Stoke Therapeutics (STOK) Jefferies London Healthcare Conference 2024 summary

Company overview and pipeline

• Focuses on RNA medicines for protein upregulation using splicing to increase full-length pre-mRNA and protein levels.

• Lead clinical candidate is zorevunersen for Dravet syndrome, with additional programs for autosomal dominant optic atrophy and partnerships for SYNGAP1 and Rett syndrome.

• Identified 6,500 genes with a TANGO signature, expanding potential therapeutic targets.

Dravet syndrome background and unmet needs

• Dravet syndrome is a severe developmental epileptic encephalopathy affecting about 1 in 16,000 infants, with 35,000 identified cases in the US, Canada, and major EU countries.

• 90% of patients have intractable epilepsy despite multiple therapies, and 20% die from sudden unexpected death in epilepsy.

• The disorder involves cognitive, behavioral, and movement problems beyond seizures, with current treatments focused only on seizure suppression.

• Management of seizures has not fundamentally changed in 170 years, and current drugs do not address the underlying genetic cause.

Scientific approach and mechanism

• Uses the TANGO approach (targeted augmentation of nuclear gene output) to upregulate protein by enhancing splicing of pre-mRNA.

• Targets the normal copy of the SCN1A gene to compensate for Nav1.1 protein haploinsufficiency in Dravet syndrome.

• Employs antisense oligonucleotides to enhance splicing, increasing full-length protein in a dose-dependent manner.