Entropy Neurodynamics (ASX: ENP) has reached a significant milestone in the evaluation of its major depressive disorder (MDD) treatment candidate after signing a pre-clinical trial agreement (pre-CTA) with the University of California, San Francisco (UCSF).

Under the pre-CTA, the planned phase two clinical trial will compare the company’s proprietary TRP-8803 (IV-infused psilocin) with escitalopram (Lexapro), the most widely prescribed antidepressant in the US.

The study, which will involve up to 80 young adults with MDD, marks an important expansion of the clinical development program for TRP-8803 and adds a direct head-to-head comparison with an established standard of care.

Chief executive Jason Carroll said the trial would help establish a pathway into the US by testing the treatment directly against an established antidepressant and the current standard of care in young adults with MDD.

“This is a bold and revolutionary step forward for TRP-8803 and significantly expands the clinical and regulatory pathway we are building around the program,” Mr Carroll said.

“Working with UCSF and Professor Carhart-Harris provides us with the opportunity to evaluate TRP-8803 directly against the most widely prescribed antidepressant in the US and the world, in a patient population where treatment decisions made early in the course of depression can have long-term implications.

“What is particularly compelling about this trial is that we are moving upstream in the treatment pathway. Until now, the development of novel therapies for depression have focused on patients who have already failed years on conventional treatments.

“We want to understand whether a limited number of precision-controlled TRP-8803 treatments can provide an effective alternative treatment in young adults experiencing major depression much earlier in the condition progression.”

Mr Carroll said the trial also carries strategic importance beyond MDD, with the planned US study forming part of a broader regulatory pathway for TRP-8803.

Subject to FDA clearance, establishing an IND for TRP-8803 would provide Entropy with a US regulatory foundation that could support broader development of the platform.

“As data emerges from our 72-patient Basket-design Study in Australia, this may support a pathway to advance selected indications into subsequent Phase 2b/3 studies in the US,” he said.

“We’ve been building these pieces very carefully and deliberately over the last 18 months. We now have a broad Australian clinical program underway, a proposed US trial with the world’s leading psychedelic researcher, a pathway towards an IND with the FDA and a manufacturing relationship with BioCina, designed to support TRP-8803 as the program advances.

“Together, these initiatives are intended to generate the clinical evidence required to determine where TRP-8803 may have the greatest therapeutic potential and open the company to commercial partnership discussions.”

Entropy and UCSF will now move ahead with the steps needed to develop the proposed Phase 2 trial in the US. These include finalising the clinical trial protocol and informed consent documents with UCSF.

The organisations also plan to schedule a pre-IND meeting with the FDA to confirm the protocol’s acceptability, submit an IND application to the US FDA for TRP-8803 for the proposed trial, and, after FDA clearance of the trial protocol, finalise the Clinical Trial Research Agreement (CTRA) with UCSF.

ENP was steady at 3.9¢ with a market capitalisation of $63.64 million.

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