Scholar Rock Holding Corporation · NASDAQ:SRRK

Scholar Rock — Investor Day (May 2024)

90 slides from Scholar Rock's investor day presentation, May 22, 2024

1. Slide 1: Investor Day May 22, 2024

   © 2024 Scholar Rock, Inc. All rights reserved. Investor Day May 22, 2024 1

2. Slide 2: Welcome

   © 2024 Scholar Rock, Inc. All rights reserved. Welcome Rushmie Nofsinger Vice President Investor Relations & Corporate Affairs 2

3. 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, Scholar R

4. Slide 4: Company Speakers

   © 2024 Scholar Rock, Inc. All rights reserved. Company Speakers 4 Jay Backstrom, M.D., MPH President & Chief Executive Officer Jing Marantz, M.D., Ph.D. Chief Medical Officer Tracey Sacco Chief Commercial Officer Mo Qatanani, Ph.D. Chief Scientific Officer

5. Slide 5: Expert Speakers

   © 2024 Scholar Rock, Inc. All rights reserved. Expert Speakers 5 Diana Castro, M.D. Founder of Neurology & Neuromuscular Care Center and Neurology Rare Disease Center Former Associate Professor of Pediatrics, Neurology and Neurotherapeutics, University of Texas Southwestern, Director of the Neuromus

6. Slide 6: Today's Agenda

   © 2024 Scholar Rock, Inc. All rights reserved. Today’s Agenda 6 Topic Speaker  Welcome Rushmie Nofsinger, VP of IR & Corporate Affairs  Vision & Strategic Overview Jay Backstrom, President & Chief Executive Officer  SMA: The Patient Journey Diana Castro, M.D., Neurology & Neuromuscular Care Cente

7. Slide 7: Building a Fully Integrated Biopharma Company

   © 2024 Scholar Rock, Inc. All rights reserved. Building a Fully Integrated Biopharma Company Jay Backstrom President & Chief Executive Officer

8. Slide 8: Our Mission

   8 TGF β=Transforming growth factor -beta. OUR MISSION 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 harnessing the life -changing potential of TGF β biology

9. Slide 9: What You Will Hear Today

   © 2024 Scholar Rock, Inc. All rights reserved. Selectivity is the Key The hallmark of our differentiated platform is unparalleled selectivity 1 Large Unmet Needs SMA and obesity represent high value markets offering significant potential revenue opportunities 2 Positioned for Success Experienced tea

10. Slide 10: Evolving into a Fully Integrated Biopharma Company

    © 2024 Scholar Rock, Inc. All rights reserved. Evolving into a Fully Integrated Biopharma Company A G E N D A Building a muscle-targeted franchise The road ahead – value drivers Leveraging our proprietary platform 10

11. Slide 11: Scholar Rock Has Succeeded Where Others Have Failed

    © 2024 Scholar Rock, Inc. All rights reserved. Scholar Rock’s Target Latent Growth Factor Traditional Target “Mature” Active Growth Factor Scholar Rock Has Succeeded Where Others Have Failed 11 Targeting the ‘cage’ before growth factor is released allows for exquisite selectivity Has been challengin

12. Slide 12: Growing Pipeline Across High Value Therapeutic Areas

    © 2024 Scholar Rock, Inc. All rights reserved. Growing Pipeline Across High Value Therapeutic Areas 12 *Utilized data from previously completed Ph 1 study in healthy volunteers and initiate a Ph 2 POC trial in 2024. LTBP1=Latent transforming growth factor beta binding protein 1; LTBP3=Latent transfo

13. Slide 13: High Value Growth Opportunities

    Ph 3 SAPPHIRE in SMA Apitegromab additional neuromuscular populations EMBRAZE PoC in obesity Advance SRK-439 to IND Established PoC in ccRCC End of Ph 1 meeting Advance LTBP to IND Nonclinical studies in renal and pulmonary fibrosis High Value Growth Opportunities 13 Neuromuscular Disorders Cardiome

14. Slide 14: Evolving into a Fully Integrated Biopharma Company

    © 2024 Scholar Rock, Inc. All rights reserved. Evolving into a Fully Integrated Biopharma Company A G E N D A Building a muscle-targeted franchise The road ahead – value drivers Leveraging our proprietary platform 14

