– SNTX-2643 was generally well tolerated and demonstrated predictable pharmacokinetics with no clinically significant food effect in healthy participants –

– In an exploratory target-engagement analysis, a single 3 mg dose attenuated the brain’s response to an experimentally induced psychological stressor at both two and 24 hours with concurrent responses seen in autonomic measures at both time points –

– After a single dose, pharmacodynamic activity remained evident at 24 hours as plasma exposure declines, suggesting potential durability beyond peak systemic exposure –

CAMBRIDGE, Mass., Sept. 21, 2026 /PRNewswire/ — Sensorium Therapeutics, a clinical-stage central nervous system (CNS) biotechnology company developing mechanistically novel small-molecule medicines for psychiatric and neurological disorders, today announced positive results from a Phase 1a study of SNTX-2643, its investigational, state-selective serotonin transporter (SERT) modulator in development for the treatment of social anxiety disorder (SAD) and generalized anxiety disorder (GAD). The data were presented at Psych Congress 2026 in New Orleans.

SNTX-2643 was generally well tolerated in the Phase 1a study in healthy participants and demonstrated a predictable pharmacokinetic profile across ascending doses, with no clinically significant food effect. In a randomized double-blind, placebo-controlled target-engagement cohort evaluating a single 3 mg dose of SNTX-2643 versus placebo, exploratory pharmacodynamic analyses showed measurable effects on brain activity beginning approximately two hours after dosing and remaining evident at 24 hours.

In addition, SNTX-2643 attenuated heightened neurophysiological responses to an experimentally induced psychological stressor at both two and 24 hours. Participants receiving SNTX-2643 showed reduced the activated brain state during exposure to fear- and anxiety-inducing videos compared with placebo. At 24 hours, the pharmacodynamic effect remained evident as mean plasma concentrations of SNTX-2643 declined to approximately 0.6 ng/mL from approximately 6.0 ng/mL at two hours following single-dose administration, suggesting potential durability beyond peak systemic exposure. Higher doses than 3 mg are planned for future evaluation. The mechanism, duration and clinical relevance of this finding will be evaluated in subsequent studies.

“We built Sensorium around the idea that human biology can tell us where to look for better medicines. With SNTX-2643, we started with a human observation, worked backward to understand what was different about the biology, and now our first clinical data are showing that differentiation in humans,” said Jacob Hooker, Ph.D., co-founder and Chief Executive Officer of Sensorium Therapeutics. “Seeing measurable CNS activity within hours of a single dose, with effects still evident at 24 hours, gives us greater confidence in both the program and the approach that led us here. We now have a stronger foundation to ask whether this can translate into meaningful benefit for patients.”

Key Phase 1a Findings

The Phase 1a study evaluated SNTX-2643 in 63 healthy adults and included single-ascending-dose cohorts to characterize safety and pharmacokinetics, a randomized, double-blind, placebo-controlled target-engagement cohort, and an open-label food-effect cohort. The target-engagement cohort included 25 participants randomized to a single 3 mg dose of SNTX-2643 (n=15) or placebo (n=10).

Safety and Pharmacokinetics

• SNTX-2643 was generally well tolerated.
• The majority of treatment-emergent adverse events were mild and transient.
• No serious adverse events, deaths, or discontinuations due to adverse events were observed.
• No clinically significant findings were identified on clinical laboratory assessments, ECGs or physical examinations.
• Median time to peak plasma concentration was approximately 1.5 to two hours, with a median half-life of approximately four to six hours.
• Food did not have a clinically significant effect on SNTX-2643 exposure.

Resting-State EEG

Quantitative electroencephalography, or qEEG, measures electrical activity in the brain and was used to assess the pharmacodynamic effects of SNTX-2643 as an exploratory objective.

In the 3 mg target-engagement cohort, SNTX-2643 increased beta activity and reduced relative delta activity beginning approximately two hours after dosing and persisting through 24 hours. Multiple findings remained nominally significant after adjustment for the number of EEG comparisons performed. These analyses were exploratory and were not designed to assess clinical efficacy.

Beta is faster-frequency brain activity associated with an alert and actively processing cortical state, while delta is slower-frequency activity that becomes more prominent in lower-arousal states. The pattern observed with SNTX-2643 was more consistent with cortical activation than sedation.

SNTX-2643 Attenuated the EEG Response to an Acute Stress Challenge

The target-engagement cohort also incorporated an aversive-video paradigm designed to produce a controlled and measurable psychological stress response.

The approach is based on published research showing that aversive-video exposure can increase anxiety, negative affect and cortisol, reduce heart-rate variability, and produce characteristic changes in EEG activity in healthy volunteers. For the Sensorium study, investigators selected videos from the Open Library for Affective Videos, a research library in which stimuli have been characterized for fear, anxiety, emotional valence and arousal.

During the challenge:

• Placebo-treated participants showed marked increases in beta and gamma EEG activity. In aversive settings, increases in these higher-frequency signals have been associated with heightened arousal and anxiety-related processing.
• A single 3 mg dose of SNTX-2643 significantly attenuated the beta and gamma response at both two and 24 hours.
• At two hours, gamma activity increased rapidly during the challenge in placebo-treated participants, while no appreciable increase was observed with SNTX-2643. A similar separation was evident at 24 hours.
• Additional analyses showed attenuation of stress-associated cortical activity without broad suppression of total EEG activity.

