Entropy Neurodynamics (ASX:ENP) has reported Phase 2a results suggesting a potential new direction for patients with treatment-resistant irritable bowel syndrome.
Presented at Digestive Disease Week 2026 by teams from Massachusetts General Hospital and Columbia University, the open-label pilot found that 75 per cent of participants met a predefined clinical response threshold on the IBS Symptom Severity Score after two oral psilocybin doses given with structured psychotherapy.
The trial enrolled 12 patients who had failed multiple standard treatments and delivered a response signal far stronger than typical approved therapies.
Subgroup outcomes were notable, with IBS C showing a 100 per cent response rate, IBS M 80 per cent, and IBS D 50 per cent.
Investigators linked symptom improvement to psychological mechanisms. Reductions in psychological inflexibility and gains in psychological insight correlated with clinical benefit, while gut-specific anxiety showed minimal change. That pattern supports a gut-brain axis mechanism acting on central pathways rather than simply masking peripheral symptoms.
Entropy frames the oral psilocybin program TRP 8802 as a mechanistic de-risking step for its next-generation product TRP 8803, an IV-infused psilocin formulation. The company argues that intravenous dosing should provide faster onset and more precise, controllable exposure than oral psilocybin and that the Phase 2a data strengthen TRP 8803s commercial and partnering proposition.
CEO Jason Carroll said, “These results represent a breakthrough moment for Entropy and for the treatment of IBS. To deliver a 75 per cent response rate in a treatment-resistant population, where existing therapies typically achieve only modest outcomes, is clinically unprecedented. Importantly, the dataset is mechanistically coherent. 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 8802 has now de-risked both the indication and the mechanism, while TRP 8803 is designed to unlock the full commercial potential of this opportunity. We see a clear pathway to building a leading, differentiated franchise in gut-brain disorders.”
The company said larger, controlled, and subtype-stratified trials are needed to confirm durability, safety, and effect size.