Scholar Rock Holding Corporation · NASDAQ:SRRK
Scholar Rock — Technical Presentation (April 2022)
16 slides from Scholar Rock's technical presentation, April 2022
Slide 1: Apitegromab in SMA: Analysis of Multiple Efficacy Endpoints in the TOPAZ Trial
Apitegromab in Spinal Muscular Atrophy (SMA): An Analysis of Multiple Efficacy Endpoints in the TOPAZ Trial T.O. Crawford Johns Hopkins University School of Medicine, Baltimore, MD On behalf of the entire TOPAZ Study Team TOPAZ (NCT03921528) Please Send an Email with Your Medical Questions to the Fo
Slide 2: Author Disclosures
Author Disclosures Dr. Crawford is lead principal investigator of the TOPAZ trial Consulting/Ad Boards: Study Site Investigations: Patient Organizations • Biogen • Biogen • CureSMA • Roche/Genentech • Avexis • SMA Foundation • Avexis / Novartis • Cytokinetics • Muscular Dystrophy • Pfizer • Parexel
Slide 3: Disclaimers
Disclaimers The TOPAZ trial is sponsored by Scholar Rock, a biopharmaceutical company developing and investigating apitegromab for SMA Apitegromab is an investigational product candidate that is currently being evaluated in a clinical development program for the treatment of spinal muscular atro
Slide 4: TOPAZ Study Team
TOPAZ Study Team PIs: PTs: CRCs: • Darras, Basil1 • Maczek, Elizabeth1 • Smith, Emily9 • Levine, Alexis1 • Finanger, Erika2 • Pasternak, Amy1* • Fern-Bueno , Anna10 • McCarthy, Bryn2 • Gurgel, Brittany2 • Harrington, Andrew11 • McCary, Isabella3 • DeVivo, Darryl3 • Karras Conklin, Terrie4 • Proud, C
Slide 5: Myostatin Is An Important Negative Regulator Of Skeletal Muscle Growth
Myostatin Is An Important Negative Regulator Of Skeletal Muscle Growth Whose Inhibition Leads To Improved Muscle Function In Patients With SMA1,2 Apitegromab: A Fully Human Monoclonal Antibody That Blocks Cleavage Of The Myostatin Prodomain, Thereby Inhibiting Myostatin Activation2 Selective Targeti
Slide 6: Apitegromab: A Potential Muscle-Directed Therapy Intended to Complement SMN Upregulators
Apitegromab: A Potential Muscle-Directed Therapy Intended to Complement SMN Upregulators SMN upregulators target one part of the motor unit, the motor neurons1 Apitegromab targets muscle- specific regulation of Motor neuron contractile protein mass*2-4 degeneration SMN upregulators prevent further m
Slide 7: TOPAZ Phase 2 Trial Design: Three pilot cohorts to identify therapeutic opportunities
TOPAZ Phase 2 Trial Design: Three pilot cohorts to identify therapeutic opportunities All SMA Types 2/3, groups defined by age and present ambulatory status Non-Ambulatory > Age 2 Cohort • Type 2; had started SMN upregulator before age 5 • Apitegromab (2 or 20 mg/kg IV q4w) + nusinersen 57 Patients*
Slide 8: TOPAZ Baseline Characteristics
TOPAZ Baseline Characteristics Patients were well into chronic maintenance phase of background therapy Non Ambulatory Age >2 Non Ambulatory Ages 5-21 Ambulatory Ages 5-21 With Higher dose Lower dose Monotherapy nusinersen Pooled 20 mg/kg +nusinersen Pooled 20 mg/kg 2 mg/kg 20 mg/kg 20 mg/kg N 10 10
Slide 9: TOPAZ Topline Results Demonstrate that Apitegromab Improves Motor Function in Late Onset SMA
TOPAZ Topline Results Demonstrate that Apitegromab Improves Motor Function in Patients with Late Onset SMA1 NonAmbulatory Patients HFMSE Ambulatory Patients RHS Type 2; Age >2 Cohort* Type 2/3; Ages 5-21 Cohort* Type 3 Cohort† Apitegromab Apitegromab Apitegromab Primary Analysis (2 mg/kg) (20 mg/kg)
Slide 10: Greater Hammersmith Improvements Inversely Correlate With Scoliosis & Contractures
Greater improvements in Hammersmith Scores Inversely Correlate With Characteristics of Advanced Disease- Scoliosis & Contractures NonAmbulatory Type 2 & Type 2/3 SMA Ambulatory Cohort Type 3 SMA (Pooled HFMSE)* (Pooled RHS)† Mean Change in Motor Function 8 No(n=14) Yes (n=17) No(n=9) Yes(n=22) 2 No
Slide 11: Nonambulatory Cohorts: Substantial RULM Improvements with Apitegromab
Nonambulatory Cohorts: Substantial RULM Improvements with Apitegromab 1 Nonambulatory Patients (Hammersmith Functional Motor Scale Expanded; HFMSE) Type 2/3; Ages Type 2; Age >2 Cohort* 5-21 Cohort* Primary Analysis (ITT population) Apitegromab Apitegromab Apitegromab Pooled (20 mg/kg) (2 mg/kg) +nu
Slide 12: Nonambulatory >2 Cohort: Both Dosage Groups Manifest Early Benefit
Type 2 Nonambulatory > Age 2 Cohort: Both Dosage Groups Manifest Early Benefit, A Greater Latency Of The Low Dose Cohort Supports Apitegromab Attributable Effect Time to first reach 1-point improvement Time to first reach 3-point improvement Time to first reach 5-point improvement 1.0 0.8 0.8 0.6 0.
Slide 13: Safety Results from TOPAZ 12-Month Top-Line Analysis Support Phase 3 Evaluation
Safety Results from TOPAZ 12-Month Top-Line Analysis Support Evaluation of Apitegromab in a Phase 3 Trial Treatment-emergent adverse events (TEAEs) Apitegromab 2 mg/kg Apitegromab 20 mg/kg Total (n=58) (n=10) (n=48) Any TEAE 9 (90.0%) 44 (91.7%) 53 (91.4%) Any Serious TEAE 1 (10.0%) 4 (8.3%) 5 (8.6%
Slide 14: Summary
Summary Motor function improvements were observed in the primary and secondary efficacy endpoints in the Phase 2 TOPAZ clinical trial at 12 months. Dose responsive improvement in time to reach motor function confirmed apitegromab benefit on top of underlying nusinersen benefit. Positive correl
Slide 15: Backup
Backup Apitegromab is an investigational product candidate being evaluated for the treatment of SMA. Apitegromab has not been approved by any regulatory authority and its safety and efficacy have not been established. © Scholar Rock, Inc. All rights reserved. April 2022
Slide 16: A Post-hoc Analysis of Prior Nusinersen Treatment Duration
A Post-hoc Analysis of Prior Nusinersen Treatment Duration... No correlation with HFMSE in Non-Ambulant patients # of nusinersen maintenance doses at enrollment, Non- Across both non-ambulatory cohorts in TOPAZ... Ambulatory Types 2 and 3 Patients enrolled in TOPAZ were already in the Change from
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