Encoded Therapeutics Inc., a clinical-stage biotechnology company developing genetic medicines for severe neurological disorders, today announced positive interim results from its ongoing POLARIS clinical development program evaluating ETX101 in children with SCN1A+ Dravet syndrome. The data will be featured in an oral presentation at the American Epilepsy Society (AES) Annual Meeting today and again tomorrow in a poster session.
The POLARIS program includes three ongoing open-label, dose-escalation trials of ETX101 in the US (ENDEAVOR Part 1), UK (EXPEDITION), and Australia (WAYFINDER). POLARIS is evaluating the safety and preliminary efficacy of ETX101 in children 6 months to 7 years of age with Dravet syndrome due to variants in the SCN1A gene. ETX101 is administered via a single intracerebroventricular injection into the cerebrospinal fluid (CSF). Across these studies, 19 participants received ETX101 at one of four dose levels: 5.0E11 (n=3), 1.9E12 (n=4), 3.3E12 (n=3), or 6.6E12 vg/mL CSF (n=9). Interim results are reported with a data cutoff of November 10, 2025, including safety data from all four dose levels and efficacy data for the first three dose levels.
ETX101 demonstrated dose-dependent and sustained reductions in monthly countable seizure frequency (MCSF) in drug-resistant participants during a worsening period typically associated with increasing seizure burden. Progressive and clinically meaningful neurodevelopmental gains were observed in both the caregiver interview-based Vineland Adaptive Behavior Scales (VABS-3) and the clinician-administered Bayley Scales of Infant and Toddler Development (Bayley-4) through 52 weeks of observation. In children treated before 2 years of age, substantial acceleration in cognitive skill acquisition was evident by 16 weeks, supporting the potential for ETX101 to prevent neurodevelopmental stagnation with early intervention. To date, ETX101 has been well-tolerated, with no treatment-related serious adverse events reported through the fourth and highest dose level.
“These results point to the possibility of a one-time treatment that not only reduces seizures, but also addresses the profound neurodevelopmental stagnation that affects the ability of children with Dravet syndrome to communicate, learn, and function independently,” said Joseph Sullivan, M.D., Professor of Neurology & Pediatrics, University of California, San Francisco, and Principal Investigator on the ENDEAVOR study. “These early signals of developmental rescue in our youngest patients offer real hope for families facing the challenges of living with this disease.”
“While early, the emerging clinical impact of ETX101 underscores its potential as a one-time, disease-modifying medicine for Dravet syndrome,” said Kartik Ramamoorthi, Ph.D., Chief Executive Officer of Encoded Therapeutics. “We’re incredibly grateful to the study participants and their families, clinicians, and advocacy partners whose commitment and collaboration have made this progress possible. We look forward to presenting efficacy data from the fourth and final dose level as we seek to advance ETX101 toward a pivotal clinical trial in 2026.”
Safety: Well-Tolerated Across all Dose Levels
To date, ETX101 has shown a favorable safety profile and has been well-tolerated across all four dose levels with no treatment-related serious adverse events (n=19). The most common treatment-related adverse events were expected transaminase elevations (a known AAV class effect), which were clinically asymptomatic and resolved in all participants.
Efficacy: Seizure Reduction
Substantial antiseizure effects were observed through 7 months at the third dose level (n=3), with a 78% median reduction in MCSF in drug-resistant participants already receiving the best available antiseizure medications. These reductions occurred during a worsening period typically associated with increasing seizure burden in young children with Dravet syndrome.
Efficacy: Neurodevelopmental Improvements
Neurodevelopmental improvements were observed across all three initial dose levels, supporting the disease-modifying potential of ETX101.
- On VABS-3, four participants across dose levels 1 and 2 have reached 52 weeks of follow-up, all of whom showed meaningful positive divergence from untreated children in the ENVISION natural history study. The most notable improvements were in receptive and expressive communication and motor function, with significant progress also seen in self-care and social interaction.
