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.

• Dravet Syndrome significantly impairs seizure control, cognition, behavior, speech, and motor function, with most patients falling further behind neurotypical peers over time.

• Despite advances in anti-seizure medications, over 90% of patients lack adequate seizure control, and non-seizure symptoms remain largely unaddressed.

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 communication, behavior, independence, and developmental/intellectual disability, not just seizure reduction.

• Small improvements in non-seizure symptoms or daily living skills can have a large impact on patient and caregiver quality of life.

• 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.