15. Slide 15: Distinct & High Value Opportunities for Myostatin Inhibition

    © 2024 Scholar Rock, Inc. All rights reserved. Distinct & High Value Opportunities for Myostatin Inhibition 15 Selective Myostatin Inhibition Apitegromab SRK-439 Therapeutic Area Current Market Size 1 Revenue as of Biogen 4Q23 financial update, Roche 4Q23 financial update, and Novartis 4Q23 financia

16. Slide 16: Global Rights Across the Portfolio

    © 2024 Scholar Rock, Inc. All rights reserved. Global Rights Across the Portfolio 29 patent families pending Exclusivity through 2036 to 2043 for key assets Novel Scientific Platform Robust Pipeline across 5 therapeutic areas 3 clinical programs Multiple preclinical programs Established Markets with

17. Slide 17: Leveraging Our Building Blocks, Transformative 18 Months Ahead

    © 2024 Scholar Rock, Inc. All rights reserved. Phase 3 SAPPHIRE Trial Proof of Concept in Obesity Significant Inflection Points in Next Year Preparing to Launch SMA in US and EU* Global Rights Across the Portfolio 29 patent families pending Exclusivity through 2036 to 2043 for key assets Novel Scien

18. Slide 18: Evolving into a Fully Integrated Biopharma Company

    © 2024 Scholar Rock, Inc. All rights reserved. Evolving into a Fully Integrated Biopharma Company A G E N D A Building a muscle-targeted franchise The road ahead – value drivers Leveraging our proprietary platform 18

19. Slide 19: Near-Term 2024 & 2025 Anticipated Milestones

    © 2024 Scholar Rock, Inc. All rights reserved. Near-Term 2024 & 2025 Anticipated Milestones 19 Milestones 2024 2025 SRK-181 data at ASCO • Oral presentation June 3 • Developmental Therapeutics-Immunotherapy SRK-439 data at American Diabetes Association • Oral presentation June 23 • New Insights into

20. Slide 20: Strategic Roadmap: Our Vision for 2030

    © 2024 Scholar Rock, Inc. All rights reserved. Strategic Roadmap: Our Vision for 2030 20 Multi-Billion Dollar Global Neuromuscular Franchise Established in key major markets 5 Clinical Programs Including additional neuromuscular assets Multiple Research Programs Across TGFβ superfamily of growth fac

21. Slide 21: From a World-Class Scientific Platform to a World-Class Biopharma Company

    © 2024 Scholar Rock, Inc. All rights reserved. From a World-Class Scientific Platform to a World-Class Biopharma Company 21 I N S U M M A R Y PLATFORM PIPELINE PEOPLE Unparalleled selectivity to optimize efficacy and safety Broad opportunities to improve patient outcomes in areas of high unmet need

22. Slide 22: Apitegromab: Development Program

    © 2024 Scholar Rock, Inc. All rights reserved. Apitegromab: Development Program Jing Marantz Chief Medical Officer 22

23. Slide 23: Upcoming Catalyst: Topline Data Expected in Q4 2024

    © 2024 Scholar Rock, Inc. All rights reserved. Upcoming Catalyst: Topline Data Expected in Q4 2024 23 A P I T E G R O M A B D E V E L O P M E N T P R O G R A M Where We Were Phase 2 Where We Are Phase 3 12-Month COMPLETE COMPLETE 12-Month IN PROCESS Future 48-Month EXTENSION Long-Term EXTENSION • Q4

24. Slide 24: Apitegromab for SMA Development Program

    © 2024 Scholar Rock, Inc. All rights reserved. Apitegromab for SMA Development Program A G E N D A 24 Evidence supporting apitegromab’s potential Pivotal SAPPHIRE trial: Why we are confident Where we plan to go

25. Slide 25: Why We Are Confident

    © 2024 Scholar Rock, Inc. All rights reserved. 25 Why We Are Confident A P I T E G R O M A B F O R S P I N A L M U S C U L A R A T R O P H Y Selective muscle-targeting designed to improve motor function while minimizing off-target effects >90% patient retention,1 well tolerated profile supports dura

