Stoke Therapeutics (STOK) 2024 Cantor Fitzgerald Global Healthcare Conference summary

Platform and scientific approach

• Utilizes oligonucleotide technology to upregulate protein expression, targeting genetic diseases with haploinsufficiency, especially in the CNS.

• Platform allows precise, cell-specific modulation of protein levels, reducing risk of overexpression.

• Initial focus is on Dravet syndrome, with plans to expand into other indications, including autosomal dominant optic atrophy.

• Collaboration with Acadia covers programs in Rett syndrome, SYNGAP1, and an undisclosed indication.

• Animal and early clinical data support the platform’s ability to double deficient proteins and improve disease outcomes.

Clinical data and patient impact

• Lead candidate zorevunersen showed up to 80% seizure reduction in Dravet patients on top of standard care.

• Improvements observed in cognition, communication, and motor skills, measured by validated tools like the Vineland Adaptive Behavior Scale.

• Families prioritize improvements in quality of life, such as communication and behavior, over seizure reduction alone.

• Phase 1/2 and open-label extension studies indicate sustained benefits up to nine months and beyond.

• Disease-modifying effects are central to regulatory and payer discussions, aiming for meaningful clinical and economic value.

Regulatory and development strategy

• Ongoing discussions with FDA, EMA, and PMDA to finalize phase III design, with seizure reduction as the likely primary endpoint.

• Secondary endpoints will assess cognition and behavior, with studies powered to show statistical significance.

• Phase III protocol expected to be public later this year; pivotal data may be available by 2026.

• For autosomal dominant optic atrophy, first patient dosing is targeted before year-end, with annual intravitreal injections planned.

• Natural history studies provide baseline data for both Dravet and optic atrophy programs, supporting clinical trial design.