Positive Topline Results From Phase 3 Panorama Study of DT120 ODT in Generalized Anxiety Disorder

Definium Therapeutics today announced positive topline results from Panorama, the second phase 3 study of DT120 (lysergide) orally disintegrating tablet (ODT) in adults with generalized anxiety disorder (GAD).¹ This is Definium’s third positive phase 3 readout for DT120 ODT, following the positive Emerge results in major depressive disorder (MDD) announced in June,² and the positive Voyage results in GAD announced in August.³

DT120 ODT is an ergoline derivative belonging to the group of classic serotonergic psychedelics, which acts as a partial agonist at 5-hydroxytryptamine serotonin-2A (5-HT2A) receptors. Definium is currently studying DT120 ODT in a spectrum of psychiatric disorders, including GAD), major depressive disorder (MDD), and posttraumatic stress disorder (PTSD), and is exploring its potential applications in other serious brain health disorders. DT120 has received Breakthrough Therapy designation from the US Food and Drug Administration (FDA) for GAD and MDD.⁴

“The Panorama results again met our high expectations and confirmed the unprecedented efficacy of DT120 in GAD,” said Rob Barrow, the chief executive officer of Definium Therapeutics. “With strong positive results across 4 complementary studies, we have built a compelling body of evidence that increases our confidence in the potential best-in-class profile of DT120.”

About the Panaroma Study

Panorama (MM120-301) was a phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of DT120 ODT in adults with GAD. Investigators enrolled 245 participants across 32 study centers aged 18 to 74 years with a DSM-5-confirmed primary diagnosis of GAD and a minimum Hamilton Anxiety Rating Scale (HAM-A) total score of 20 at screening and baseline. Eligible participants were randomly assigned 2:1:2 to receive a single dose of DT120 ODT 100 µg, DT120 ODT 50 µg, or matching placebo, with the 50 µg arm included to help mitigate functional unblinding.

The study consisted of a 12-week double-blind treatment period (Part A) followed by a 40-week open-label extension (Part B), during which participants were eligible to receive up to 4 additional doses of DT120 ODT 100 μg based on symptom severity, for a total study duration of approximately 56 weeks. The primary endpoint was change from baseline in HAM-A total score at week 12. Key secondary multiplicity-controlled endpoints were change from baseline in Clinical Global Impression-Severity (CGI-S) scale score at week 12, change from baseline in HAM-A total score at week 1, and change from baseline in CGI-S score at day 2.

Panaroma Results

Panorama met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement from baseline compared with placebo, as measured by the change in HAM-A total score at week 12. The Least Squares (LS) mean change from baseline in HAM-A total score at week 12 in participants who received DT120 ODT 100 µg was -9.8 compared with -4.7 for participants who received placebo, an LS mean difference of -5.1 points (P<0.0001), corresponding to a standardized effect size of d=0.64. Efficacy was rapid, with changes seen as early as day 2 and sustained at all post-baseline timepoints in Part A.

Participants were monitored for a minimum of 8 hours on dosing day and were assessed hourly beginning 5 hours after dosing on a structured end-of-session checklist (EoSC). The average time to meet EoSC criteria was 6.2 hours for participants receiving DT120 ODT 100 μg, with a median of 6.0 hours and 94% of participants meeting EoSC criteria by hour 8. Across more than 1000 treatment sessions in the phase 3 program through September 10, 2026, 97% of participants met EoSC criteria by hour 8.

"Patients with generalized anxiety disorder often work through 2 or 3 medications before finding one they can tolerate, and even then, daily dosing brings its own burden, sedation, weight change, sexual [adverse] effects, and for some classes of medications, real dependence risk," said Scott Aaronson, MD, the chief science officer at the Institute for Advanced Diagnostics and Therapeutics at Sheppard Pratt, and a Panorama investigator. "What stands out about DT120 ODT is that a single dose has the potential to hold a response for months without the patient managing a pill every day. For a condition this chronic and this undertreated, a treatment that removes daily adherence with a novel mechanism of action and a unique effect on cognitive processes underlying anxiety could change how we think about long-term management, not just acute relief."

Panorama included a DT120 ODT 50 µg control arm (n=52) that was not designed or powered for statistical comparisons. Consistent with the dose-response profile demonstrated in the phase 2b trial, DT120 ODT 50 µg demonstrated a placebo-adjusted change of -3.5 and -3.6 at weeks 4 and 12, approximately 50% and 29% lower than was observed for DT120 ODT 100 µg.

DT120 ODT Safety Profile

DT120 ODT 100 μg was generally well tolerated, with most treatment-emergent adverse events (TEAEs) mild to moderate in severity, transient, and predominantly occurring on the day of dosing. No new safety signals were identified, including no suicidality signal or suicidal behavior. There were no drug-related serious adverse events.

Overall discontinuation rates were similar between DT120 ODT 100 μg, DT120 50 μg, and placebo groups (10.4%, 11.5%, and 10.3%). The overall TEAE rate for DT120 ODT 100 μg, DT120 50 μg, and placebo was 94.8%, 96.1%, and 62.9%. The most common TEAEs (>10%) in the DT120 ODT 100 μg and 50 μg arms on dosing day were illusion (68%, 61%), nausea (37%, 26%), and headache (24%, 28%).

Next Steps

“Building on this momentum, we are advancing toward an NDA submission and look forward to aligning with the FDA at our upcoming pre-NDA meeting. We are deeply grateful to the participants, investigators, site personnel, and our team whose commitment and hard work made this progress possible,” shared Barrow.

References

1. Definium Therapeutics announces positive topline results from phase 3 Panorama study of DT120 ODT in generalized anxiety disorder. News release. September 14, 2026. Accessed September 14, 2026. https://ir.definiumtx.com/news-events/press-releases/detail/251/definium-therapeutics-announces-positive-topline-results-from-phase-3-panorama-study-of-dt120-odt-in-generalized-anxiety-disorder

2. Kuntz L. Positive topline results from phase 3 Emerge study of DT120 ODT in major depressive disorder. Psychiatric Times. June 22, 2026. https://www.psychiatrictimes.com/view/positive-topline-results-from-phase-3-emerge-study-of-dt120-odt-in-major-depressive-disorder

3. Duerr HA. DT120 (Lysergide) shows rapid, lasting relief for generalized anxiety in phase 3 trial. Psychiatric Times. August 12, 2026. https://www.psychiatrictimes.com/view/dt120-lysergide-shows-rapid-lasting-relief-for-generalized-anxiety-in-phase-3-trial

4. Kuntz L. DT120 (Lysergide) ODT receives breakthrough therapy designation for treatment of MDD. Psychiatric Times. September 8, 2026. https://www.psychiatrictimes.com/view/dt120-lysergide-odt-receives-breakthrough-therapy-designation-for-treatment-of-mdd