Stoke Therapeutics (STOK) 43rd Annual J.P. Morgan Healthcare Conference 2025 summary

Platform and scientific approach

• Focuses on upregulating protein production using RNA-based technology, targeting diseases by enhancing the body's natural gene expression mechanisms.

• Approach is mutation-agnostic, acting as a 'gene therapy light' by increasing normal gene output via splicing.

• Programs include Dravet syndrome (zorevunersen), OPA1 upregulation for optic atrophy, and collaborations on Rett and SYNGAP1 syndromes.

• TANGO technology enables targeting of over 6,500 genes, with ongoing search for partners to expand reach.

Clinical progress and data

• Zorevunersen demonstrated dramatic and sustained seizure reduction in Dravet syndrome, with up to 87% reduction at eight months.

• Improvements in cognition and behavior observed, measured by Vineland-3, with benefits maintained and increasing over 24 months.

• Safety profile generally well tolerated; most adverse events related to procedure, not drug.

• Over 600 doses administered, with only one discontinuation due to increased CSF protein, a lab finding without clinical symptoms.

Regulatory and trial design

• Achieved regulatory alignment for a single global phase 3 trial (MONARCH) across the US, EU, and Japan.

• Phase 3 will be the longest Dravet study to date, focusing on both seizure reduction (primary endpoint) and cognition/behavior improvements (key secondary endpoints).

• Vineland-3 accepted by regulators and payers as a valid measure for non-seizure benefits.

• Trial will enroll 150 patients aged 2 to under 18 with SCN1A mutations, with a 52-week treatment period.