Market Overview

Entasis Therapeutics Announces Positive Topline Results from Phase 2 Trial of ETX2514SUL in Patients with Complicated Urinary Tract Infections including Acute Pyelonephritis


ETX2514SUL was generally well tolerated

Phase 3 to initiate first quarter 2019

, a clinical-stage biopharmaceutical company focused on
the discovery and development of novel antibacterial products, reported
positive topline results from the company's multi-national Phase 2
clinical trial of its β-lactamase inhibitor, ETX2514, in combination
with sulbactam (the combination referred to as ETX2514SUL) in the
treatment of complicated urinary tract infections (cUTI) including acute
pyelonephritis (kidney infection) in adults. In this trial, ETX2514SUL,
administered with imipenem/cilastatin (IMI), was generally well
tolerated. In addition, ETX2514SUL plus IMI eradicated pathogens
non-susceptible to imipenem in 3 out of 3 patients. Entasis plans to
initiate a Phase 3 clinical trial focusing on carbapenem-resistant Acinetobacter
infections in the first quarter of 2019.

"We are extremely pleased with the results of this study," stated Robin
Isaacs, Chief Medical Officer of Entasis. "Infections due to Acinetobacter
are of significant concern, particularly
carbapenem-resistant infections which are associated with mortality
rates approaching 50% with Colistin-based treatment regimens and are
particularly difficult to treat. The results of this study add to a
substantial body of preclinical and clinical data supporting further
development of ETX2514SUL as a treatment for serious Acinetobacter

"Infections caused by Gram-negative bacteria are a major healthcare
challenge today, as resistance to older antibiotics is growing," said
Manos Perros, Chief Executive Officer of Entasis. "The results of this
Phase 2 trial support progression of ETX2514SUL into Phase 3, an
important next step in developing our pipeline of pathogen-targeted
products against drug-resistant bacterial infections."

The Phase 2 double-blind, randomized, placebo-controlled clinical trial
evaluated the safety and efficacy of intravenous (IV) ETX2514SUL in
adult patients with complicated urinary tract infections including acute
pyelonephritis. Eighty patients were randomized to receive either a dose
of ETX2514SUL (ETX2514 1 g plus sulbactam 1 g) or a matching placebo
every six hours for seven days. Patients in both arms also received
background therapy with 500mg IV IMI every six hours. ETX2514SUL plus
IMI showed similar microbiological success in the microbiologically
evaluable population as placebo plus IMI (80% vs. 81%) and both
treatment groups achieved 100% clinical success in the clinically
evaluable population. ETX2514SUL was generally well tolerated. The
adverse event profile of ETX2514SUL was similar to placebo with no
serious adverse events (SAEs) reported in either arm.

In an exploratory analysis, the trial evaluated the efficacy of
ETX2514SUL plus IMI against cUTIs caused by imipenem-non-susceptible
pathogens. Eight patients had a cUTI caused by imipenem-non-susceptible
pathogens (three in the treatment arm and five in the placebo arm).
ETX2514SUL plus IMI eradicated isolates in all patients (100% [3/3])
compared to 60% (3/5) in patients receiving placebo plus IMI.

Entasis plans to present additional detail from the Phase 2 trial at an
upcoming medical conference.

About ETX2514

ETX2514 is a potent and broad-spectrum inhibitor of class A, C, and D
β-lactamases. ETX2514 restores the in vitro activity of multiple
β-lactams against Gram-negative, multidrug-resistant (MDR) pathogens.
Entasis Therapeutics is initially developing ETX2514SUL, the combination
of ETX2514 and sulbactam, for the treatment of severe A. baumannii
infections. Sulbactam is a generic β-lactam which has intrinsic activity
against A. baumannii but suffers from widespread
β-lactamase-mediated resistance. In preclinical studies, ETX2514
restored sulbactam antibacterial activity against A. baumannii.
ETX2514 has completed single- and multi-ascending dose Phase 1 trials
and a Phase 2 trial, in combination with sulbactam, in cUTI. The U.S.
Food and Drug Administration (FDA) has granted Qualified Infectious
Disease Product (QIDP) designation and Fast Track status to ETX2514SUL
for the treatment of hospital-acquired and ventilator-acquired bacterial
pneumonia and bloodstream infections due to A. baumannii.

About Entasis

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), a Non-Beta-lactam PBP inhibitor (targeting Gram-negative
infections), and zoliflodacin (targeting Neisseria gonorrhoeae).

View Comments and Join the Discussion!