Stoke Therapeutics (STOK) TD Cowen Genetic Medicines & RNA Summit summary

Key clinical updates and data insights

• Up to 85% reduction in convulsive seizures observed at higher doses in phase I/II Dravet studies, with improvements in both cognition and behavior noted over 9-12 months.

• Loading dose of 70 mg followed by 45 mg maintenance every four months proposed, with ongoing discussions to finalize dosing regimen for phase III.

• Sustained seizure reduction and cognitive gains contrast with natural history data, where no improvements are seen despite maximal anti-seizure medications.

• Vineland assessment identified as a key cognitive endpoint, with meaningful improvements in communication domains aligning with caregiver and clinician priorities.

• Over 90% rollover rate into open-label extension, providing robust long-term safety and efficacy data.

Phase III design and regulatory strategy

• Phase III to be a global, single trial across US, Europe, UK, and Japan, enrolling patients aged 2-18, with additional studies planned for younger and adult populations.

• Primary endpoint likely to be annualized seizure reduction, with cognition and behavior as key secondary endpoints, measured at 6-12 months.

• Study design and endpoints to be finalized in consultation with multiple regulatory agencies, aiming for a broad label for Dravet syndrome with SCN1A mutation.

• Phase III population, dosing, and endpoints closely mirror phase I/II, de-risking the program.

• Next regulatory and study design update expected in the second half of the year, with data presentations planned for major medical meetings.

Pipeline expansion: STK-002 for ADOA

• Phase I for STK-002 in ADOA to start in the second half of the year, with site initiation underway in the UK and EU.

• Preclinical data show upregulation of OPA1 protein and improved mitochondrial function in retinal ganglion cells.

• Intravitreal injection may be required only once per year, with dosing regimen to be determined in phase I.

• Multiple functional and structural assessments, including direct mitochondrial function measurement, will be used to track efficacy.