Scholar Rock Holding Corporation · NASDAQ:SRRK
Scholar Rock — Technical Presentation (June 2021)
50 slides from Scholar Rock's technical presentation, Jun 15, 2021
Slide 1: Apitegromab Positioned to be the Potential Next Transformative Therapy for Patients Suffering with SMA
Apitegromab Positioned to be the Potential Next Transformative Therapy for Patients Suffering with SMA KOL Event and Panel DiscussionJune 15, 2021
Slide 2: Disclaimers
Disclaimers Various statements in this presentation concerning the future expectations, plans and prospects of Scholar Rock, Inc. (“Scholar Rock”), including without limitation, Scholar Rock’s expectations regarding its strategy, its product candidate selection and development timing, including timi
Slide 3: Agenda
Agenda 3 Opening Remarks and Spinal Muscular Atrophy Treatment Landscape Tony KingsleyPresident & CEO Apitegromab TOPAZ Phase 2 Proof-of-Concept Trial ResultsApitegromab Phase 3 Trial Design Considerations Yung Chyung M.D.CMO Moderated byYung Chyung, M.D. Panel Discussion with TOPAZ Trial Investigat
Slide 4: Apitegromab Shows Transformative Potential in Patients with Type 2 and 3 SMA
Apitegromab Shows Transformative Potential in Patients with Type 2 and 3 SMA Spinal Muscular Atrophy (SMA) remains a devastating and debilitating disease despite the utilization of SMN upregulatorsMulti-pronged approach may be needed in treating SMA; muscle-directed therapy may further improve motor
Slide 5: Spinal Muscular Atrophy Overview
5 Spinal Muscular Atrophy Overview Significant, progressive motor functionimpairment; many lose ambulation Infantile onset; unable to sit upindependently Severe, progressive disabilities and unable to walk independently Type 114% Type 251% Type 335% Global disease with 30,000-35,000affected in U.S.
Slide 6: Potential to Pioneer a New Treatment Era: Opportunity for Muscle-Directed Therapy
6 Potential to Pioneer a New Treatment Era: Opportunity forMuscle-Directed Therapy to Complement SMN Upregulators Phase 3Trial Design Indication MarketPenetration Non-ambulatory Type 2/32-12 years of agePrimary endpoint: Mean change from baseline in HFMSE at 15 months >11,000* patients treated WW$2+
Slide 7: Apitegromab: Muscle-Directed Therapy Aimed at Complementing SMN Upregulators
Apitegromab: Muscle-Directed Therapy Aimed at Complementing SMN Upregulators 7 Myostatin is a negative regulatorof skeletal muscle growthApitegromab is a fully human, mAb that specifically binds to proforms of myostatin and inhibits myostatin activation Apitegromab is a muscle-directed approach aime
Slide 8: Cure SMA
Cure SMA Jill Jarecki, PhDCSO June 15, 2021
Slide 9: Cure SMA
Cure SMA We fund groundbreaking research and provide families thesupport they need for today.Annual budget of $15M$85 Million in research funding 36 Chapters in the US9,000 affected individuals in membership database300 newly diagnosed contacts annuallyNewly diagnosed care and info packetsInfo on cl
Slide 10: The Evolving Landscape in SMA
The Evolving Landscape in SMA The FDA-approval of 3 new therapies has revolutionized and dramatically changed the natural history of SMAEarly identification and treatment dramatically alter long-termoutcomes, most strikingly presymptomaticallySymptomatic treatment providing improvements through incr
Slide 11: 45% of SMA Patients Remain Untreated at End of Q1 2021
45% of SMA Patients Remain Untreated at End of Q1 2021 Percent of SMA Patients 70%60%50%40%30%20%10%0%17Q1 Q2 Q3 Q4 18Q1 Q2 Q3 Q4 19Q1 Q2 Q3 Q4 20Q1 Q2 Q3 Q4 21Q1Year QuarterActuals through the end of Q1 2021, with projections for the three quarters after.
