Definium Therapeutics, Inc. Announces First Patient Dosed In Ascend, The Second Phase 3 Pivotal Study Of DT120 ODT In Major Depressive Disorder
DFTX
Published on 05/12/2026 at 09:21 am EDT
Definium Therapeutics, Inc. (Nasdaq: DFTX) dosed the first patient in Ascend, its second Phase 3 study evaluating DT120 ODT (lysergide tartrate) for the treatment of major depressive disorder (MDD). The Ascend study will evaluate the efficacy and safety of DT120 ODT versus placebo and is expected to enroll 175 participants in the United States. The primary endpoint will measure the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) score at Week 6 between DT120 Orally Disintegrating Tablet (ODT) 100 µg and placebo.
Ascend builds on positive Phase 2b study results in generalized anxiety disorder, which showed the potential antidepressant effects of DT120. Topline data from the 12-week double-blind period is anticipated in 2027. The design of Ascend is aligned with Emerge, as well as the Company?s Phase 3 trials of DT120 ODT in generalized anxiety disorder (GAD), and is conducted in two parts: Part A, a 12-week, randomized, double-blind, placebo-controlled, parallel-group period; and Part B, a 40-week extension period during which participants will be eligible for open-label treatment with DT120 ODT based on symptom severity.
As with the Company?s Panorama study of DT120 ODT in GAD, participants will be randomized 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.
This approach continues to build on the Company?s Phase 2b study of DT120 in GAD, which the Company believes demonstrated that DT120's clinical activity is not attributable to functional unblinding and aligns with FDA guidance on the use of complementary designs across our DT120 clinical development program. The primary endpoint of Ascend is the change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS) at Week 6 between DT120 ODT 100 µg and placebo. DT120 ODT is an ergoline derivative belonging to the group of classic serotonergic psychedelics, which acts as a partial agonist at serotonin-2A (5-HT2A) receptors.
DT120 ODT is Definium?s proprietary and pharmaceutically optimized formulation of LSD. DT120 ODT is an advanced formulation incorporating Catalent?s Zydis® ODT fast-dissolve technology, designed to deliver several unique advantages, including faster absorption and onset of transient cognitive, perceptual, and affective changes, improved bioavailability, and a lower incidence of gastrointestinal side effects. Definium is developing DT120 ODT, the tartrate salt form of lysergide, for generalized anxiety disorder (GAD), major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and is exploring its potential applications in other serious brain health disorders.
Definium maintains a strong foundation to protect and extend the long-term value of the DT120 ODT franchise through a multi-layered intellectual property strategy spanning composition, formulation, and methods-of-use patents. Lysergide (LSD) is one of the most extensively studied psychopharmaceuticals in history, with over 1,000 published reports. First synthesized in 1938 by Swiss chemist Albert Hofmann in his search for active principles from ergot fungus, its profound psychological effects were discovered in 1943, which transformed psychiatric research.
LSD, a definitional classic psychedelic, temporarily alters perception, cognition, and emotion, is physiologically safe, non-addictive, and isn?t associated with withdrawal. While its precise mechanism of action in the treatment of psychiatric illness is unknown, its acute perceptual, cognitive, and affective effects are mediated by agonism of the serotonin 5-hydroxytryptamine 2A (5-HT2A) receptor, and mechanistic hypotheses suggest that it causes sustained increases in neuroplasticity in a variety of brain regions.