Australian psychedelic biotechnology company Entropy Neurodynamics (ASX: ENP) has secured Human Research Ethics Committee (HREC) approval to begin what it describes as the world’s first Phase 1b/2a basket trial evaluating an intravenous psilocin therapy across eight separate disorders.
The study will assess the company’s lead candidate, TRP-8803, in 72 participants and represents a significant expansion of its clinical development strategy beyond single-indication trials. Rather than pursuing separate studies for each condition, Entropy will investigate multiple disorders within a single clinical framework to identify where the therapy demonstrates the strongest clinical potential.
The company has also signed an expanded Clinical Trial Research Agreement with Swinburne University, which will provide additional clinical infrastructure and specialist expertise to support the study.
Eight disorders in one trial
The open-label study will evaluate the safety, tolerability and preliminary efficacy of TRP-8803 across eight conditions characterised by significant unmet medical need and, according to the company, overlapping biological mechanisms.
The indications include:
- Treatment-resistant depression
- Generalised anxiety disorder
- Post-traumatic stress disorder (PTSD)
- Obsessive-compulsive disorder (OCD)
- Anorexia nervosa
- Body dysmorphic disorder
- Fibromyalgia
- Irritable bowel syndrome (IBS)
Treatment-resistant depression will be studied in two separate cohorts, allowing researchers to compare outcomes in patients taking antidepressants with those who are not.
Participants will receive two intravenous doses of TRP-8803 approximately two weeks apart alongside structured psychedelic-assisted psychotherapy. Researchers will also collect MRI, functional MRI, EEG, speech analysis and patient-reported outcome data to better understand both clinical responses and potential biomarkers.
Building on encouraging binge eating disorder data
The basket study follows encouraging early results from Entropy’s Phase 2 binge eating disorder program, where the first patient cohort recorded a 100% clinical response rate and 50% remission rate, according to the company.
Entropy believes evaluating multiple disorders simultaneously will allow it to identify the most promising commercial and clinical opportunities while expanding the safety database for its intravenous psilocin platform.
Chief Executive Officer Jason Carroll said the approach could substantially accelerate development compared with pursuing each indication individually.
“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.”
Why intravenous psilocin?
Unlike conventional oral psilocybin, TRP-8803 delivers psilocin—the active metabolite responsible for psychedelic effects—directly into the bloodstream via intravenous infusion.
Entropy says this approach offers several potential advantages, including:
- More consistent drug exposure between patients
- Greater control over treatment intensity
- Faster onset
- Shorter treatment sessions
- The ability for clinicians to pause or stop the infusion if clinically required
The company argues these features could make psychedelic-assisted therapy more predictable and potentially more practical for clinical use than oral psilocybin.
A platform rather than a single drug program
Beyond evaluating individual disorders, Entropy says the trial is designed to test a broader transdiagnostic hypothesis—that several psychiatric and chronic pain conditions share common mechanisms involving cognitive rigidity, altered brain network function and reduced cognitive flexibility.
By collecting biomarker data across all eight conditions, researchers hope to determine whether common biological changes correlate with clinical improvements regardless of diagnosis.
If successful, the findings could help prioritise future late-stage development programs while supporting the company’s broader IV psilocin platform strategy.
