atai Life Sciences (NASDAQ: ATAI) (“atai” or “Company”), a clinical-stage biopharmaceutical company aiming to transform the treatment of mental health disorders, today announced positive preliminary results from the Phase 1b trial of VLS-01, its proprietary oral transmucosal film formulation of N,N-dimethyltryptamine (DMT) that is applied to the buccal surface.

The Phase 1b trial was designed to evaluate the relative safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of VLS-01 compared to intravenous (IV) DMT. The single center, open-label study enrolled a total of 17 healthy participants, each of whom received a single dose of IV DMT followed by 3 different doses of VLS-01 buccal film—20mg (N=8), 60mg (N=6), 120mg (N=14) or 160mg (N=16)—with a 28-day washout window between administrations.

Key takeaways:

• Peak plasma concentrations (Cmax) were dose-proportional and comparable between the higher VLS-01 buccal film doses (120mg and 160mg) and the 30mg IV DMT dose; peak plasma concentrations were achieved within 30-45 minutes (Tmax).
• Dose-dependent and robust subjective effects were seen at the 120mg and 160mg doses.
• In the 120mg dose cohort:
  • 13/14 participants achieved Subjective Intensity Rating Scale (SIRS) scores greater than seven out of ten.
  • Subjective effects, assessed with the SIRS, were fully resolved by 120 minutes.
  • Participants reported that the experience was ‘psychologically meaningful’ with ‘increased levels of self-reflection’.

Safety and tolerability:

• VLS-01 demonstrated a favorable safety profile and was well tolerated, with all adverse events classified as either mild or moderate, and most resolving on the day of dosing.
• The most common treatment-emergent adverse events (TEAEs) were headache, dissociation, euphoric mood and nausea.
• No TEAEs of vomiting or local irritation were noted at doses of 120mg or lower, and only 1 subject out of 14 (7%) reported nausea at the 120mg dose.
• There were no observed adverse events related to blood pressure, heart rate or suicidality.

“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,” stated Dr. Srinivas Rao, Co-Chief Executive Officer and Co-founder of atai.

“In this trial, the 120mg dose was found to strike a balance between psychedelic effect intensity and safety as well as tolerability. These encouraging findings, if replicated in Phase 2, suggest that VLS-01 could become a best-in-class treatment for TRD, one that offers a well-tolerated, convenient oral dosing and a short psychedelic experience that fits into the two-hour in-clinic commercial paradigm established within interventional psychiatry. These Phase 1b results lay a strong foundation for our Phase 2 trial in patients with treatment-resistant depression, which is set to begin around year-end.”

Based on the positive results from the Phase 1b trial, the Company plans to initiate a randomized, double-blind, placebo-controlled Phase 2 study (NCT06524830) to assess the safety, efficacy and durability of response of repeated doses of VLS-01 in patients with treatment-resistant depression (TRD). The Phase 2 trial will consist of two treatment periods.

In the first treatment period, approximately 142 patients will be randomized 1:1 to receive a 120mg dose of VLS-01 buccal film or placebo on Day 1, followed by a second dose of the same intervention at Week 2. The primary endpoint is the change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score at Week 4 and the last double-blind assessment visit will be at Week 14. The first treatment period will provide 12 weeks of durability data following two doses of VLS-01 administered in a placebo-controlled fashion.

The second treatment period starts at Week 14 and will explore the response to two different dose levels of VLS-01. Patients will be randomized 1:1 to receive a third dose of either 60mg or 120mg of VLS-01. Final safety and efficacy assessment will be conducted two weeks after administration of the third dose.

atai expects to initiate the Phase 2 trial around year-end 2024, with topline data anticipated around year-end 2025.