Slide 12: Almost Half of Those with SMA Type I Currently Sit without Support
Almost Half of Those with SMA Type I Currently Sit without Support 12.90 % 21.90 % 35.37 % 37.66 % 44.64 % 87.10% 78.08% 64.63% 62.30% 55.36% 100%90%80%70%60%50%40%30%20%10%0% 2017 (n=93) 2019 (n=147) 2020 (n=231) 2021 (n=56) 2018 (n=146)Sit without Support Cannot sit without support
Slide 13: Can Stand With or Without Support Currently among SMA Type II
Can Stand With or Without Support Currently among SMA Type II 10.94% 11.44% 17.05% 18.36% 89.06% 88.56% 82.95% 81.64% 100%90%80%70%60%50%40%30%20%10%0% 2017(n=265) 2018(n=271) 2019(n=258) 2020(n=414) Can stand (with or without) support Cannot stand (with or without) support2017 & 2018: Question was
Slide 14: What Comes Next - SMA is Not Cured Yet
What Comes Next - SMA is Not Cured Yet Need More Impact for older ages and stage of SMADifferent for symptomatic vs NBS patientsSlow to Stop to Reverse Reverse – Restore Function -FutureStop Progression – Prevent SymptomsSlower Progression -ImprovementNatural History - Untreated
Slide 15: Unmet Needs that Future Therapies will Address
Unmet Needs that Future Therapies will Address – From Adults in the 2020 Community Update Survey 75% 75% 81%80% 71% 29% 89% 89% 81%82%80% 39% 31% 94%94%98% 90% 15% 94% 94% 94% 100%90%80%70%60%50%40%30%20%10%0% Reducing Fatigue Improving breathing function Improving swallowing Gaining muscle strength
Slide 16: Therapeutic Strategies – SMN Independent
NeuroprotectionNeural transmissionRegenerative targetsMuscle enhancementApitegromab - Scholar RockGenetic modifiersCombinations of above with SMNenhancer Therapeutic Strategies – SMN Independent
Slide 17: Thank You!
Thank You!
Slide 18: Cure SMA
Cure SMA Jill Jarecki, PhDCSO June 15, 2021
Slide 19: Apitegromab Showed Transformative Potential in SMA Phase 2 Trial
Apitegromab Showed Transformative Potential in SMA Phase 2 Trial Yung Chyung, M.D.Chief Medical Officer
Slide 20: TOPAZ: Evolving Understanding of Apitegromab's Transformative Potential
TOPAZ: Evolving Understanding of Apitegromab’sTransformative Potential in Type 2 and Type 3 SMA June 2021Additional Analyses April 202112-month top-line October 20206-month interim Showed Initial Proof-of-Concept Interim data showed the therapeutic potential of apitegromab in Type 2 and 3 SMA as add
Slide 21: TOPAZ Top-Line Data Showed Apitegromab's Transformative Potential in Type 2/3 SMA
21 TOPAZ Top-Line Data Showed Apitegromab’sTransformative Potential in Patients with Type 2/3 SMA ✔ Apitegromab treatment (as add-on to background nusinersen) led to improvements inHFMSE in both non-ambulatory cohorts * Pooled cohorts of non-ambulatory patients treated with apitegromab 20 mg/kg and
Slide 22: Exploratory Analyses to Understand the Therapeutic Response
Evaluating range of exploratory analyses to better understand the therapeutic responseInitial findings from non-ambulatory cohorts:HFMSE improvements observed across age range with relatively larger gains from earlier treatmentDuration of prior nusinersen treatment not correlated with HFMSE increase
Slide 23: Expectations for Patients on Background SMN Upregulator Therapy
23 Expectations for Patients on BackgroundSMN Upregulator Therapy Yung Chyung, M.D. Chief Medical Officer
Slide 24: Patients Continue to Experience Major Functional Deficits Despite Nusinersen
Patients with Type 2 and 3 SMA Continue to Experience MajorFunctional Deficits Despite Improvement from Nusinersen 24 Darras, B., et.al. Nusinersen in later-onset spinal muscular atrophy. Neurology. May 2019; 92 (21) e2492-e2506.This third-party information is provided for background only and is not
Slide 25: Nusinersen Does Not Increase HFMSE in Children Initiating After Age 5
†Mercuri E, et.al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018;378:625-635.This third-party information is provided for background only and is not intended to convey or imply a comparison to the TOPAZ clinical trial results. CHERISH Trial in Non-Ambulato
Slide 26: Plateauing of HFMSE Increases After First 15 Months of Nusinersen
