Stoke Therapeutics (STOK) Status Update summary

Disease Overview and Unmet Need

• Dravet syndrome is a severe genetic epileptic encephalopathy, with 85% of cases due to SCN1A haploinsufficiency, leading to 50% Nav1.1 protein expression.

• About 35,000 people are affected in the US, Canada, Japan, Germany, France, and the UK; 1 in 16,000 babies are born with the condition.

• Up to 20% of children and adolescents with Dravet syndrome die before adulthood, often from SUDEP or seizure-related causes.

• Seizures are inadequately controlled in 90% of patients despite multiple anti-seizure medications.

• Symptoms extend beyond seizures, including learning, behavioral, communication, cognition, speech, movement, and sleep impairments, with early onset and a widening developmental gap over time.

Current Treatment Landscape and Caregiver Perspectives

• Standard anti-seizure medicines do not meaningfully reduce convulsive seizure frequency or halt neurodevelopmental decline.

• Caregivers and families prioritize improvements in developmental/intellectual disability, speech/language, behavior, communication, and independence as highly meaningful outcomes.

• Small improvements in non-seizure symptoms and daily living skills are described as profoundly impactful for patients and caregivers, offering hope for greater independence and reduced caregiver burden.

• Meaningful change in adaptive behavior is considered a 2-3 point increase in Vineland-3 subdomains, especially in communication and motor skills.

Disease Progression and Natural History

• Cognitive and adaptive function in Dravet syndrome plateaus early, with a widening gap compared to neurotypical peers.

• Language and communication delays persist regardless of seizure burden or anti-seizure medication use.

• Regression analysis shows substantial neurodevelopmental gaps that widen over time, despite standard care.