Definium Therapeutics Inc (DFTX) Study result summary

Study Overview and Design

• The Phase 3 Voyage study evaluated DT120 ODT, a proprietary lysergide tartrate formulation, in adults with generalized anxiety disorder (GAD), enrolling 214 participants aged 18–74 with DSM-5-confirmed GAD and baseline HAM-A ≥20, randomized 1:1 to DT120 ODT or placebo across 35 US sites.

• The study included a 12-week double-blind period (Part A) and a 40-week open-label extension (Part B), with participants tapered off background medications and receiving a single dose of DT120 or placebo, followed by blinded efficacy assessments.

• The primary endpoint was change from baseline in HAM-A total score at week 12, assessed by independent raters; key secondary endpoints included CGI-S at week 12, HAM-A at week 1, and CGI-S at day 2.

• Panorama, a second pivotal Phase 3 study, is ongoing and includes a low-dose arm to address potential unblinding.

• DT120 ODT is an advanced, fast-dissolving formulation of lysergide (LSD), designed for improved absorption and tolerability, and has received FDA Breakthrough Therapy designation for GAD.

Efficacy Results

• DT120 ODT achieved a 5.4-point placebo-adjusted improvement on HAM-A at week 12 (LS mean change: -11.6 DT120 vs. -6.2 placebo, p<0.0001, Cohen's d=0.81), with rapid onset as early as day 2 and sustained efficacy at all post-baseline timepoints.

• Key secondary endpoints were met, including significant improvements in CGI-S at week 12 and day 2, and HAM-A at week 1.

• Response (≥50% HAM-A reduction) and remission (HAM-A ≤7) rates at week 12 were higher for DT120 ODT (up to 60% remission, 51% response) vs. placebo (up to 23% remission, 16% response), with efficacy consistent across subgroups, including those with prior treatment failures.

• Statistically significant improvements were observed for both HAM-A and CGI-S scores at all timepoints.

• Efficacy was consistent across subgroups, including those with two or more prior treatment failures.

Safety and Tolerability

• DT120 ODT was generally well tolerated, with all adverse events mild to moderate, transient, and mostly resolving on dosing day; no serious adverse events or suicidality signals were observed.

• Most common adverse events included transient perceptual, affective, cognitive, and behavioral changes, as well as illusion, nausea, euphoric mood, and headache.

• Average session duration was 6.4 hours, with over 90% of participants meeting end-of-session criteria by hour eight.

• The end-of-session checklist, developed with FDA input, assesses readiness to leave and is expected to translate well to clinical practice.

• No new safety signals or suicidality detected in the DT120 ODT arm.