- On Bayley-4, four out of five participants treated before 2 years of age showed substantial acceleration of cognitive skill acquisition as early as 16 weeks, with progressive gains through 52 weeks of observation. The rate of cognitive development in these participants treated with ETX101 represents an important deviation from the developmental slowing and eventual plateauing observed in the ENVISION natural history study, supporting the potential of ETX101 to prevent neurodevelopmental stagnation with early intervention.
Presentation Details
“POLARIS Phase 1/2 Program Interim Safety and Preliminary Efficacy Results of ETX101, a One-Time Gene Regulation Therapy, in Young Children with Dravet Syndrome” will be presented by Joseph Sullivan, M.D.
Oral Session: Platform session B.02
Date & Time: Friday, December 5, 2025, 12:45–1:00 pm ET
Location: Georgia World Congress Center Room B313
Poster Session: Poster #1.308
Date & Time: Saturday, December 6, 2025, 12:00–6:00 pm ET (Poster displayed); 12:00–2:00 pm ET (Author present)
Location: Georgia World Congress Center Exhibit Hall B2
About Dravet Syndrome
Dravet syndrome is a severe, lifelong developmental and epileptic encephalopathy (DEE) that begins in infancy. Most cases are caused by variants in the SCN1A gene, resulting in reduced NaV1.1 protein in the brain. Seizures typically begin within the first year of life and are frequent, prolonged, and difficult to control, even with treatment. As the disease progresses, people experience cognitive and developmental delays, motor and balance difficulties, sleep disturbances, and behavioral challenges. Dravet syndrome carries a high risk of SUDEP (Sudden Unexpected Death in Epilepsy), with up to 1 in 5 children dying before adulthood. Dravet syndrome affects approximately 35,000 people in the United States, United Kingdom, EU4 and Japan. Currently, there are no approved disease-modifying therapies for Dravet syndrome, leaving a significant and urgent unmet need for patients and families. More information about Dravet syndrome can be found at www.dravetfoundation.org.
About ETX101
ETX101 is a potential one-time, disease-modifying AAV9-based gene regulation therapy for SCN1A+ Dravet syndrome. ETX101 is designed to target the underlying cause of Dravet syndrome by increasing SCN1A expression in GABAergic inhibitory neurons. By addressing this root mechanism, ETX101 has the potential to treat the full spectrum of Dravet syndrome symptoms, including seizures, communication and cognitive impairment, behavioral issues, and motor dysfunction. ETX101 has received Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug Designations from the FDA, as well as Orphan Designation from the EMA.
About the POLARIS Program
The POLARIS program is a comprehensive clinical investigation of ETX101 in children with SCN1A+ Dravet syndrome, comprising multiple Phase 1-3 clinical trials. The first phase of POLARIS comprises three open-label, Phase 1/2 dose-escalation, multi-center trials (ENDEAVOR (US), EXPEDITION (UK), and WAYFINDER (Australia)) in infants and young children 6 months to 7 years of age. The primary objective of the studies is to assess the safety and tolerability of ETX101. Secondary objectives are to evaluate the preliminary efficacy of ETX101 by assessing the percent change from baseline in monthly countable seizure frequency (MCSF), as well as the impact on the neurodevelopmental symptoms of Dravet syndrome, including cognition, communication, and motor function.
About Encoded Therapeutics
Encoded Therapeutics is a clinical-stage genetic medicines company developing one-time therapies for severe neurological disorders. Our vector engineering platform enables highly selective, potent, and durable gene modulation. The lead program, ETX101, is designed to address the underlying cause of Dravet syndrome by durably upregulating SCN1A and is currently in Phase 1/2 clinical trials. Building on this foundation, we are advancing programs to modulate validated genetic targets in chronic pain, Angelman syndrome, and Alzheimer’s disease/tauopathies. With integrated discovery, development, and manufacturing capabilities, we are positioned to efficiently move programs from concept through the clinic. We are driven by a mission to meaningfully improve the lives of patients and families affected by devastating neurological conditions. For more information, please visit www.encoded.com.
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