26. Slide 26: Selectively Targets Muscle to Address Unmet Needs

    © 2024 Scholar Rock, Inc. All rights reserved. * Based on Animal Model Data; 1. Long KK, et al. Hum Mol Genet. 2019;28(7):1077-1088; 2. Pirruccello-Straub M, et al. Sci Reports. 2018;8(1):2292. doi:10.1038/s41598-018-20524-9 3. Figure 26 adapted from: SMA Foundation Overview. http://www.smafoundatio

27. Slide 27: Motor Function Improvements Were Substantial & Sustained Over 36 Months

    © 2024 Scholar Rock, Inc. All rights reserved. 0.6 1.3 2.3 2.4 0 1 2 3 4 Baseline 6 months 12 months 24 months 36 months 27 Motor Function Improvements Were Substantial & Sustained Over 36 Months n= 35 29 32 29 28 95% CI= (1.4, 4.1) (1.2, 6.0) (1.9, 6.6) (1.0, 6.9) Pooled Nonambulatory Patients Age

28. Slide 28: SAPPHIRE Phase 3 Design is Optimized by Insights from TOPAZ

    © 2024 Scholar Rock, Inc. All rights reserved. 28 SAPPHIRE Phase 3 Design is Optimized by Insights from TOPAZ # 3 P H A S E 3 S A P P H I R E T R I A L O P T I M I Z E D F O R S U C C E S S TOPAZ Learnings HFMSE=Hammersmith Functional Motor Scale Expanded. *Nonambulatory is defined as unable to inde

29. Slide 29: SAPPHIRE Trial Design - Calibrated and Targeted

    © 2024 Scholar Rock, Inc. All rights reserved. 29 SAPPHIRE Trial Design - Calibrated and Targeted # 3 P H A S E 3 S A P P H I R E T R I A L O P T I M I Z E D F O R S U C C E S S Randomized, double-blind, placebo-controlled (enrolled n=188) Enrolled patients receiving SMN-targeted therapy (nusinersen

30. Slide 30: SAPPHIRE – Clear Goals

    © 2024 Scholar Rock, Inc. All rights reserved. 30 SAPPHIRE – Clear Goals # 3 P H A S E 3 S A P P H I R E T R I A L O P T I M I Z E D F O R S U C C E S S Improved motor function (HFMSE1 and RULM) across broad SMA patients ages 2-21 and regardless of type of SMN-targeted therapy Improved caregiver-rep

31. Slide 31: Well Tolerated Safety Profile & Low Discontinuation Rate

    © 2024 Scholar Rock, Inc. All rights reserved. 31 Well Tolerated Safety Profile & Low Discontinuation Rate # 4 T O P A Z S A F E T Y P R O F I L E RIGHT TIME Latent Form Myostatin RIGHT TARGET • >90% of patients on combination therapy remain on study after 4 years of treatment1 • Consistent treatmen

32. Slide 32: Apitegromab for SMA Development Program

    © 2024 Scholar Rock, Inc. All rights reserved. Apitegromab for SMA Development Program A G E N D A 32 Evidence supporting apitegromab’s potential Pivotal SAPPHIRE trial: Why we are confident Where we plan to go

33. Slide 33: Evidence from TOPAZ to Support Apitegromab's Potential in SMA

    © 2024 Scholar Rock, Inc. All rights reserved. Evidence from TOPAZ to Support Apitegromab’s Potential in SMA SMN therapies generally plateau after initial gains Substantial HFMSE gains on top of SMN therapy Motor function improvement showed dose response and no clear correlation with nusinersen expo

34. Slide 34: Unmet Need to Address Muscle Atrophy

    © 2024 Scholar Rock, Inc. All rights reserved. -2 -1 0 1 2 3 4 Unmet Need to Address Muscle Atrophy 34 Overall population age 2-25 Change in HFMSE* Over Four Years with Risdiplam2 Risdiplam n= 120 120 119 117 109 106 89 99 101 97 Placebo n= 60 60 58 58 Risdiplam Placebo (months 0-12) Mean (+/-SE) Ch

