Encoded Therapeutics has linked its Dravet syndrome gene therapy ETX101 to a 78% reduction in seizures, keeping the biotech on track to start a pivotal study next year.
The Californian company’s Polaris program is assessing ETX101 in three open-label, dose-escalation trials. Each study is enrolling children aged 6 months to 7 years with SCN1A-positive Dravet syndrome. The AAV9-based therapy is designed to improve outcomes in the patient population by boosting expression of the SCN1A gene that is implicated in most cases of the epileptic encephalopathy condition.
Encoded arrived at the American Epilepsy Society Annual Meeting Friday with data on 19 patients who received one of four doses of ETX101. The biotech only has efficacy data for the 10 patients treated at the first three dose levels.
No treatment-related serious adverse events were reported at any of the four doses, the company noted.
At the third dose, Encoded reported a 78% median reduction in monthly countable seizure frequency. The figure comes from seven months of monitoring of three patients who were receiving anti-seizure medications at baseline. Encoded said the assessment covered a period that is typically associated with increasing seizure burden in young children.
The biotech also shared a look at neurodevelopmental endpoints. All four of the children on the two lowest doses with 52 weeks of follow-up have shown “meaningful positive divergence” from untreated children in a natural history study, Encoded said. Receptive and expressive communication and motor function were the most notable improvements, followed by self-care and social interaction.
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,” Encoded said. The biotech called the rate of cognitive development “an important deviation from the developmental slowing and eventual plateauing” seen in its natural history study.
The suggestion that ETX101 is most beneficial to children aged under 2 years has implications for the positioning of the gene therapy. While Dravet typically begins in the first year of life, Stoke Therapeutics is enrolling people aged 2 to 18 years in a phase 3 trial of its Biogen-partnered antisense oligonucleotide zorevunersen. The candidate is designed to increase levels of productive SCN1A messenger RNA.
Stoke has a lead over Encoded, putting zorevunersen on course to be the first disease-modifying Dravet drug. Encoded expects to start a pivotal study in 2026. The biotech’s calendar for next year also includes reporting efficacy data from the fourth and final dose cohort. With the top dose appearing safe and tolerable, the readout could position Encoded to surpass the efficacy seen so far.
Based on Encoded’s February update, the biotech will need to raise money or ink a partnership to fund the pivotal program. The company’s cash runway ran into the third quarter of 2026 as of the update. The runway reflected a 29% reduction in Encoded’s head count and decision to focus resources on ETX101.