Stoke Therapeutics (STOK) Goldman Sachs 45th Annual Global Healthcare Conference summary

Recent clinical progress and data highlights

• End-of-phase II data for zorevunersen showed 70–85% seizure reduction and significant cognitive and behavioral improvements in Dravet syndrome patients already on maximum therapy.

• Improvements in cognition and behavior were observed across ages 2–18, with no age-related differences in response.

• Open-label extension studies confirmed persistent seizure reduction and cognitive gains over 12 months, with 80% of patients achieving at least 50% seizure reduction.

• Zorevunersen was generally well-tolerated, with most adverse events related to lumbar puncture and mild increases in spinal fluid protein.

• The drug is currently studied as an add-on therapy but may have potential as a monotherapy in the future.

Disease background and unmet needs

• Dravet syndrome is a severe genetic epilepsy affecting 1 in 16,000 births, with high rates of sudden death and significant cognitive and behavioral challenges.

• 90% of patients have seizures that are not adequately controlled by existing anti-seizure medications.

• Cognitive and behavioral deficits are linked to NaV1.1 protein deficiency, not just seizure activity.

• Natural history studies show persistent, refractory seizures and stagnant or worsening development over time.

Pipeline and future plans

• Phase III study for zorevunersen in Dravet syndrome is planned, with primary endpoint of seizure frequency and secondary endpoints in cognition and behavior.

• Regulatory meetings with FDA, EMA, and PMDA are scheduled for the second half of 2024 to finalize phase III design.

• STK-002 for autosomal dominant optic atrophy (ADOA) is entering phase 1/2, with preclinical data showing increased OPA1 protein and improved mitochondrial function.

• Additional preclinical programs in SYNGAP1 and Rett syndrome are progressing, with a disease-modifying approach targeting underlying protein deficiencies.