spectrum beta-lactamase inhibitor currently in Phase 1 clinical trials. Data highlights include:

• ETX0282 inhibition of Class A and C beta-lactamases and Class D oxacillinases and its ability to restore activity of beta-lactams against extended-spectrum beta-lactamase (ESBL) producing and carbapenem-resistant Enterobacteriaceae (CRE)
• High susceptibility of a globally diverse collection of recent Enterobacteriaceae isolates to ETX0282 combined with cefpodoxime in vitro
• Activity of orally administered ETX0282 combined with cefpodoxime against multiple ESBL-producing, CRE, and fluoroquinolone-resistant Enterobacteriaceae in murine infection models
• Susceptibility of multi-drug-resistant (MDR) and carbapenem-resistant strains of Acinetobacter baumannii and Pseudomonas aeruginosa to ETX2514 in combination with various beta-lactams

“The increasing emergence of resistance to currently available oral treatments against Enterobacteriaceae creates a serious medical need which we are addressing with the development of ETX0282,” said Manos Perros, CEO. “We are very encouraged by the preclinical profile of ETX0282, which has the potential to deliver an oral treatment with strong antibacterial activity against tough-to-treat pathogens including ESBLs and CREs. In partnership with CARB-X, we are working to rapidly progress ETX0282 to the clinic.”

“Our preclinical work demonstrates the broader utility of ETX2514 in combination with beta-lactams against multiple drug-resistant Gram-negative pathogens,” said Ruben Tommasi, CSO. “ETX0282, also discovered from our innovative drug discovery platform, validates our approach to building a portfolio of innovative treatments for patients suffering from serious Gram-negative infections.”

ETX0282 Presentations:

Oral Presentation Title: ETX1317, the Active Component of the Orally Available, Novel Diazabicyclooctenone ETX0282, Demonstrates Potential Utility against Multidrug Resistant Enterobactericeae Due to its Potent, Broad Spectrum Inhibition of Serine Beta-Lactamases

Poster #278: ETX0282/Cefpodoxime Proxetil: A Novel, Oral Beta-Lactam/Beta-Lactamase Inhibitor Combination to Treat the Emerging Threat of Multidrug Resistant Enterobacteriaceae

Poster #279: The Antibacterial Activity of Cefpodoxime and the Novel Beta-Lactamase Inhibitor ETX1317 against Recent Clinical Isolates of Beta-Lactamase-Producing Enterobacteriaceae from Urinary Tract Infections

ETX2514 Presentations:

Poster #82: The Antibacterial Activity of Sulbactam and the Novel Beta-Lactamase Inhibitor ETX2514 Combined with Imipenem or Meropenem against Recent Clinical Isolates of Acinetobacter baumannii and Pseudomonas aeruginosa

Poster #277: Reversibility of ß-Lactamase Inhibition by the Broad-Spectrum Diazabicyclooctenone Serine ß-Lactamase Inhibitor ETX2514

About ETX2514
ETX2514 is a potent and broad spectrum inhibitor of class A, C, and D beta-lactamases. ETX2514 restores the in vitro activity of multiple beta-lactams against Gram-negative, multi-drug resistant (MDR) pathogens. Entasis Therapeutics is initially developing ETX2514SUL, the combination of ETX2514 and sulbactam, for the treatment of severe A. baumannii infections. A. baumannii is a Gram-negative bacterium that causes severe infections which are associated with high mortality rates. A. baumannii infections are frequently multi-drug resistant and there is an urgent need to identify new safe and effective agents to treat affected patients. Sulbactam is a generic beta-lactam which has intrinsic activity against A. baumannii but suffers from widespread beta-lactamase-mediated resistance. In preclinical studies, ETX2514 restores sulbactam’s antimicrobial activity against A. baumannii. ETX2514 is currently in Phase 1 clinical trials.

About ETX0282
ETX0282 is an orally available, broad spectrum inhibitor of class A and C beta-lactamases. Entasis is developing ETX0282 in combination with cefpodoxime, an orally available cephalosporin approved for treating a variety of bacterial infections but lacking in efficacy due to beta-lactamase mediated resistance. In preclinical studies, ETX0282 restores cefpodoxime’s antimicrobial activity against a variety of pathogens including Enterobacteriaceae resistant to fluoroquinolones, cephalosporins, and carbapenems. Entasis is initially developing ETX0282CPDP, the combination of ETX0282 and cefpodoxime, for the treatment of infections caused by Enterobacteriaceae. ETX0282CPDP is powered by CARB-X.

About Entasis Therapeutics Inc.
Entasis Therapeutics is developing a portfolio of innovative cures for serious drug-resistant bacterial infections, a global health crisis affecting the lives of millions of patients. Entasis’ anti-infective discovery platform has produced a pipeline of meaningfully differentiated programs which target serious bacterial infections, including ETX2514SUL (targeting Acinetobacter baumannii infections), ETX0282CPDP (targeting Enterobacteriaceae infections), and zoliflodacin (targeting Neisseria gonorrhoeae). www.entasistx.com