35. Slide 35: Motor Function Gains Were Substantial & Sustained Over 36 Months

    © 2024 Scholar Rock, Inc. All rights reserved. 35 Motor Function Gains Were Substantial & Sustained Over 36 Months # 2 S U B S T A N T I A L H F M S E G A I N S W I T H A P I T E G R O M A B O N T O P O F S M N T H E R A P Y n= 35 29 32 29 28 95% CI= (1.4, 4.1) (1.2, 6.0) (1.9, 6.6) (1.0, 6.9) Age 2

36. Slide 36: Motor Function Improvement Mainly Attributable to Apitegromab

    © 2024 Scholar Rock, Inc. All rights reserved. Motor Function Improvement Mainly Attributable to Apitegromab 36 HFMSE, Hammersmith Functional Motor Scale Expanded. Dose response graph: Crawford TO, et al. Neurology. 2024; 102 (5). Scatter plot of prior nusinersen treatment duration vs change in HFMS

37. Slide 37: Caregivers Report Improved Self-Sufficiency and Fatigue

    © 2024 Scholar Rock, Inc. All rights reserved. 37 Time (weeks) No. of observations Time (weeks) No. of observations IMPROVEMENT Change from baseline ( ±SE) -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 0 0 8 16 24 32 40 52 68 84 104 120 136 156 -2 -1 0 1 2 3 4 5 0 0 8 16 24 32 40 52 68 84 104 120 136 156 Year 1 Yea

38. Slide 38: >90 Percent of Patients on Combination Therapy Remain on Study

    © 2024 Scholar Rock, Inc. All rights reserved. • 57 enrolled • 8 discontinued: 2 due to COVID-19 concerns; 1 due to work schedule, 5 on monotherapy due to perceived lack of benefit • >90% of patients on combination therapy remain on study with 4 years of treatment1 • 58 enrolled • 57 completed prima

39. Slide 39: Apitegromab for SMA Development Program

    © 2024 Scholar Rock, Inc. All rights reserved. Apitegromab for SMA Development Program A G E N D A 39 Evidence supporting apitegromab’s potential Pivotal SAPPHIRE trial: Why we are confident Where we plan to go

40. Slide 40: Where We Plan to Go: Expanding to Benefit More People Living with SMA

    © 2024 Scholar Rock, Inc. All rights reserved. Where We Plan to Go: Expanding to Benefit More People Living with SMA *Pending approval 40 2024 2025 Q4 Data Readout • BLA /MAA Filing • Regulatory Approval* • Study in SMA Patients < 2 Years of Age ‒ Study design endorsed by EMA’s paediatric committee

41. Slide 41: Advancing a Novel Muscle-Targeted Therapy for SMA

    © 2024 Scholar Rock, Inc. All rights reserved. Advancing a Novel Muscle-Targeted Therapy for SMA 41 I N S U M M A R Y • High confidence based on proof-of-concept data in SMA • Q4 pivotal readout with potential 2025 regulatory approval & commercialization • Studies planned to support additional indic

42. Slide 42: Apitegromab: Commercial Readiness

    © 2024 Scholar Rock, Inc. All rights reserved. Apitegromab: Commercial Readiness Tracey Sacco Chief Commercial Officer 42

43. Slide 43: Apitegromab: Commercial Readiness

    © 2024 Scholar Rock, Inc. All rights reserved. Apitegromab: Commercial Readiness A G E N D A SMA market insights Commercialization planning 43

44. Slide 44: Our Purpose: Create Possibilities for Those Living with SMA

    © 2024 Scholar Rock, Inc. All rights reserved. Our Purpose: Create Possibilities for Those Living with SMA 44 Muscle is everything. I want to live knowing that I have the strength to take care of myself if left alone. - Lyza

45. Slide 45: Listening to the Customer Voice to Stay Focused on Our Purpose

    © 2024 Scholar Rock, Inc. All rights reserved. Listening to the Customer Voice to Stay Focused on Our Purpose 45 Building Deep Insights • >15 market research and insights projects with US, EU, and UK participants  250+ caregivers of or people living with SMA  340+ HCPs, including both neurologists

