- Entropy’s lead IV-infused psilocin candidate TRP-8803 will be compared to widely used antidepressant escitalopram (Lexapro)
- Company secures pre-CTA with the University of California, San Francisco (UCSF) to develop a Phase II head-to-head trial in major depressive disorder
- Entropy says escitalopram is most widely prescribed antidepressant in the US, providing an established benchmark to directly evaluate TRP-8803
Special Report: Entropy’s lead intravenously infused psilocin candidate TRP-8803 will go head-to-head with one of the most widely prescribed antidepressants escitalopram (Lexapro) in a landmark trial.
Entropy Neurodynamics (ASX:ENP) has signed a pre-Clinical Trial Agreement (pre-CTA) with the University of California, San Francisco (UCSF) to undertake a Phase II trial to compare its proprietary IV-infused psilocin TRP-8803 with escitalopram.
The company said escitalopram was the most widely prescribed antidepressant in the US and world. It will be compared to TRP-8803 in up to 80 young adults with Major Depressive Disorder (MDD) in the Phase II trial.
Entropy said 21 million US adults experienced a major depressive episode annually, with prevalence highest among 18-25 year olds at 18.6%.
Standard treatment for MDD is with selective serotonin reuptake inhibitors (SSRIs), such as escitalopram, with ~37m prescriptions to 8.8m patients of the medication administered to patients in the US alone in 2023.
Entropy said treatment typically involved ongoing daily dosing and use could be associated with emotional blunting, sexual dysfunction and other tolerability issues that may affect quality of life and treatment adherence.
“Response to SSRIs can also vary widely between patients, creating a need for alternative treatment approaches that can deliver meaningful and durable outcomes without reliance on continuous daily medication,” the company said.
Stepping in the ring with escitalopram
The proposed Phase II trial will investigate whether a limited course of TRP-8803 can deliver meaningful clinical and functional outcomes to patients when compared directly with conventional daily SSRI treatment in young adults experiencing MDD.
The trial will recruit young adults in the US with MDD and assess depression severity over eight weeks and six months.
It will use established measures of depression together with treatment adherence, tolerability and key safety assessments.
Secondary measures will be included to assess patient wellbeing, meaning and connectedness, work, social functioning and longer-term outcomes.
The trial is also expected to incorporate EEG measures, including complexity, spectral power and network dynamics, to investigate potential mechanistic differences between precision controlled IV psilocin and conventional SSRI treatment.
Leading figure in field to head trial
Entropy said the proposed Phase II trial was expected to start in H1 CY27 and with principal investigator Professor Robin Carhart-Harris, one of the world’s foremost researchers in psychedelic therapies.
He is the Ralph Metzner Distinguished Professor of Neurology and Psychiatry at UCSF, with the trial to build on his landmark New England Journal of Medicine (NEJM) study directly comparing oral psilocybin with escitalopram in patients with moderate-to-severe MDD.
TRP-8803 has been designed to address key limitations associated with oral psilocybin administration, delivering rapid onset, precise control over treatment duration, intensity and predictability of the psychedelic experience.
“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,” Carhart-Harris said.
“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.”
He said the proposed trial would 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,” he said.
“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.”
‘Bold and revolutionary step forward for TRP-8803’
The proposed trial advanced two key elements of Entropy’s development strategy for TRP-8803.
The first is evaluating the treatment at an earlier timepoint in the depression treatment pathway.
“This is a bold and revolutionary step forward for TRP-8803 and significantly expands the clinical and regulatory pathway we are building around the program,” Entropy CEO Jason Carroll said.
“What is particularly compelling about this trial is that we are moving upstream in the treatment pathway.
“Until now, the development of novel therapies for depression have focused on patients who have already failed years on conventional treatments.
“We want to understand whether a limited number of precision-controlled TRP-8803 treatments can provide an effective alternative treatment in young adults experiencing major depression much earlier in the condition progression.”
Entropy and UCSF are now progressing activities required to develop the proposed Phase II trial in the US, including preparing to submit an investigational new drug application (IND) with the US Food and Drug Administration for TRP-8803.
Establishing an IND for TRP-8803 is the second key element in its proposed development strategy, providing a US regulatory foundation that could support broader development beyond MDD.
Entropy announced earlier this month it had received Human Research Ethics Committee (HREC) approval for a 72-patient, eight-indication Phase 1b/2a Basket-design trial with Swinburne University of Technology.
The trial is intended to generate indication-specific efficacy signals to guide future development priorities.
Entropy is also undertaking a phase II trial of TRP-8803 in binge eating disorder (BED) with Swinburne University of Technology.
“As data emerges from our 72-patient Basket-design Study in Australia, this may support a pathway to advance selected indications into subsequent Phase 2b/3 studies in the US,” Carroll said.
Contract Development and Manufacturing Organisation (CDMO) BioCina is set to manufacture TRP-8803 and matched placebo vials for the US clinical program, providing the scalable manufacturing capabilities to support future clinical development.
Entropy last week announced it had entered a new development and manufacturing services deal for TRP-8803 BioCina.
“We’ve been building these pieces very carefully and deliberately over the last 18 months,” Carroll said.
“We now have a broad Australian clinical program underway, a proposed US trial with the world’s leading psychedelic researcher, a pathway towards an IND with the FDA and a manufacturing relationship with BioCina, designed to support TRP-8803 as the program advances.
“Together, these initiatives are intended to generate the clinical evidence required to determine where TRP-8803 may have the greatest therapeutic potential and open the company to commercial partnership discussions.”
This article was developed in collaboration with Entropy Neurodynamics, a Stockhead advertiser at the time of publishing.
This article does not constitute financial product advice. You should consider obtaining independent advice before making any financial decisions.
