Engrail Therapeutics initiates ENX-102 Phase 2 trial in generalized anxiety disorder

Engrail Therapeutics, a neuroscience company committed to advancing transformational therapies, announced the start of a multi-center Phase 2 clinical trial, dubbed the ENCALM trial.

The trial aims to examine the efficacy and safety of ENX-102, a highly selective GABA-A α2,3,5 positive allosteric modulator (PAM) and antagonist at α1-containing GABA-A channels, in patients suffering from generalized anxiety disorder (GAD).

ENX-102 is being tested for its groundbreaking approach to treating GAD. It targets the gamma-aminobutyric acid A (GABA-A) receptor, a widely recognized therapeutic approach for anxiety and other centrally-mediated disorders. However, broad-spectrum GABA-A modulators like benzodiazepines have limitations, particularly driven by GABA-A α1 subunit containing channels, that restrict their chronic use. ENX-102, an investigational subtype-selective GABA-A PAM, is designed to enhance GABA neurotransmission in receptors containing the α2, α3, and α5 subunits while blocking α1, aiming to offer anxiolytic efficacy and a favorable safety profile without the adverse effects linked to α1.

Launched in 2019, Engrail Therapeutics is a clinical-stage pharmaceutical company backed by a long-term capital commitment from Pivotal Life Sciences. The company aims to become a leader in the field of neuroscience.

“Translational and phase 1 clinical data indicate central target engagement with a highly differentiated safety and tolerability profile for ENX-102 vs. non-selective GABA-A PAMs such as benzodiazepines. ENX-102 exhibits a long half-life and can be dosed once daily without titration. These data support further evaluation of ENX-102 for efficacy in generalized anxiety disorder,” said Kimberly Vanover, chief scientific officer of Engrail Therapeutics.