46. Slide 46: SMA Has Evolved – Patients are Diagnosed, Treated, and Surviving Longer

    © 2024 Scholar Rock, Inc. All rights reserved. SMA Has Evolved – Today Patients are Diagnosed, Treated, and Surviving Longer • Newborn screening leading to earlier treatment • Broad and expanding global access to treatment • Concentrated care in US and EU • Engaged and organized global patient advoc

47. Slide 47: Patient Demand, HCP Feedback, and Payer Proactivity Suggest: More is Still Needed

    © 2024 Scholar Rock, Inc. All rights reserved. Patient Demand, HCP Feedback, and Payer Proactivity Suggest: More is Still Needed Sources: Cure SMA. Education on adult patient expectations according to copy number and disease status at time of report. September 2022. Internal Scholar Rock market rese

48. Slide 48: Progressive Muscle Weakness Remains a Core Unmet Need

    © 2024 Scholar Rock, Inc. All rights reserved. Progressive Muscle Weakness Remains a Core Unmet Need 48 Personal hygiene, using the toilet and the shower on my own would be huge. My four-year-old can do it on her own. It’s degrading. – US Patient Patients treated with [nusinersen and risdiplam] are

49. Slide 49: SMA is the Right Opportunity for Scholar Rock's First Launch

    © 2024 Scholar Rock, Inc. All rights reserved. 1. 2. 3. 4. SMA is the Right Opportunity for Scholar Rock’s First Launch 49 Clear Unmet Need Concentrated and Proactive Care Engaged Patient Community Payer Receptivity • Patient, HCP, and payer communities recognize remaining needs in SMA • Patients al

50. Slide 50: Apitegromab: Commercial Readiness

    © 2024 Scholar Rock, Inc. All rights reserved. Apitegromab: Commercial Readiness A G E N D A SMA market insights Commercialization planning 50

51. Slide 51: Why We Are Confident About Potential Commercial Success of Apitegromab

    © 2024 Scholar Rock, Inc. All rights reserved. Why We Are Confident About Potential Commercial Success of Apitegromab 51 Gold standard efficacy measure in SMA • HFMSE is a SMA-specific, validated functional scale • Commonly used in practice by both HCPs and payers Long-term treatment experience in S

52. Slide 52: SMA Represents a Significant Opportunity for Apitegromab

    © 2024 Scholar Rock, Inc. All rights reserved. SMA Represents a Significant Opportunity for Apitegromab 52 ~$4.5B1 global revenue for three SMN targeted therapies Apitegromab global revenue potential >$1.0B2 1 Revenue as of Biogen 4Q23 financial update, Roche 4Q23 financial update, and Novartis 4Q23

53. Slide 53: Commercialization Approach: Three Key Elements

    © 2024 Scholar Rock, Inc. All rights reserved. Commercialization Approach: Three Key Elements 53 1. Engagement 2. Patient Experience 3. Execution • Partnering with SMA communities • Ensure excellent patient experience • Build team to deliver US launch & global expansion Commercialization Plan

54. Slide 54: Partnering With the SMA Community

    © 2024 Scholar Rock, Inc. All rights reserved. Partnering With the SMA Community 54 1 . E N G A G E M E N T • MSL team on the ground • Continued engagement with US and EU patient advocacy © 2024 Scholar Rock, Inc. All rights reserved. MSL= Medical Science Liaison • Amplify patient voice with muscle-

55. Slide 55: Secure Access and Customize Treatment to Meet Patient Needs

    © 2024 Scholar Rock, Inc. All rights reserved. Secure Access and Customize Treatment to Meet Patient Needs 55 2 . P A T I E N T E X P E R I E N C E Optimize Treatment Experience Ensure Access Provide Support Vision for Patient Experience Engage payers early and focus on value demonstration Design fo

56. Slide 56: Building to Achieve Commercial Success

    © 2024 Scholar Rock, Inc. All rights reserved. Building to Achieve Commercial Success 56 3 . E X E C U T I O N Geographic Expansion • Commercialize in selected European countries* • Remaining EU and ROW expansion through distributorships & partnerships U.S. Launch* • Expand commercial capabilities •

57. Slide 57: Path to Achieving Commercial Success in SMA

    © 2024 Scholar Rock, Inc. All rights reserved. Path to Achieving Commercial Success in SMA 57 I N S U M M A R Y  Clear unmet need and favorable market dynamics  Competitive and attractive potential profile  Engagement, patient-focus & execution The right market The right medicine The right plan A

