Scholar Rock Holding Corporation · NASDAQ:SRRK
Scholar Rock — Investor Presentation (January 2020)
34 slides from Scholar Rock's investor presentation, Jan 13, 2020
Slide 1: Deep Insights Impactful Medicines
January 2020 Deep Insights Impactful 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: Our Purpose
3 Our Purpose Relentlessly focused on seeing new possibilities in validated biologies and antibody technologies to allow us to move with speed and urgency to deliver transformative medicines to patients with devastating diseases Differentiated Pipeline Portfolio • Two lead product candidates, SRK -
Slide 4: Differentiated Approach to Highly Sought After Growth Factors Implicated in Devastating Diseases
4 Differentiated Approach to Highly Sought After Growth Factors Implicated in Devastating Diseases Scholar Rock’s Target Growth Factor Precursor (Latent Form) Targeting the activation of growth factor precursors to : • Optimize potency and selectivity • Localize effect Growing number of preclinical
Slide 5: 2019: Year of Execution and Progress
5 • Initiated and completed enrollment in TOPAZ Phase 2 proof - of - concept trial - 3 cohorts of patients with Type 2 and Type 3 SMA • Announced compelling preliminary PK/PD data from TOPAZ trial • Presented positive data from Phase 1 healthy volunteer trial 2019: Year of Execution and Progress Acc
Slide 6: 2020/2021: Transformative Years with Multiple Clinical Read-Outs
6 2020/2021: Transformative Years with Multiple Clinical Read - Outs 2H20 4Q20 - 1Q21 Mid - 2020 1Q20 Initiation of SRK - 181 Phase 1 POC trial • Two part trial with dose escalation (Part A) and dose expansion cohorts (Part B) • Patients with locally advanced or metastatic solid tumors • Exhibit pri
Slide 7: Building Differentiated Pipeline; Pairing Revolutionary Approach with Proven Modality
7 Building Differentiated Pipeline; Pairing Revolutionary Approach with Proven Modality SRK-015 (Pro/Latent Myostatin) Spinal Muscular Atrophy (SMA) Interim Efficacy and Safety Results Mid-2020 SRK-015 Myostatin-Related Disorders Identify Next Indication in 2020 SRK-181 (Latent TGFβ1 Context Indepen
Slide 8: SRK-181: Potential Transformative Backbone for a New Era of Cancer Immunotherapy
SRK - 181: Potential Transformative Backbone for a New Era of Cancer Immunotherapy
Slide 9: Human Tumor Analyses Reveal TGFβ as Key Determinant of Primary Resistance to Checkpoint Inhibitor Therapies
9 Human Tumor Analyses Reveal TGF β as Key Determinant of Primary Resistance to Checkpoint Inhibitor (CPI) Therapies Why do nearly 80% † of patients not respond to CPIs ? Clinically - derived rationale points to significant opportunity to increase checkpoint therapy responses TGF β1 creates “immune
Slide 10: Implicating TGFβ as the Resistance Culprit and Selecting Preclinical Models
10 Implicating TGF β 1 as the Resistance Culprit and Selecting Preclinical Models with Clinically Relevant Features Matching syngeneic mouse tumor models to human tumor biology †† • Immune exclusion • Minimal or no response to anti - PD - (L)1 • High TGF β 1 over TGF β 2/3 expression • Evidence for
Slide 11: Strong preclinical data shows potential of SRK-181 in overcoming primary resistance to checkpoints
11 Strong preclinical data shows potential of SRK - 181 in overcoming primary resistance to checkpoints • ~80% of patients with metastatic solid tumors do not respond to CPIs † • Strong human translational data and preclinical models implicate TGFβ as key culprit in primary resistance to CPIs † † •