Plateauing of HFMSE Increases Observed After First 15Months of Nusinersen Treatment in Type 2 and 3 SMA 26 “Longer-term treatment with nusinersen: results in later-onset spinal muscular atrophy from the SHINE study” P.257, World Muscle Society Congress 2020This third-party information is provided fo
Slide 27: Review of Positive TOPAZ Top-Line Results
27 Review of Positive TOPAZ Top-Line Results Yung Chyung, M.D. Chief Medical Officer
Slide 28: Apitegromab Phase 2 Trial Design
Apitegromab Phase 2 Trial Design 28 Patients with Type 2 and 3 SMA Ambulatory Type 3 patients (ages 5-21)Apitegromab 20 mg/kg IV Q4W monotherapy or withchronic nusinersen maintenance Key objectives: RHS and safety at 12 months Non-ambulatory Type 2 patients (ages ≥2) on chronicmaintenance nusinersen
Slide 29: Baseline Characteristics
Baseline CharacteristicsNusinersen-treated patients well into chronic maintenance phase 29 Non-Ambulatory,Ages ≥2 and initiated nusinersen <5 years Non-Ambulatory,Ages 5-21 Ambulatory,Ages 5-21 20 mg/kg+nusinersen 2 mg/kg+nusinersen Pooled 20 mg/kg+nusinersen 20 mg/kg monotherapy 20 mg/kg+nusinersen
Slide 30: Patients Enrolled in TOPAZ Already in Chronic Maintenance Phase of Nusinersen
Patients Enrolled in TOPAZ Already in Chronic MaintenancePhase of Nusinersen Treatment 30 *Reflects non-ambulatory cohorts in TOPAZ**The HFMSE time course plot for background nusinersen effect is hypothetical and intended for illustrative purposes only. The data presented here do not reflect any cro
Slide 31: Non-Ambulatory Cohort: Initiated Nusinersen Age <5
Non-Ambulatory Type 2 Cohort:Initiated nusinersen age <5 31 Apitegromab (20 mg/kg) + nusinersen n=8 Mean change from baseline in HFMSE(95% CI) +7.1(1.8, 12.5) # (%) patients achieving: ≥1-pt increase in HFMSE 7/8 (88%) ≥3-pt increase in HFMSE 5/8 (63%) ≥5-pt increase in HFMSE 5/8 (63%) Baseline char
Slide 32: Non-Ambulatory Type 2/3 Cohort: Initiated Nusinersen Age ≥5
Non-Ambulatory Type 2/3 Cohort:Initiated nusinersen age ≥5 Apitegromab (20 mg/kg) + nusinersen Per Protocol Population* (n=13) Intent-to-Treat Population (n=14) Mean change from baseline in HFMSE (95% CI) +1.2(-0.5, 2.9) +0.6(-1.4, 2.7) # (%) patients achieving: ≥1-pt increase in HFMSE 9/13 (69%) 9/
Slide 33: TOPAZ Results Supporting Evaluation of Apitegromab in Phase 3 Trial: Adverse Events
TOPAZ Results SuppPhase 3 Trial ort Evaluation of Apitegromab in Treatment-emergent adverse events (TEAEs) Apitegromab 2 mg/kg (n=10) Apitegromab 20 mg/kg (n=48) Total (n=58) Any TEAE 9 (90.0%) 44 (91.7%) 53 (91.4%) Any Serious TEAE 1 (10.0%) 4 (8.3%) 5 (8.6%) Any TEAE leading to study drug disconti
Slide 34: Serious and Severe Treatment-Emergent Adverse Events
Serious and Severe Treatment-Emergent Adverse Events(TEAEs) 34 Treatment-emergent adverse events (TEAEs) are defined as AEs that start after the first dose of study drug or start prior to the administration of study drug and worsen in severity/grade or relationship to investigational medication afte
Slide 35: Additional Exploratory Analyses Further Support Apitegromab's Potential
35 Additional Exploratory Analyses Further Support Apitegromab’s Potential Additive Benefit on Top of Nusinersen Yung Chyung, M.D.Chief Medical Officer
Slide 36: HFMSE Improvements Observed Across Age Range of Non-Ambulatory Patients
HFMSE Improvements Observed Across Age Range of Non-AmbulatoryPatients with Relatively Larger Gains from Earlier Treatment *Pooled cohorts of non-ambulatory patients treated with apitegromab 20 mg/kg and 2 mg/kg; excludes 4 patients who each missed 3 doses of apitegromab due to COVID-19-related site
Slide 37: Increases in HFMSE Not Correlated with Duration of Prior Nusinersen Treatment
Increases in HFMSE Not Correlated with Duration of PriorNusinersen Treatment Change in HFMSE Not Correlated With Number ofNusinersen Maintenance Doses(post-hoc analysis of TOPAZ non-ambulatory patients) Further data suggesting increases inHFMSE may be attributable to apitegromab No correlation betwe
