Entropy Neurodynamics Ltd (ASX:ENP, OTC:TYPTF) has secured a pre-clinical trial agreement with the University of California, San Francisco (UCSF) for a proposed US Phase 2 study comparing its precision-controlled psychedelic therapy TRP-8803 directly with widely prescribed antidepressant escitalopram.
The head-to-head trial is planned to enrol up to 80 young adults with Major Depressive Disorder (MDD) and is expected to begin in the first half of 2027, subject to US Food and Drug Administration (FDA) regulatory clearance.
Professor Robin Carhart-Harris, the Ralph Metzner Distinguished Professor of Neurology and Psychiatry at UCSF and a leading researcher in psychedelic therapies, will serve as principal investigator.
Carhart-Harris said, “Our previous trial comparing psilocybin with escitalopram provided encouraging evidence for the potential of psychedelic therapy in MDD and raised important questions about how these different treatment approaches compare clinically and mechanistically.
“TRP-8803 provides an opportunity to build on that work using an IV formulation of psilocin designed to offer greater precision, predictability and control over the treatment experience. These characteristics are particularly interesting from a research perspective because they may enable us to examine the effects of psilocin with a level of control that is difficult to achieve with oral psilocybin.
“The proposed trial will also examine an important patient population. By studying young adults experiencing major depression, we have an opportunity to investigate psychedelic therapy earlier in the course of the condition and directly compare a limited intervention with conventional daily antidepressant treatment.
“I look forward to working with Entropy and the team at UCSF to develop and undertake a rigorous trial that can advance our understanding of both the clinical and mechanistic potential of precision-controlled psilocin therapy.”
Testing TRP-8803 against established treatment
The study will compare Entropy’s proprietary intravenous psilocin formulation with escitalopram, marketed as Lexapro, using measures of depression severity over eight weeks and six months.
It will also assess treatment adherence, tolerability, safety and broader measures including wellbeing, social and work functioning and longer-term outcomes.
Entropy intends to use the trial to examine whether TRP-8803 could be introduced earlier in the depression treatment pathway, rather than being limited to patients who have failed conventional therapies.
TRP-8803 is designed to overcome some limitations of oral psilocybin by delivering psilocin intravenously, allowing rapid onset and greater control over the intensity, duration and predictability of the psychedelic experience.
US regulatory pathway
Under the agreement, Entropy and UCSF will develop the clinical protocol, informed consent documentation and electronic data capture systems.
Entropy will act as sponsor of the Investigational New Drug (IND) application with the FDA and progress regulatory activities required to begin the study.
An accepted IND could also provide the company with a broader US regulatory foundation for future clinical development of TRP-8803, including potential Phase 2b and Phase 3 programs informed by data from its ongoing Australian studies.
The company is currently conducting a 72-patient, eight-indication Phase 1b/2a basket study with Swinburne University of Technology.
Next steps
Entropy and UCSF will finalise the proposed trial protocol and informed consent documentation before seeking a pre-IND meeting with the FDA.
The company then plans to submit its IND application for TRP-8803 and, subject to FDA clearance, finalise a Clinical Trial Research Agreement with UCSF.
The trial is expected to be funded from existing cash reserves, option conversions and pending research and development tax incentives.
About Entropy Neurodynamics
Entropy Neurodynamics is a clinical-stage biotechnology company developing proprietary psilocin formulations in combination with psychotherapy for diseases with unmet medical needs.
Its lead program, TRP-8803, uses IV-infused psilocin — the active metabolite of psilocybin — with the aim of shortening treatment onset, controlling the depth and duration of psychedelic effects and reducing the overall length of treatment.
The company’s development program builds on Phase 2a trials using oral psilocybin in binge eating disorder, irritable bowel syndrome and fibromyalgia.