Poster
49
(#49) VLS-01 Buccal Film: A novel formulation of a serotonin agonist under development for the treatment of Treatment-Resistant Depression (TRD)
Psych Congress 2025
Abstract: Background:
Major depressive disorder is a substantial disability with 10-30% of patients meeting criteria for TRD. VLS-01-BU (buccal film containing N,N-dimethyltryptamine (DMT)) is a serotonin agonist, which partially to fully agonizes 5-hydroxytryptamine receptor subtypes, including 5 HT1/2/6/7-receptors.
Methods:
An initial Ph1a study in healthy adults characterized safety, tolerability, PK, and defined the approximate exposure required to elicit perceptual changes following single intravenous dose of VLS-01 or buccal transmucosal administration of VLS-01-BU. Building on this data, a non-randomized, open-label repeat-dose Ph1b study in healthy adults assessed the comparability of exposures, within-participant PK variability, safety and tolerability of an intravenous infusion and an optimized buccal transmucosal film. Perceptual changes were measured using the Subjective-Intensity-Rating-Scale (SIRS).
Results:
In Ph1b, an intravenous infusion (30mg over 57min) and up to 3 additional buccal transmucosal doses (20-160 mg) were administered (N=16). The mean (SD) VLS-01 Cmax [37.7 (16.2) ng/mL], AUClast [28.1 (10.9) hr*ng/mL)] and T1/2 [0.32 (0.10) hours] during slow infusion were most closely matched by the120mg buccal dose, 36.5 (17.6), 33.9 (15.7), and 0.32 (0.06) respectively.
Mean (SD) post-dose SIRS scores peaked after 40min for intravenous [6.5 (3.2)] and after 30min for the 120mg buccal administration [7.5 (3.5)].
In 91 subjects across studies, no severe and one serious treatment-emergent AEs were observed. The most common TEAEs were headache, dissociation, nausea; all mild to moderate in severity.
Conclusions:
VLS-01-BU was generally well-tolerated and generated sufficient exposure at the 120mg dose to proceed with efficacy testing. A Ph2, double-blind, randomized, placebo-controlled trial in TRD is ongoing.
Short Description: VLS-01-BU (buccal film containing N,N-dimethyltryptamine (DMT)) is a serotonin agonist, which partially to fully agonizes 5-hydroxytryptamine receptor subtypes, including 5 HT1/2/6/7-receptors. Building ph1a data, a ph1b, non-randomized, open-label repeat-dose Ph1b study in healthy adults assessed the comparability of exposures, within-participant PK variability, safety and tolerability of an intravenous infusion and an optimized buccal transmucosal film. VLS-01-BU was generally well-tolerated and generated sufficient exposure at the 120mg dose to proceed with efficacy testing in TRD.
Name of Sponsoring Organization(s): atai Therapeutics
Major depressive disorder is a substantial disability with 10-30% of patients meeting criteria for TRD. VLS-01-BU (buccal film containing N,N-dimethyltryptamine (DMT)) is a serotonin agonist, which partially to fully agonizes 5-hydroxytryptamine receptor subtypes, including 5 HT1/2/6/7-receptors.
Methods:
An initial Ph1a study in healthy adults characterized safety, tolerability, PK, and defined the approximate exposure required to elicit perceptual changes following single intravenous dose of VLS-01 or buccal transmucosal administration of VLS-01-BU. Building on this data, a non-randomized, open-label repeat-dose Ph1b study in healthy adults assessed the comparability of exposures, within-participant PK variability, safety and tolerability of an intravenous infusion and an optimized buccal transmucosal film. Perceptual changes were measured using the Subjective-Intensity-Rating-Scale (SIRS).
Results:
In Ph1b, an intravenous infusion (30mg over 57min) and up to 3 additional buccal transmucosal doses (20-160 mg) were administered (N=16). The mean (SD) VLS-01 Cmax [37.7 (16.2) ng/mL], AUClast [28.1 (10.9) hr*ng/mL)] and T1/2 [0.32 (0.10) hours] during slow infusion were most closely matched by the120mg buccal dose, 36.5 (17.6), 33.9 (15.7), and 0.32 (0.06) respectively.
Mean (SD) post-dose SIRS scores peaked after 40min for intravenous [6.5 (3.2)] and after 30min for the 120mg buccal administration [7.5 (3.5)].
In 91 subjects across studies, no severe and one serious treatment-emergent AEs were observed. The most common TEAEs were headache, dissociation, nausea; all mild to moderate in severity.
Conclusions:
VLS-01-BU was generally well-tolerated and generated sufficient exposure at the 120mg dose to proceed with efficacy testing. A Ph2, double-blind, randomized, placebo-controlled trial in TRD is ongoing.
Short Description: VLS-01-BU (buccal film containing N,N-dimethyltryptamine (DMT)) is a serotonin agonist, which partially to fully agonizes 5-hydroxytryptamine receptor subtypes, including 5 HT1/2/6/7-receptors. Building ph1a data, a ph1b, non-randomized, open-label repeat-dose Ph1b study in healthy adults assessed the comparability of exposures, within-participant PK variability, safety and tolerability of an intravenous infusion and an optimized buccal transmucosal film. VLS-01-BU was generally well-tolerated and generated sufficient exposure at the 120mg dose to proceed with efficacy testing in TRD.
Name of Sponsoring Organization(s): atai Therapeutics