58. Slide 58: SRK-439: Selective Anti-Myostatin Designed for Optimal Profile in Obesity

    © 2024 Scholar Rock, Inc. All rights reserved. SRK-439: Selective Anti-Myostatin Designed for Optimal Profile in Obesity Mo Qatanani Chief Scientific Officer 58

59. Slide 59: A Differentiated Approach

    © 2024 Scholar Rock, Inc. All rights reserved. A Differentiated Approach A G E N D A Different approaches to muscle preservation SRK-439: novel asset, differentiated profile 59 Best-in-class platform for selectivity

60. Slide 60: Differentiated Approach to Targeting Growth Factors

    © 2024 Scholar Rock, Inc. All rights reserved. Differentiated Approach to Targeting Growth Factors 60 S E L E C T I V I T Y D R I V E S S U C C E S S Transformational Medicines Deep structural insights to validated targets Industry-leading antibody design and protein engineering to selectively targe

61. Slide 61: Platform and Expertise Drive Success in Clinic

    © 2024 Scholar Rock, Inc. All rights reserved. Platform and Expertise Drive Success in Clinic 61 Superb Engineering Clinic SRK-439 IND in 2025 SRK-181 Anti-PD1 Anti-PD1/ SRK-181-mIgG1 T R A N S L A T I O N A L S U C C E S S T O T H E C L I N I C Apitegromab Muscle stimulation (Hz) Muscle strength (t

62. Slide 62: A Differentiated Approach

    © 2024 Scholar Rock, Inc. All rights reserved. A Differentiated Approach A G E N D A Different approaches to muscle preservation SRK-439: novel asset, differentiated profile 62 Best-in-class platform for selectivity

63. Slide 63: Muscle is Critical for Overall Health

    © 2024 Scholar Rock, Inc. All rights reserved. Muscle is Critical for Overall Health 1. Aristizabal JC et al. Eur J Clin Nutr 2015; 2. Lindegaard B et al. J Clin Endocrinol Metab 2008; 3. Srikanthan P, Karlamangla AS J Clin Endocrinol Metab 2011; 4. Severinsen et al. Endocr Rev. 2020; 5. Wewege MA,

64. Slide 64: Myostatin is the Right Target for Muscle Growth

    © 2024 Scholar Rock, Inc. All rights reserved. Advantages Myostatin is the Right Target for Muscle Growth Myostatin is specific to muscle1 Validated genetically with no evident safety liabilities 1-4 Inhibition leads to muscle growth in adults5 Selective targeting leads to improved motor function as

65. Slide 65: Multiple Risks Associated with Non-Selective Targeting

    © 2024 Scholar Rock, Inc. All rights reserved. Signaling receptor shared by Myostatin, GDF-11 & Activin A Multiple Risks Associated with Non-Selective Targeting 1. Barrett et al., Adv Therapy 2021; 2. Crawford et al., Neurology 2024; 3. Garito T et al Clin Endocrinol 2018; 4. Amato AA et al Neurolog

66. Slide 66: A Differentiated Approach

    © 2024 Scholar Rock, Inc. All rights reserved. A Differentiated Approach A G E N D A Different approaches to muscle preservation SRK-439: novel asset, differentiated profile 66 Best-in-class platform for selectivity

67. Slide 67: Why We Are Confident in SRK-439

    © 2024 Scholar Rock, Inc. All rights reserved. Why We Are Confident in SRK-439 67 • A new anti-myostatin specifically suited for obesity • Targets pro and latent forms of myostatin designed to minimize undesirable off-target effects • Preclinical data demonstrated favorable muscle mass preservation

68. Slide 68: SRK-439: Differentiated Profile

    © 2024 Scholar Rock, Inc. All rights reserved. SRK-439: Differentiated Profile 68 Exquisite selectivity for myostatin Potential for healthier weight loss in combination with GLP-1 RA Low efficacious dose and competitive profile 1 3 2

