Scholar Rock Holding Corporation · NASDAQ:SRRK
Scholar Rock — Investor Presentation (June 2019)
40 slides from Scholar Rock's investor presentation, Jun 24, 2019
Slide 1: Disclaimers
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, including timing for the initiation of and
Slide 2: A Novel Approach to Targeting Growth Factor Signaling
A Novel Approach to Targeting Growth Factor Signaling Traditional approaches to targeting growth factors have been limited by: • • • Structural similarities Overlapping sets of related receptors Diverse and overlapping physiological roles Scholar Rock’s novel approach: • • • Targeting signaling prot
Slide 3: Robust Pipeline Portfolio
Robust Pipeline Portfolio End of 2019 Biotech, Inc 4 *CBTs = checkpoint blockade therapies Target / Program Indication Discovery / Early Preclinical Preclinical Phase 1 Phase 2 Rights / Partner Next Anticipated Milestone INTERNAL PROPRIETARY PROGRAMS Pro/Latent Myostatin SRK-015 Spinal Muscular Atro
Slide 4: Summary
Summary 5 Market cap $450-$500 million Cash, cash equivalents, and marketable securities ~$160 million as of March 31, 2019 Use of proceeds To fund research and development activities for planned SRK-181 Phase 1 proof of concept clinical trial in patients with solid tumors, SRK-015 Phase 3 readiness
Slide 5: Scholar Rock Achievements Since IPO
Scholar Rock Achievements Since IPO Executed strategic fibrosis collaboration with GILD -$80M upfront ($50M cash and $30M equity at $30.60/share). Up to $1.45B in potential milestones. EC granted Orphan Medicinal product designation for SRK-015 in SMA Presented additional preclinical data at AACR Tr
Slide 6: Upcoming Key R&D Milestones
Upcoming Key R&D Milestones Initiate Phase 2 SMA proof-of-concept trial by the end of 1Q19 Commence patient dosing in Phase 2 SMA proof-of-concept trial in 2Q19 Present final Phase 1 results at Cure SMA Annual Conference being held June 28-July 1, 2019 Announce Phase 2 trial read-outs: •Preliminary
Slide 7: SRK-015: Inhibitor of Myostatin Activation
SRK-015: Inhibitor of Myostatin Activation Potential First Muscle-Directed Therapy for SMA
Slide 8: SRK-015: Highly Specific Inhibitor of Latent Myostatin
SRK-015: Highly Specific Inhibitor of Latent Myostatin • Myostatin is a genetically-validated, negative regulator of muscle mass expressed in skeletal muscle tissue Vertebrates lacking the myostatin gene are healthy and display increased muscle mass and strength • 9 Differentiated approach with SRK-
Slide 9: SRK-015 Opportunity in Spinal Muscular Atrophy
SRK-015 Opportunity in Spinal Muscular Atrophy Overall Prevalence of 30,000-35,000 in U.S. and Europe Relative Prevalence Among Patients Living With SMA Type I: • Infant-onset; often fatal Focus of Phase 2 Trial Type II and non-ambulatory type III: • • Later-onset but still early childhood Severe de
Slide 10: Significant Unmet Need Remains Despite Current Therapies
Significant Unmet Need Remains Despite Current Therapies Muscle Function in SMA (Human) Hammersmith Functional Motor Scale Expanded (HFMSE) 80 SMN Upregulator Therapies Muscle-Directed Therapies (SRK-015) Total Possible HFMSE Score of 66 60 Unmet Medical Need for Functional Improvement with Muscle-D
Slide 11: SRK-015 Preclinical and Phase 1 Data Support Evaluation in SMA
SRK-015 Preclinical and Phase 1 Data Support Evaluation in SMA Preclinical and translational data support myostatin as a drug target in SMA • • • Confirmed presence of target in disease setting Achieved multi-fold increase in serum latent myostatin levels indicating target engagement Treatment of SM
Slide 12: SRK-015 Target Profile in SMA
SRK-015 Target Profile in SMA GOALS EVIDENCE TO DATE Translational/preclinical data support myostatin as a drug target in SMA Preclinical data demonstrate potential for substantial increases in muscle strength Phase 1 PD data demonstrate SRK-015 can successfully engage the target in a durable fashio
Slide 13: SRK-015 Phase 2 Trial Design
SRK-015 Phase 2 Trial Design Co h o r t 2 Co h o r t 1 Co h o r t 3 • Double-blind, randomized (1:1) Design • 12-month treatment period Subjects Primary Objectives HFMSE – Hammersmith Functional Motor Scale Expanded; RHS – Revised Hammersmith Scale 14 •Safety •Mean change from baseline in HFMSE •Saf
Slide 14: SRK-015: Path to Top-Line Results in SMA
