Encoded raises $275M to advance gene therapy for Dravet syndrome
Funds will support expansion study of ETX101, manufacturing upgrades
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Encoded Therapeutics has raised $275 million in Series F financing to support the clinical development of its experimental gene therapy ETX101 for infants and young children with Dravet syndrome.
The funds will also support an expansion study in children and adolescents up to age 18, and the commercial scale-up of Encoded’s internal good manufacturing practice capabilities to support potential commercial production should the therapy be approved.
The financing follows recent Phase 1/2 data from POLARIS, Encoded’s clinical development program for ETX101. The program includes several clinical trials, including the ongoing pivotal ENDEAVOR (NCT05419492) Part 2 study, the results of which are intended to support potential regulatory approval of the therapy. The new results extended earlier findings, showing that a single administration of ETX101 was associated with substantial and sustained reductions in seizure frequency in children with Dravet.
The gene therapy was also associated with continued cognitive gains in children treated before age 2 and improvements in adaptive development across the evaluated age range.
“The interim Phase 1/2 POLARIS data we recently shared at the European Epilepsy Congress demonstrate substantial and sustained seizure frequency reductions alongside encouraging developmental gains. This progress strengthens our conviction in ETX101 and the potential of our approach to meaningfully alter the course of Dravet syndrome,” Kartik Ramamoorthi, PhD, CEO of Encoded, said in a company press release. “With pivotal development underway, this financing gives us the resources to advance ETX101 toward registration while continuing to build the capabilities and pipeline that will define Encoded’s next stage.”
EXT101 targets underlying disease mechanism
Dravet syndrome is a severe form of epilepsy that usually begins in infancy. Most cases are caused by disease-causing variants in the SCN1A gene, which result in insufficient function of NaV1.1, a sodium channel important for communication by inhibitory nerve cells in the brain. Along with frequent, difficult-to-control seizures, people with Dravet may experience developmental, cognitive, behavioral, and motor problems.
ETX101 is a one-time AAV9-based gene therapy designed to increase SCN1A gene activity and restore sodium channel function in nerve cells. It is administered directly into the brain’s fluid-filled cavities and is intended to address the underlying disease mechanism rather than only controlling seizures.
The initial phase of the ongoing POLARIS clinical program is evaluating escalating doses of ETX101 in infants and young children ages 6 months to 7 years across three open-label Phase 1/2 studies: ENDEAVOR in the U.S., EXPEDITION (NCT06283212) in the U.K., and WAYFINDER (NCT06112275) in Australia.
An ENDEAVOR expansion study is enrolling children and adolescents ages 4 to 18, while the pivotal ENDEAVOR Part 2 study is evaluating seizure and neurodevelopmental outcomes in children ages 6 months to 4 years.
The latest POLARIS update reported reductions in seizure frequency among children treated with ETX101. From week five through week 52 (about a year), or at their latest study visit, monthly countable seizures fell by a median of 76% in five children receiving the third dose and 60% in nine receiving the fourth dose. Among those who completed 52 weeks of follow-up, seizures decreased by 79% in three children at the third dose and by 89% in five at the fourth dose.
The emerging clinical profile of ETX101 is increasingly compelling with durable seizure control and promising neurodevelopmental signals, reinforcing its potential as a transformative therapy.
In children treated before age 2, cognitive development also improved over time, with scores increasingly approaching those expected in neurotypical children. Improvements in communication, motor skills, socialization, and daily living skills were also seen.
“The emerging clinical profile of ETX101 is increasingly compelling with durable seizure control and promising neurodevelopmental signals, reinforcing its potential as a transformative therapy,” said Brendan Bulik-Sullivan, PhD, general partner at GV, which co-led the financing. “We are pleased to co-lead this financing and support Encoded as it advances ETX101 through pivotal development.”
ETX101 remained generally well tolerated across all four dose levels, with follow-up lasting up to 117 weeks (about 2.25 years). No treatment or procedure-related serious adverse events were reported. Among 21 participants, seven had treatment-related elevations in liver enzymes, and three had low platelet counts; both issues were clinically asymptomatic and resolved.
“Progress with ETX101 provides important validation of Encoded’s differentiated approach to genetic medicine and the broader potential of its platform,” said David Schenkein, MD, general partner and co-lead of life sciences at GV. “Encoded is well positioned to build a significant portfolio of medicines across neurological diseases, where more precise and durable biological intervention could meaningfully improve outcomes.”
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