Atai's DMT Depression Drug Shows Promise, Prepares For Phase II Trial And Future Collaboration With Pharma Giant

Atai Life Sciences ATAI announced promising preliminary results on Tuesday for its DMT-based depression therapy, VLS-01. As BioSpace reported, these findings from a Phase Ib study position Atai to move forward with a Phase II trial later this year, targeting patients with treatment-resistant depression.

Promising Phase Ib Results For DMT-Based Depression Therapy

VLS-01, an oral formulation of N,N-dimethyltryptamine (DMT), is designed to be administered via a buccal film applied to the lining of the cheek. This delivery method aims to induce a short, controlled psychedelic experience, potentially offering relief to those suffering from treatment-resistant depression. The active ingredient is different from other psychedelic therapies, such as Lykos Therapeutics' MDMA, which was recently rejected by the FDA, or Compass Pathways' psilocybin treatments, VLS-01 provides a unique approach to addressing mental health challenges, say company officials.

The Phase Ib Study

The research involved 17 healthy volunteers, who received a single intravenous dose of DMT followed by three different doses of the buccal formulation, administered 28 days apart. The study aimed to compare the safety, tolerability, pharmacokinetics and pharmacodynamics of the buccal film to the intravenous form. The results were encouraging, with the two higher doses (120mg and 160mg) achieving peak plasma concentrations comparable to the intravenous dose.

Atai reported “dose-dependent and robust subjective effects” at these higher doses, with 13 out of 14 participants scoring greater than 7 out of 10 on the Subjective Intensity Rating Scale at the 120mg dose. The effects were noted to resolve completely after two hours, with participants describing the experience as “psychologically meaningful” and highlighting an increase in “levels of self-reflection.”

Safety Profile And Next Steps

The safety profile of VLS-01 was another positive outcome of the study. The most common treatment-emergent adverse events (TEAEs) reported were headache, dissociation, euphoric mood, and nausea. All adverse events were mild or moderate and resolved on the day of dosing, with no reports of vomiting or local irritation at doses of 120mg or less. Only one participant reported nausea at the 120mg dose, and there were no incidents of suicidality.

Building on these results, Atai has filed to conduct a Phase II trial by the end of 2024, which will compare VLS-01 to a placebo in 142 patients with treatment-resistant depression. This study will evaluate the efficacy, safety, and durability of repeated doses of VLS-01 in patients with TRD, and is expected to provide topline data by the end of 2025.

Strategic Positioning And Future Outlook

"We're delighted with the positive results from the VLS-01 Phase 1b study, which further support its potential as a promising therapeutic option for the 100 million people worldwide suffering from treatment-resistant depression," said Dr. Srinivas Rao, co-CEO and co-founder of Atai.

Atai's strategic approach to developing a psychedelic that can be administered within a two-hour clinic visit could align it with existing infrastructure used for administering Johnson & Johnson's ketamine-based depression drug, Spravato.

Atai co-CEO Florian Brand, speaking at H.C. Wainwright's Neuro Perspectives Conference in June 2024, highlighted the potential to leverage the “very compelling infrastructure” established by Spravato’s more than 4,000 certified clinics. “With [J&J] now guiding to achieve beyond a billion of sales this year, we believe we have a very compelling infrastructure that we can leverage with this compound,” Brand said.

Cover image made with AI