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Definium Therapeutics (NASDAQ:DFTX) is approaching what Chief Executive Officer Rob Barrow described as an “incredibly exciting time,” with pivotal data expected this year for DT120, the company’s proprietary form of LSD being studied in generalized anxiety disorder (GAD) and major depressive disorder (MDD). Barrow, speaking during a Needham conference fireside chat moderated by biotech analyst Ami Fadia, said the company is preparing for three Phase III readouts, beginning with MDD data in late Q2 and the first GAD readout in early Q3.
Lead program DT120 and upcoming catalysts
Barrow positioned DT120 as part of “the next wave of really promising treatments in psychiatry,” emphasizing the company’s focus on trial design and execution as it heads into key readouts. He said the company’s MDD program will be followed by GAD results, noting the potential to “have a huge impact for patients out in the world.”
MDD Phase III EMERGE design and endpoints
After week 12, participants enter a 40-week extension period. Karlin said patients who reach “a moderate or worse severity on the MADRS” can receive up to four additional open-label treatments, at which point they are no longer randomized. He said the extension is designed both to encourage retention and to generate longer-term data while maintaining the initial blind for participants who have not yet received open-label retreatment.
Karlin said EMERGE is “80% powered to detect a 5-point difference on the MADRS,” adding that a placebo-adjusted 5-point change would be “remarkable relative to the current existing standard.”
Retreatment triggers and long-term follow-up
Karlin detailed how retreatment is triggered in the extension portion of the studies. Patient-reported PHQ-9 scores are collected biweekly, and centrally rated MADRS assessments are scheduled monthly or can be triggered by a PHQ-9 score of 10 or higher. A centrally rated MADRS score of 20 or higher makes a participant eligible for an open-label DT120 treatment.
He said the MADRS threshold was chosen to align with moderate symptom severity, which the company views as a practical proxy for functional impairment and likely real-world treatment decisions. Barrow added that, in the company’s view, value in these disorders is driven by improvements in severity and function rather than the number of prior treatment failures.
How Phase II GAD data inform expectations in MDD
Fadia asked how Definium’s prior Phase II GAD data—where the company also measured MADRS—supports confidence in the MDD Phase III program. Karlin said there is substantial overlap between GAD and MDD constructs and between the Hamilton Anxiety Scale (HAM-A) and MADRS measures. He argued that improvements observed across both scales in Phase II support “read-across” into an MDD population.
Karlin also noted that participants in the Phase II GAD trial were not in a major depressive episode, meaning baseline MADRS scores were lower than in the MDD program. He said a higher starting point in the MDD study (which requires MADRS of 26 or greater at baseline) provides “more room to separate” versus placebo.
On comorbidity, Karlin said “just over half” of the Phase II GAD participants also had an MDD diagnosis history, clarifying that GAD studies allow a history of major depressive episodes but exclude patients currently in an episode, while the MDD studies require patients to be in an active major depressive episode.
GAD Phase III program, sample size re-estimation, and commercial considerations
Barrow said the Phase III GAD trials use a design “virtually identical” to the MDD study: a single dose, 12 weeks of follow-up, and a nine-month extension with up to four open-label doses. Patients must have GAD and a baseline HAM-A score of 20 or greater.
He explained that a Phase II design without an extension led to higher dropout, particularly among non-responders and placebo participants. In Phase III, Definium incorporated the extension to improve retention. Barrow said that in the VOYAGE study’s interim sample size re-estimation, dropout and other “nuisance parameters” were “better than we anticipated,” and the company did not need to increase the sample size, targeting N=200. He said updates on the PANORAMA study’s re-estimation would be shared at an upcoming event.
Discussing powering for VOYAGE based on interim assumptions, Barrow said the trial would only need “a little bit over a 2-point difference” on HAM-A to achieve statistical significance if the observed parameters held, and would have “in excess of 99% power for a 5-point difference.” He contrasted that with the Phase II result he cited of a 7.7-unit placebo-adjusted difference for the 100-microgram dose.
On clinical relevance and differentiation, Barrow said a statistically significant 2.5-point delta “wouldn’t be all that exciting,” while a 4-point or better placebo-adjusted difference in GAD would compare favorably with approved anxiolytics. For MDD, he said many approved therapies show around a 3.5-point placebo-adjusted delta, and that results exceeding 4 or reaching the study’s 5-point target would be viewed more favorably.
Turning to durability, Barrow said Definium’s Phase II data suggested a single dose provided “at least 12 weeks of durability” in GAD on anxiety and depressive symptom measures, and that Phase III is designed to better characterize retreatment frequency over time. He said the company expects to share “some early findings” related to durability with top-line Phase III data later this year.
On prior psychedelic use, Barrow said the company captures that information in its trials, but does not stratify randomization by it, arguing the variable has relatively low incidence and uncertain impact. He said the company does not view it as a substantial confounder, though it monitors variables that have been discussed publicly.
On the commercial landscape, Barrow said GAD diagnosis and treatment have been growing faster than MDD, citing newer research indicating U.S. adult GAD prevalence “in excess of 10%,” compared with older estimates around 3%. Karlin added that standard chronic treatments, primarily SRIs, are “not very effective for anxiety cluster symptoms,” while benzodiazepines are increasingly used cautiously for chronic anxiety.
Karlin also discussed a potential clinic-based model for monitored dosing sessions, pointing to existing reimbursement mechanisms such as evaluation and management (E&M) billing and time-based psychotherapy codes, as well as a possible “buy and bill” margin for clinics that dispense the drug. Barrow said the company has engaged in discussions with the FDA around safety and access considerations, including potential REMS requirements, and emphasized a “data-driven approach” aimed at avoiding unnecessary barriers to care.
Finally, Barrow described a “white glove” support concept, citing Definium’s trial operations as a template for helping clinics and patients adopt the treatment approach if the drug reaches the market, with the goal of making site setup and patient support more efficient than typical psychiatric care pathways.
About Definium Therapeutics (NASDAQ:DFTX)
Definium Therapeutics, Inc, a clinical stage biopharmaceutical company, develops novel products to treat brain health disorders. The company’s lead product candidates include MM120, which is in phase 3 for the treatment of generalized anxiety disorder and attention deficit hyperactivity disorder; and DT402, a R-enantiomer of 3,4-methylenedioxymethamphetamine, which is in phase 2a clinical trials for the treatment of core symptoms of autism spectrum disorder. The company was formerly known as Mind Medicine (MindMed) Inc and changed its name to Definium Therapeutics, Inc in January 2026.
