Definium Therapeutics Teases 3 Key DT-120 Data Readouts This Year, Highlights De-Risked Phase 3 Design

Executives from Definium Therapeutics (NASDAQ:DFTX) outlined clinical, regulatory, and commercial priorities for its lead psychedelic-derived program during a management discussion, emphasizing multiple pivotal readouts expected later this year and a focus on trial design intended to address common execution risks in psychiatric studies.

Lead program: DT-120 in anxiety and depression

Management described DT-120 as a proprietary tartrate form of LSD (Lysergide Tartrate) being developed for generalized anxiety disorder (GAD) and major depressive disorder (MDD). The company said it has a breakthrough therapy designation for its GAD program and characterized its approach as “data-driven,” seeking to challenge assumptions that have historically shaped the field.

The company’s near-term focus is on upcoming pivotal data. Management noted that “most of the attention” is on DT-120, with top-line results from three studies expected later this year.

MDD: rationale, effect size expectations, and durability

In discussing the upcoming MDD readout, management argued that GAD and MDD are “highly overlapping,” including overlap in commonly used clinical rating scales. As one example, management pointed to item 6 on the Hamilton Anxiety Rating Scale (HAM-A)—depressed mood—as illustrating how symptom measurement can intersect across diagnoses.

Management said Definium’s Phase II evidence base came from a GAD population rather than a standalone MDD trial, but noted that baseline depression severity in that anxiety study was substantial. According to the company, participants had baseline MADRS scores in the mid- to upper-20s—around or slightly above the threshold used for enrollment in Definium’s MDD study—despite not being in a depressive episode.

Management highlighted Phase II changes measured 12 weeks after a single dose, describing:

• More than an 18-point improvement in depression symptoms (MADRS) and a 22-point improvement on HAM-A after a single dose.
• At the 100 microgram dose, a 6.4-point advantage versus placebo on MADRS and a 7.7-point advantage versus placebo on HAM-A.

The team said one limitation in the Phase II dataset was “bottoming out” on the scale, which can reduce sensitivity when baseline scores are lower. By contrast, Definium expects MDD patients in a depressive episode to enter studies with higher baseline MADRS scores (the company referenced low- to mid-30s), which it said could improve the ability to detect change if responses track similarly.

On statistical powering, management said the MDD study is powered at 80% for a 5-point MADRS difference. The company said it is “very focused” on that bar but not worried, adding that if efficacy were similar to what has been observed with psilocybin in treatment-resistant depression (TRD), it would expect a statistically positive study. Management also commented that an effect size under a 4-point change would be “underwhelming” relative to what it has seen to date.

Regarding durability, Definium said patients remain blinded for 12 weeks in Part A after a single dose, with eligibility for open-label treatment after that if moderate or worse symptoms return. The primary endpoint in depression is set at 6 weeks, which management framed as a comparability choice relative to other studies and approved products, while emphasizing interest in durability out to 12 weeks and beyond. The company said it hopes to see response patterns that could include “a year or more durability” for some patients, potentially requiring only a few doses over a year.

GAD Phase III: Voyage and Panorama designs

Management said its Phase II GAD study was a “comprehensive dose response” trial in the field, testing four doses versus placebo, and that 100 micrograms was selected as the “appropriate and maximally efficacious” dose. It cited Phase II outcomes that included an approximately 20.9-point improvement on active drug and a 7.7-point separation versus placebo on HAM-A.

The company described two complementary Phase III GAD trials:

• Voyage: 100 micrograms versus placebo, with about 100 patients per arm.
• Panorama: includes 100 micrograms versus placebo, plus a third “decoy” arm of 50 micrograms with half the allocation (about 50 patients) intended to mitigate expectancy and functional unblinding concerns by reducing certainty about receiving the full active dose.

Both studies are powered to detect a 5-point difference at 90% and include a blinded sample size re-estimation. Management said Voyage has already passed that re-estimation and reported a 10% not-evaluable rate and a 6.7 standard deviation for the primary endpoint, which it said implies 99% power to detect a 5-point difference under those assumptions.

Asked about whether positive results would require success in both Phase III studies, management said it is committed to positive outcomes in the trials and expects to have regulatory discussions based on the nature of the readouts. It added that the current regulatory climate is “quite accommodating” and that supportive evidence could matter across different scenarios, while expressing confidence in demonstrating positive results across all three studies expected to read out.

Trial execution, regulatory discussions, and funding

On trial quality concerns such as “professional patients,” management said it aims not to blame participants for outcomes and instead emphasized process controls designed to ensure the enrolled population matches protocol intent. Definium described a multi-layered approach at enrollment, including a site-level diagnostic assessment, a remote third-party diagnostic assessment, and a separate remote severity assessment, along with internal medical review of documentation (excluding identifiers). The company also emphasized frequent communication with study sites.

On functional unblinding, management argued that the phenomenon occurs across psychiatric drugs and said it has not identified functional unblinding as a reason for regulatory concern in the available regulatory record it reviewed, including in the context of the MDMA complete response letter. It added that Definium has taken extensive steps—particularly with the Panorama design—to mitigate expectancy-related concerns.

Management also said the company has had “great dialogue” with the FDA, and that demonstrating a 12-week durable effect after a single dose is a durability benchmark it believes is reasonable. It said patients are followed for a year and that post-12-week observations are intended to inform labeling and retreatment patterns, with Part B allowing up to 400 milligrams of drug under a design discussed with the FDA.

On financial position, Definium said it ended the year with $412 million in cash and referenced an October financing that supported preparations ahead of expected readouts, including NDA preparation, market access planning, and key opinion leader education. The company also announced it plans to host an investor and analyst day on April 22 to discuss expectations for top-line data and the commercial opportunity.

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.