Entropy Neurodynamics has signed an agreement with the University of California, San Francisco (UCSF), to develop a US Phase 2 trial comparing its intravenous psilocin treatment TRP-8803 with the widely used antidepressant escitalopram in young adults with major depressive disorder.
The proposed study, which is expected to begin in the first half of 2027 subject to US Food and Drug Administration clearance, would recruit up to 80 participants and compare a limited course of TRP-8803 with daily escitalopram. It will assess depression severity over eight weeks and six months, alongside safety, tolerability, adherence, wellbeing and social and work functioning.
TRP-8803 is an intravenous formulation of psilocin, the active metabolite of psilocybin. The trial will test whether a psychedelic-assisted treatment can compete earlier in the depression treatment pathway rather than being reserved for people who have exhausted conventional options.
Entropy will sponsor the investigational new drug application to the FDA and will work with UCSF to finalise the study protocol, consent material and electronic data systems. If the FDA permits the study to proceed, the IND could provide a foundation for further US development across other conditions studied in the company’s Australian program.
The trial will be led by Professor Robin Carhart-Harris, the UCSF neurologist and psychiatrist whose earlier research helped place psychedelic therapies back at the centre of mainstream psychiatric debate. Carhart-Harris was lead author of the 2021 New England Journal of Medicine trial that compared psilocybin therapy with escitalopram in people with moderate-to-severe depression.
Entropy’s broader development program includes an Australian 72-patient basket study across eight indications with Swinburne University of Technology. It has also appointed BioCina to manufacture GMP-grade TRP-8803 and matched placebo vials for the US program. The company says these elements are intended to create a scalable clinical and manufacturing base as it decides which conditions should move into later-stage trials.
