atai Life Sciences Reports Positive Phase 1b Results for VLS-01 (Buccal Film DMT)

atai Life Sciences, a clinical-stage biopharmaceutical company, recently announced promising preliminary results from its Phase 1b trial of VLS-01. This proprietary oral transmucosal film formulation of N,N-dimethyltryptamine (DMT) is designed to be applied to the buccal surface. VLS-01 aims to treat mental health disorders, particularly treatment-resistant depression (TRD).

The Phase 1b trial was structured to assess the safety, tolerability, and pharmacokinetics (PK) and pharmacodynamics (PD) of VLS-01 in comparison to intravenous (IV) DMT. Conducted at a single center, the open-label study involved 17 healthy participants who were administered a single dose of IV DMT followed by three varying doses of VLS-01 buccal film—20mg, 60mg, 120mg, or 160mg—with a 28-day washout period between doses.

Key findings from the trial included that peak plasma concentrations of VLS-01 were dose-proportional and similar between the higher doses of VLS-01 (120mg and 160mg) and the 30mg IV DMT dose. These concentrations were reached within 30-45 minutes. Participants experienced robust, dose-dependent subjective effects at the 120mg and 160mg doses. In the 120mg dose group, 13 out of 14 participants achieved Subjective Intensity Rating Scale (SIRS) scores above seven out of ten, with subjective effects generally resolving within 120 minutes. Participants also reported the experience as psychologically meaningful, fostering increased levels of self-reflection.

VLS-01 demonstrated a favorable safety profile and was well tolerated, with all adverse events classified as mild or moderate. The most common adverse events included headache, dissociation, euphoric mood, and nausea, with most resolving on the day of dosing. Importantly, no adverse events related to blood pressure, heart rate, or suicidality were observed.

Dr. Srinivas Rao, Co-Chief Executive Officer and Co-founder of atai, expressed enthusiasm about the positive results, noting that the 120mg dose balanced psychedelic effect intensity, safety, and tolerability. If these findings are replicated in Phase 2, VLS-01 could emerge as a leading treatment for TRD, offering a convenient oral dosing method and a short psychedelic experience fitting within the established two-hour in-clinic commercial paradigm in interventional psychiatry.

Based on these encouraging results, atai plans to initiate a randomized, double-blind, placebo-controlled Phase 2 study to evaluate the safety, efficacy, and durability of repeated doses of VLS-01 in patients with TRD. This trial will consist of two treatment periods. The first period will involve approximately 142 patients, randomized to either a 120mg dose of VLS-01 buccal film or placebo, with a second dose at Week 2. The primary endpoint will be the change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score at Week 4, with the last double-blind assessment at Week 14. The second period, starting at Week 14, will explore responses to two different dose levels of VLS-01, with a final safety and efficacy assessment two weeks after the third dose.

atai expects to begin the Phase 2 trial around the end of 2024, with topline data anticipated around the end of 2025.

VLS-01, referred to as VLS-01-BU, is a proprietary oral transmucosal film formulation of DMT developed for TRD patients. Pharmacologically, DMT is a partial agonist of the 5-HT 1A/2A/2C receptors, known for its short psychedelic effect duration. Clinical evidence indicates that a single IV DMT dose can offer rapid and durable antidepressant effects in major depressive disorder patients. atai's buccal film formulation aims to eliminate the need for IV administration and maximize therapeutic potential within a two-hour in-clinic setting.

atai Life Sciences was founded to address the significant unmet needs and lack of innovation in mental health treatment. The company is committed to efficiently developing innovative therapeutics for depression, anxiety, addiction, and other mental health disorders. By pooling resources and best practices, atai aims to accelerate the development of new medicines to achieve sustained behavioral change in mental health patients, with the ultimate vision of healing mental health disorders globally.