Slide 1: Positive Topline Results from Pivotal Phase 3 SAPPHIRE Trial of Apitegromab in SMA
© 2024 Scholar Rock, Inc. All rights reserved. Positive Topline Results from Pivotal Phase 3 SAPPHIRE Trial of Apitegromab in Spinal Muscular Atrophy (SMA) October 7, 2024 1
Slide 2: Agenda
© 2024 Scholar Rock, Inc. All rights reserved. Agenda 2 Jay Backstrom, M.D., MPH, President & Chief Executive Officer Introduction Jing Marantz , M.D. Ph.D., Chief Medical Officer SAPPHIRE Results Jay Backstrom, M.D., MPH, President & Chief Executive Officer Concluding Remarks Q&A Session
Slide 3: Forward-Looking Statements
© 2024 Scholar Rock, Inc. All rights reserved. Forward - Looking Statements Various statements in this presentation concerning the future expectations, plans and prospects of Scholar Rock Holding Corporation and Scholar Rock, Inc . (collectively, “Scholar Rock”), including, without limitation, Schol
Slide 4: Introduction
© 2024 Scholar Rock, Inc. All rights reserved. Introduction Jay Backstrom, M.D., MPH President & Chief Executive Officer 4
Slide 5: Our Purpose: Create Possibilities for Those Living with SMA
© 2024 Scholar Rock, Inc. All rights reserved. Our Purpose: Create Possibilities for Those Living with Spinal Muscular Atrophy (SMA) 5 Muscle is everything. I want to live knowing that I have the strength to take care of myself if left alone. - Lyza
Slide 6: Positive Phase 3 SAPPHIRE Trial: Transformative Benefit in SMA
© 2024 Scholar Rock, Inc. All rights reserved. 6 CONSISTENT clinically meaningful benefit across all age groups (2 - 21) FAVORABLE SAFETY profile consistent with >48 months experience in Phase 2 TOPAZ trial 30 % of apitegromab patients ACHIEVED ≥3 POINT IMPROVEMENT IN HFMSE † 1.8 (p=0.0192) POINT IM
Slide 7: Phase 3 SAPPHIRE Topline Results
© 2024 Scholar Rock, Inc. All rights reserved. Jing Marantz, M.D., Ph.D. Chief Medical Officer Phase 3 SAPPHIRE Topline Results
Slide 8: SAPPHIRE Trial Design
© 2024 Scholar Rock, Inc. All rights reserved. 8 Randomized, double - blind, placebo - controlled, parallel arm design (n=188) Patients on standard of care (nusinersen or risdiplam) TREATMENT (52 weeks) Apitegromab (20 mg/kg IV q4w) + SOC Apitegromab (10 mg/kg IV q4w) + SOC Placebo (IV q4w) + SOC SC
Slide 9: Prespecified Statistical Analysis Plan
© 2024 Scholar Rock, Inc. All rights reserved. 9 Prespecified Statistical Analysis Plan SAPPHIRE – APITEGROMAB IN SMA Apitegromab (20 mg/kg) + SOC Apitegromab (10 mg/kg) + SOC Placebo + SOC R 1:1:1 • Prespecified analyses to assess dose: combined apitegromab doses (10 mg/kg + 20 mg/kg), 20 mg/kg, an
Slide 10: 188 Patients Underwent Randomization
© 2024 Scholar Rock, Inc. All rights reserved. 10 *1 patient from 2 - 12 age group opted not to enroll in the ONYX study. † 1 subject (1%) in the 20 mg/kg apitegromab arm in the 2 - 12 age group withdrew consent. 1 subject (3%) in the 20 mg/kg apitegro mab arm in the 13 - 21 age group withdrew conse
Slide 11: Baseline Demographics and Disease Characteristics Well Balanced
© 2024 Scholar Rock, Inc. All rights reserved. 11 Baseline Demographics and Disease Characteristics Well Balanced Max=Maximum; Min = Minimum; SD = standard deviation; SMN = Survival Motor Neuron; SMA = Spinal Muscular Atrophy , SOC=standard of care. SAPPHIRE – APITEGROMAB IN SMA Ages 13 - 21 Ages 2
Slide 12: Despite Chronic SMN Therapy, SMA Patients Continue To Lose Function Over Time
© 2024 Scholar Rock, Inc. All rights reserved. 12 Finkel RS et al. “Final Safety and Efficacy Data From the SHINE Study in Participants With Infantile - Onset and Later - Onset SMA.” Presented at Cure SMA Annual Conference, July 2024 *Patient age based on those received active treatment (mean or med
Slide 13: Primary Endpoint Met: Change from Baseline in HFMSE Total Score
© 2024 Scholar Rock, Inc. All rights reserved. 13 *Hochberg method prespecified for multiplicity adjustment; **nominal p value HFMSE=Hammersmith Functional Motor Scale Expanded. Unadjusted P - value Results (vs Placebo, n=50) n Analysis 0.0192* 1.8 106 Apitegromab 10+20 mg/kg combined 0.1149* 1.4 53
Slide 14: Improvement in HFMSE Consistent Across Doses and Age Groups
© 2024 Scholar Rock, Inc. All rights reserved. -5 -4 -3 -2 -1 0 1 2 3 4 5 14 Improvement in HFMSE Consistent Across Doses and Age Groups SAPPHIRE – APITEGROMAB IN SMA LS Mean Difference (95% CI) [Active - Placebo] 1.8 (0.30, 3.32) 2 - 12 years apitegromab combined dose (10 & 20 mg/kg; n=106) vs. pla
Slide 15: Early and Increasing HFMSE Improvement vs. Placebo
© 2024 Scholar Rock, Inc. All rights reserved. 15 CI=Confidence Interval; EXP=Exploration Subpopulation; HFMSE=Hammersmith Functional Motor Scale Expanded; LS=Least Squares; M EP= Main Efficacy Population; SOC=standard of care. SAPPHIRE – APITEGROMAB IN SMA Early and Increasing HFMSE Improvement vs.
