Definium Therapeutics, Inc. ("Definium" or the "Company"), a late-stage clinical biopharmaceutical company developing a new generation of therapeutics intended to address underlying causes of psychiatric and neurological disorders, today announced positive topline results from Emerge, its first randomized, double-blind, placebo-controlled Phase 3 study evaluating a single dose of DT120 (lysergide) ODT 100 µg in adults with major depressive disorder (MDD).

Emerge met its primary endpoint, demonstrating a statistically significantand 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, 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, 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."

DT120 ODT was generally well tolerated with 99% of treatment-emergent adverse events mild to moderate in severity, transient, and predominantly occurring on the day of dosing. 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, Ph.D., Emerge principal investigator, 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."