TRIAL SUCCESS

Definium's single-dose DT120 clears MDD Phase 3 with an 8.1-point MADRS edge

Emerge, the first of two pivotal Phase 3 studies for the 5-HT2A psychedelic, hit its primary endpoint with rapid, durable separation from placebo and no new safety signal.

Definium Therapeutics reported that its Phase 3 Emerge trial of a single 100 microgram dose of DT120 (lysergide) orally disintegrating tablet met its primary endpoint in major depressive disorder.

By AppliedXLJune 22, 2026Trial NCT06941844

Executive Summary

Definium's Phase 3 trial of a single-dose psychedelic in major depressive disorder met its primary endpoint, separating from placebo on the standard depression rating scale used across the field.
This is the first of two pivotal trials the company needs before it can pursue FDA submission, and the effect showed up within a week of dosing and persisted through twelve weeks.
The company reported no new safety signal, including no increase in suicidal ideation, in a mechanism class where tolerability has been a central question.
The result lands in a Phase 3 field where several 5-HT2A-acting psychedelics are advancing toward the same indication, none of which has yet secured FDA approval in depression.
A second, differently designed pivotal trial in the same program must still confirm the finding before the company can move toward regulatory submission.

The result

Definium Therapeutics, Inc. announced on June 22, 2026 that Emerge, its Phase 3 trial of DT120 (lysergide) orally disintegrating tablet 100 micrograms in adults with major depressive disorder, met its primary endpoint. Participants receiving DT120 showed a least-squares mean reduction of 13.3 points on the Montgomery-Asberg Depression Rating Scale (MADRS) at Week 6, compared with 5.2 points for placebo, a difference of 8.1 points (p<0.0001). The trial, registered as NCT06941844, is a randomized, double-blind, placebo-controlled, triple-masked study that enrolled 149 adults across 20 U.S. sites, with a mean baseline MADRS score of 35.0 in the DT120 group and 34.0 in the placebo group. The primary completion date moved up from November 1, 2026 to May 20, 2026 as the trial closed enrollment on schedule and reported out early. Definium+2

Probability of Success

Endpoint Met77%

Completes81%

Clinical Significance40%

Regulatory58%

Speed and durability

Beyond the Week 6 primary readout, the placebo-adjusted effect reached 14.2 points at Week 1 and held at 7.3 points at Week 12, both at p<0.0001. "The Emerge topline results represent unprecedented and highly differentiated efficacy, demonstrating that a single dose of DT120 ODT can deliver rapid and durable relief in MDD," said Rob Barrow, Definium's chief executive officer. John Sonnenberg, the trial's principal investigator and a clinical psychologist at Northwestern University Feinberg School of Medicine, said the results "stand apart from existing treatments, representing a potentially new paradigm for the management of major depression". Definium

Safety and tolerability

Definium reported that DT120 ODT was generally well tolerated, with 99% of treatment-emergent adverse events mild to moderate, transient, and occurring mostly on dosing day. The company said no new safety signals emerged, including no increase in suicidal ideation or behavior, and that discontinuation rates were low and comparable between arms. On dosing day, participants were monitored hourly from hours 5 to 8 using a structured end-of-session checklist; the average time to meeting checklist criteria was 5.8 hours, with all participants clearing the checklist by hour 8. Definium

Where this sits in the field

DT120 acts as a 5-HT2A receptor partial agonist, a mechanism shared with a Phase 3 field that includes Intra-Cellular Therapies' lumateperone, COMPASS Pathways' psilocybin, and Definium's own MM120 program in generalized anxiety disorder. None of these programs has yet reached FDA approval in a mood-disorder indication on the evidence available here. Field activity around the 5-HT2A target has slowed, with 81 recent trials against 1,851 older ones, even as several late-stage single-dose psychedelic programs push toward the same MDD endpoint Emerge just cleared. Against that backdrop, the bar for DT120 is less about beating any single rival and more about whether the magnitude and durability seen here reproduce in Ascend, the second pivotal trial in the same program, which adds a low-dose arm designed to test whether the effect survives functional unblinding. Definium

What comes next

Definium said the Emerge findings "could support" advancing DT120 toward FDA submission, but the company has structured its MDD program around two pivotal trials, and Ascend has not yet read out. Ascend randomizes participants 2:1:2 to 100 microgram, 50 microgram, or placebo arms, a design the company says builds on its earlier Phase 2b generalized-anxiety-disorder study intended to show DT120's effect is not attributable to participants correctly guessing their treatment assignment. Definium

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.