Slide 16: 30% of Apitegromab Patients Achieved ≥3 Points on HFMSE
© 2024 Scholar Rock, Inc. All rights reserved. 16 30% of Apitegromab Patients Achieved ≥3 Points on HFMSE HFMSE=Hammersmith Functional Motor Scale Expanded; SOC = standard of care. SAPPHIRE – APITEGROMAB IN SMA ≥3 Point Improvement in HFMSE 30.4% 12.5% 0% 5% 10% 15% 20% 25% 30% 35% Apitegromab Combi
Slide 17: Well-Tolerated Safety Consistent With Phase 2 TOPAZ Trial
© 2024 Scholar Rock, Inc. All rights reserved. 17 Well - Tolerated Safety Consistent With Established Profile Observed in Phase 2 TOPAZ Trial AE=Adverse Event; SOC = standard of care. All AEs are coded using the MedDRA version 26.1. Ages 13 - 21 Ages 2 - 12 Summary of Adverse Events (AE) Apitegromab
Slide 18: Potential to Transform Standard of Care in SMA
© 2024 Scholar Rock, Inc. All rights reserved. 18 Potential to Transform Standard of Care in SMA 1.8 - point improvement in HFMSE (p=0.0192) compared to placebo Patients improving on apitegromab vs. declining on placebo Favorable safety profile supports durability of treatment >48 months treatment e
Slide 19: Conclusion
© 2024 Scholar Rock, Inc. All rights reserved. Conclusion Jay Backstrom, M.D., MPH President & Chief Executive Officer
Slide 20: Our Mission
© 2024 Scholar Rock, Inc. All rights reserved. TGFβ=Transforming growth factor - beta. O UR MISSI ON To discover, develop, and deliver life - changing therapies by harnessing cutting - edge science to create new possibilities for people living with serious diseases We are a global leader in harnessi
Slide 21: Innovating a New Era in the Treatment of Spinal Muscular Atrophy
© 2024 Scholar Rock, Inc. All rights reserved. Scholar Rock has an industry - leading, highly selective antibody engineering platform that has succeeded where others have failed. Apitegromab is the first and only muscle targeted therapy to show clinically meaningful and statistically significant fun
Slide 22: Apitegromab Has the Potential to Transform Standard of Care in SMA
© 2024 Scholar Rock, Inc. All rights reserved. 22 CONSISTENT clinically meaningful benefit across all age groups (2 - 21) FAVORABLE SAFETY profile consistent with >48 months experience in Phase 2 TOPAZ trial 30% of apitegromab patients ACHIEVED ≥3 POINT IMPROVEMENT IN HFMSE † 1.8 (p=0.0192) POINT IM
Slide 23: Upcoming Planned Key Milestones
© 2024 Scholar Rock, Inc. All rights reserved. 23 Upcoming Planned Key Milestones * If approved by relevant health authorities • Submit FDA and EMA applications in Q1 2025 • Request priority review (FDA) and accelerated assessment (EMA) Apitegromab Regulatory Submissions • US launch in Q4 2025 and E
Slide 24: Q&A Session
© 2024 Scholar Rock, Inc. All rights reserved. Q&A Session 24
Slide 25: Thank you!
© 2024 Scholar Rock, Inc. All rights reserved. 25 Thank you!
Slide 26: Appendix
© 2024 Scholar Rock, Inc. All rights reserved. 26 Appendix
Slide 27: Total Latent Myostatin Levels Over Time
© 2024 Scholar Rock, Inc. All rights reserved. 27 Total Latent Myostatin Levels Over Time MEP=main efficacy population; SD=standard deviation. • Robust and sustained target engagement were observed following apitegromab dosing • Similar levels of target engagement were observed for 10 mg/kg and 20 m
Slide 28: Well-Tolerated Safety Consistent With Established Profile
© 2024 Scholar Rock, Inc. All rights reserved. 28 Well - Tolerated Safety Consistent With Established Profile AE = Adverse Event; SAE= serious adverse event; SOC=standard of care; SMN=survival motor neuron; ADA=anti - drug antibodies; all AEs are coded using the MedDRA version 26.1. Exploratory Subp