Scholar Rock Holding Corporation · NASDAQ:SRRK

Scholar Rock — 42nd Annual J.P. Morgan Healthcare Conference (January 2024)

32 slides from Scholar Rock's conference presentation, Jan 8, 2024

  1. Slide 1: Advancing New Possibilities for Patients

    © 2024 Scholar Rock, Inc. All rights reserved. Advancing New Possibilities for Patients 42nd ANNUAL J.P. MORGAN HEALTHCARE CONFERENCE JANUARY 9, 2024

  2. Slide 2: Forward-Looking Statements

    © Scholar Rock, Inc. All rights reserved. 2024. Forward-Looking Statements 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 pro

  3. Slide 3: Our Mission

    3 TGFβ=Transforming growth factor-beta. SMA=Spinal muscular atrophy *Christopher is a participant in the TOPAZ and ONYX clinical trials. OUR MISSION To discover, develop, and deliver life-changing therapies by harnessing cutting-edge science to create new possibilities for people living with serious

  4. Slide 4: Building a Fully Integrated Therapeutics Company

    4 Building a Fully Integrated Therapeutics Company SMA=Spinal muscular atrophy; EMA=European Medicines Agency; FDA=United States Food and Drug Administration; R&D=research and development. Apitegromab in SMA Potential therapy in Ph 3 designed to improve motor function to help address remaining unmet

  5. Slide 5: Selectivity Drives Success: Targeting Latent Growth Factors

    Traditional Target “mature” active growth factor Scholar Rock’s Target Latent Growth Factor Our Approach S e l e c t i v i t y D r i v e s S u c c e s s Industry-leading antibody design and protein engineering to selectively target latent growth factors Optimized for efficacy and mitigates off-targe

  6. Slide 6: Advancing a Robust Pipeline with Our Differentiated Platform

    Latent Myostatin SPINAL MUSCULAR ATROPHY Apitegromab CARDIOMETABOLIC DISORDERS Apitegromab in Obesity* SRK-439 (novel antimyostatin antibody) Latent TGFβ-1 IMMUNO-ONCOLOGY SRK-181 (selective context-independent, anti-latent TGFβ-1) FIBROSIS Selective context-dependent (LTBP1 & LTBP3) anti-latent TGF

  7. Slide 7: Antimyostatin Program: Apitegromab in Spinal Muscular Atrophy

    © 2024 Scholar Rock, Inc. All rights reserved. Antimyostatin Program: Apitegromab in Spinal Muscular Atrophy

  8. Slide 8: Hallmarks of SMA

    8 Hallmarks of SMA Motor Neuron Loss and Muscle Atrophy Leads to Progressive Muscle Weakness SMA=Spinal muscular atrophy; SMN=Survival motor neuron. Hua Y, et al. Nature. 2011;478(7367):123-6. Figure adapted from: SMA Foundation Overview. http://www.smafoundation.org/wp-content/uploads/2012/03/SMA-O

  9. Slide 9: SMA Leads to Deterioration in Essential Muscle Function

    SMA Leads to Deterioration in Essential Muscle Function Quotes are from patient advocates who participated in 2022 Cure SMA FDA Patient-Led Listening Session and not from the pictured individuals. Summary of the listening session can be found on the FDA website at https://www.curesma.org/cure-sma-ho

  10. Slide 10: SMA Today: More Patients Screened and Treated

    10 SMA Today: More Patients Screened and Treated CHF=Swiss franc; LTM=last twelve months; SMA=Spinal muscular atrophy; SMN=Survival motor neuron; WW=worldwide. Cure SMA 2022 Report: 9042022_State-of-SMA_vweb.pdf (curesma.org) Lally et al. Indirect estimation of the prevalence of spinal muscular atro

  11. Slide 11: Muscle-Targeted Therapy: A New Treatment Frontier

    11 Muscle-Targeted Therapy: A New Treatment Frontier *Percentages represent percent of patients who named these unmet needs when asked, “What are your most significant current unmet needs that you hope new therapies would address?” HFMSE=Hammersmith Functional Motor Scale-Expanded. 1. Mercuri E et a

  12. Slide 12: Apitegromab Offers Significant Potential to Address Unmet Needs

    12 Apitegromab Offers Significant Potential to Address Unmet Needs * 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. S P I N A L M U S C U L A R A T R O P H Y Apitegroma

