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 collaborations for SYNGAP1 and Rett syndrome.

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

Dravet syndrome disease context

• 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 before adulthood.

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

Scientific approach and mechanism

• Uses the TANGO approach (targeted augmentation of nuclear gene output) to upregulate protein by enhancing splicing of pre-mRNA, specifically targeting the normal SCN1A gene copy.

• Antisense oligonucleotide (ASO) therapy increases Nav1.1 protein by splicing out poison exons, compensating for haploinsufficiency.