Scholar Rock Holding Corporation · NASDAQ:SRRK
Scholar Rock — Technical Presentation (June 2023)
23 slides from Scholar Rock's technical presentation, June 2023
Slide 1: Effect of Apitegromab on Motor Function and PEDI-CAT and PROMIS at 36 Months
EFFECT OF APITEGROMAB ON MOTOR FUNCTION AND PEDICAT AND PROMIS AT 36-MONTHS IN PATIENTS WITH TYPE 2 AND NONAMBULATORY TYPE 3 SPINAL MUSCULAR ATROPHY: COMBINED PRESENTATION OF THE PHASE 2 TOPAZ STUDY Thomas O Crawford, MD Professor of Neurology and Pediatrics Johns Hopkins University On behalf of the
Slide 2: Author Disclosures
Author Disclosures Dr Crawford is lead principal investigator of the TOPAZ trial. Consulting/Ad Boards: Study Site Investigations: Patient Organizations: • AveXis/Novartis • AveXis • A-T Children’s Project® • Biogen • Biogen • Cure SMA • Pfizer • Catalyst • MDA • Roche/Genentech • Cytokinetics • SMA
Slide 3: Apitegromab is a fully human monoclonal antibody that targets muscle
Apitegromab is a fully human monoclonal antibody that targets muscle to improve motor function in SMA1-3 TGFβ ligands through ActRIIB signaling1-3 Promyostatin Pro-GDF-11 Proactivin SMN1 gene Decreased SMN Apitegromab activity Motor neuron Myostatin GDF-11 Activin A degeneration Target of current Mu
Slide 4: Apitegromab inhibits myostatin activation
Apitegromab inhibits myostatin activation1,2 Prodomain Mature Prodomain Mature Pro- domain Mature Prodomain Mature Prodomain Mature Pro- domain Mature proprotein tolloid convertase protease Apitegromab Pro Latent Apitegromab myostatin myostatin Active mature growth factor • Apitegromab binds to both
Slide 5: Disease burden persists despite current SMA treatments
Disease burden persists despite current SMA treatments 80 Total possible HFMSE score of 66 HFMSE Score at Month 15 60 Limitations in mobility and 40 daily activities continue2,3 20 0 Mean improvement in HFMSE in Type 2 and nonambulatory Type 3 SMA in the Phase 3 CHERISH nusinersen trial1 HFMSE, Hamm
Slide 6: TOPAZ Phase 2 trial design
TOPAZ Phase 2 trial design1,2 Nonambulatory patients aged at least 2 years (Cohort 3) • Type 2; started SMN targeted therapy before age 5 years • Apitegromab (2 or 20 mg/kg IV q4w) and nusinersen Data presented today Nonambulatory patients aged 5-21 years (Cohort 2) First 12- Second Third • Types 2
Slide 7: TOPAZ Phase 2 trial baseline characteristics
TOPAZ Phase 2 trial baseline characteristics1,2 Nonambulatory Nonambulatory, Ambulatory Aged at least 2 years Aged 5-21 years Aged 5-21 years (Cohort 3) (Cohort 2) (Cohort 1) 20 mg/kg 2 mg/kg 20 mg/kg with with 20 mg/kg 20 mg/kg with nusinersen nusinersen Pooled with nusinersen alone nusinersen Pool
Slide 8: Motor function with SMN therapies appear to plateau after initial gains
Motor function with SMN therapies appear to plateau after initial gains Change in HFMSE over four years with nusinersen1 Change in MFM over four years with risdiplam2 Overall population aged 2-12 years Overall population aged 2-25 years Nusinersen in CHERISH and SHINE Sham control in CHERISH Risdipl
Slide 9: Improved HFMSE at 12 months in Phase 2 TOPAZ study
Improved HFMSE at 12 months in Phase 2 TOPAZ study Post hoc analysis of nonambulatory groups Type 2 & nonambulatory Type 3 SMA Aged 2-12 years (Apitegromab 20 mg/kg) (n=16*) HFMSE gains also notable in individuals who started Primary efficacy endpoint at 12 months: nusinersen at ≥5 years old: +4.4 (
Slide 10: TOPAZ Phase 2 study patient disposition
TOPAZ Phase 2 study patient disposition N = 58 Eligible Patients Enrolled Cohort 3 (N = 20) Cohort 2 (N = 15) Cohort 1* (N = 23) Type 2 SMA Type 2 & Nonambulatory Ambulatory Type 3 SMA Aged ≥2 years; SMN <5 Type 3 SMA Aged 5-21 years; SMN ≥5 Aged 5-21 years; SMN ≥5 No SMN Therapy SMN Therapy N = 10
Slide 11: Effect of Apitegromab on Motor Function at 36 Months
EFFECT OF APITEGROMAB ON MOTOR FUNCTION AT 36-MONTHS IN PATIENTS WITH TYPE 2 AND NONAMBULATORY TYPE 3 SPINAL MUSCULAR ATROPHY
Slide 12: HFMSE improvements sustained over 36 months
