Scholar Rock Holding Corporation · NASDAQ:SRRK
Scholar Rock — Investor Presentation (August 2018)
34 slides from Scholar Rock's investor presentation, Aug 13, 2018
Slide 1: From New Insights to New Medicines
August 2018 From New Insights to New Medicines
Slide 2: Disclaimers
2 Disclaimers Various statements in this presentation concerning Scholar Rock’s future expectations, plans and prospects, including without limitation, Scholar Rock’s expectations regarding its strategy, its product candidate selection and development timing, inclu din g timing for the initiation of
Slide 3: Scholar Rock's Mission
3 Scholar Rock’s Mission Leverage our newly elucidated understanding of growth factor activation to develop highly selective therapies for underserved patients Compelling Strategy • Utilize our proprietary platform to unlock the therapeutic potential of targeting growth factor signaling in the disea
Slide 4: Highly Experienced Leadership Team
4 Highly Experienced Leadership Team ALAN BUCKLER, PHD Chief Scientific Officer NAGESH MAHANTHAPPA, PHD CEO & President ELAN EZICKSON COO & Head, Corporate Development YUNG CHYUNG, MD Chief Medical Officer RHONDA CHICKO, CPA Chief Financial Officer
Slide 5: Well-established Modality (Monoclonal Antibodies)
5 Well - established Modality (Monoclonal Antibodies) Localization of Effect High Selectivity Nature’s Way of Regulating Growth Factor Activity Target Signaling Proteins at the Cellular Level (Based on Scholar Rock’s Structural Biology Insights) Traditional Challenges: • Focused on inhibiting the gr
Slide 6: Nature's Activation Machinery
6 Nature’s Activation Machinery Active form of the growth factor TGF β1 propeptide which forms a “cage” Cage renders the growth factor inactive or “latent” Shi, M., et al. Nature 474, 7351, 343 - 9 (2011) TGF β Superfamily: More than 30 Related Growth Factors that Mediate Diverse Biological Processe
Slide 7: Proprietary Platform to Target Growth Factor Activation
7 Proprietary Platform to Target Growth Factor Activation Design and Purification of Challenging Proteins (e.g. latent growth factor complexes) Proprietary Assays that Recapitulate Nature’s Activation In Vitro Sophisticated Selection Strategies Utilizing Recombinant Antibody Libraries SCHOLAR ROCK D
Slide 8: Robust Pipeline Portfolio
8 Robust Pipeline Portfolio PROGRAM STAGE OF DEVELOPMENT STATUS Target Indication Late - Stage Discovery Preclinical Phase 1 Phase 2 Phase 3 Worldwide Rights Next Anticipated Milestone SRK - 015 Program Latent Myostatin Spinal Muscular Atrophy Phase 1 Trial Ongoing Latent Myostatin Additional Myosta
Slide 9: SRK-015: Inhibitor of Myostatin Activation
SRK - 015: Inhibitor of Myostatin Activation Potential First Muscle - Directed Therapy for SMA
Slide 10: Spinal Muscular Atrophy (SMA): Severe and Debilitating Disorder
10 Spinal Muscular Atrophy (SMA): Severe and Debilitating Disorder Overview Symptoms Treatment Options Rare neuromuscular disorder -------------- A child with SMA is born roughly every day in the U.S. ------------- Caused by mutation or deletion in SMN1 gene leading to loss of motor neurons Debilita
Slide 11: SMN Upregulators Do Not Directly Address Muscle Atrophy
11 Adapted from images that were courtesy of the SMA Foundation SMN Upregulators Do Not Directly Address Muscle Atrophy Mean improvement in HFMSE score experienced by patients with later - onset SMA in the Phase 3 CHERISH clinical trial of nusinersen . 0 20 40 60 80 HFMSE Score at Month 15 Mean Base
Slide 12: SRK-015: Muscle-Directed Approach to Treating SMA
12 SRK - 015: Muscle - Directed Approach to Treating SMA • Myostatin is a genetically - validated, negative regulator of muscle mass expressed in skeletal muscle tissue • There has been high interest from pharma as a potential drug target • Clinical trial results with traditional systemic inhibitors
