Encoded Therapeutics Reports Durable Seizure Reduction and Neurodevelopmental Gains With ETX101 in Dravet Syndrome
Encoded Therapeutics, Inc., a clinical-stage biotechnology company focused on developing precision genetic medicines for severe neurological disorders, has announced new Phase 1/2 clinical data for ETX101, its investigational AAV9-based gene regulation therapy being developed as a potential one-time, disease-modifying treatment for patients with SCN1A-positive (SCN1A+) Dravet syndrome.
The latest findings from the POLARIS clinical program were presented during an oral session at the 16th European Epilepsy Congress (EEC) in Athens, Greece. Professor Ingrid Scheffer, Pediatric Neurologist and Laureate Professor of Pediatric Neurology at The University of Melbourne, presented the data.
The updated results provide longer-term evidence on seizure control following a single administration of ETX101. In addition to reductions in monthly countable seizure frequency, the presentation included findings related to cognition and adaptive behavior, suggesting that the investigational therapy may have potential beyond reducing seizures. Safety and tolerability findings from extended follow-up were also reported.
Durable Seizure Reductions Observed Through 52 Weeks
A key finding from the latest POLARIS analysis was the continued reduction in monthly countable seizure frequency (MCSF) among participants who received ETX101.
In the cumulative analysis covering Week 5 through Week 52, or through each participant’s most recent available study visit, participants treated at dose level 3 (DL3) and dose level 4 (DL4) experienced substantial median reductions in MCSF.
Among the five participants treated at DL3, the median reduction in MCSF was approximately 76%. For the nine participants who received DL4, the corresponding median reduction was approximately 60%.
Longer-term observations among participants who completed 52 weeks of follow-up showed continued seizure reductions. At Month 12, defined as Weeks 49 through 52, the median MCSF reduction was approximately 79% among three DL3 participants. Among five participants treated at DL4, the median reduction reached approximately 89%.
These findings indicate that seizure reductions observed after treatment were maintained over extended periods of observation rather than representing only short-term changes.
Sal Rico, M.D., Ph.D., Chief Medical Officer of Encoded, said the company is encouraged by both the magnitude and durability of seizure reduction following a single administration of ETX101.
According to Rico, the emerging clinical profile is also extending beyond seizure control. Continued improvements in cognitive and adaptive behavior measures are providing additional evidence that ETX101 could potentially address broader manifestations associated with Dravet syndrome.
Investigating the Broader Impact of Dravet Syndrome
Dravet syndrome is a severe neurological disorder in which recurrent seizures are accompanied by a range of developmental and functional challenges. Because the disease can affect multiple aspects of a child’s development, treatment approaches that address seizures alone may not fully address the overall burden experienced by patients and their families.
For this reason, the neurodevelopmental findings presented from the POLARIS study represent an important component of the emerging ETX101 clinical profile.
The new data showed progressive gains in measures of cognition and adaptive behavior among treated participants. Particularly notable findings were observed in children who received treatment before reaching two years of age.
Cognitive Development Shows Continued Progress
Cognitive outcomes were evaluated using the Bayley Scales of Infant and Toddler Development, Fourth Edition, commonly referred to as the Bayley-4.
The analysis focused on cognitive growth scale values (GSVs), which provide a way to monitor developmental progress over time. Among participants treated before two years of age, the available results demonstrated substantial gains in cognitive development following treatment.
With follow-up extending to as long as 76 weeks, participants demonstrated continued developmental progress. Their developmental trajectories increasingly approached the range expected for neurotypical children.
The POLARIS findings were also compared with observations from the ENVISION natural history study. The company reported that treated participants showed progressive divergence from the stagnation observed in the natural history cohort.
This distinction is important because Dravet syndrome can be associated with developmental difficulties that persist or worsen as children age. Continued gains over time could therefore represent a potentially meaningful change in developmental trajectory, although longer-term studies and additional participants will be needed to further characterize the durability and clinical significance of these observations.
Adaptive Behavior Improvements Across Multiple Domains
The latest EEC presentation also included findings from the Vineland Adaptive Behavior Scales, Third Edition (VABS-3).
The VABS-3 evaluates adaptive functioning across several areas that influence a child’s ability to communicate, interact socially, perform daily activities and develop motor skills.
According to the POLARIS data, participants demonstrated clinically meaningful improvements across all evaluated VABS-3 domains. These included communication, motor skills, socialization and daily living skills.
Improvements were particularly notable in receptive communication, expressive communication and motor function. The gains in these areas substantially narrowed the developmental gap between treated participants and neurotypical peers.
The findings add another dimension to the seizure data. While seizure frequency remains an important measure of treatment response in Dravet syndrome, changes in communication, movement, socialization and daily living skills may have a direct impact on a child’s independence and quality of life.
Encoded said the combination of seizure reduction and developmental improvements supports further evaluation of ETX101 as a potential disease-modifying approach.
Long-Term Outcome Highlighted in Oldest DL4 Participant
The EEC presentation also highlighted the experience of the oldest participant treated with DL4.
The participant received ETX101 at 3 years and 9 months of age and was followed for 52 weeks. During this period, the participant experienced a substantial reduction in seizure frequency, along with an extended period of seizure freedom.
The participant also demonstrated meaningful developmental gains during the observation period.
The individual case provides an additional example of the types of outcomes being monitored in the POLARIS program. While a single participant’s experience cannot establish treatment efficacy, the combination of seizure-related and developmental observations contributes to the broader dataset being generated by the study.
