SOUTH SAN FRANCISCO, Calif. – May 13, 2026
Encoded Therapeutics presented expanded clinical data from its ongoing POLARIS Phase 1/2 trials evaluating ETX101, an investigational AAV9-based gene regulation therapy for SCN1A+ Dravet syndrome, during the Presidential Symposium at the 2026 American Society of Gene & Cell Therapy (ASGCT) Annual Meeting. The updated findings demonstrated robust and durable seizure reduction following a single dose of ETX101, alongside clinically meaningful improvements in neurodevelopmental and adaptive behavior outcomes across treated children. Importantly, the therapy showed the potential to reverse the severe developmental stagnation commonly associated with Dravet syndrome in children treated before the age of two, with cognitive trajectories approaching neurotypical developmental patterns through 52 weeks of observation. The data strengthen ETX101’s position as a potentially transformative one-time genetic medicine targeting the underlying biological cause of this severe pediatric neurological disorder.
ETX101 Demonstrates Durable Seizure Reduction Across Dose Levels
According to Encoded Therapeutics, ETX101 produced strong dose-dependent anti-seizure activity across the ongoing POLARIS studies, with durable efficacy maintained through at least 52 weeks after treatment. Patients receiving the third dose level (DL3) experienced an approximately 76% median reduction in monthly countable seizure frequency (MCSF) from Week 5 through Week 52. Researchers noted that these reductions occurred during a developmental period typically associated with worsening seizure burden despite aggressive treatment with multiple standard-of-care anti-seizure medications.
The company also presented early findings from the highest dose cohort (DL4), which demonstrated continued dose-dependent therapeutic activity. Investigators observed the strongest responses among patients who did not receive sirolimus, an immunosuppressive agent sometimes used during AAV gene therapy administration. Encoded stated that molecular and preclinical data suggest sirolimus may reduce therapeutic protein expression, potentially dampening ETX101’s biological activity. Importantly, no safety differences were observed between patients who received sirolimus and those who did not.
Dravet syndrome is a severe genetic epilepsy disorder caused primarily by mutations in the SCN1A gene, leading to impaired sodium channel function in inhibitory neurons within the brain. Patients often develop treatment-resistant seizures beginning in infancy, accompanied by progressive cognitive decline, communication impairment, motor dysfunction, and behavioral abnormalities. Existing therapies largely focus on symptom management rather than addressing the underlying disease mechanism. Encoded believes ETX101 may represent one of the first therapies capable of fundamentally altering disease progression through targeted gene regulation.
Neurodevelopmental Rescue Signals Major Advancement in Dravet Therapy
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Beyond seizure control, the ASGCT 2026 data highlighted potentially groundbreaking improvements in neurodevelopmental outcomes among treated children. Patients who completed 52 weeks of follow-up demonstrated meaningful gains across multiple adaptive behavior domains measured using the Vineland Adaptive Behavior Scales (VABS-3). The most notable improvements were observed in expressive communication, receptive communication, and motor function, while additional progress was seen in self-care skills and social interaction.
The strongest developmental effects were observed in children treated before two years of age. According to Encoded, these patients showed progressive cognitive gains as early as Week 16, continuing through Week 52 based on assessments using the Bayley Scales of Infant and Toddler Development (Bayley-4). Researchers stated that treated children rapidly diverged from the severe developmental stagnation typically observed in the natural history of Dravet syndrome, with cognitive trajectories increasingly resembling neurotypical developmental patterns over time.
Investigators and patient advocacy leaders described the findings as highly encouraging because developmental impairment remains one of the most devastating long-term consequences of Dravet syndrome. While many anti-seizure therapies can reduce seizure burden, very few interventions have demonstrated evidence of restoring or preserving neurodevelopmental progress. Encoded executives stated that the emerging data support the hypothesis that early intervention with ETX101 may help preserve neural circuitry and improve long-term developmental outcomes by correcting the disease-driving biological defect at its source.
Favorable Safety Profile Supports Continued Clinical Development
Encoded reported that ETX101 has demonstrated a favorable safety and tolerability profile across all four dose levels evaluated to date. No treatment-related or procedure-related serious adverse events have been reported during the ongoing studies. The most common treatment-related adverse events were transient transaminase elevations, a known class effect associated with AAV-based gene therapies. These liver enzyme increases were asymptomatic and resolved in all treated participants.
The broader POLARIS clinical development program includes multiple international Phase 1–3 trials evaluating ETX101 across infants, children, and adolescents with SCN1A+ Dravet syndrome. Ongoing studies include ENDEAVOR in the United States, EXPEDITION in the United Kingdom, and WAYFINDER in Australia, alongside a pivotal Phase 3 expansion study focused on younger pediatric patients.
ETX101 has received multiple regulatory designations from the FDA, including Breakthrough Therapy, Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Rare Pediatric Disease, and Orphan Drug designations, reflecting the urgent unmet medical need and the therapy’s potential clinical significance. The therapy has also received Orphan designation from the European Medicines Agency (EMA).
As investment in neurological gene therapies accelerates globally, Encoded Therapeutics is positioning ETX101 as a next-generation precision genetic medicine capable of delivering long-term disease modification through a single administration. The company believes the latest ASGCT data provide some of the strongest evidence yet that targeted gene regulation therapies may fundamentally change outcomes for children affected by severe monogenic neurological diseases.
Source: Encoded Therapeutics press release
