Engrail Therapeutics Initiates ENX-104 Clinical Program for the Treatment of Major Depressive Disorder Characterized by Anhedonia

• The first-in-human Phase 1 clinical study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic profile of ENX-104 in healthy volunteers

SAN DIEGO, Sept. 18, 2024 (GLOBE NEWSWIRE) — Engrail Therapeutics, a precision neuroscience company focused on the development of transformational therapies to improve the lives of patients, today announced initiation of a Phase 1 single ascending dose clinical study for ENX-104 in healthy volunteers. ENX-104 is a potent and selective dopamine D₂/D₃ receptor antagonist designed to enhance dopamine neurotransmission by preferential autoreceptor inhibition at low doses. The lead indication for ENX-104 is the treatment of major depressive disorder (MDD) characterized by anhedonia (aMDD). Anhedonia is the inability to experience pleasure in normally pleasurable activities and is a core symptom of MDD that is largely unresponsive to currently approved antidepressants.

“Dysregulation of dopamine in the reward centers of the brain is believed to underlie anhedonia which is experienced by 60-70% of MDD patients. ENX-104 provides a novel and targeted approach to enhancing dopamine modulation and represents a potential new therapeutic modality for the treatment of patients with aMDD,” said Vikram Sudarsan, PhD, chief executive officer of Engrail. “The initiation of this Phase 1 study is a significant step forward for ENX-104 and an important milestone for Engrail as our second clinical-stage program.”

The ENX-104 Phase 1 study is a randomized, double-blind, placebo-controlled single ascending dose clinical study that is expected to enroll up to 48 healthy adult volunteers. The primary objective is to evaluate the safety and tolerability of ENX-104 after a single oral administration of increasing doses in separate cohorts. Each dose cohort will include 8 subjects, with 6 subjects randomized to ENX-104 and 2 to placebo. The study is also designed to measure pharmacokinetics and explore the pharmacodynamic effects of ENX-104 on biomarkers associated with changes in dopamine neurotransmission in order to ascertain target engagement.

About ENX-104
ENX-104 is a potent dopamine D₂/D₃ receptor antagonist in development for major depressive disorder (MDD) characterized by anhedonia (aMDD). Dysregulated dopaminergic neurotransmission, particularly in brain reward systems, is believed to underlie anhedonia, a hallmark symptom of MDD. ENX-104 was designed to directly modulate dopaminergic transmission in brain reward systems by increasing dopamine release via potent antagonism of presynaptic D₂/D₃ autoreceptors at low doses. ENX-104 is in Phase 1 clinical development.

About Engrail Therapeutics
Engrail is a clinical-stage pharmaceutical company with a rich pipeline of precision-targeted neuroscience programs designed to improve the lives of patients with neuropsychiatric and neurodevelopmental diseases. ENX-102, a next-generation GABA_A positive allosteric modulator, is in Phase 2 clinical development for the treatment of generalized anxiety disorder. ENX-104, a potent dopamine D₂/D₃ receptor antagonist, is in Phase 1 clinical development for the treatment of major depressive disorder characterized by anhedonia. Additional programs in development are intended to address significant unmet medical needs for the treatment of posttraumatic stress disorder, anxiety-, mood- and stress-related disorders and rare neurological conditions. At Engrail, we apply precision chemistry and pharmacology to develop transformative medicines for patients who are underserved by existing treatments.

For more information, visit engrail.com.

Media Contact:
Anil Vootkur, PharmD
Engrail Therapeutics
anil@engrail.com