Improvements in motor function outcomes by HFMSE scores are sustained over 36 Months Aged 2-21 years Aged 2-12 years 8 8 Mean Change from Baseline in 7 7 6 6 HFMSE (+ SE) 5 5 5.2 4.6 4.8 4 4 4.2 4.0 3 3.6 3 3.4 2.8 2 2 1 1 0 0 6 months 12 months 24 months 36 months 6 months 12 months 24 months 36 mo
Slide 13: RULM improvements sustained over 36 months
Improvements in motor function outcomes by RULM scores are sustained over 36 months Aged 2-21 years Aged 2-12 years 4 4 Mean Change from Baseline in 3 3 RULM (+ SE) 2 2 2.8 2.3 2.4 1 1 2.2 1.3 1.2 0.6 0.2 0 0 6 months 12 months 24 months 36 months 6 months 12 months 24 months 36 months n= 28 31 31 2
Slide 14: New WHO development milestones achieved
New WHO development milestones achieved WHO MILESTONE Age Hands & knees Standing with Walking with Standing Walking (years) crawling assistance assistance alone alone 2 X 4 X X 5 X SMN Treatment 2 X X (< age 5) 2 4 X 5 8 X SMN Treatment 9 X X X X (≥ age 5) 19 X Proportion of patients gaining new mil
Slide 15: Effect of Apitegromab on PEDI-CAT and PROMIS-Fatigue at 36 Months
EFFECT OF APITEGROMAB ON PEDI-CAT AND PROMIS-FATIGUE QUESTIONNAIRE AT 36-MONTHS IN PATIENTS WITH TYPE 2 AND NONAMBULATORY TYPE 3 SPINAL MUSCULAR ATROPHY
Slide 16: PEDI-CAT assessment: Description
PEDI-CAT assessment: Description The PEDI-CAT assesses four domains of function: 1. Daily Activities 2. Mobility 3. Social/Cognitive 4. Responsibility Possible daily activities questions: • “Tucks in shirt or blouse” • “Dries hair with a towel” Coster WJ, et al. Autism. 2016;20(1):14-25. doi:10.1177
Slide 17: PEDI-CAT daily activities and mobility over 36 months, ages 2-21
Mean changes in PEDI-CAT daily activities and mobility scaled scores over 36 months in patients aged 2-21 years 4 Daily activities domain 4 Mobility domain Mean Change from Baseline in 3 3 PEDI-CAT(+ SE) 2 2.2 2.2 2 1.7 1.4 1 1.3 1 1.2 1.0 .7 0 0 6 months 12 months 24 months 36 months 6 months 12 mo
Slide 18: PEDI-CAT daily activities and mobility over 36 months, ages 2-12
Mean changes in PEDI-CAT daily activities and mobility scaled scores over 36 months in patients aged 2-12 years 4 Daily activities domain 4 Mobility domain Mean Change from Baseline in PEDI-CAT(+ SE) 3 3 2 2 1.9 1.9 1.7 1.4 1 1 0.9 1.0 0.8 .7 0 0 6 months 12 months 24 months 36 months 6 months 12 mo
Slide 19: Improvement in PROMIS fatigue scores over 36 months
Improvement in PROMIS fatigue scores (caregiver proxy) over 36 months Aged 2-21 years, apitegromab: all doses Aged 2-12 years, apitegromab: all doses 0 0 -0.5 -1 -1.4 -1 Mean Change from Baseline in PROMIS Parent Proxy (+ SE) -2 -2.4 -2 -2.9 -2.9 -3 -3.2 -3 -4 -4 -4.3 -4.6 -5 -5 -6 -6 -7 -7 6 months
Slide 20: Patient-reported outcomes and motor function measures over time
Patient-reported outcomes and motor function measures over 36 months in patients aged 2-21 years PEDI-CAT Daily Activities HFMSE 5 7 6 Change from Baseline Change from Baseline 4 5 Improvement Improvement 3 4 (± SE) (± SE) 2 3 1 2 1 0 0 # of -1 # of -1 observations 31 29 30 21 23 25 25 27 22 23 16 1
Slide 21: TOPAZ safety summary over 36 months
TOPAZ safety summary over 36 months Apitegromab 2 mg/kg Apitegromab 20 mg/kg Total TEAEs* N=10 N=48 N=58 n (%) n (%) n (%) Any TEAE 10 (100) 46 (95.8) 56 (96.6) Any serious TEAE 5 (50) 16 (33.3) 21 (36.2) Any TEAE leading to study drug discontinuation 0 1 (2.1) 1 (1.7) Any grade 3 (severe) or higher
Slide 22: Summary
Summary Improvements in motor function outcomes are sustained over 36 months with apitegromab treatment in Type 2 and nonambulatory Type 3 SMA Results on caregiver-reported outcomes are consistent with improvements in motor function as assessed by the HFMSE and RULM New WHO development milesto
Slide 23: TOPAZ Study Team
TOPAZ Study Team Investigators: Physical Therapists: CROs and Scientific • Crawford, Thomas O (Lead Study PI)1 • Pasternak, Amy7* • Sink, Teresa9 Vendors: Advisors: • Finanger, Erika2 • Maczek, Elizabeth7 • Smith, Emily9 • Medpace • Day, John W17 • De Vivo, Darryl3 • Gurgel, Brittany2 • Fern-Bueno,
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