Updated phase 1/2 data from the POLARIS clinical development program demonstrated sustained reductions in seizure frequency and progressive improvements across cognitive and adaptive behavior measures following a single administration of investigational ETX101 (Encoded Therapeutics) in children with SCN1A+ Dravet syndrome.
The findings, presented at the 16th European Epilepsy Congress in Athens, Greece, included follow-up through 52 weeks for seizure outcomes and up to 76 weeks for selected neurodevelopmental measures.
Seizure Reductions and Neurodevelopmental Gains
At dose level 3 (DL3; n = 5) and dose level 4 (DL4; n = 9), participants experienced median reductions in monthly countable seizure frequency (MCSF) of approximately 76% and 60%, respectively, from week 5 through week 52 or their latest available study visit.
Among those who completed 52 weeks of observation, median MCSF reductions at month 12 were approximately 79% in the DL3 group (n = 3) and 89% in the DL4 group (n = 5).
Sal Rico, MD, PhD, Chief Medical Officer of Encoded, said, “With longer follow-up and additional data available, we are encouraged by the magnitude and durability of seizure reduction following a single administration of ETX101. Importantly, the emerging clinical profile extends beyond seizure control, with continued improvements across cognitive and adaptive behavior measures supporting the potential to address the broader manifestations of Dravet syndrome.”
Seizure Reductions Remain Sustained
The updated seizure findings showed continued reductions following a single ETX101 administration. Across the cumulative analysis from week 5 through week 52 or the participant’s latest study visit, median MCSF declined by approximately 76% with DL3 and 60% with DL4.
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Among participants with a full 52 weeks of observation, reductions were approximately 79% with DL3 and 89% with DL4 during weeks 49-52.
These data extend the earlier seizure findings presented at AES 2025, which observed a dose-dependent effect on MCSF, with a median 78% reduction emerging at week 32 among the small DL3 cohort.
Neurodevelopmental Measures Continue to Show Gains
Beyond seizure control, the updated POLARIS findings included measures of cognition and adaptive behavior, areas of substantial clinical importance in Dravet syndrome.
Among participants treated before 2 years of age, Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4) cognitive growth scale values demonstrated continued gains over time.
With up to 76 weeks of follow-up, Encoded reported that developmental trajectories continued to diverge from the stagnation observed in the ENVISION natural history study and approached the range expected for neurotypical children.
Adaptive behavior, assessed using the Vineland Adaptive Behavior Scales, Third Edition (VABS-3), also showed progressive improvements across evaluated domains, including communication, motor skills, socialization, and daily living skills.
The improvements in adaptive behavior are particularly noteworthy, as they suggest that ETX101 may have a positive impact on the daily lives of children with Dravet syndrome, enabling them to interact more effectively with their environment and develop essential skills for independence.
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Safety Profile and Advancement into Later-Stage Development
ETX101 continued to demonstrate a favorable safety profile across all 4 dose levels, according to Encoded. With up to 117 weeks of follow-up, there were no treatment- or procedure-related serious adverse events reported.
Treatment-related adverse events included transaminase elevations in 7 of 21 participants and thrombocytopenia in 3 of 21 participants. All were clinically asymptomatic and resolved, according to the company.
The POLARIS clinical development program currently includes multiple phase 1/2 studies evaluating ETX101 in children and adolescents with SCN1A+ Dravet syndrome.
The updated findings provide longer-term evidence from the early-stage program supporting continued investigation of ETX101. However, the small sample sizes, open-label design of the phase 1/2 studies, and reliance in part on comparisons with natural-history data remain important considerations when interpreting the observed seizure and developmental changes.
As the program moves forward into later-stage testing, it will be important to gather randomized data to determine whether the seizure and neurodevelopmental trajectories observed to date are due to ETX101.
Encoded will continue to monitor the safety and efficacy of ETX101 in ongoing studies.
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The company’s goal is to develop a treatment that can improve the lives of children with Dravet syndrome.
Dravet syndrome is a severe form of epilepsy that affects children.
It is characterized by frequent seizures and developmental delays.
There is currently no cure for Dravet syndrome, but researchers are working to develop new treatments.
Sal Rico, MD, PhD, is the Chief Medical Officer of Encoded Therapeutics.
Encoded Therapeutics is a biotechnology company that is developing new treatments for genetic disorders.