Slide 38: Clinical Outcome Measures: Progressive Levels of Difficulty in Measuring Gross Motor Functions
Clinical Outcome Measures: Progressive Levels of Difficultyin Measuring Gross Motor Functions 38 WHO Motor Milestones – Different and MoreChallenging Tests of Self-Sufficient Locomotion 6 gross motor skills considered to be universal* Sitting without support – head erect for at least 10seconds; no u
Slide 39: WHO Motor Development Milestone Achievements Further Support Apitegromab
WHO Motor DevelopmSupport Apitegromab’ ent Milestos Potentia ne Achievemenl to Improve Mot ts Furtheror Function Non-ambulatory Type 2/3 Patients Pooled, 20 mg/kg Initiated nusinersen age <5 Initiated nusinersen age ≥5 # of patients gaining ≥1 WHO motor milestone(s) 7/35 4/10 3/15 39 WHO motor miles
Slide 40: Apitegromab to Advance to Phase 3 Trial in Non-Ambulatory Type 2/3 SMA
Apitegromab to Advanceto Phase 3 Trial in Patients with Non-Ambulatory Type 2/3 SMA Yung Chyung, M.D.Chief Medical Officer
Slide 41: Initial Development Strategy Focuses on Non-Ambulatory Patients on Background SMN Upregulators
41 Initial Development Strategy Focuses on Non- Ambulatory Patients on Background SMN Upregulators Global disease with30,000-35,000 affected inU.S. and Europe alone A Ambulatory patients Smaller population but high unmet need as benefits of SMN regulators not well-establishedTOPAZ suggests potential
Slide 42: Preliminary Thoughts on Apitegromab Phase 3 Trial Design
42 Preliminary Thoughts on Apitegromab Phase 3 Trial Design Design Subjects Key Objectives Timeline Non-ambulatory Type 2 and Type 3 SMAPediatric population in chronic maintenance phase of SMN therapy HFMSESafety Aim to initiate by end of 2021 Randomized, double-blind, placebo-controlled12-month tre
Slide 43: Additional Opportunities May Be Pursued With Separate Development Strategies
43 Additional Opportunities May Be Pursued With Separate Development Strategies Global disease with30,000-35,000 affected inU.S. and Europe alone A Ambulatory patients Smaller population but high unmet need as benefits of SMN regulators not well-establishedTOPAZ suggests potential clinical benefit i
Slide 44: Panel Discussion on Apitegromab's Therapeutic Potential in SMA
Panel Discussion onApitegromab’s Therapeutic Potential in SMA Thomas Crawford, M.D.Johns Hopkins Medicine Basil Darras, M.D.Boston Children’s HospitalHarvard Medical School
Slide 45: Esteemed Panelists: TOPAZ Trial Investigators
Esteemed Panelists: TOPAZ Trial Investigators Member of the Department of Neurology at Johns Hopkins since 1987.Practice involves general child neurology with a principal interest in caring for children with neuromuscular, neuromotor, and ataxic disorders.On the Medical and Scientific Advisory Board
Slide 46: Thank You for Participating!
Thank You for Participating! Pictures of individuals with SMA courtesy of Cure SMA 46
Slide 47: Appendix
Appendix $$$ ScholarRock
Slide 48: Majority of Ambulatory Patients Maintained or Improved in RHS Score from Baseline
Majority of Ambulatory Patients Maintained or Improved inRHS Score from Baseline 48 Apitegromab 20 mg/kg monotherapy Apitegromab 20 mg/kg + nusinersen Mean change from baseline in RHS (95% CI) -0.4 (-3.9, 3.1) -0.3 (-2.0, 1.4) # (%) patients achieving: ≥0-pt increase in RHS 6/11 (55%) 7/12 (58%) ≥1-
Slide 49: Dose Response Observed in PD and Efficacy Data
Non-Ambulatory Type 2 Cohort (Age ≥2 years):Dose Response Observed in PD and Efficacy Data Mean (±SEM) change from baseline 20 mg/kg dose numerically offered greater HFMSE increasesthan 2 mg/kg dose across all timepointsDurability of effect observed through 12-months of treatment Greater target enga
Slide 50: Planned apitegromab Phase 3 program in SMA by year-end 2021
50 Gilead fibrosis-focused TGFβ collaboration DRAGON Part A: dose escalation and continued follow-up Apitegromab Spinal Muscular Atrophy (SMA) SRK-181Immuno-Oncology and Oncology Preclinical/ Platform TOPAZ12M topline data Planned apitegromab Phase 3 program in SMA by year-end 2021: Potential for An
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