Slide 1: Zorevunersen continues to demonstrate potential as a disease-modifying therapy in long-term OLE studies
December 5, 2025 Zorevunersen continues to demonstrate potential as a disease-modifying therapy in long-term open-label extension studies of patients with Dravet syndrome Joseph Sullivan, M.D.1, M Scott Perry, M.D.2, Andreas Brunklaus, M.D.3, J Helen Cross, M.B., Ch.B., Ph.D.4, Linda Laux, M.D.5, Jo
Slide 2: Dravet syndrome: a severe developmental and epileptic encephalopathy
Dravet syndrome: a severe developmental and epileptic encephalopathy1 >90% of DS cases are caused by SCN1A gene variants → 50% reduction in NaV1.1 sodium channel expression2–6 Current ASMs only target seizures; up to Natural history data show 57% of patients fail to achieve ≥50% adaptive behavior an
Slide 3: Phase 1/2a and OLE studies investigating zorevunersen safety, PK, and effectiveness
Phase 1/2a and OLE studies investigating zorevunersen safety, PK, and effectiveness in children and adolescents with Dravet syndrome PRIMARY OBJECTIVES SECONDARY OBJECTIVES EXPLORATORY OBJECTIVES • Safety and tolerability • Change in convulsive seizure frequency, overall clinical status, and QoL • C
Slide 4: Reductions in seizure frequency and improvements in cognition and behavior maintained through 3 years
Reductions in Substantial improvements major motor in seizure cognition, frequency behavior, wereandmaintained overall clinical throughstatus through 3 years of 3 treatment years of treatment with zorevunersen with zorevunersen on top ofinSoC theinOLE thestudies OLE studies Change in Vineland-3 sub
Slide 5: Propensity Score Weighting: Balancing treatment and natural history groups to mimic randomization
Propensity Score Weighting (PSW): Balancing treatment and natural history groups to mimic randomization What is Propensity Score Weighting? Advantages A statistical method to create a pseudo-randomization comparison between treated and Compared to simple propensity untreated (natural history) patien
Slide 6: Zorevunersen significantly reduced major motor seizure frequency at 6 months
Zorevunersen significantly reduced major motor seizure frequency at 6 months 6-month timepoint and dosing are consistent with the Phase 3 study (EMPEROR) primary endpoint Propensity score weighted analysis of major motor seizure frequency at 6 months LS mean % change in seizure frequency 50 50 from
Slide 7: Significant improvements across multiple Vineland-3 subdomains compared to natural history
Significant improvements across multiple Vineland-3 subdomains with zorevunersen compared to natural history At 18 months, cumulative dosing is similar and consistent to that evaluated in the Phase 3 study (EMPEROR) 20 Propensity score weighted analysis of Vineland-3 subdomains at 18 months 20 LS me
Slide 8: Durable and significant reduction in seizure frequency and improvement in cognition and behavior at 24 months
Durable and significant reduction in seizure frequency and improvement in cognition and behavior at 24 months with zorevunersen, compared to natural history PSW analysis of major motor seizure PSW analysis of Vineland-3 subdomains at 24 months frequency at 24 months 20 20 P<0.0001 LS mean change in
Slide 9: Zorevunersen was generally well tolerated with long-term dosing
Zorevunersen was generally well tolerated with long-term dosing • 30% of patients experienced a study drug–related TEAE Phase 1/2a o Most common: CSF protein elevations (14%) and procedural vomiting (5%) studies • 22% of patients experienced a TESAE All were unrelated to the study drug except for on
Slide 10: OLE study findings support the potential of zorevunersen as a durable, disease-modifying therapy
OLE study findings, including comparisons to natural history, support the potential of zorevunersen as a durable, disease-modifying therapy for patients with Dravet syndrome Patients receiving zorevunersen on top of SoC experienced substantial and durable reductions in major motor seizure frequency