Positive Topline Results From Phase 3 Emerge Study of DT120 ODT in Major Depressive Disorder

Definium Therapeutics today announced positive topline results from phase 3 study Emerge evaluating a single dose of DT120 (lysergide) ODT 100 µg in adults with major depressive disorder (MDD). Notably, the study met primary and all key secondary efficacy endpoints.¹

Emerge was a phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of a single 100 µg dose of DT120 ODT vs placebo in adult participants with MDD. The study consisted of 2 parts: (1) a 12-week double-blind phase, known as Part A, followed by a (2) 40-week open-label extension phase, known as Part B, during which participants were eligible to receive DT120 ODT based on symptom severity. The study enrolled a total of 149 participants aged 18 to 74 years across 20 sites with a DSM-5-confirmed diagnosis of MDD, a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of at least 26, and a Clinical Global Impression–Severity (CGI-S) score of at least 4 at screening and baseline. The primary endpoint was change from baseline in the MADRS total score at week 6. Key secondary endpoints are change from baseline in CGI-S score at week 6, week 12, and day 2 and change from baseline in MADRS total score at week 12 and week 1.

Emerge achieved its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement from baseline compared with placebo, as measured by the change in MADRS total score at week 6. The Least Squares (LS) mean change from baseline in MADRS total score at week 6 in participants who received DT120 ODT 100 µg was -13.3 compared with -5.2 for patients who received placebo, equating to a LS mean difference of -8.1 points (P<0.0001).

Beyond the primary endpoint, the effect was rapid with a placebo-adjusted LS mean reduction in MADRS total score at week 1 of -14.2 (P <0.0001) and durable with a placebo-adjusted LS mean reduction in MADRS total score of -7.3 at week 12 (P <0.0001).

“The Emerge topline results represent unprecedented and highly differentiated efficacy, demonstrating that a single dose of DT120 ODT can deliver rapid, robust, and durable relief in MDD,” said Rob Barrow, the chief executive officer of Definium Therapeutics. “As the first of our phase 3 studies to report results, Emerge marks a major milestone in our development program and strengthens our confidence in DT120 as a potential best-in-class treatment for mental health disorders. These findings could support a fundamentally new approach to treating MDD for patients and providers who continue to face the limitations of existing treatment options. We are deeply grateful to the patients and investigators who participated in this trial. Grounded in decades of scientific research, these results bring us one step closer to potentially delivering a transformative new treatment option as we advance toward FDA submission.”

As to safety profile, DT120 ODT was generally well tolerated with 99% of treatment-emergent adverse events being mild to moderate in severity, transient, and predominantly occurring on dosing day. No new safety signals were identified, including no increase in suicidal ideation or behavior, and discontinuation rates were low and comparable between treatment groups. On the day of dosing, participants were assessed hourly from hours 5 to 8 on a structured end of session checklist (EoSC). The average time to meeting EoSC criteria was 5.8 hours for participants receiving DT120 ODT in Part A, with a median of 5.1 hours and 100% of participants meeting the EoSC criteria by hour 8.

“Many patients with MDD aren't helped by existing treatments, often experiencing partial responses, frequent medication changes, and long-term side effects,” said John Sonnenberg, PhD, principal investigator of Emerge, clinical psychologist, founder of Uptown Research Institute, and faculty member at Northwestern University Feinberg School of Medicine. "The Emerge topline results demonstrate that a single dose of DT120 ODT can produce a meaningful and durable benefit for people with depression. Importantly, these results stand apart from existing treatments, representing a potentially new paradigm for the management of major depression."

Emerge is 1 of 2 pivotal phase 3 studies in MDD. The second phase 3 study, Ascend, also includes a low dose arm and is conducted in 2 parts. Part A consists of a 12-week, randomized, double-blind, placebo-controlled, parallel-group period; Part B id a 40-week extension period during which participants will be eligible for open-label treatment with DT120 ODT based on symptom severity. Investigators will randomly assign participants 2:1:2 to receive DT120 ODT 100 µg, DT120 ODT 50 µg, or placebo. The 50 µg arm is intended to confound participants’ ability to accurately assess the dose condition to which they have been randomized. The primary endpoint of Ascend is change from baseline in MADRS total score at week 6 between DT120 ODT 100 µg and placebo.²

References

1. Definium Therapeutics announces positive topline results from phase 3 Emerge study of DT120 orally disintegrating tablet (ODT) in major depressive disorder. June 22, 2026. Accessed June 22, 2026. https://www.businesswire.com/news/home/20260622572802/en/Definium-Therapeutics-Announces-Positive-Topline-Results-from-Phase-3-Emerge-Study-of-DT120-Orally-Disintegrating-Tablet-ODT-in-Major-Depressive-Disorder

2. A Phase 3 Trial of DT120 for Major Depressive Disorder (Ascend). Clinicaltrials.gov. Accessed June 22, 2026. https://clinicaltrials.gov/study/NCT07592689