Definium’s DT120 ODT Delivers Positive Phase 3 Results in GAD

Definium Therapeutics reported positive topline results from the Phase 3 Panorama trial of DT120 (lysergide) orally disintegrating tablet (ODT) in adults with generalized anxiety disorder (GAD), with the 100-µg dose producing a statistically significant and clinically meaningful reduction in anxiety symptoms at Week 12.

DT120 Meets the Phase 3 Primary Endpoint

Panorama met its primary endpoint, showing that a single 100 µg dose of DT120 ODT significantly reduced Hamilton Anxiety Rating Scale (HAM-A) scores versus placebo. At Week 12, the least-squares mean change from baseline was -9.8 points with DT120 compared with -4.7 points with placebo, producing a placebo-adjusted difference of -5.1 points (p<0.0001; Cohen’s d=0.64).

The treatment effect emerged rapidly, with improvements reported as early as Day 2 and sustained across post-baseline assessments during the 12-week double-blind period. DT120 also met its key secondary endpoints, including changes in Clinical Global Impression-Severity (CGI-S) at Week 12, HAM-A at Week 1, and CGI-S at Day 2.

At Week 12, 32% of patients receiving 100 µg achieved at least a 50% reduction in HAM-A scores versus 14% with placebo. HAM-A remission, defined as a score of 7 or lower, occurred in 15% versus 4%, respectively. An additional measure showed that 35% of patients receiving 100 µg had mild or better anxiety severity, defined as a HAM-A score below 16, compared with 17% with placebo (p<0.01).

Trial Design and Single-Dose Treatment

Panorama enrolled 245 adults aged 18 to 74 years with DSM-5-confirmed GAD and baseline HAM-A scores of at least 20. Participants were randomized 2:1:2 to a single dose of 100 µg DT120 ODT, 50 µg DT120 ODT, or matching placebo. The 50-µg arm was included to help mitigate functional unblinding and was not designed or powered for statistical efficacy comparisons.

The study included a 12-week double-blind treatment period followed by a 40-week open-label extension. During the extension, eligible participants could receive up to four additional 100 µg doses based on symptom severity, giving the study an approximate total duration of 56 weeks.

Safety and Dosing-Day Monitoring

DT120 ODT 100 µg was generally well tolerated. Most treatment-emergent adverse events were mild to moderate, transient, and occurred predominantly on the day of dosing. Definium reported no new safety signals, including no suicidality signal or suicidal behavior, and no drug-related serious adverse events.

Overall discontinuation rates were similar across the 100 µg, 50 µg, and placebo groups at 10.4%, 11.5%, and 10.3%, respectively. Common dosing-day adverse events with 100 µg included illusion (68%), nausea (37%), and headache (24%).

Because DT120 produces acute perceptual and cognitive effects, participants were monitored for at least eight hours on dosing day. In Panorama, 94% of patients receiving 100 µg met structured end-of-session criteria by hour 8, with an average time to meeting the criteria of 6.2 hours and a median of 6.0 hours. Across more than 1,000 treatment sessions in the Phase 3 program through September 10, 2026, 97% of participants met the criteria by hour 8.

Serotonergic Psychedelic Mechanism

DT120 ODT is Definium’s proprietary formulation of lysergide, an ergoline-derived classic serotonergic psychedelic and partial agonist of the serotonin 5-HT2A receptor. The formulation incorporates Catalent’s Zydis fast-dissolve ODT technology.

The precise mechanism underlying lysergide’s sustained therapeutic effects in psychiatric disorders remains uncertain. Its acute perceptual, cognitive, and affective effects are mediated through 5-HT2A receptor activity, while sustained changes in neuroplasticity have been proposed as a potential contributor to longer-lasting therapeutic effects.

GAD remains a substantial treatment gap. Definium estimates that approximately 26 million U.S. adults are affected, while pharmacologic innovation in the disorder has remained limited, with the last new drug approval occurring in 2007.

NDA Filing Expected in 2027

Panorama is the second positive Phase 3 trial for DT120 ODT in GAD and the company’s third positive Phase 3 readout overall, following the positive Voyage study in GAD and Emerge study in major depressive disorder.

Definium expects to meet with the FDA for a pre-NDA meeting in the fourth quarter of 2026 and anticipates filing an NDA in the first half of 2027. DT120 ODT has received FDA Breakthrough Therapy designation for both GAD and MDD.

Reference

Definium Therapeutics Announces Positive Topline Results from Phase 3 Panorama Study of DT120 ODT in Generalized Anxiety Disorder, Definium, 14 September 2026

A Phase 3 Trial of MM120 for Generalized Anxiety Disorder (Panorama), ClinicalTrials.gov ID NCT06809595