SRK-015: Path to Top-Line Results in SMA 1Q19 4Q20-1Q21 2Q19 End of 2019 1H 2020 Initiated trial Commenced patient dosing Preliminary PK/PD data from subset of patients Top-line results Interim efficacy and safety analysis by cohort - Start-up activities, including contracts and IRB submissions with
Slide 15: TGFβ1: Significant Opportunities in Oncology/Immuno-oncology and Fibrosis
TGF1: Significant Opportunities in Oncology/Immuno-oncology and Fibrosis
Slide 16: TGFβ1 Plays Central Role in Multiple Diseases with Unmet Need
TGF1 Plays Central Role in Multiple Diseases with Unmet Need Immuno-Oncology Tumor-Directed Therapy Oncology Myeloproliferative Disorders Upfront cash and equity investment: $80 million* One-time preclinical milestone: $25 million Additional milestones across 3 programs: Up to $1,425 million High si
Slide 17: Inhibition of TGFβ1: Multipronged Approach for Immuno-Oncology
Inhibition of TGF1: Multipronged Approach for Immuno-Oncology Nature (on-line), Feb. 14, 2018 TGF1 is a key driver of immune system evasion by cancer cells Regulatory T cell TGF1 Tumor Associated Macrophage Cancer Associated Fibroblasts (Stromal cells) Tumor cells 18 •Pathway analysis points to TGF1
Slide 18: Renewed Industry Interest in Potential Role of TGFβ Inhibition in Immuno-Oncology
Renewed Industry Interest in Potential Role Inhibition in Immuno-Oncology of TGF Feb. 5, 2019 “GSK and Merck KGaA, Darmstadt, Germany announce global alliance to jointly develop and commercialise M7824, a novel immunotherapy with potential in multiple difficult-to-treat cancers” June 10, 2019 “Merck
Slide 19: TGFβ1 is the Predominant Isoform in Most Human Tumors
TGF1 is the Predominant Isoform in Most Human Tumors The Cancer Genome Atlas RNAseq analysis: >10,000 samples spanning 33 tumor types T G FB 1 T G FB 2 T G FB 3 k idney c lear c ell c ar c inom a s c a le ( % o f p at ie n t s a m p l e s ( + ) f o r T G F b i s o f o r m ) 100 80 c er v ic al & end
Slide 20: TGFβ1 Blockade with SRK-181-mIgG1 Rendered Tumor Models Susceptible to Anti-PD1
TGF1 Blockade with SRK-181-mIgG1 Rendered Preclinical Tumor Models Susceptible to Anti-PD1 Therapy Bladder Cancer Melanoma Anti-PD1 (10 mg/kg BIW) SRK-181-mIgG1 (30 mg/kg QW) SRK-181-mIgG1* (10 mg/kg QW) Anti-PD1 (10 mg/kg BIW) Endpoint 3/12 0/12 Responders 0/12 0/13 Anti-PD1/ SRK-181-mIgG1 (30 mg/k
Slide 21: Inhibiting TGFβ1 Alone Sensitized TGFβ1/3-Expressing Breast Cancer Model
Inhibiting TGF1 Alone Was Sufficient to Sensitize Preclinical TGF1/3-Expressing Breast Cancer Model Control Anti-PD1 (10 mg/kg BIW) Endpoint Responders 0/9 0/9 Anti-PD1/ SRK-181-mIgG1 (10 mg/kg QW) SRK-181-mIgG1* (10 mg/kg QW) 0/10 5/10 Days after treatment initiation Preclinical data shown above as
Slide 22: SRK-181-mIgG1 Combined with Anti-PD1 Led to Survival Benefit
SRK-181-mIgG1† Combined with Anti-PD1 Therapy Led to Significant Survival Benefit in Preclinical Tumor Models MBT-2 Bladder Cancer Model Cloudman S91 Melanoma Model EMT6 Breast Cancer Model ** ** * *** *** Days after treatment initiation Days after treatment initiation Days after treatment initiatio
Slide 23: SRK-181-mIgG1 Combination Enabled CD8+ T Cell Infiltration
SRK-181-mIgG1 Combination Therapy Enabled Infiltration and Expansion of CD8+ T cells in Preclinical Bladder Cancer Model Anti-PD1 Combination treatment with anti-PD1/SRK-181-mIgG1 led to: • Significant increase in effector T cells (p<0.05) o Expansion of CD8+ population to an average of 34% of the t
Slide 24: TGFβ1 Isoform Specificity of SRK-181 Improved Toxicity Profile
TGF1 Isoform Specificity of SRK-181 Improved Toxicity Profile Preclinical Repeat dose pilot toxicology study in adult female Sprague Dawley rats Legend Unremarkable Minimal Slight Moderate • Animals dosed with pan-TGF inhibitors, LY2109761 (inhibitor of ALK5, common TGF receptor kinase) or pan-TGF a
Slide 25: SRK-181: Advancing Development for Cancers Resistant to Checkpoint Blockade Therapies
SRK-181: Advancing Development for Treatment of Cancers Resistant to Checkpoint Blockade Therapies (CBTs) SRK-181 is a fully human antibody designed to bind to, and prevent the activation of, latent TGF1 with high affinity and high selectivity types for which CBTs is approved or showed clinical acti
Slide 26: RGMc Program: Targeting the BMP6 Signaling Pathway
RGMc Program: Targeting the BMP6 Signaling Pathway
Slide 27: Anti-RGMc Therapy for Iron-Restricted Anemias
Anti-RGMc Therapy: Rational Solution that Directly Addresses the Underlying Pathobiology of Iron-Restricted Anemias Genetically validated pathway of iron regulation in humans RGMa and RGMb play many different physiological roles BMP6 RGMc (HJV) Iron homeostasis BMP6 RGMc BMP Receptor Inflam-mation P
