Slide 1: Zorevunersen demonstrates potential as a disease-modifying therapy in Dravet syndrome
Zorevunersen demonstrates potential as a disease- modifying therapy in patients with Dravet syndrome through durable seizure reduction and improvements in cognition, behavior, and quality of life through 36 months of treatment in open-label extension studies Linda Laux, M.D.,1 Kelly G Knupp, M.D.,2
Slide 2: Disclosures
Disclosures • Speaker • Serves as a Principal Investigator for research grants from Stoke Therapeutics, Encoded Therapeutics, Praxis Precision Medicine, and Longboard Pharmaceuticals • Receives consulting fees from Stoke Therapeutics and Biocodex • Receives payment/honoraria for lectures, presentati
Slide 3: Dravet syndrome: A severe developmental and epileptic encephalopathy
Dravet syndrome: A severe developmental and epileptic encephalopathy The effects of Dravet syndrome go beyond just seizures, impacting all aspects of life, not only for the individual living with Dravet syndrome but also for their caregivers and families Seizures Stress Developmental Financial defic
Slide 4: An urgent need for disease-modifying therapies addressing the underlying genetic cause of Dravet syndrome
An urgent need for disease-modifying therapies addressing the underlying genetic cause of Dravet syndrome 1 out of ~16,000 >90% of Dravet syndrome cases are caused by babies are born with SCN1A gene variants 50% reduction Dravet syndrome1,2 in NaV1.1 sodium channel expression4–6 There is an urgent
Slide 5: Cognition and behavior are commonly evaluated in Dravet syndrome using the Vineland-3
Cognition and behavior are commonly evaluated in Dravet syndrome using the Vineland-3 assessment tool Domains COMMUNICATION MOTOR SKILLS SOCIALIZATION DAILY LIVING SKILLS Receptive: Gross Motor: Interpersonal Personal: Responds upon hearing Moves, scoots, or crawls Relationships: Cooperates in dress
Slide 6: Substantial neurodevelopmental gap between patients and neurotypical peers that widens with age
Substantial neurodevelopmental gap between patients with Dravet syndrome and neurotypical peers that widens with age Regression analysis of adaptive behavior composite score for all Vineland-3 domains at baseline* 100 Neurotypical 80 Standard Score 60 Dravet syndrome Natural History 40 20 2 4 6 8 10
Slide 7: Phase 1/2a and OLE studies investigating zorevunersen safety, PK, and efficacy
Phase 1/2a and OLE studies investigating zorevunersen safety, PK, and efficacy in children and adolescents with Dravet syndrome PRIMARY ENDPOINTS1 SECONDARY ENDPOINTS1 EXPLORATORY ENDPOINTS1 • Safety profile • Change in convulsive seizure frequency, overall clinical • Change in adaptive behavior • P
Slide 8: Reductions in major motor seizure frequency maintained through 3 years of treatment
Reductions in major motor seizure frequency were maintained through 3 years of treatment with zorevunersen on top of SoC in the OLE studies Change in major motor seizure frequency from Phase 1/2a baseline All enrolled patients who received doses of less than 70 mg zorevunersen in Phase 1/2a (n=16–53
Slide 9: Continuing improvements in cognition and behavior through 3 years in the OLE studies
After Phase 1/ 2a, continuing improvements in cognition and behavior were observed through 3 years of treatment in the OLE studies* 12 Expressive Communication 10 Change from OLE baseline Receptive in raw scores (95% CI) 8 Communication Interpersonal 6 Relationships Personal Skills 4 Coping Skills 2
Slide 10: Significant and durable improvement in cognition and behavior at 24 months vs natural history
Significant and durable improvement in cognition and behavior at 24 months with zorevunersen, compared to natural history Propensity score weight (PSW) analysis of Vineland-3 subdomains at 24 months 20 20 P<0.0001 LS mean change in Vineland-3 raw scores 15 P<0.0001 P=0.6385 P=0.0046 15 from naive ba
Slide 11: Patients with multiple loading doses showed greatest improvements in quality of life
Patients who received multiple loading doses of 70 mg in Phase 1/2a showed the greatest improvements in quality of life All enrolled patients (n=51–62) 70 mg 2 or 3 doses in Phase 1/2a (n=7) from Phase 1/2a baseline (95% CI) 60 Mean change in EQ-VAS scores EQ-VAS is a validated, 40 visual analogue s
Slide 12: 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 (n=81)1 o All were unrelated to the study drug excep
Slide 13: OLE study findings support potential of zorevunersen as a durable, disease-modifying therapy
OLE study findings support the potential of zorevunersen as a durable, disease-modifying therapy for patients with Dravet syndrome There is an urgent need for disease-modifying therapies to address the underlying genetic cause of Dravet syndrome as developmental gaps widen over time despite use of c