  13. Slide 13: TOPAZ Functional Outcomes Over Time

    © 2024 Scholar Rock, Inc. All rights reserved. Time (weeks) No. of observations N = 35; Baseline mean age=7.3 |Time on SMN Rx=24.1m PRO=patient reported outcomes; HFMSE=Hammersmith Functional Motor Scale Expanded; OC=observed case; PEDI-CAT=Pediatric Evaluation of Disability Inventory Computer Adapt

  14. Slide 14: TOPAZ: Well Tolerated Safety Profile & Low Discontinuation Rate

    14 TOPAZ Over 36 Months Well Tolerated Safety Profile & Low Discontinuation Rate S P I N A L M U S C U L A R A T R O P H Y RIGHT TIME L a t e n t F o r m M y o s t a t i n RIGHT TARGE T Crawford et al., Cure SMA 2023 * Excludes patients on monotherapy >90% of patients on combination therapy remained

  15. Slide 15: SAPPHIRE Phase 3 Design is Optimized by Insights from TOPAZ

    15 SAPPHIRE Phase 3 Design is Optimized by Insights from TOPAZ HFMSE=Hammersmith Functional Motor Scale Expanded. TOPAZ Learnings SAPPHIRE Design Elements Phase 3 SAPPHIRE Trial Registrational trial with topline 12-month data readout expected in Q4 2024 S T U D Y P O P U L A T I O N Substantial HFMS

  16. Slide 16: Apitegromab: Potential to Maximize Outcomes for People Living with SMA

    16 Apitegromab: Potential to Maximize Outcomes for People Living with Spinal Muscular Atrophy (SMA) Apitegromab is an investigational drug candidate being evaluated for the treatment of spinal muscular atrophy (SMA). Apitegromab has not been approved for any use by the FDA or any other regulatory ag

  17. Slide 17: Expanding to Benefit More People Living with SMA

    17 Expanding to Benefit More People Living with SMA *Subject to regulatory approval. SMA=Spinal muscular atrophy; Sub-Q=Subcutaneous S P I N A L M U S C U L A R A T R O P H Y WHERE WE ARE WHERE WE WERE WHERE WE ARE GOING P H A S E 2 12-Month COMPLETE 24-Month EXTENSION COMPLETE 36-Month EXTENSION CO

  18. Slide 18: Next Horizon Antimyostatin Program: Cardiometabolic Disorders

    © 2024 Scholar Rock, Inc. All rights reserved. Next Horizon Antimyostatin Program: Cardiometabolic Disorders

  19. Slide 19: Obesity is Recognized as a Top Global Public Health Issue

    Obesity is Recognized as a Top Global Public Health Issue 1. The World Obesity Foundation, World Obesity Atlas 2022; 2. Ward ZJ, Bleich SN, Long MW, Gortmaker SL (2021) Association of body mass index with health care expenditures in the United States by age and sex. PLoS ONE 16(3): e0247307. BY 2030

  20. Slide 20: Loss of Lean Muscle Significant with GLP-1 RA Therapy

    20 Loss of Lean Muscle Significant with GLP-1 RA Therapy Lean muscle is essential to healthy metabolic function GLP-1 RA=Glucagon-like peptide-1 receptor agonists. 1. Muller TD, et al Anti-obesity drug discovery: advances and challenges. Nature Reviews Drug Discovery 2022; 21, 201–223; 2. Wilding JP

  21. Slide 21: Maintaining Muscle is Important for Healthy Weight Loss

    21 Maintaining Muscle is Important for Healthy Weight Loss GLP-1 RA=Glucagon-like peptide-1 receptor agonist. 1. Aristizabal JC, Freidenreich DJ, Volk BM, et al. Effect of resistance training on resting metabolic rate and its estimation by a dual-energy X-ray absorptiometry metabolic map. Eur J Clin

  22. Slide 22: Our Antibodies Selectively Inhibit Activation of Myostatin

    22 Our Antibodies Selectively Inhibit Activation of Myostatin ActRIIB=Activin Receptor IIB; FSH=Follicle stimulating hormone; GDF-11=Growth and differentiation factor 11; TGF-β=Transforming growth factor-beta. 1. Oh SP & Li E. Genes Dev. 1997 Jul 15;11(14):1812-26; 2. Garito T, et al. Clin Endocrino

