THE PHARMACOKINETIC PROPERTIES AND TARGET ENGAGEMENT EFFECTS OF THE NOVEL SEROTONIN TRANSPORTER MODULATOR, SNTX-2643, IN HEALTHY ADULTS

The SENS-01 program used artificial intelligence and nature-derived design insights to identify, SNTX-2643, a novel, potentially rapid-acting modulator of the serotonin transporter (SERT) that is under investigation for the treatment of anxiety disorders. Anxiety disorders are highly prevalent yet often underdiagnosed, inadequately treated, and debilitating conditions that can impair a patient’s quality of life and ability to function in all areas. SERT is a genetically and pharmacologically validated target – modulation of which through a unique uncompetitive inhibition mechanism with SNTX-2643, may restore balance to dysregulated neuronal networks implicated in the development of anxiety disorders. The aim of the ongoing Phase 1a study is to determine the pharmacokinetic (PK) profile and pharmacodynamics (PD) of SNTX-2643 in healthy adults. In this ongoing randomized, double-blind, placebo-controlled study, heathy adults receive SNTX-2643 in single ascending dose (SAD cohorts). The study also incorporates additional cohorts to evaluate various aspects of drug activity: 1) A food effect (FE) cohort to investigate the impact of food on rate of absorption and bioavailability and 2) a target engagement (TE) cohort utilizing quantitative electroencephalography (qEEG). The FE cohort is being conducted as an open-label twoperiod, two-treatment crossover, with a washout period of at least 5 days between dosing periods, in which subjects receive two separate (fasting vs fed) single-dose administrations of SNTX-2643. The objective of the TE Cohort is to evaluate resting qEEG, event-related potentials, and an anxiety inducing aversive video paradigm following a single 3 mg dose of SNTX-2643 versus placebo in a randomized, double-blinded fashion to characterize CNS target engagement. A sufficient number of subjects will be enrolled to allow evaluation of 32 subjects in at least 4 SAD Cohorts (8 subjects per cohort with 6 receiving active and 2 receiving placebo), 14 subjects in the FE cohort all (14 receiving active treatment in both the fasting and fed conditions), and 25 subjects (15 subjects receiving active and 10 receiving placebo) in the TE Cohort. An effort will be made to enroll male and female subjects in each cohort with at least 30% of either sex in each cohort. The following PK parameters will be assessed across all cohorts: maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), elimination rate constant (λz), elimination half-life (T1/2), area under the plasma concentration-time curve to the final sample concentration > the limit of quantification (AUClast), area under the curve from time 0 hours to infinity (AUCinf), oral clearance (CL/F), and volume of distribution in the terminal phase (Vz/F). Safety analyses are included in the study. The study is planned for completion in the first half of 2026 and will be the first evaluation of SNTX-2643 in humans. The study will provide an analysis of SNTX-2643’s PK and PD properties as well as effects potentially relevant to the treatment of anxiety disorders.