Entropy, UCSF Pre-CTA for Ph2 psilocin vs Lexapro in MDD

Melbourne, Australia-based biotech Entropy Neurodynamics has signed a Pre-Clinical Trial Agreement (Pre-CTA) with the University of California, San Francisco (UCSF) to develop a US-based Phase 2 trial comparing its precision-controlled IV psilocin treatment directly against escitalopram (Lexapro), the most widely prescribed antidepressant in the US.

Entropy Neurodynamics is a clinical-stage biotechnology company developing precision-controlled psychedelic therapies. The proposed trial is an important expansion of the clinical development programme for Entropy’s proprietary TRP- 8803 (IV-infused psilocin), establishing a pathway into the US and evaluating the treatment directly against an established antidepressant treatment, and the current standard of care in young adults with Major Depressive Disorder (MDD).

MDD is standardly treated with selective serotonin reuptake inhibitors (SSRIs), such as escitalopram. Escitalopram recorded ~37 million prescriptions across 8.8 million US patients in 2023, while ~21 million US adults experience a major depressive episode each year.

While SSRIs are widely used, treatment typically involves ongoing daily dosing and their use can be associated with emotional blunting, sexual dysfunction, and other tolerability issues that may affect quality of life and treatment adherence.

Psilocin is the active metabolite of psilocybin, and Entropy’s TRP-8803 platform is designed to provide rapid onset and greater control over the duration, intensity, and predictability of the psychedelic experience compared with oral administration.

The proposed study will recruit up to 80 young adults with MDD. It will be led by Professor Robin Carhart-Harris, who is the Ralph Metzner Distinguished Professor of Neurology and Psychiatry at UCSF and one of the world’s foremost researchers in psychedelic therapies. His research has played a significant role in advancing the modern scientific understanding of psychedelic therapies, including as lead author of the landmark New England Journal of Medicine trial directly comparing psilocybin therapy with escitalopram in patients with moderate-to-severe MDD.

The proposed trial will build on Dr Carhart-Harris’ NEJM trial to evaluate whether the precision, predictability, and control offered by TRP-8803 can further enhance the potential of psychedelic therapy when compared directly with an established SSRI.

Under the pre-CTA agreement, Entropy and UCSF will work closely to develop the clinical trial protocol, informed consent, and establish the electronic data capture forms for the proposed trial. Entropy will act as the FDA Investigational New Drug (IND) sponsor and, with UCSF’s support, progress the required regulatory activities to support commencement of the trial in the United States.

Importantly, establishing an FDA IND for TRP-8803 provides a broader US regulatory foundation for the clinical development programme, including those informed by results from Entropy’s ongoing 72-patient, eight-indication Phase 1b/2a Basket-design Study with Swinburne University of Technology.

The trial is expected to also incorporate EEG measures, including complexity, spectral power, and network dynamics, to investigate potential mechanistic differences between precision-controlled IV psilocin and conventional SSRI treatment.

BioCina will manufacture the GMP-grade TRP-8803 and matched placebo vials for the US clinical programme, providing the scalable manufacturing capabilities to support future clinical development.

Entropy’s CEO and executive director, Jason Carroll, stated: “We’ve been building these pieces very carefully and deliberately over the last 18 months. We now have a broad Australian clinical programme 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 programme 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."

Psychedelics continue to be an ever-more-popular mental health R&D area: only last month, Eli Lilly bought AtaiBeckley in a $3.8bn deal for the psychedelic medicine company's two lead programmes: BPL-003, an intranasal formulation of mebufotenin benzoate that generated positive results in a phase 2b trial in treatment-resistant depression (TRD); and VLS-01, a buccal film formulation of DMT for major depressive disorder (MDD).