69. Slide 69: SRK-439 Selectively Binds Latent Myostatin

    © 2024 Scholar Rock, Inc. All rights reserved. SRK-439 Selectively Binds Latent Myostatin Scholar Rock’s Target: Latent Myostatin SRK-439: Exquisite Selectivity for Myostatin 69 # 1 S E L E C T I V E F O R M Y O S T A T I N • Increasing SRK-439 concentrations lead to increased signal of binding to m

70. Slide 70: SRK-439: Potential for Healthier Weight Loss Management in Combination with GLP-1 RA

    © 2024 Scholar Rock, Inc. All rights reserved. SRK-439: Potential for Healthier Weight Loss Management in Combination with GLP-1 RA 70 # 2 C O M B I N A T I O N G L P - 1 R A D A T A I N O B E S I T Y M O D E L S • Considerable lean mass loss with semaglutide treatment • Combination with SRK-439 led

71. Slide 71: SRK-439: Further Improvement of Metabolic Health

    © 2024 Scholar Rock, Inc. All rights reserved. 0 50 100 150 200 250 SRK-439 Further Improvement in Fasting Glucose in SemaglutideTreated Animals Fasting Glucose (mg/dL) 0.1 0.3 1 3 Control + Sema Control SRK-439 Treatment ✱ ✱ ✱ SRK-439: Further Improvement of Metabolic Health 71 # 2 C O M B I N A T

72. Slide 72: Are We Limiting Efficacy with Selective Targeting of Myostatin?

    © 2024 Scholar Rock, Inc. All rights reserved. Are We Limiting Efficacy with Selective Targeting of Myostatin? 72 S E L E C T I V I T Y T O M Y O S T A T I N I S C R I T I C A L Signaling receptor shared by Myostatin, GDF-11 & Activin A Promyostatin Pro-GDF-11 Proactivin GDF-11 Activin A ActRIIA/B A

73. Slide 73: SRK-439: More Potent than Anti-ActRII Antibody at Maintaining Lean Mass

    © 2024 Scholar Rock, Inc. All rights reserved. SRK-439: More Potent than Anti-ActRII Antibody at Maintaining Lean Mass 73 # 3 L O W E F F I C A C I O U S D O S E A N D C O M P E T I T I V E P R O F I L E Head-to-Head Comparison to Non-Selective Myostatin Inhibitor in DIO Mouse Model -20 -15 -10 -5 0

74. Slide 74: SRK-439: Best in Class Potential

    © 2024 Scholar Rock, Inc. All rights reserved. SRK-439: Best in Class Potential 74 SRK-439 ActRII Ab Ligand Trap Adnectin Selectivity for myostatin Action limited to muscle Combination GLP-1 RA data in obesity preclinical models1-3 Low efficacious dose in preclinical obesity models1-3 Lower risk of

75. Slide 75: SRK-439: The Right Molecule for Healthy Weight Loss

    © 2024 Scholar Rock, Inc. All rights reserved. SRK-439: The Right Molecule for Healthy Weight Loss 75 I N S U M M A R Y  Highly selective approach  Targets muscle  Efficacy without potential liabilities of non-selective approaches  Designed for subcutaneous low frequency dosing with robust subcu

76. Slide 76: Cardiometabolic Development Program Aiming for Healthier Weight Loss

    © 2024 Scholar Rock, Inc. All rights reserved. Cardiometabolic Development Program Aiming for Healthier Weight Loss Jing Marantz Chief Medical Officer 76

77. Slide 77: Cardiometabolic Development Program

    © 2024 Scholar Rock, Inc. All rights reserved. Cardiometabolic Development Program A G E N D A Overview of muscle-targeted opportunity SRK-439 Development Pathway 77

78. Slide 78: Significant Proportion of Weight Loss Due to Loss of Lean Muscle Mass

    © 2024 Scholar Rock, Inc. All rights reserved. Significant Proportion of Weight Loss Due to Loss of Lean Muscle Mass 78 L O S S O F L E A N M U S C L E S I G N I F I C A N T W I T H G L P - 1 A G O N I S T T H E R A P Y GLP-1 Agonist=Glucagon-like peptide-1 receptor agonist 1. Muller TD, et al Anti-

