Slide 1: Changing the Course of NPC: Long-term Evidence for Disease Modification in a Heterogenous Population
Changing The Course of NPC: Long-term Evidence for Disease Modification in a Heterogenous Population Eugen Mengel, MD SphinCS, Clinical Science for LSD Hochheim, Germany MRC-2500071 09/25
Slide 2: Disclaimer
Disclaimer • Eugen Mengel has received investigator fees and/or consultant honoraria from Cyclo Therapeutics, Amicus, Idorsia, Intrabio, Denali, JCR, Prevail, Freeline Therapeutics, Alexion, Zevra, Sanofi Genzyme, and Takeda.
Slide 3: Arimoclomol Improves Lysosomal Function in NPC1
Arimoclomol Improves Lysosomal Function in NPC1 Endoplasmic reticulum 1 2 MIPLYFFA Arimoclomol Golgi 1 apparatus activates These genes then Transcription express more of the transcription factors, leading to factors 2 2 NPC1 protein as well NPC1 CLEAR upregulation of protein proteins as other protei
Slide 4: Design of Pivotal Study and Open-Label Extension
Design of Pivotal Study 002 and Open-Label Extension1-3 12-Month 4-year Double-Blind Phase Open-Label Extension (OLE) Enrollment Arimoclomol + N = 50 Routine Clinical Care N = 34 Arimoclomol + N = 27 2:1* Routine Clinical Care continued Placebo + N = 41 from Routine Clinical Care NPC-001 N = 16 Pre-
Slide 5: Arimoclomol Clinical Program Designed for a Broad NPC Population
Arimoclomol Clinical Program Designed for a Broad NPC Population NPC-001 NPC-002 NPC-002 OLE Substudy Observational Randomized, Open-Label Open-label Study Double-Blind, Pediatric subset Extension Placebo Controlled aged 6 to <24 months 6-14 months 12 months 4 years 12 months N = 36 N = 50 N = 41 N=
Slide 6: Study NPC-002 Met the Pre-specified 5DNPCCSS Primary Endpoint
Study NPC-002 Met the Pre-specified 5DNPCCSS Primary Endpoint1 FULL POPULATION 3.5 3.0 2.5 Estimated change from Arimoclomol demonstrates clinically baseline 5DNPCCSS 2.0 Placebo relevant slowing of disease (n=16) 1.5 Δ1.40 p=0.0456 progression in the primary analysis 1.0 A treatment difference of ≥
Slide 7: Study NPC-002 - 5DNPCCSS Participants on Concomitant Miglustat
Study NPC-002 - 5DNPCCSS Participants on Concomitant Miglustat1 Participants ON CONCOMITANT MIGLUSTAT 3.5 3.0 2.5 Arimoclomol demonstrates a Estimated change from highly significant slowing of baseline 5DNPCCSS Placebo + miglustat 2.0 (n=13) disease progression 1.5 compared with placebo in 1.0 Δ2.06
Slide 8: Adverse Events Were Generally Mild to Moderate in Severity, and Few Led to Withdrawal
Adverse Events Were Generally Mild to Moderate in Severity, and Few Led to a Withdrawal of Treatment MIPLYFFA Placebo with miglustat with miglustat Adverse Reaction n=26 n=13 n (%) n (%) Upper respiratory tract infection* 8 (31) 2 (15) Common adverse reactions Diarrhea 6 (23) 3 (23) occurring in ≥8%
Slide 9: Arimoclomol has Demonstrated Long-Term Effectiveness of up to 5 years
Arimoclomol has Demonstrated Long-Term Effectiveness of up to 5 years1,2 Continued effectiveness in open-label extension (OLE) • Observed disease severity progressed slowly over the 48 months, with a stepwise progression pattern2 • Expected annual progression based on natural history and double-blin
Slide 10: Arimoclomol was Well-Tolerated with No New Safety Signals Observed over 4 Years
Arimoclomol was Well-Tolerated with No New Safety Signals Observed over 4 Years1 The overall pattern of frequently reported AEs was stable over the 48 months and consistent with MIPLYFFA observations from the double-blind phase of the with miglustat trial. The 3 most common AEs were: N=41 n (%) • 38
Slide 11: US Expanded Access Program Effectiveness
US Expanded Access Program Effectiveness The US EAP included NPC patients ages 2 - 64.5 • There were 248 AEs with 241 being classified as treatment-emergent (TEAEs) Error bars: standard error of the mean Zevra Data on File
Slide 12: Pediatric Sub-Study
Pediatric Sub-Study The pediatric sub-study was conducted to assess the safety and tolerability of arimoclomol treatment in children under 2 years of age with NPC. • 5 patients, aged 14–23 months, all receiving miglustat treatment were included up to 36 months. • Of 108 AEs reported, majority were m
Slide 13: Summary
Summary • Arimoclomol addresses the underlying pathology of NPC • Arimoclomol has established effectiveness across the Zevra would like to thank all 12-month clinical trial, 4-year open label extension, and the participants, families & US Expanded Access Program datasets caregivers, clinical sites &