Atai Life Sciences Completes Phase 1 Clinical Study Of Oral Film DMT Formulation

Clinical-stage biopharma company atai Life Sciences ATAI has completed its Phase 1 study evaluating proprietary oral transmucosal film (OTF) DMT formulation VLS-01 in 74 healthy participants.

A DMT formulation, VLS-01 works as a partial agonist of the 5-HT 1A/2A/2C receptors, with an intrinsically short duration of psychedelic effect and a half-life of less than 10 minutes.

As clinical evidence suggests DMT’s IV administration provides rapid-acting antidepressant effects in Major Depressive Disorder (MDD) patients, atai’s proprietary OTF formulation aims to eliminate the need for injectable administration, provide improved pharmacokinetics (PK) and a psychedelic effect lasting 45 minutes, allowing for an enhanced 2-hour in-clinic patient visit.

The Phase 1 study assessed the safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD) of VLS-01 applied to the sublingual and buccal surfaces compared to intravenous (IV) DMT. The doses administered were sublingual 80mg (n=8), buccal 80mg with backing layer (n=10), and buccal 160mg with backing layer (n=8).

Results showed:

• The compound was reportedly well-tolerated with a favorable safety profile, with effects increasing with dose although most participants showed subjective effects with all doses.

• 160mg with a backing layer via buccal administration elicited the most robust and consistent increases in exposure and subjective effects compared to the other cohorts.

• These results were comparable to the IV cohort, confirming the efficacy of DMT’s systemic delivery via the oral, transmucosal route.

The trial demonstrated the compound’s “supportive” PK/PD profile, and now the company aims to test “a further optimized version” of its OTF formulation in an upcoming Phase 1b trial -also in healthy participants- before initiating a Phase 2 in Treatment-Resistant Depression (TRD) patients, stated co-founder and CEO Florian Brand.

The Phase 1b study is expected to explore doses up to 160 mg with an OTF version that incorporates taste masking, an intrinsic backing layer, and enhancements to increase permeability, the participant experience and pharmacokinetics. 

atai has submitted a protocol to regulatory authorities and expects to enroll the first study participants in the first half of 2024.

Photo: Benzinga edit with photo by CDC on Pexels and Jynto on Wikimedia Commons.