Definium Therapeutics Inc (DFTX) Study result summary

Study design and methodology

• Phase III EMERGE study was a randomized, double-blind, placebo-controlled trial evaluating a single 100 µg dose of DT120 ODT in adults with major depressive disorder (MDD) over 12 weeks, followed by a 40-week open-label extension (Part B).

• 149 participants aged 18–74 with DSM-5-confirmed MDD were enrolled; 84–85% completed Part A, with demographics representative of the MDD population and high baseline severity (MADRS 34.5).

• Participants were tapered off background antidepressants and anxiolytics, with no concurrent psychotherapeutic intervention.

• The primary endpoint was MADRS score at week six, assessed by blinded central raters; key secondary endpoints included MADRS and CGI-S changes at Weeks 1, 6, and 12.

• Part B allowed up to four open-label doses over 40 weeks for those with moderate or worse symptoms, with interim analysis showing mean MADRS at entry of 26.5.

Efficacy results

• DT120 ODT showed rapid, robust, and durable efficacy, with an 8.1-point placebo-adjusted improvement on MADRS at week six and 7.3 points at week 12 (p<0.0001).

• Rapid onset observed: 14.2-point MADRS separation from placebo at week one (p<0.0001).

• Response (≥50% MADRS reduction) at week six was 35–41% for DT120 vs 7–13% for placebo; remission (MADRS ≤12) was 24% for DT120 vs 3% for placebo.

• Statistically and clinically significant improvements were observed on all primary and key secondary endpoints, including CGI-S.

• Efficacy was consistent across key subgroups, including those with treatment-resistant depression and prior psychedelic exposure.

Safety and tolerability

• DT120 ODT was generally well tolerated; 99% of adverse events were mild to moderate, transient, and resolved on dosing day.

• No serious adverse events, no suicidality signal, and no study withdrawals due to adverse events.

• Most common adverse events included illusion (64%), euphoric mood (29%), and nausea (27%), with perceptual, affective, and behavioral changes expected during dosing.

• Treatment session duration was predictable: average time to clear end-of-session checklist was 5.8 hours, with all participants cleared by 8 hours.