Slide 28: RGMc-Selective Antibodies Show Potent Increase in Serum Iron In Vivo
Scholar Rock’s RGMc-Selective Antibodies Show Potent Increase in Serum Iron In Vivo Antibodies resulted in increases in serum iron and decreases in UIBC Antibodies showed up to 3 weeks prolonged increase in serum iron in SD rats after a single 20 mpk dose * * 600 500 400 300 200 300 200 100 0 29 UIB
Slide 29: Upcoming Key R&D Milestones
Upcoming Key R&D Milestones Initiate Phase 2 SMA proof-of-concept trial by the end of 1Q19 Commence patient dosing in Phase 2 SMA proof-of-concept trial in 2Q19 Present final Phase 1 results at Cure SMA Annual Conference being held June 28-July 1, 2019 Announce Phase 2 trial read-outs: •Preliminary
Slide 30: Building Value in All Dimensions
Building Value in All Dimensions Building on Strong Financial Foundation Advancing Clinical Development Executing Strategic Collaboration Growing Innovative Pipeline 31
Slide 31: Building Value in All Dimensions
Building Value in All Dimensions Building on Strong Financial Advancing Clinical Development e Executing Strategic Collaboration Growing Innovative Pipeline SCHOLAR ROCK aL
Slide 32: SRK-015: Aligning Therapeutic Approach with Myostatin Biology
SRK-015: Aligning Therapeutic Approach with Myostatin Biology Scholar Rock’s Guiding Principles for Neuromuscular Indication Selection Key Characteristics of Spinal Muscular Atrophy (SMA) Substantial deficit in fast-twitch fibers muscle fibers 33 Younger populationGenetic disorder with onset in chil
Slide 33: Traditional Approaches Can Raise Significant Safety Concerns
Traditional Approaches Can Raise Significant Safety Concerns Traditional Approaches Lack Selectivity Scholar Rock Approach • 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 multi
Slide 34: Review of Preclinical Data in SMN7 Mouse Models
Review of Preclinical Data in SMN7 Mouse Models More Severe Model Less Severe Model NA SMN upregulator + muSRK-015P SMN upregulator only muSRK-015P* Achieved multi-fold increase in serum latent myostatin levels indicating target engagement Confirms presence of target in disease setting Treatment imp
Slide 35: SRK-015 Phase 1 Trial Design
SRK-015 Phase 1 Trial Design KEY OBJEC TIVES OF P HASE 1 Evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of SRK-015 IV S I NGL E - A S CE ND I NG D O S E ( S A D ) MU LTIP LE - A S C END I NG D O S E ( M A D ) Design Subjects Dosing 36 Q2W dosing for 3 doses at: 10, 20,
Slide 36: SRK-015 Well Tolerated in Phase 1 Healthy Volunteer Trial
SRK-015 Well Tolerated in Phase 1 Healthy Volunteer Trial • • Well-tolerated with no apparent safety signals SAD cohort: AEs* were observed in 30% (9/30) SRK-015-vs. 50% (5/10) placebo-treated subjects • No dose-limiting toxicities identified up to highest evaluated dose of 30 mg/kg - Most frequentl
Slide 37: Phase 1 Pharmacokinetic Data Support Infrequent Dosing
Phase 1 Pharmacokinetic (PK) Data Support Infrequent Dosing Single-Ascending Dose Multiple-Ascending Dose 38 SRK-015 Displayed Well-Behaved, Linear PK Profile •Minimal variability observed, consistent with that commonly observed with monoclonal antibodies •Dose-proportional serum drug exposure Half-
Slide 38: Phase 1 Pharmacodynamic Data Demonstrate Sustained Target Engagement
Phase 1 Pharmacodynamic (PD) Data Demonstrate Robust Sustained Target Engagement and Single-Ascending Dose Multiple-Ascending Dose 10,000 1,000 Placebo 10 mg/kg 20 mg/kg 30 mg/kg 100 10 1 0 14 28 42 56 70 84 98 112 126 140 Time (days) 39 Latent Myostatin (ng/mL) Robust Target Engagement Observed •Si
Slide 39: Highlights of Strategic Fibrosis Collaboration with Gilead
Highlights of Strategic Fibrosis Collaboration with Gilead Collaborating to Develop Innovative Therapies for Fibrotic Diseases Responsible for antibody discovery and preclinical research thru product candidate nomination for three TGF programs Upon option exercise, responsible for preclinical and cl
Slide 40: Highlights of Strategic Fibrosis Collaboration with Gilead
Highlights of Strategic Fibrosis Collaboration with Gilead ee (J GILEAD SCHOLAR ROCK . Responsible for antibody discovery Colla borating Upon option exercise, eee research thru product to Develop Innovative responsible for preclinical candidate nomination for three . 8 nf Therapies for Fibrotic and
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