Entropy Neurodynamics Gains Ethics Approval for Eight-Indication TRP-8803 Trial

Entropy Neurodynamics (ASX: ENP) has secured Human Research Ethics Committee approval for a Phase 1b/2a basket study of TRP-8803 across eight disorders and signed a Clinical Trial Research Agreement (CTRA) with Swinburne University.

The open-label study is expected to enrol 72 participants across nine cohorts of eight, with treatment-resistant major depressive disorder assessed in separate groups of patients receiving stable antidepressant therapy and those not taking antidepressants.

Other indications comprise anorexia nervosa, body dysmorphic disorder, obsessive compulsive disorder, generalised anxiety disorder, post-traumatic stress disorder, fibromyalgia, and irritable bowel syndrome.

Recruitment is due to begin shortly, with first dosing expected during the current quarter and dosing in one or more indication cohorts anticipated before the end of calendar year 2026.

Parallel Trial Design

Each participant will receive two doses of TRP-8803—Entropy’s proprietary intravenous  psilocin formulation—approximately two weeks apart alongside a structured psychedelic-assisted psychotherapy program.

Safety is the primary endpoint, while secondary and exploratory measures will assess anxiety, quality of life, disease-specific symptoms, and broader patient-reported outcomes.

The study will also examine magnetic resonance imaging (MRI), functional MRI, electroencephalography (EEG), speech analysis, and qualitative interviews to characterise biological and clinical effects across the indications.

“Rather than pursuing these indications sequentially, our world-first basket study enables us to evaluate them in parallel, significantly accelerating our understanding of where TRP-8803 has the greatest clinical and commercial potential,” chief executive officer Jason Carroll said.

"With first dosing expected later this quarter, we believe Entropy is entering one of the most active and value-generating periods in its history, with the potential to deliver multiple clinical milestones and further establish TRP-8803 as a differentiated precision-controlled psychedelic therapy.”

Platform Evidence Expanding

The study follows Phase 2 binge eating disorder (BED) results in which the first patient cohort achieved a 100% clinical response, 50% remission, and significant improvements in anxiety and depression.

TRP-8803 delivers psilocin directly into the bloodstream, avoiding gastrointestinal absorption and conversion from psilocybin while allowing clinicians to control treatment intensity and pause or terminate an infusion if clinically required.

Entropy expects the basket structure to provide a capital-efficient comparison of safety, clinical response, quality of life and treatment mechanisms across multiple disorders within a common protocol and biomarker framework.

The study is expected to cost approximately A$3.2 million before potential R&D tax incentive refunds, compared with the substantially greater investment required to conduct separate trials for every indication.

Increased Capacity from Swinburne

The expanded CTRA gives Entropy access to additional clinical infrastructure, multiple dedicated treatment rooms and a broader multidisciplinary team spanning investigators, psychiatrists, physicians, psychologists and psychedelic therapists.

This capacity is intended to improve patient throughput and support recruitment and dosing across several cohorts in parallel while providing a scalable research platform for future clinical programs.

The basket design will generate indication-specific findings and a broader transdiagnostic dataset examining whether cognitive rigidity, altered brain-network activity and related mechanisms respond to TRP-8803 across different conditions.

Entropy plans to use the resulting safety, efficacy and biomarker signals to prioritise future development opportunities and refine patient-selection strategies.

Recruitment and Next Steps

Following HREC approval, Entropy must complete remaining regulatory and site-governance requirements, including clinical trial notification acknowledgement and site-specific approvals, before treatment begins.

The group expects recruitment and dosing progress, cohort-level outcomes, additional BED data and biomarker analyses to provide several clinical milestones over the next 12 months.

Positive results could support the selection of lead indications for later-stage development, regulatory engagement and expanded biomarker work while creating potential development and partnering opportunities.

Success will be assessed through acceptable safety, encouraging efficacy signals, meaningful improvements in participant quality of life and functioning, as well as biomarker findings capable of informing future development decisions.