On the heels of last week’s FDA rejection of Lykos’ MDMA-assisted PTSD therapy, Atai announced Tuesday positive preliminary results for its DMT-based treatment for depression from a Phase Ib study.
Atai Life Sciences said Tuesday its psychedelic depression drug candidate generated positive preliminary results in a Phase Ib trial, positioning the biotech to start studying the molecule in patients this year.
The candidate, VLS-01, is an oral formulation of N,N-dimethyltryptamine (DMT). Applied to the lining of the cheek, the investigational treatment is designed to induce a short psychedelic experience that helps people with treatment-resistant depression. The active ingredient is different from those used in Lykos Therapeutics’ recently rejected MDMA candidate and Compass Pathways’ psilocybin treatment.
Atai ran the Phase Ib study to compare the safety, tolerability, pharmacokinetics and pharmacodynamics of VLS-01 to intravenous DMT. All 17 healthy volunteers in the trial received a single intravenous dose followed by three different doses of DMT delivered using a buccal film. Investigators gave the doses 28 days apart.
The trial found the two higher buccal doses, 120mg and 160mg, achieved peak plasma concentrations comparable to the intravenous dose. Atai said “dose-dependent and robust subjective effects” were seen at the 120mg and 160mg doses. At 120mg, 13 out of 14 participants scored greater than 7 out of 10 on the Subjective Intensity Rating Scale.
Subjective effects resolved completely after two hours. Subjects in the study called the experience “psychologically meaningful” and said it increased their “levels of self-reflection,” according to the company.
Atai said VLS-01 was well tolerated. The most common treatment-emergent adverse events (TEAEs) were headache, dissociation, euphoric mood and nausea. All adverse events were mild or moderate and most resolved on the day of dosing. No participants taking 120mg or less of buccal DMT had vomiting or local irritation. One subject on the 120mg dose reported nausea. There were no reports of suicidality.
The biotech has already filed to run a Phase II trial that will compare VLS-01 to placebo in 142 patients with treatment-resistant depression. Subjects will take two 120mg doses two weeks apart. The primary endpoint will look at the change from baseline on the Montgomery-Åsberg Depression Rating Scale after 29 days. A second dosing period will start after 14 weeks and compare 60mg and 120mg doses.
A Phase II study, which is scheduled to report top-line data around the end of 2025, is a key moment for a program that Atai began in 2019. Back then, the biotech was looking for a psychedelic that could be given in a two-hour in-clinic patient visit. Psilocybin, the active ingredient in magic mushrooms, has an oral halflife that necessitates longer visits. Atai identified DMT as a molecule with its desired properties.
Selecting a molecule that can be given in a two-hour in-clinic patient visit could position Atai to benefit from infrastructure established to support the administration of Johnson & Johnson’s ketamine-based depression drug Spravato. Atai co-CEO Florian Brand discussed in June 2024 at H.C. Wainwright’s Neuro Perspectives Conference how fitting into the Spravato paradigm could support uptake of VLS-01.
“With [J&J] now guiding to achieve beyond a billion of sales this year and more than 4,000 clinics certified, we believe we have a very compelling infrastructure that we can leverage with this compound,” Brand said.
