Wave Life Sciences (WVE) Chardan's 8th Annual Genetic Medicines Conference summary

Key 2024 milestones and clinical progress

• Achieved first human translation of allele-specific silencing in Huntington's disease, with 46% reduction in mutant protein and no change in wild-type.

• Interim analysis in DMD showed 9% dystrophin production, with 89% of patients exceeding 5%, and strong safety profile.

• Upcoming Q4 data expected for RNA editing in alpha-1 antitrypsin, marking first human clinical data for ADAR-based editing.

• Inhibin E siRNA program for obesity to enter clinical trials in early next year, with submissions by year-end.

• Continued focus on translating novel chemistry into meaningful clinical outcomes, with further inflection points anticipated.

DMD program insights and regulatory strategy

• Consistent dystrophin expression and drug distribution observed, with high concentrations in heart and diaphragm.

• Histology showed improved muscle fiber health and functional dystrophin localization.

• Safety profile included only mild events, supporting potential for monthly dosing.

• 48-week follow-up will assess clinical endpoints like 95% stride velocity, important for global regulatory acceptance.

• Engaging regulators on platform umbrella trial design for multiple exons, leveraging efficient manufacturing.

Huntington's disease program and clinical surrogate endpoints

• Demonstrated selective knockdown of mutant protein with quarterly dosing potential.

• First clinical correlation between mutant protein reduction and slowing of caudate atrophy.

• Imaging endpoints now correlate with clinical measures, supporting use as surrogate endpoints.

• Engaged with regulators to define path forward using surrogate endpoints, enabling smaller, focused studies.

• Awaiting partner opt-in decision, but committed to pursuing the most efficient registrational pathway.