Slide 13: Optimal Setting for Myostatin Inhibition
13 Optimal Setting for Myostatin Inhibition Key Characteristics of Spinal Muscular Atrophy (SMA) Younger population Genetic disorder with onset in childhood Muscle disease with at least partially intact innervation Incomplete loss of motor neurons Need for increase in fast - twitch muscle fibers Sub
Slide 14: Traditional Approaches Can Raise Significant Safety Concerns
14 Traditional Approaches Can Raise Significant Safety Concerns Activin A GDF11 Myostatin BMP9 • Most inhibitors of active myostatin also inhibit GDF11 and may inhibit other growth factors as well • Antibodies to ActRIIb and ligand trap approaches inhibit signaling of multiple ligands Developmental:
Slide 15: SRK-015: High Selectivity by Targeting Precursor Form of Myostatin
15 SRK - 015: High Selectivity by Targeting Precursor Form of Myostatin Scholar Rock Approach proMyostatin proActivin A proGDF - 11 Myostatin Activin A GDF - 11 SRK - 015 Specific Inhibition of Myostatin Activation Exquisite Selectivity for Myostatin SRK - 015 Inhibition Latent myostatin Latent GDF1
Slide 16: Fast-Twitch Muscle Fibers May Be Preferentially Benefited by SRK-015
16 Fast - Twitch Muscle Fibers May Be Preferentially Benefited by SRK - 015 Vehicle SRK - 015 (3 mg/kg) Biceps Gastrocnemius +18% +22% Healthy Non - Human Primate ( Cyno ) Pronounced Effect on Fast - Twitch Muscle Vehicle SRK - 015 (3 mg/kg) Vehicle SRK - 015 (3 mg/kg) Slow - twitch muscle fibers Fa
Slide 17: SRK-015 Demonstrates Potential Benefits Across SMA Severities
17 SRK - 015 Demonstrates Potential Benefits Across SMA Severities Genetic Model of SMA (“∆7 Mouse”) Demonstrate Improved In Vivo Muscle Force Generation Strength of Plantarflexor Muscle Group SMN upregulator + SRK - 015 SMN upregulator only
Slide 18: SRK-015 Phase 1 Trial Design
18 SRK - 015 Phase 1 Trial Design • Double - blind, placebo - controlled • 3:1 randomization • Single - and multiple - ascending dose Design • Adult healthy volunteers (ages 18 - 55) • Anticipate enrolling ~60 subjects total Subjects • Safety and tolerability of SRK - 015 IV • PK/PD • Immunogenicity
Slide 19: SRK-015 Opportunity in Spinal Muscular Atrophy
19 SRK - 015 Opportunity in Spinal Muscular Atrophy Overall Prevalence of 30,000 - 35,000 in U.S. and Europe Potential to use SRK - 015 in conjunction with current standard of care Potential to use SRK - 015 as monotherapy RELATIVE PREVALENCE AMONG PATIENTS LIVING WITH SMA Type I 14% Type II 51% Typ
Slide 20: Potential Opportunities for SRK-015 in Additional Muscle-Wasting Disorders
20 Examples of Potential Opportunities for SRK - 015 in Additional Muscle - Wasting Disorders Muscle Atrophy due to Partial Denervation Amyotrophic Lateral Sclerosis Duchenne Muscular Dystrophy Incomplete Spinal Cord Injury Identify Next Indication for SRK - 015 in 1H19 Potential for SRK - 015 to Im
Slide 21: Recent Achievements and Upcoming Milestones
21 Recent Achievements and Upcoming Milestones x Orphan Drug Designation granted by FDA x Completed IND - enabling toxicology studies x IND in SMA submitted to FDA in March and cleared in April 2018 x Initiated Phase 1 clinical trial in healthy volunteers in May 2018 x Advanced to multiple - ascendi
Slide 22: TGFβ1: Significant Opportunities in Oncology/Immuno-Oncology and Fibrosis
TGFβ1: Significant Opportunities in Oncology/Immuno - oncology and Fibrosis
Slide 23: TGFβ1 Plays Central Role in Multiple Diseases with Unmet Need
23 TGF β1 Plays Central Role in Multiple Diseases with Unmet Need Organ Fibrosis Myelofibrosis Skin Fibrosis Immuno - Oncology Tumor - Directed Therapy Oncology Fibrosis
