Scholar Rock Holding Corporation · NASDAQ:SRRK
Scholar Rock — Investor Presentation (May 2021)
35 slides from Scholar Rock's investor presentation, May 26, 2021
Slide 1: Deep Insights, Impactful Medicines
Deep Insights,Impactful Medicines May 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: Potential for Another Transformative Year
Gilead fibrosis-focused TGFβ collaboration DRAGON Part A: dose escalation and continued follow-up ApitegromabSpinal Muscular Atrophy (SMA) SRK-181 Immuno-Oncology and Oncology Preclinical/ Platform TOPAZ 12M topline data Planned apitegromab Phase 3 program in SMA by year-end 2021: Potential for Anot
Slide 4: Bringing a Revolutionary Approach to Highly Sought-After Growth Factors
4 Bringing a Revolutionary Approach to Highly Sought-After Growth Factors Implicated in Devastating Diseases Scholar Rock’s Target Growth Factor Precursor (Latent Form) Scholar Rock’s R&D PlatformTransform Medical Practice Pursue important targets with well-validated biology but are difficult to dru
Slide 5: Apitegromab: Transformative Potential Demonstrated in TOPAZ Phase 2 Trial
Apitegromab: Transformative Potential Demonstrated in TOPAZ Phase 2 Trial for Patients with Type 2 and 3 SMA
Slide 6: Apitegromab Positioned to be Next Potential Transformative Therapy for SMA
6 Apitegromab Positioned to be Next Potential Transformative Therapy for Patients Suffering with SMA Spinal Muscular Atrophy (SMA) remains a devastating and debilitating illness despite the availability of SMN upregulatorsTo improve motor function, a muscle-directed approach like apitegromab is need
Slide 7: Spinal Muscular Atrophy Overview
7 Spinal Muscular Atrophy Overview Significant, progressive motor function impairment, many lose ambulation Infantile onset; unable to sit up independently Severe, progressive disabilities and Unable to walk independently Global disease with 30,000-35,000 affected in U.S. and Europe alone TOPAZ* 12-
Slide 8: Apitegromab: Muscle-Directed Therapy Aimed at Complementing SMN Upregulators
Apitegromab: Muscle-Directed Therapy Aimed at Complementing SMN Upregulators 8 Adapted from images courtesy of the SMA Foundation Myostatin is a negative regulator of skeletal muscle growthApitegromab is a fully human, mAb that specifically binds to proforms of myostatin and inhibits myostatin activ
Slide 9: Stage is Set for New Treatment Era
9 Stage is Set for New Treatment Era: Muscle-Directed Therapy + SMN Upregulators Phase 3Trial Design Indication MarketPenetration *As of 1Q21 financial update on 4/22/21; includes patients treated worldwide in post-marketing setting, expanded access program, and clinical trials.**As of 1Q21 financia
Slide 10: Patients Continue to Experience Major Functional Deficits Despite SMN Upregulators
Patients Continue to Experience Major Functional Deficits Despite Availability of Multiple SMN Upregulator Therapies 10 Source: 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
Slide 11: Nusinersen Offers HFMSE Increases Primarily in First Year of Treatment
Non-Ambulatory Type 2/3 SMA: Nusinersen Offers HFMSE Increases Primarily in First Year of Treatment 11 “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 for ba
Slide 12: Plateauing of Nusinersen Effect Post Initial Months of Treatment
Plateauing of Nusinersen Effect Observed Post Initial 15 Months of Treatment in Non-Ambulatory Type 2/3 SMA 12 “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 provide
Slide 13: Apitegromab Phase 2 Trial Design
Apitegromab Phase 2 Trial Design 13 Patients with Type 2 and 3 SMA Ambulatory Type 3 patients (ages 5-21)Apitegromab 20 mg/kg IV Q4W monotherapy or with chronic nusinersen maintenance Key objectives: RHS and Safety at 12 months Non-ambulatory Type 2 patients (ages ≥2) on chronic maintenance nusiners
