Encoded Therapeutics’ AAV Gene Therapy ETX101 Shows 78% Seizure Reduction in Dravet Syndrome Trial

SOUTH SAN FRANCISCO, Calif. – December 5, 2025 –Encoded Therapeutics delivered encouraging clinical data for its AAV gene therapy candidate, ETX101, at the American Epilepsy Society Annual Meeting last Friday. The data links the investigational treatment to a 78% median reduction in countable seizures, positioning the biotech to launch a pivotal study for the AAV-delivered therapy in 2026.

Encoded’s ongoing Polaris program is currently assessing ETX101 in three open-label, dose-escalation trials. The studies are targeting children aged 6 months to 7 years diagnosed with SCN1A-positive Dravet syndrome. ETX101, an AAV9-based gene therapy, is specifically engineered to address the underlying cause of the condition by boosting the expression of the SCN1A gene, which is implicated in the majority of Dravet syndrome cases.

The company presented initial findings on 19 patients who had received one of four doses of the AAV therapy. Efficacy results were available for the 10 patients treated at the first three dose levels. Crucially, no treatment-related serious adverse events were reported across any of the four doses of the AAV vector.

Strong Efficacy and Neurodevelopmental Gains

At the third dose level, Encoded reported a 78% median reduction in monthly countable seizure frequency. This figure was derived from three patients monitored over seven months, all of whom were also receiving baseline anti-seizure medications. Encoded highlighted that this reduction occurred during a period typically associated with increasing seizure burden in young children with Dravet syndrome.

Beyond seizure control, the AAV gene therapy also appears to be driving significant neurodevelopmental improvements. Encoded stated that all four children on the two lowest doses with 52 weeks of follow-up have shown “meaningful positive divergence” when compared to untreated children in a natural history study. Improvements in receptive and expressive communication and motor function were the most pronounced, followed by gains in self-care and social interaction.

The data strongly suggests that the AAV treatment may be most beneficial when administered early. Four of the five children treated before two years of age “showed substantial acceleration of cognitive skill acquisition as early as 16 weeks, with progressive gains through 52 weeks of observation,” the company noted. Encoded described this rapid rate of cognitive development as an “important deviation from the developmental slowing and eventual plateauing” typically observed in the natural history of Dravet syndrome.

Competitive Landscape and Future Outlook

The positive data positions Encoded against competitors like Stoke Therapeutics, whose Biogen-partnered antisense oligonucleotide, zorevunersen, is currently in a Phase 3 trial. While Stoke has a head start, putting zorevunersen on track to potentially be the first disease-modifying drug for Dravet, the early data on Encoded’s AAV gene therapy suggests strong potential, particularly for very young patients.

Encoded expects to initiate its pivotal study in 2026. The company’s plans for the coming year also include reporting efficacy data from the fourth and final dose cohort of the AAV treatment trials. With the highest dose proving safe and tolerable, this upcoming readout could potentially demonstrate even greater efficacy than seen so far.

Based on previous financial disclosures, Encoded’s current cash runway extends into the third quarter of 2026. This runway was extended following a 29% reduction in head count and a strategic decision to focus resources almost entirely on the development and manufacturing of the ETX101 AAV gene therapy. The company will likely need to secure further financing or a partnership to fully fund the pivotal program.