Slide 24: Scholar Rock TGFβ1 Activation Inhibitor Demonstrates Selectivity and In Vitro Activity
24 Latent TGF β 1 Multiple concentrations Latent TGF β 2 Latent TGF β 3 Scholar Rock TGF β 1 Activation Inhibitor Demonstrates Selectivity and In Vitro Inhibitory Activity SR - AB1 Binds to Latent TGFβ1 with High Affinity SR - AB1 Shows Dose - Dependent Inhibition of TGFβ1 Activity SR - AB1 Control
Slide 25: Selective Inhibitor Avoids Cardiac Valve Toxicity Induced by Pan-TGFβ Inhibitors
25 Heart Example, microscopic findings Test article PBS (control) SR - AB1 pan - TGF β AB* Legend: Dose (mg/kg) 3 30 100 100 Animals/group 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 Unremarkable: Minimal: Myocardium degeneration/necrosis x Slight: Hemorrhage, atrium x Moderate: Hemorrhage, my
Slide 26: Inhibition of TGFβ1: Multipronged Approach for Immuno-Oncology
26 Inhibition of TGF β 1: Multipronged Approach for Immuno - Oncology TGF β 1 is a key driver of immune system evasion by cancer cells TGF β 1 Regulatory T cell Tumor Associated Macrophage Cancer Associated Fibroblasts (Stromal cells) Nature (on - line), Feb. 14, 2018 • Pathway analysis points to TG
Slide 27: TGFβ is the Predominant Isoform in Most Human Tumors
27 TGF β 1 is the Predominant Isoform in Most Human Tumors TGFB1 TGFB2 TGFB3 bladder urothelial carcinoma head & neck squamous cell carcinoma kidney clear cell carcinoma kidney papillary cell carcinoma liver hepatocellular carcinoma lung adenocarcinoma skin cutaneous melanoma stomach adenocarcinoma
Slide 28: Inhibition of Latent TGFβ1 Activation Suppresses Treg Activity
28 SR - AB1.2 suppresses mouse Treg Activity In Vivo T cell Transfer Colitis Model Immuno - Oncology: Inhibition of Latent TGF β 1 Activation Suppresses Treg Activity SR - AB1.2 suppresses Human Treg Activity Ex Vivo Human Treg Suppression Assay
Slide 29: TGFβ is a Central Driver of Fibrotic Disease
29 TGF β is a Central Driver of Fibrotic Disease Acute Kidney Fibrosis Model (mouse UUO): Gene Expression ‡ 1D11 is an inhibitor of all three isoforms of mature TGF β PAI - 1 (Plasminogen Activator Inhibitor 1) CTGF (Connective Tissue Growth Factor) TGF β1 (Transforming Growth Factor beta 1)
Slide 30: Inhibition of Latent TGFβ1 Activation Prevents Fibrosis
30 Picrosirius red stain Blue segmentation mask Degree of Fibrosis Á ͳܦͳͳ ݅ݏ ܽ݊ ݄ܾ݅݊݅݅ݐݎ ݂ ݈݈ܽ ݐ݄ݎ݁݁ ݅ݏ݂ݎ݉ݏ ݂ ݉ܽݐݑݎ݁ ܶܩܨߚ Inhibition of Latent TGF β 1 Activation Prevents Fibrosis Acute Kidney Fibrosis Model (mouse UUO): Histomorphometry
Slide 31: Targeting Latent TGFβs Creates Multiple Handles For Selectivity
31 Targeting Latent TGF β s Creates Multiple “Handles” For Selectivity Context - Dependent Inhibition of TGF β 1 LRRC33 presents TGF β on macrophages Latent TGF - β GARP T reg Integrin expressing cell GARP presents TGF β on T regs Latent TGF - β LRRC33 Macrophage Integrin expressing cell LTBP1 & 3 p
Slide 32: Recent Achievements and Upcoming Milestones
32 Recent Achievements and Upcoming Milestones x Observed inhibition of TGF β 1 activation in vitro and immunomodulatory and anti - fibrotic activity in multiple in vivo disease models x Completed 28 - day pilot toxicology study of our leading antibody x Have not observed any drug - related toxicity
Slide 33: Recent Achievements and Upcoming Milestones
33 □ Initiate Phase 2 proof - of - concept study of SRK - 015 in patients with later - onset SMA in 1Q19 □ Identify next indication for SRK - 015 in 1H19 □ Nominate product candidate and lead indication in TGFβ1 program by the end of 1H19 □ Top - line results from Phase 2 proof - of - concept study
Slide 34: Building for Success
34 Building for Success Robust Pipeline Compelling Strategy Clear Mission Experienced Management and Board Continued Execution
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