Slide 14: Baseline Characteristics
Baseline CharacteristicsNusinersen-treated patients well into chronic maintenance phase 14 Non-Ambulatory,Ages 2-6 Non-Ambulatory,Ages 8-19 Ambulatory 20 mg/kg +nusinersen 2 mg/kg +nusinersen Pooled 20 mg/kg +nusinersen 20 mg/kgmonotherapy 20 mg/kg +nusinersen Pooled N 10 10 20 15 11 12 23 Mean age
Slide 15: Non-Ambulatory Cohort (Ages 2-6): Sizable HFMSE Increases
Non-Ambulatory Cohort (Ages 2-6): Sizable HFMSE Increases of Up to 20-points 15 Non-Ambulatory Type 2 SMA(Intent-to-Treat Population) Apitegromab 20 mg/kg + nusinersen (n=8) Apitegromab 2 mg/kg + nusinersen (n=9) Pooled (n=17) Mean change from baseline in HFMSE (95% CI) +7.1 (1.8, 12.5) +5.3 (-1.5,
Slide 16: Non-Ambulatory Cohort (Ages 8-19): Majority Attained Increases in HFMSE
Non-Ambulatory Cohort (Ages 8-19): Majority of Patients Attained Increases in HFMSE Non-Ambulatory Type 2 and Type 3 SMA Apitegromab (20 mg/kg) + nusinersenPer Protocol Population* (n=13) Apitegromab (20 mg/kg) + nusinersenIntent-to-Treat Population (n=14) Mean change from baseline in HFMSE (95% CI)
Slide 17: Safety Results from TOPAZ 12-Month Top-Line Analysis
Safety Results from TOPAZ 12-Month Top-Line Analysis Support Evaluation of Apitegromab in Phase 3 Trial 17 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
Slide 18: Initial Regulatory Strategy Focuses on Non-Ambulatory Patients
18 Initial Regulatory Strategy Focuses on Non-Ambulatory Patients on Background SMN Therapy Global disease with 30,000-35,000 affected in U.S. and Europe alone Apitegromab in non-ambulatory Type 2 and 3 with background SMN upregulators 1 Ambulatory patients Smaller population but high unmet need as
Slide 19: Preliminary Thoughts on Apitegromab Phase 3 Trial Design
19 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 12-month treatment periodApitegromab IV Q4W as add-on to
Slide 20: Additional Opportunities May Be Pursued With Separate Regulatory Strategies
20 Additional Opportunities May Be Pursued With Separate Regulatory Strategies Global disease with 30,000-35,000 affected in U.S. and Europe alone Apitegromab in non-ambulatory Type 2 and 3 with background SMN upregulators 1 Ambulatory patients Smaller population but high unmet need as benefits of S
Slide 21: Majority of Ambulatory Patients Maintained or Improved in RHS Score
Majority of Ambulatory Patients Maintained or Improved in RHS Score from Baseline 21 Ambulatory Type 3 SMA (Intent-to-Treat Population) Apitegromab (20 mg/kg)monotherapy (n=11) Apitegromab (20 mg/kg) + nusinersen (n=12) Pooled (n=23) Mean change from baseline in RHS (95% CI) -0.4 (-3.9, 3.1) -0.3 (-
Slide 22: Additional TOPAZ Data and Analyses Will Further Understanding
22 Additional TOPAZ Data and Analyses Will Further Our Understanding of Apitegromab’s Potential in SMA Exploratory analyses, including patient-level dataAdditional outcome measuresAdditional safety data Plan to present 12-month top-line data and additional analyses at medical congresses in coming mo
Slide 23: SRK-181: Potential Transformative Backbone for Cancer Immunotherapy
23 SRK-181: Potential Transformative Backbone for a New Era ofCancer Immunotherapy
Slide 24: Significant Interest in Potential Role of TGFβ Inhibition in Immuno-Oncology
Significant Interest in Potential Role of TGFβ Inhibition in Immuno-Oncology Nature (online), Feb. 14, 2018. AuthorsWilly Hugo, Jesse M. Zaretsky, Lu Sun, Douglas B. Johnson, Antoni Ribas, Roger S. Lo Volume 165, Issue 1, 24 March 2016, Pages 35-44 July 24, 2020: https://doi.org/10.1038/ s41571-020-
Slide 25: TGFβ1 as Driver of Primary Resistance to Checkpoint Inhibitors
