Definium Doses First Patient in Second Phase 3 LSD-Based Trial

NEW YORK – Definium Therapeutics Inc. has taken another step forward in its late-stage testing of a psychedelic-derived treatment for major depressive disorder. The company announced that the first participant received a dose in the Ascend study, its second Phase 3 trial of DT120 ODT.

DT120 ODT is Definium’s proprietary orally disintegrating tablet formulation of lysergide tartrate, a pharmaceutical version of LSD. The drug belongs to the class of serotonergic psychedelics and acts as a partial agonist at serotonin 2A receptors. It uses fast-dissolve technology aimed at providing faster absorption, better bioavailability, and fewer gastrointestinal side effects compared with traditional forms.

The Ascend trial is a randomized, double-blind, placebo-controlled study expected to enroll about 175 adults with major depressive disorder (MDD) in the United States. Participants will receive DT120 ODT at 100 micrograms, a 50-microgram control dose, or placebo in a 2:1:2 ratio. The primary endpoint focuses on change in Montgomery-Åsberg Depression Rating Scale scores at week six. The study includes a 12-week double-blind phase followed by a 40-week open-label extension. Topline data from the blinded portion are projected for 2027.

The scientific premise behind DT120 ODT draws from earlier work in a neighboring indication. Ascend builds on positive Phase 2b study results in generalized anxiety disorder (GAD), which showed the potential antidepressant effects of DT120. That GAD data gave Definium enough regulatory traction to secure Breakthrough Therapy Designation from the FDA for DT120 in that indication – a status that often accelerates the review process. This development builds on Definium’s ongoing Emerge Phase 3 trial in MDD, which has completed enrollment, with results anticipated later in 2026. Two GAD studies, Voyage and Panorama, are also approaching readouts within the same window, making three pivotal Phase 3 topline readouts expected within roughly six months.

Definium, rebranded from MindMed earlier this year, focuses on applying rigorous clinical standards to psychedelic compounds. Its approach seeks treatments that could address root causes of psychiatric conditions rather than only managing symptoms on an ongoing basis.

The regulatory backdrop adds context. On April 18, 2026, President Trump issued an Executive Order directing federal agencies to accelerate access to treatments for patients with serious mental illnesses, specifically psychedelics. Definium’s Chief Medical Officer, Daniel R. Karlin, M.D., M.A., said the executive order would not alter the company’s scientific direction but described the policy attention as a welcome signal for the field.

Definium also outlined an expansive commercial and intellectual property plan for DT120 ODT, positioning its proprietary LSD formulation as a potentially broad, clinic-ready treatment platform across multiple serious brain health disorders. That ambition now extends to PTSD, with the Phase 3 Haven study expected to initiate in 2027, enrolling approximately 200 participants.