Slide 12: TGFβ Blockade with SRK-181-mIgG1 Rendered Preclinical Tumor Models Susceptible to Anti-PD1 Therapy
12 TGF β 1 Blockade with SRK - 181 - mIgG1 Rendered Preclinical Tumor Models Susceptible to Anti - PD1 Therapy Preclinical data shown above as presented at American Association of Cancer Research (AACR) Annual Meeting (April 2019) Cloudman S91 melanoma model: Combination treatment led to tumor regre
Slide 13: Anti-PD1/SRK-181-mIgG1 led to increase in CD8+ cells
13 Anti - PD1/SRK - 181 - mIgG1 (10 mg/kg) led to increase in CD8+ cells Anti - PD1 SRK - 181 - mIgG1 Combination Therapy Enabled Infiltration and Expansion of CD8 + T cells Preclinical data shown above as presented at American Association of Cancer Research (AACR) Annual Meeting (April 2019) Anti -
Slide 14: TGFβ1 Isoform Specificity of SRK-181 Improved Preclinical Toxicity Profile
14 TGFβ1 Isoform Specificity of SRK - 181 Improved Preclinical Toxicity Profile • Cardiac findings were exhibited in animals dosed with an pan - TGF β antibody or LY2109761 (inhibitor of ALK5, common TGF β receptor kinase) as expected based on published data † • SRK - 181 exposure reached 2,300 µg/m
Slide 15: Phase 1 Trial to Evaluate SRK-181's Ability to Overcome Primary Resistance to CPIs
15 Phase 1 Trial to Evaluate SRK - 181’s Ability to Overcome Primary Resistance to CPIs Phase 1 Proof - of Concept Trial SRK - 181: potent and selective inhibitor of TGF β 1 activation • Evaluate as a cancer immunotherapy in combination with anti - PD - (L)1 antibodies • Patients with locally advanc
Slide 16: SRK-181 Has Potential to Increase Response to CPIs Through Clinically Relevant Resistance Pathway
16 SRK - 181 Has Potential to Increase Response to CPIs Through Clinically Relevant Resistance Pathway † Source: Company information, Wall Street research, Evaluate Pharma †† Source: Carretero - Gonzalez et al. (2018) Oncotarget 9:8706 - 8715 $22.0 $26.7 $31.1 $35.1 $39.0 $42.4 2019 2020 2021 2022 2
Slide 17: SRK-015: Potential First Muscle-Directed Therapy for Spinal Muscular Atrophy
SRK - 015: Potential First Muscle - Directed Therapy for Spinal Muscular Atrophy
Slide 18: Significant Unmet Need Remains Despite Current Therapies
18 Significant Unmet Need Remains Despite Current Therapies 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 Baseline Score Mean Improvement with nusinersen Unmet Medical Need
Slide 19: SRK-015: Selective Inhibitor of Latent Myostatin Activation
19 SRK - 015: Selective Inhibitor of Latent Myostatin Activation • Fully human mAb • Half - life of 23 - 33 days • Orphan Drug Designation for SMA granted by FDA and EC • Strong patent portfolio: ‒ US Patent 9,758,576 covers mAbs that inhibit the activation of myostatin precursor (expiry in 2034) ‒
Slide 20: Treatment of SMNΔ7 Mouse Models Show Improvement in Muscle Strength
20 Treatment of SMN Δ 7 Mouse Models Show Improvement in Muscle Strength *muSRK - 015P is the parental clone of SRK - 015 on a mouse IgG1 framework Preclinical data published Nov 2018: Long, K., O’Shea, K., Khairallah, R., et al. Specific Inhibition of Myostatin Activation is Beneficial in Mouse Mod
Slide 21: Preliminary TOPAZ Biomarker Data Provide First Demonstration of Target Engagement in Patients with SMA
21 Preliminary TOPAZ Biomarker Data Provide First Demonstration of Target Engagement in Patients with SMA Robust Target Engagement Observed • ~100 - fold increases in serum latent myostatin levels following single 20 mg/kg dose in all cohorts • Confirms presence of latent myostatin in patients with
Slide 22: SRK-015 Phase 2 Trial Design