79. Slide 79: Lean Muscle Is Essential to Healthy Metabolic Function

    © 2024 Scholar Rock, Inc. All rights reserved. Lean Muscle Is Essential to Healthy Metabolic Function 79 L O S S O F L E A N M U S C L E S I G N I F I C A N T W I T H G L P - 1 A G O N I S T T H E R A P Y GLP-1 Agonist=Glucagon-like peptide-1 receptor agonist 1. Aristizabal JC, Freidenreich DJ, Volk

80. Slide 80: Potential Benefits Our Solution Delivers

    © 2024 Scholar Rock, Inc. All rights reserved. Potential Benefits Our Solution Delivers Attractive Clinical Risk/Benefit Profile 80 • Inhibition of myostatin, a negative regulator of muscle, is known to promote muscle growth and function • Apitegromab, a selective myostatin inhibitor, has been shown

81. Slide 81: Cardiometabolic Development Program

    © 2024 Scholar Rock, Inc. All rights reserved. Cardiometabolic Development Program 81 Overview of muscle-targeted opportunity SRK-439 Development Pathway A G E N D A

82. Slide 82: Apitegromab in SMA Improved Motor Function from Baseline

    © 2024 Scholar Rock, Inc. All rights reserved. 82 Apitegromab in SMA Improved Motor Function from Baseline C A R D I O M E T A B O L I C D E V E L O P M E N T P R O G R A M n= 35 29 32 29 28 95% CI= (1.4, 4.1) (1.2, 6.0) (1.9, 6.6) (1.0, 6.9) Age 2-21 Years Pooled Nonambulatory Patients (N=35) 2.8 3

83. Slide 83: Leveraging Apitegromab POC Study to Inform SRK-439 Development

    © 2024 Scholar Rock, Inc. All rights reserved. Leveraging Apitegromab POC Study to Inform SRK-439 Development 83 C A R D I O M E T A B O L I C D E V E L O P M E N T P R O G R A M Tests hypothesis of selective anti-myostatin in obese population POC study start* POC data readout* Ph 2 proof-of-concept

84. Slide 84: EMBRAZE Proof-of-Concept Study

    © 2024 Scholar Rock, Inc. All rights reserved. 84 Effect of apitegromab to preserve lean mass in obese or overweight patients receiving a GLP-1 agonist Safety and tolerability data to provide initial support for long-term chronic use Explore the potential effect of apitegromab to improve metabolic p

85. Slide 85: Launching Phase 2 Proof-of-Concept Study of Apitegromab in Obesity

    © 2024 Scholar Rock, Inc. All rights reserved. Launching Phase 2 Proof-of-Concept Study of Apitegromab in Obesity 85 E M B R A Z E T R I A L D E S I G N Randomized, double-blind, placebo-controlled (n=100) Enrolling patients who are overweight or obese Enrollment expected to start in 2Q 2024 Screeni

86. Slide 86: FDA Guidelines Added Clinical Benefit Regulatory Pathway

    © 2024 Scholar Rock, Inc. All rights reserved. FDA Guidelines Added Clinical Benefit 86 Regulatory Pathway C A R D I O M E T A B O L I C D E V E L O P M E N T P R O G R A M *Clinical Outcome Assessment: Frequently Asked Questions: https://www.fda.gov/about-fda/clinical-outcome-assessment-coa-frequen

87. Slide 87: Platform and Expertise Drive Success in Clinic

    © 2024 Scholar Rock, Inc. All rights reserved. Platform and Expertise Drive Success in Clinic 87 T R A N S L A T I O N A L S U C C E S S T O T H E C L I N I C Apitegromab SRK-181 SRK-439 Anti-PD1 Anti-PD1/ SRK-181-mIgG1 Muscle stimulation (Hz) Muscle strength (torque) Differentiated Engineering Tran

88. Slide 88: Cardiometabolic Program Has Key Ingredients For Success

    © 2024 Scholar Rock, Inc. All rights reserved. 88 Cardiometabolic Program Has Key Ingredients For Success I N S U M M A R Y : A D I F F E R E N T I A T E D A P P R O A C H Regulatory Path Forward FDA guidance supports combination strategy; SRK-439 development has the potential to improve function &

89. Slide 89: Closing Remarks

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Scholar Rock Holding — Investor Day (May 2024) on 6ix