Entropy Neurodynamics (ASX: ENP) has announced breakthrough results from a Phase 2a study of TRP-8802 in patients with treatment-resistant irritable bowel syndrome (IBS).
The open-label study evaluated two doses of the oral psilocybin administered with structured psychotherapy in 12 patients who had previously failed multiple standard treatments.
The findings showed that 75% of patients achieved clinically meaningful improvements, demonstrating strong association between changes in symptoms and changes in psychological drivers, including insight and flexibility.
This confirmed that the therapy was acting on central brain pathways (not just masking symptoms) and engaging the gut-brain axis (which is a core driver of IBS), which aligns with Entropy’s mechanism-based development strategy.
One serious adverse event was recorded and resolved with appropriate clinical support, underscoring the importance of standard psychological screening and integration procedures.
Strong Response Rates
The results exceeded response rates of between 17% and 44% typically observed with approved IBS therapies, where treatment failure and relapse are common, thereby providing compelling evidence that psychedelic-assisted therapy can deliver mechanistically coherent benefits in one of the most difficult-to-treat chronic conditions.
Entropy expects the mechanistic coherence to significantly de-risk its drug development program and support progression to larger controlled studies.
“To deliver a 75% response rate in a treatment-resistant population, where existing therapies typically achieve only modest outcomes, is clinically unprecedented,” chief executive officer Jason Carroll said, calling the results a “breakthrough moment for Entropy and for the treatment of IBS.”
“Importantly, […] we are seeing clear alignment between clinical outcomes and improvements in psychological drivers—reinforcing that we are targeting the root cause of disease through the gut-brain axis.”
TRP-8803 Development
The TRP-8802 program was designed to inform the development of TRP-8803, Entropy’s proprietary intravenous (IV) infused psilocin formulation.
TRP-8803 offers several advantages over oral psilocybin including faster onset of action, along with precise control over the dose, depth, and duration of therapeutic effect.
This provides both an improved patient and therapist experience and a more commercially scalable treatment model.
The Phase 2a trial provided direct mechanistic validation for the use of TRP-8803 for the treatment of IBS, significantly enhancing its commercial and partnering profile.
Mr Carroll said Entropy would continue to review its IBS dataset as it commences its planning for new US-based clinical trials and pursues non-dilutive grant funding to advance such trials using TRP-8803 in IBS.
Chronic Gut Disorder
IBS is a chronic gut‑brain disorder characterised by pain, bloating, constipation, diarrhoea, urgency, and impaired quality of life.
It is believed to affect 10.4 million people in the US and over 1 million in Australia, with high unmet need in treatment-resistant populations.
IBS patients commonly cycle through up to 10 therapies, demonstrating a strong willingness to adopt new treatments despite incurring substantial out-of-pocket costs.
Entropy believes TRP-8803 has the potential to deliver a best-in-class therapeutic profile in the multi-billion dollar global IBS market.
