Guess the Therapy Answer May 22, 2026
Encoded Therapeutics currently has which AAV9-mediated gene therapy candidate in clinical development for SCN1A-positive Dravet syndrome?
Answer: ETX101
See below for further reading on ETX101:
May 13, 2026 — Interim findings from the ongoing POLARIS phase 1/2 program suggest that Encoded Therapeutics’ investigational gene therapy ETX101 may produce substantial seizure reductions and early neurodevelopmental improvements in young children with SCN1A-positive Dravet syndrome, supporting continued advancement of the program as it enters pivotal-stage development.
Presented at the 2026 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, the updated data included outcomes from 21 treated participants across the ENDEAVOR, WAYFINDER, and EXPEDITION studies, which together comprise the broader POLARIS clinical program evaluating ETX101, an AAV9-mediated gene regulation therapy designed to selectively upregulate endogenous SCN1A expression in GABAergic inhibitory interneurons.
Dravet syndrome, a severe developmental and epileptic encephalopathy most commonly caused by SCN1A haploinsufficiency, is associated with drug-resistant seizures, developmental slowing, and elevated mortality risk beginning in infancy. Current antiseizure medications may reduce seizure burden but do not directly address the underlying genetic deficit or alter long-term neurodevelopmental trajectory. ETX101 was engineered to overcome historical gene therapy limitations associated with the large SCN1A coding sequence and the need for cell-type specificity. Previous preclinical work published in Human Gene Therapy demonstrated that the therapy’s engineered transcription factor approach could selectively increase SCN1A expression in inhibitory interneurons, laying the groundwork for clinical development.
March 25, 2026 — Encoded Therapeutics announced FDA alignment on the pivotal study design for ETX101 (an AAV9-based gene regulation therapy) in SCN1A+ Dravet syndrome following a completed Initial Comprehensive Multidisciplinary Regenerative Medicine Advanced Therapy (RMAT) meeting. The 30-patient ENDEAVOR Part 2 trial—now initiated—will evaluate a single intracerebroventricular administration versus sham control over 52 weeks in children aged 6 months to younger than 4 years, with monthly seizure frequency reduction and Bayley-4 cognitive scores as primary and key secondary end points, respectively. An open-label expansion cohort (part 1B) will assess safety and preliminary efficacy in patients aged 4 to younger than 18 years. Enrollment completion and initial data readouts are expected by end of 2026 and 2027, respectively.
