Engrail Therapeutics Initiates the ENCALM Phase 2 Clinical Trial of ENX-102 in Patients with Generalized Anxiety Disorder

  • ENX-102 is an investigational GABA-A α2,3,5 positive allosteric modulator that blocks α1
  • The ENCALM Trial is a multi-center phase 2 trial to evaluate the efficacy and safety of ENX-102 as a monotherapy treatment in patients with generalized anxiety disorder

SAN DIEGO–(BUSINESS WIRE)–Engrail Therapeutics™ (Engrail) (the Company), a precision neuroscience company focused on the acquisition, development, and commercialization of transformational therapies, today announced initiation of a multi-center phase 2 clinical trial, the ENCALM Trial, to evaluate the efficacy and safety of ENX-102 in patients with generalized anxiety disorder (GAD). ENX-102 is an investigational, highly selective GABA-A α2,3,5 positive allosteric modulator (PAM) and antagonist at α1-containing GABA-A channels. ENX-102 represents a first-in-class approach to the treatment of GAD.

“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, PhD, chief scientific officer of Engrail.

“While there are a variety of options for treating GAD, they all have significant drawbacks – particularly limiting safe and tolerable long-term use. Engrail’s approach of selectively targeting GABA-A α2, α3, and α5 subunits holds promise for providing strong anxiolytic effect while reducing the risk of sedation and abuse potential,” said Charles Nemeroff, MD, PhD, chair and professor with the Department of Psychiatry and Behavioral Sciences at the Dell Medical School, University of Texas at Austin.

Vikram Sudarsan, Ph.D., chief executive officer and president of Engrail added, “We are excited by the best-in-class profile of ENX-102 and look forward to further elucidating its efficacy and safety profile in phase 2. The initiation of phase 2 and further advancement of the rest of our precision neuroscience pipeline makes 2023 a hallmark year for the organization.”

For more information on the ENCALM Trial, visit clinicaltrials.gov.

About ENX-102

Targeting the gamma-aminobutyric acid A (GABA-A) receptor is a well-validated pharmacological approach for the treatment of anxiety and other centrally-mediated disorders. However, broad-spectrum GABA-A modulators, such as benzodiazepines, have several liabilities limiting chronic use, primarily driven by GABA-A α1 subunit containing channels. ENX-102 is an investigational subtype-selective GABA-A PAM acting to enhance GABA neurotransmission in receptors containing the α2, α3, and α5 subunits while blocking α1. This profile is thought to contribute to anxiolytic efficacy and result in a favorable safety profile without the undesirable effects associated with α1.

About Engrail Therapeutics

Engrail Therapeutics is a clinical-stage pharmaceutical company founded in 2019 with the aspiration of becoming a leader in neuroscience. We are committed to rapidly advancing our innovative, precision-targeted therapeutics. Our purpose is to deliver transformational therapies that improve the lives of patients with devastating neurologic, neuropsychiatric, and neurodevelopmental disorders.

Engrail is supported by a long-term capital commitment from Pivotal Life Sciences. For more information, visit engrail.com.