Slide 1: Zorevunersen demonstrates disease-modifying potential in patients with Dravet syndrome
Zorevunersen demonstrates disease-modifying potential in patients with Dravet syndrome with improvements in seizure burden, quality of life, and overall clinical status Kelly Knupp, M.D.,1 M Scott Perry, M.D.,2 J Helen Cross, M.B., Ch.B., Ph.D.,3 Linda Laux, M.D.,4 Colin M Roberts, M.D.,5 John M Sch
Slide 2: Dravet syndrome: A severe genetic developmental and epileptic encephalopathy
Dravet syndrome: A severe genetic developmental and epileptic encephalopathy >90% of DS cases are caused by SCN1A gene variants reduced functional NaV1.1 expression1–4 Current ASMs only target seizures; up to Natural history data show widening 1 out of ~16,000 babies gaps in adaptive functioning a
Slide 3: 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 Phase 1/2a studies (N=81) OLE studies (N=75 at OLE baseline; studies ongoing) Loading dose(s) Treatment-free Maintenance doses up to Screening Baseline 10–70 mg zorevunerse
Slide 4: Reductions in major motor seizure frequency were maintained through 4 years of treatment
Reductions in major motor seizure frequency were maintained through 4 years of treatment with zorevunersen on top of SoC in the OLE studies Most substantial seizure reductions seen in patients who received 70 mg Phase 1/2a regimens At baseline, 81% of patients were on ≥3 ASMs; 51% were on ≥4 ASMs1 D
Slide 5: Frequency of the most severe seizure types was reduced following treatment with zorevunersen
Frequency of the most severe seizure types was reduced following treatment with zorevunersen in the OLE studies Change in GTC and focal-to-BTC seizure frequency from Phase 1/2a baseline These severe seizure types are the leading risk factor for SUDEP (≥3 GTC seizures per year OR: 15.46)1–3 Data cut
Slide 6: Clinically meaningful improvements in adaptive functioning and behaviour continuing through 4 years
Clinically meaningful improvements1 in adaptive functioning and behaviour continuing through 4 years of treatment in the OLE studies Change in Vineland-3 subdomain scores from OLE baseline P<0.01 statistical significance was achieved in the 5 key Phase 3 subdomains for each year compared with OLE ba
Slide 7: Improvements in quality of life following treatment with zorevunersen
Improvements in quality of life following treatment with zorevunersen Change in EQ-VAS scores from Phase 1/2a baseline Substantial increases in quality of life were observed in addition to reductions in seizure frequency and improvements in adaptive functioning and behaviour Data cut date: 19 Februa
Slide 8: The safety profile of zorevunersen with long-term dosing
The safety profile of zorevunersen with long-term dosing • 30% (24/81) of patients experienced a study drug–related TEAE o Most common: CSF protein elevations (14%) and procedural vomiting (5%) Phase 1/2a • 22% (18/81) of patients experienced a TESAE studies o TESAEs for 17/18 patients were assessed
Slide 9: Long-term dosing of zorevunersen has now extended past 5 years
Long-term dosing of zorevunersen has now extended past 5 years Phase 1/2a (N=81) and OLE (N=75) studies Parameter Result Median treatment days per patient 1,255 Median doses per patient 11 Total exposure, patient-years 260.7 Maximum duration of years 5.33 Patients on treatment at data cutoff* 58 >93
Slide 10: Key findings
Key findings • Patients receiving zorevunersen on top of SoC experienced substantial reductions in major motor seizure frequency through 4 years of treatment in the OLEs • Patients receiving zorevunersen in the OLEs experienced substantial reductions in the frequency of the most severe seizure types