  23. Slide 23: SRK-439: Novel Myostatin Inhibitor

    23 SRK-439: Novel Myostatin Inhibitor Preclinical candidate in development with potential to address muscle loss associated with weight loss mTLL2 IC50: Inhibitory concentration at 50% as measure of in vitro potency of the antibody in its ability to inhibit the activation of latent myostatin by its

  24. Slide 24: SRK-439 Reversed Lean Mass Loss and Enhanced Fat Mass Loss with Semaglutide

    24 SRK-439 Reversed Lean Mass Loss and Enhanced Fat Mass Loss Induced by Semaglutide Treatment† † In Mouse Diet Induced Obesity (DIO) Model. Figure showed the effects of increasing doses of SRK-439 in combination with semaglutide on lean mass (left panel) and fat mass (right panel) in DIO mouse mode

  25. Slide 25: Opportunity for Safe, Durable Weight Loss: Add Antimyostatin to GLP-1 RA

    25 Opportunity for Safe, Durable Weight Loss: Add Highly Selective Antimyostatin to GLP-1 RA to Preserve Lean Muscle GLP-1 RA=Glucagon-like peptide-1 receptor agonist. 1. Pirruccello-Straub M et al. Blocking extracellular activation of myostatin as a strategy for treating muscle wasting. Sci Reports

  26. Slide 26: Expedite Cardiometabolic Program with Ph2 Proof-of-Concept Study of Apitegromab in Obesity

    26 Expedite Cardiometabolic Program with Ph2 Proof-of-Concept Study of Apitegromab in Obesity * Anticipated milestones. Creates additional anticipated milestones in next 18-24 months O B E S I T Y 2024 2025 Spinal Muscular Atrophy Apitegromab SAPPHIRE Topline Q4* Potential Commercial Launch* Cardiom

  27. Slide 27: Key Accomplishments and 2024 Strategic Priorities

    Building on this success, in 2024 we are focused on 27 Key Accomplishments and 2024 Strategic Priorities 2023 ACCOMPLISHMENTS COMPLETED SAPPHIRE enrollment EXPANDED antimyostatin program into cardiometabolic disorders SUCCESSFUL $98M public offering, extending projected runway into second half of 20

  28. Slide 28: Appendix

    © 2024 Scholar Rock, Inc. All rights reserved. Appendix

  29. Slide 29: Proven Expertise in Anti-Latent TGFB & Antimyostatin Inhibition

    29 Proven Expertise in Anti-Latent TFGB & Antimyostatin Inhibition * Contingent upon receipt of regulatory approval. IND=Investigational new drug; SMA=Spinal muscular atrophy; LTBP1=Latent transforming growth factor beta binding protein 1; LTBP3=Latent transforming growth factor beta binding protein

  30. Slide 30: SRK-439 Maintained Lean Mass When Combined with GLP-1 RA Therapy

    -10 -5 0 5 10 -60 -40 -20 0 20 40 60 30 SRK-439 Maintained Lean Mass When Combined with GLP-1 RA Therapy† ANOVA=Analysis of variance; GLP-1 RA=Glucagon-like peptide-1 receptor agonist; IgG=Immunoglobulin G; qNMR=Quantitative nuclear magnetic resonance. † In Mouse Diet Induced Obesity (DIO) Model. Fi

  31. Slide 31: SRK-181: Targeting Latent TGFB1 to Overcome Immunotherapy Resistance

    SRK-181: Targeting Latent TGFB1 to Overcome Immunotherapy Resistance PD-1=Programmed cell death ligand 1; TGFβ=Transforming growth factor-beta; ccRCC=Clear cell renal cell carcinoma 1.Sumanta Kumar Pal et al. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell

  32. Slide 32: Promising Anti-tumor Activity in Heavily Pretreated ccRCC Patients

    32 Promising Anti-tumor Activity in Heavily Pretreated ccRCC Patients; Biomarker Data Supports Proof of Mechanism Across Multiple Tumor Types ccRCC=Clear cell renal cell carcinoma Data cutoff August 29, 2023 CD8 Stain – Melanoma Pre-Treatment Continued Tolerability & Promising Anti-Tumor Activity in

Scholar Rock Holding — 42nd Annual J.P. Morgan Healthcare Conference (January 2024) on 6ix