Cancer Genome Atlas RNAseq analysis of >10,000 samples spanning 33 tumor types* Substantial % of solid tumors exhibit immune exclusion Emerging Evidence Implicates TGFβ1 as Driving Primary Resistance to Checkpoint Inhibitors Human Tumor Analyses Reveal TGFβ1 as Most Likely Driver of TGFβ Signaling P
Slide 26: SRK-181: Unique TGFβ1-Selective Approach to Overcoming Checkpoint Inhibitor Resistance
SRK-181: Unique TGFβ1-Selective Approach to Overcoming Checkpoint Inhibitor Resistance 26 Inhibits TGFβ1 pathway - implicated in CPI resistanceHighly selective targeting - avoids inhibiting latent TGFβ2 and TGFβ3 isoformsAimed at increasing therapeutic window – potentially avoids toxicities associat
Slide 27: DRAGON Phase 1 POC Trial to Evaluate SRK-181
DRAGON Phase 1 POC Trial to Evaluate SRK-181’s Ability to Overcome Primary Resistance to Checkpoint Inhibitors NCT04291079 on www.clinicaltrials.gov. 27 Part A Part B Cohort A: non-small cell lung cancer (NSCLC) A1: SRK-181 all-comers A2: SRK-181+anti-PD-(L)1; non-responders to prior anti-PD-(L)1 SR
Slide 28: Potential for Another Transformative Year
Gilead fibrosis-focused TGFβ collaboration DRAGON Part A: dose escalation and continued follow-up ApitegromabSpinal Muscular Atrophy (SMA) SRK-181 Immuno-Oncology and Oncology Preclinical/ Platform TOPAZ 12M topline data Planned apitegromab Phase 3 program in SMA by year-end 2021: Potential for Anot
Slide 29: Appendix
Appendix YR $8 ScholarRock
Slide 30: Guiding Principles for Neuromuscular Indication Selection
Scholar Rock’s Guiding Principles for Neuromuscular Indication Selection Key Characteristics of Spinal Muscular Atrophy (SMA) Younger population Genetic disorder with onset in childhood At least partially intact innervation and no structural muscle abnormalities Partial neural connectivity and atrop
Slide 31: Pharmacokinetic and Pharmacodynamic Data Supportive of Clinically Observed Effects
Dose-proportional and sustained drug exposure following chronic administration of apitegromab Pharmacokinetic and Pharmacodynamic Data are Supportive of Clinically Observed Effects Both 2 mg/kg and 20 mg/kg doses yielded high levels of target engagement (>100-fold increase from baseline)20 mg/kg dos
Slide 32: Inhibition of TGFβ1: Multipronged Approach for Immuno-Oncology
Inhibition of TGFβ1: Multipronged Approach for Immuno-Oncology 32 TGFβ1 Regulatory T cell Tumor Associated Macrophage Cancer Associated Fibroblasts (Stromal cells) Tumor cells TGFβ1 is a key driver of immune system evasion by cancer cells Pathway analysis in patient tumors points to TGFβ1 as major d
Slide 33: TGFβ1 Blockade with SRK-181-mIgG1 Rendered Preclinical Tumor Models Susceptible to Anti-PD1
33 TGFβ1 Blockade with SRK-181-mIgG1 Rendered Preclinical Tumor Models Susceptible to Anti-PD1 Therapy Preclinical data published in Science Translational Medicine. Martin CJ, et al. Sci Transl Med. 2020 Mar 25;12(536):eaay8456. https://scholarrock.com/platform/publications. Melanoma (Cloudman S91)
Slide 34: TGFβ1 Blockade with SRK-181-mIgG1 Rendered Preclinical Tumor Models Susceptible to Anti-PD1
TGFβ1 Blockade with SRK-181-mIgG1 Rendered Preclinical Tumor Models Susceptible to Anti-PD1 Therapy Days after treatment initiation Tumor volume (mm3) Anti-PD1/SRK-181-mIgG1(10 mg/kg QW) Anti-PD1/SRK-181-mIgG1(3 mg/kg QW) 4/14 8/14 Preclinical data published in Science Translational Medicine. Martin
Slide 35: TGFβ1 Isoform Specificity of SRK-181 Improved Preclinical Toxicity Profile
TGFβ1 Isoform Specificity of SRK-181 Improved Preclinical Toxicity Profile Preclinical data published in Science Translational Medicine. Martin CJ, et al. Sci Transl Med 2020 Mar 25;12(536): eaay8456. *Source: Anderton MJ, et al. Induction of heart valve lesions by small-molecule ALK5 inhibitors. To
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