22 SRK - 015 Phase 2 Trial Design Cohort 1 Cohort 3 Design Patients • N= 20; ages 5 - 21 • Open - label, single - arm • 20 mg/kg SRK - 015 IV Q4W • 12 - month treatment period • Ambulatory Type 3 SMA • Receiving treatment with approved SMN upregulator or as monotherapy Cohort 2 • N= 15; ages 5 - 21
Slide 23: SRK-015 Opportunity in Spinal Muscular Atrophy
23 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 SMN upregulators Potential to use SRK - 015 as monotherapy or in conjunction with SMN upregulators Lally et al, Orphanet Journal of Rare Disease
Slide 24: Building Differentiated Pipeline Through Highly Productive Platform
Building Differentiated Pipeline Through Highly Productive Platform
Slide 25: Proprietary Platform to Target Latent Growth Factor Activation
25 Proprietary Platform to Target Latent 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 SCHOLA
Slide 26: Strategic collaboration focused on fibrosis
26 Strategic collaboration focused on fibrosis Gilead has exclusive options to license worldwide rights to product candidates from 3 TGFβ programs: • Inhibitors that target activation of latent TGFβ1 • Inhibitors that selectively target activation of latent TGFβ1 localized to extracellular matrix •
Slide 27: Fibrosis Partnership with Gilead Advances with Achievement of First Milestone
27 Fibrosis Partnership with Gilead Advances with Achievement of First Milestone Upfront cash and equity investment: $80 million* One - time preclinical milestone: $25 million (achieved end of 2019) Additional milestones across 3 programs: Up to $1,425 million High single - to low double - digit tie
Slide 28: Potential New Approach for Iron-Restricted Anemias
28 Potential New Approach that Directly Addresses the Underlying Pathobiology of Iron - Restricted Anemias BMP6 RGMc BMP Receptor SMAD 1/5/8 SMAD 4 P Hepcidin BMP6 Genetically validated pathway of iron regulation in humans Adapted from Crielaard et al , Nature Reviews , 2017 Antibodies resulted in i
Slide 29: Upcoming Key R&D Milestones
29 Upcoming Key R&D Milestones • Interim efficacy and safety results from SRK - 015 TOPAZ Phase 2 trial in mid - 2020 ‒ All 3 fully enrolled cohorts with 6 months of treatment exposure • Top - line results (12 months) from SRK - 015 TOPAZ trial in 4Q20 - 1Q21 ‒ Patients are eligible to continue trea
Slide 30: Appendix
Appendix SCHOLAR ROCK
Slide 31: TGFβ Blockade with SRK-181-mIgG1 Rendered Preclinical Tumor Models Susceptible to Anti-PD1 Therapy
31 TGF β 1 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) SRK - 181 - mIgG1* (10 mg/kg QW) 0/13 4/14 8/14 Ant
Slide 32: Traditional Approaches Can Raise Significant Safety Concerns
32 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 GDF11 Deletion
Slide 33: To Date Demonstrates Proof-of-Mechanism of First Ever Approach to Targeting Latent Myostatin
33 To Date Demonstrates Proof - of - Mechanism of First Ever Approach to Targeting Latent Myostatin Preclinical and clinical evidence consistent thus far; TOPAZ interim efficacy/safety results mid - 2020 SMN Δ 7 Mouse Models TOPAZ Phase 2 Trial Prelim PK/PD Presence of latent myostatin target Confir
Slide 34: Later-Onset SMA: High Unmet Need to Improve Motor Function
34 Later - Onset SMA: High Unmet Need to Improve Motor Function Nusinersen CHERISH Trial in Later - Onset SMA Source: Mercuri, E. et.al. Nusinersen versus Sham Control in Later - Onset Spinal Muscular Atrophy, N Engl J Med 2018; 378:625 - 635 Nusinersen (N=66) Control (N=34) Change from Baseline to
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