The resting-state and stress-challenge findings showed different effects depending on the setting. At rest, SNTX-2643 shifted brain activity toward a more activated cortical profile. During acute psychological stress, it reduced the increase in high-frequency activity produced by the challenge.

“The target-engagement cohort was an exploratory analysis designed to ask whether a single 3 mg dose produced activity indicating functionally relevant CNS effects,” said Cole Brown, M.D., Chief Medical Officer of Sensorium Therapeutics. “We saw a qEEG signal at rest, attenuation of the EEG response to an acute psychological stressor, and complementary autonomic changes, without significant changes in most exploratory measures of attention or information processing. These remain exploratory findings in healthy volunteers, but the consistency across independent readouts is encouraging from a translational standpoint.”

Pharmacodynamic Activity Remained Evident at 24 Hours

Mean SNTX-2643 plasma concentration was approximately 6.0 ng/mL at two hours, near peak exposure for 3 mg, and approximately 0.6 ng/mL at 24 hours.

As plasma exposure declined, separation from placebo during the aversive-video challenge remained evident at 24 hours, suggesting potential durability of the pharmacodynamic effect beyond peak systemic exposure. Further studies will evaluate the mechanism and duration of this finding and whether it translates into clinical benefit.

No Changes in Exploratory Measures associated with Attention or Information Processing

Sensorium also evaluated event-related potentials, or ERPs as an exploratory analysis, which measure the brain’s electrical response to specific stimuli and can detect changes in attention, perception and information processing.

The CNS pharmacodynamic effects across the ERP tasks conducted following SNTX-2643 administration were not accompanied by clinically significant impairment in exploratory measures of attention, information processing or perceptual judgment evaluated in the study.

Exploratory autonomic analyses provided an additional physiological measure. At two hours, SNTX-2643 was associated with reduced heart rate relative to placebo and increased heart-rate variability, a pattern consistent with increased parasympathetic tone. Similar directional effects were observed at 24 hours.

“For people living with an anxiety disorder, this is not the everyday anxiety we all experience from time to time. It can be disabling, affecting work, relationships and the ability to participate fully in daily life,” Andrew J Cutler, MD, Clinical Professor of Psychiatry, SUNY Upstate Medical University and study author. “Yet treatment still relies heavily on medicines developed decades ago that can take weeks to work or carry tolerability, sedation and dependence concerns. These early data do not establish clinical efficacy, but seeing measurable CNS effects within hours of a single dose and a distinct response during an acute stress challenge provides a compelling rationale to evaluate SNTX-2643 in patients.”

Presentation at Psych Congress 2026

The Phase 1a results were presented at the Psych Congress 2026 Annual Meeting in New Orleans, Louisiana.

Poster 199: The Novel Serotonin Transporter Modulator SNTX-2643: Results from a Pharmacokinetic and Target Engagement Evaluation in Healthy Adults
Authors: Andrew J. Cutler, M.D.; Colville Brown, M.D.; Jacob Hooker, Ph.D.; Jerry Rosenbaum, M.D.
Presenting Author: Colville Brown, M.D.

About SNTX-2643 (SENS-01 Program)

SNTX-2643 is Sensorium’s lead investigational therapy from the SENS-01 program and is being developed for social anxiety disorder and generalized anxiety disorder, with potential applicability to multiple other CNS disorders. It is a first-in-class state-selective serotonin modulator, differentiated from standard of care anxiolytics, designed for rapid onset, reduced off-target effects, and with the potential to avoid sedation and other adverse events commonly associated with benzodiazepines and SSRIs.

About the Phase 1a Study

The Phase 1a study of SNTX-2643 is a randomized, double-blind, placebo-controlled, and open-label (food-effect cohort) clinical study designed to characterize the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profile of SNTX-2643 in healthy adult volunteers following single-dose administration, and to inform the design of subsequent clinical studies.

The study includes single-ascending dose cohorts designed to evaluate escalating doses of SNTX-2643; a target engagement cohort using quantitative electroencephalography (qEEG), including resting-state measures, event-related potentials, and an anxiety-inducing stimulus paradigm to characterize CNS target engagement; and a food-effect cohort designed to evaluate the impact of food on the rate and extent of SNTX-2643 absorption.

Safety is the primary endpoint of the study. Secondary endpoints include plasma PK, with exploratory endpoints including target engagement and qEEG measures.

About Sensorium Therapeutics

Sensorium Therapeutics is a clinical-stage central nervous system (CNS) biotechnology company developing mechanistically novel small-molecule medicines for psychiatric and neurological disorders. The company applies its proprietary SensAI discovery platform, which integrates chemistry, pharmacology, behavioral science, and neuroscience, to systematically predict drug candidates with differentiated mechanisms of action.

Founded by researchers from Harvard and Massachusetts General Hospital, Sensorium is advancing a pipeline led by SNTX-2643, a Phase 1 investigational therapy for anxiety disorders. The company’s pipeline also includes SENS-03, a preclinical program for epilepsy, and SENS-08, a National Institutes of Health (NIH)-supported preclinical program targeting cognitive enhancement.

For more information, visit www.sensorium.bio.

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