Engrail Therapeutics Launches ENX-104 Clinical Program for Anhedonic Major Depressive Disorder

Engrail Therapeutics, a precision neuroscience company dedicated to developing transformative therapies for patients, has announced the commencement of a Phase 1 clinical trial for ENX-104. The trial aims to assess the safety, tolerability, pharmacokinetics, and pharmacodynamic profile of ENX-104 in healthy individuals. This investigational drug acts as a potent and selective dopamine D2/D3 receptor antagonist and is being developed primarily for the treatment of major depressive disorder (MDD) characterized by anhedonia (aMDD).

Anhedonia is a symptom of MDD that involves the inability to feel pleasure in activities that are usually enjoyable. This symptom affects 60-70% of MDD patients and is typically resistant to currently approved antidepressants. The dysregulation of dopamine in the brain's reward centers is believed to be a key factor behind anhedonia. ENX-104 aims to address this by modulating dopamine neurotransmission through autoreceptor inhibition at low doses.

Dr. Vikram Sudarsan, the CEO of Engrail Therapeutics, emphasized the innovative approach of ENX-104, stating that it represents a new therapeutic modality for treating aMDD by enhancing dopamine modulation. The initiation of this Phase 1 study marks a significant milestone for both ENX-104 and Engrail, as it is the company's second program to enter clinical stages.

The Phase 1 study is designed as a randomized, double-blind, placebo-controlled single ascending dose trial. It will enroll up to 48 healthy adults to evaluate the safety and tolerability of ENX-104 after a single oral dose. Each dose cohort will consist of 8 subjects, with 6 receiving ENX-104 and 2 receiving a placebo. The study will also investigate the pharmacokinetics and explore the pharmacodynamic effects on biomarkers related to dopamine neurotransmission to confirm target engagement.

ENX-104 was specifically designed to modulate dopaminergic transmission in the brain's reward systems. By antagonizing presynaptic D2/D3 autoreceptors at low doses, ENX-104 aims to increase dopamine release. This mechanism is particularly relevant for treating aMDD, where dysregulated dopamine neurotransmission is a core issue.

In addition to ENX-104, Engrail Therapeutics is advancing other precision-targeted neuroscience programs. ENX-102, a next-generation GABAA positive allosteric modulator, is in Phase 2 clinical development for generalized anxiety disorder. Engrail's pipeline also includes treatments for posttraumatic stress disorder, anxiety, mood and stress-related disorders, and rare neurological conditions. The company leverages precision chemistry and pharmacology to develop transformative medicines for patients with significant unmet medical needs.

Engrail's approach is rooted in the belief that precision-targeted therapies can significantly improve the lives of patients with neuropsychiatric and neurodevelopmental diseases. This focus on innovation and patient-centric development drives their mission to deliver new treatment options for conditions that are inadequately served by current therapies.

By targeting specific neurological pathways and mechanisms, Engrail aims to provide more effective and safer treatments. The initiation of the ENX-104 Phase 1 study is a testament to their commitment to advancing science and improving patient outcomes, marking another step forward in their journey to transform neuroscience therapeutics.