Potential to Alter the Disease Trajectory
Professor Ingrid Scheffer emphasized the significant burden that Dravet syndrome places on children and their families.
Persistent seizures can require ongoing medical management and can interfere with everyday activities, while developmental challenges may affect communication, motor abilities, social interaction and independence. Families must therefore manage both the immediate consequences of seizures and the longer-term effects of the disorder.
Scheffer said the POLARIS results are notable because a single administration of ETX101 has been associated with improvements in both seizure control and neurodevelopmental measures.
The findings, she said, provide a reason for optimism that an intervention such as ETX101 could potentially influence the broader trajectory of Dravet syndrome rather than focusing exclusively on seizure suppression.
Favorable Safety and Tolerability Profile Reported
Encoded also reported safety and tolerability data from the ETX101 clinical program.
As of the August 3, 2026 data cutoff, the investigational therapy had been evaluated across all four dose levels, with follow-up extending to as long as 117 weeks.
The company reported that ETX101 has demonstrated a favorable safety profile to date and has been well tolerated across the four dose levels evaluated.
Importantly, no treatment-related or procedure-related serious adverse events had been reported in the available dataset.
The treatment-related adverse events identified included transaminase elevations and thrombocytopenia. Transaminase elevations were reported in seven of 21 participants, while thrombocytopenia occurred in three of 21 participants.
According to Encoded, both types of events were clinically asymptomatic and resolved in all affected participants.
The extended safety follow-up provides additional information as the company continues to evaluate the potential of a one-time administration approach. Nevertheless, the safety profile will require continued monitoring as clinical development progresses and additional patients are exposed to treatment.
ETX101 Continues Clinical Development
ETX101 is being investigated as an AAV9-based gene regulation therapy intended to provide a one-time treatment for patients with SCN1A+ Dravet syndrome.
The latest POLARIS findings add to the clinical evidence being generated around the investigational therapy. The combination of sustained seizure reductions, observations of seizure freedom in individual participants, and progressive improvements in cognitive and adaptive behavior measures provides multiple areas for continued investigation.
The data are particularly notable because the reported changes extend beyond seizure frequency. Measures of cognitive development and adaptive functioning may offer insight into whether treatment could potentially influence aspects of Dravet syndrome that affect children over the longer term.
At the same time, the findings remain clinical-stage investigational data. The current analysis includes relatively small participant groups at individual dose levels, and some developmental analyses involve children treated at specific ages. Additional follow-up and larger datasets will be important for determining the consistency, durability and clinical significance of the observed effects.
With follow-up extending beyond one year for some participants, the POLARIS program continues to provide longer-term information on ETX101’s potential clinical profile.
The approximately 76% and 60% median reductions in MCSF observed among DL3 and DL4 participants, respectively, in the cumulative Week 5-to-Week 52 analysis, together with median reductions of approximately 79% and 89% at Month 12 among participants completing 52 weeks, demonstrate the durability of the seizure-related findings reported to date.
Meanwhile, Bayley-4 and VABS-3 assessments point to continued developmental and functional gains across several domains.
Encoded Therapeutics believes these findings support the continued development of ETX101 as a potential one-time, disease-modifying treatment for SCN1A+ Dravet syndrome. Future clinical work will be important in establishing whether the early evidence of sustained seizure control and developmental progress can be replicated across broader patient populations and over longer periods.
All efficacy and safety analyses described in the EEC presentation reflect data available through the August 3, 2026 data cutoff.
About the POLARIS Clinical Development Program
The POLARIS program is a comprehensive clinical investigation of ETX101 in children and adolescents with SCN1A+ Dravet syndrome, comprising multiple Phase 1-3 clinical trials. The first phase of POLARIS includes three ongoing open-label, Phase 1/2 dose-escalation, multicenter trials (ENDEAVOR Part 1 (US), EXPEDITION (UK), and WAYFINDER (Australia)) in infants and young children aged 6 months to 7 years.
ENDEAVOR Part 1B, an expansion study in the US, is actively enrolling children and adolescents aged 4 to 18 years. These studies are evaluating the safety and preliminary efficacy of ETX101 in children and adolescents with Dravet syndrome due to variants in the SCN1A gene. The pivotal ENDEAVOR Part 2 study is also ongoing, evaluating seizure and neurodevelopmental outcomes in young children aged 6 months to 4 years.
About ETX101
ETX101 is an investigational AAV9-based gene regulation therapy designed to increase the expression of the SCN1A gene to restore sodium channel function in inhibitory interneurons. By targeting the 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. The therapy is administered via a single intracerebroventricular (ICV) injection and is designed for long-term benefit.
ETX101 has received Breakthrough Therapy, Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations from the FDA. It also was selected for the FDA’s CMC Development and Readiness Pilot (CDRP) program and received Orphan designation from the European Medicines Agency (EMA).
About Encoded Therapeutics
Encoded Therapeutics is a clinical-stage biotechnology company developing one-time precision genetic medicines for severe monogenic and common neurological disorders. The company’s vector engineering platform enables highly targeted and cell-type-selective control of gene expression in the brain and peripheral nervous system, allowing potent and precise modulation of disease-relevant genes to address underlying disease biology.
Encoded’s end-to-end innovation engine—spanning discovery, development, and in-house GMP manufacturing—creates a streamlined path to advance a diversified pipeline of one-time treatments across a broad range of neurological conditions. Encoded is driven by a mission to meaningfully improve the lives of patients and families affected by devastating neurological disorders.