Encoded Therapeutics has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration for ETX101, its investigational gene therapy for SCN1A+ Dravet syndrome. The designation was granted following FDA review of preliminary seizure data from patients treated in the company's ongoing Phase 1/2 program.
ETX101 is an AAV9-based gene regulation therapy designed to increase SCN1A expression in GABAergic inhibitory neurons for the treatment of SCN1A+ Dravet syndrome. The therapy already holds Fast Track, Rare Pediatric, and Orphan Drug designations from the FDA, as well as Orphan Designation from the European Medicines Agency.
"The FDA's decision to grant RMAT designation highlights the promising clinical efficacy and safety profile we have observed to date," said Kartik Ramamoorthi, PhD, Chief Executive Officer of Encoded Therapeutics. "This milestone, together with the transition to in-house GMP manufacturing, underscores both the clinical potential of ETX101 and our readiness to efficiently advance the program through development."
RMAT Designation Benefits
RMAT is an expedited program designed to facilitate development and review of regenerative medicine therapies intended to treat, modify, reverse, or cure serious or life-threatening diseases. The designation provides Encoded with early, close and frequent interactions with the FDA, organizational commitments from senior managers, and other opportunities to expedite review of ETX101.
Clinical Development Program
The POLARIS clinical development plan comprises a suite of ongoing open-label, dose-escalation clinical trials of ETX101 in infants and young children aged 6 months to less than 7 years with SCN1A+ Dravet syndrome. The studies are being conducted across the United States, United Kingdom, and Australia through three trials: ENDEAVOR Part 1, EXPEDITION, and WAYFINDER, respectively.
These studies are assessing safety, tolerability, and preliminary efficacy of ETX101. Enrollment in the dose-escalation studies is expected to complete in Q4 2025, with interim clinical efficacy data presentation planned for the same timeframe.
Manufacturing Capabilities
Encoded Therapeutics has completed construction of its state-of-the-art GMP manufacturing facility in North Carolina in Q1 2025. The facility has now initiated production of ETX101 to support pivotal trials expected in the first half of 2026. Designed to support production of multiple gene therapies, the facility enhances Encoded's strategic capabilities from early process development through commercial GMP manufacturing.
By bringing key chemistry, manufacturing, and controls (CMC) activities in-house, Encoded ensures greater control over product quality and has the opportunity to accelerate development timelines and commercial readiness.
Mechanism of Action
ETX101 is a potential one-time, disease-modifying gene regulation therapy targeting the underlying cause of SCN1A+ Dravet syndrome. The therapy delivers a transgene encoding an engineered transcription factor under the control of a cell-selective regulatory element within a clinically-validated AAV9 capsid to upregulate expression of the endogenous SCN1A gene.
This approach is expected to increase production of NaV1.1 protein sodium channels in target neurons in the brain and restore function. By targeting the underlying mechanism of disease, ETX101 has the potential to address the full range of symptoms associated with Dravet syndrome.
Disease Background
Dravet syndrome is a severe, lifelong disorder of the central nervous system that occurs in approximately 1 in 16,000 births worldwide, with the majority of cases resulting from loss-of-function variants in the SCN1A gene. This developmental and epileptic encephalopathy equally affects people of both sexes and all races.
The condition manifests with frequent, prolonged, and drug-resistant seizures that primarily begin in the first year of life of a typically developing infant. Severe cognitive and developmental stagnation, sleep abnormalities, motor impairment, and behavioral difficulties usually become clinically evident by the second or third year of a child's life.
