Scholar Rock Holding Corporation · NASDAQ:SRRK
Scholar Rock — Cure SMA 2025
12 slides from Scholar Rock's conference presentation, June 2025
Slide 1: Efficacy and safety of apitegromab in type 2 and type 3 SMA in SAPPHIRE
Efficacy and safety of apitegromab in individuals with type 2 and type 3 spinal muscular atrophy evaluated in the phase 3 SAPPHIRE trial Basil T. Darras1,Thomas O. Crawford2, Laurent Servais3, Jena Krueger4, Heike Kölbel5, Andreea Seferian6, Claude Cances7, Nancy Kuntz8, Richard S. Finkel9, Bert Yao
Slide 2: Declaration of interests
Declaration of interests Dr. Basil T. Darras is a principal investigator for the SAPPHIRE trial Consulting/advisory boards: Study site investigator: Institute/Patient organizations: • AveXis/Novartis Gene • Steering Committee • Research Support: NIH/National Therapies Member: Roche Institute of Neur
Slide 3: SMA disease pathology: motor neuron degeneration and muscle atrophy
SMA disease pathology: motor neuron degeneration and muscle atrophy SMN-targeted treatments slow further degeneration of motor neurons1 ...but do not directly Nusinersen address muscle atrophy Risdiplam Motor neuron degeneration Onasemnogene Muscle fiber abeparvovec-xioi atrophy There is further pot
Slide 4: Patients on chronic SMN-targeted treatment experience attenuation of motor function improvement over time
Patients treated chronically with an SMN-targeted treatment experience attenuation of motor function improvement over time CHERISH/SHINE: HFMSE SUNFISH Part 2: HFMSE Nusinersen treatment Overall population (2-25 years old) • On average, the TOPAZ study population is on the plateau phase of nusinerse
Slide 5: Phase 3 SAPPHIRE trial design
Phase 3 SAPPHIRE trial design Randomized, double-blind, placebo-controlled, parallel-arm design (n = 188) Key Eligibility Criteria • Patients with nonambulatory type 2 or 3 SMA, receiving an approved SMN-targeted treatment, ages 2–21 • Motor function score by HFMSE ≥10 and ≤45 at the screening visit
Slide 6: SAPPHIRE participant demographics and disease characteristics were well-balanced
SAPPHIRE participant demographics and disease characteristics were well-balanced 2–12 population 13–21 population Apitegromab Apitegromab Apitegromab Apitegromab Placebo + SOC 20 mg/kg + SOC 10 mg/kg + SOC 20 & 10 mg/kg + SOC Placebo + SOC 20 mg/kg + SOC (N = 50) (N = 53) (N = 53) (N = 106) (N = 10
Slide 7: SAPPHIRE PK and PD vs time
SAPPHIRE PK and PD vs time Apitegromab concentration over time (PK) Latent myostatin levels over time (PD) Placebo (N = 50) Apitegromab (10 mg/kg) (N = 53) Apitegromab (20 mg/kg) (N = 53) • Increase in exposure of apitegromab (PK) was generally dose-proportional • Robust and sustained target engagem
Slide 8: Primary endpoint met with consistency across doses and age groups
Primary endpoint met with consistency across doses and age groups LS mean change from baseline in HFMSE total score by visit (2–12 population) Change from baseline in HFMSE total score at month 12 for predefined population Primary endpoint met • Primary endpoint met based on the comparison of apiteg
Slide 9: Efficacy was consistent across subgroups in pooled 2–21 population
Efficacy was consistent across subgroups in pooled 2–21 population Change from baseline in HFMSE total score at month 12 – subgroup analyses for pooled population • Efficacy was consistent across prespecified subgroups (type of SMN-targeted treatment, age of SMN-targeted treatment initiation) and re
Slide 10: Secondary endpoint outcomes for the 2–12 population
Secondary endpoint outcomes for the 2–12 population ≥3-point change from baseline in HFMSE total score Any point change from baseline in HFMSE total score at month 12 at month 12 Proportion of participants • Patients treated with apitegromab demonstrated improved motor function vs placebo • Efficacy
Slide 11: Well-tolerated safety consistent with established profile
Well-tolerated safety consistent with established profile 2–12 population 13–21 population Summary of AEs Apitegromab Apitegromab Apitegromab Apitegromab n (%) Placebo + SOC 20 mg/kg + SOC 10 mg/kg + SOC 20 & 10 mg/kg + SOC Placebo + SOC 20 mg/kg + SOC (N = 50) (N = 53) (N = 53) (N = 106) (N = 10 )
Slide 12: Conclusions
Conclusions • Apitegromab treatment resulted in statistically significant and clinically meaningful1-3 improvements in motor function – Efficacy results were consistent across outcomes measures (HFMSE, RULM, and WHO) – Efficacy results were consistent across age, background SMN-targeted treatment, a