Scholar Rock Holding Corporation · NASDAQ:SRRK
Scholar Rock — Investor Presentation (March 2019)
32 slides from Scholar Rock's investor presentation, Mar 13, 2019
Slide 1: From New Insights to New Medicines
March 2019 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: 2018: Transformative Year for Scholar Rock
3 2018: Transformative Year for Scholar Rock Established Strong Financial Foundation • Transitioned to public company with successful $86M IPO Transitioned to Clinical - Stage Company • SRK - 015 Phase 1 trial supports advancement to Phase 2 SMA proof - of - concept trial Executed Strategic Collabor
Slide 4: Nature's Growth Factor Activation Machinery
4 Nature’s Growth Factor 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 G rowth F actors that Mediate Diverse Bi
Slide 5: Robust Pipeline Portfolio
5 Program / Target Indication Discovery / Early Preclinical Preclinical Phase 1 Phase 2 Rights / Partner Next Anticipated Milestone INTERNAL PROPRIETARY PROGRAMS Pro/Latent Myostatin SRK - 015 Spinal Muscular Atrophy Initiate Phase 2 POC Trial in 1Q19 SRK - 015 Myostatin - Related Disorders Identify
Slide 6: SRK-015: Inhibitor of Myostatin Activation
SRK - 015: Inhibitor of Myostatin Activation Potential First Muscle - Directed Therapy for SMA
Slide 7: SRK-015: Highly Specific Inhibitor of Latent Myostatin
7 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 Vertebrates lacking the myost
Slide 8: Traditional Approaches Can Raise Significant Safety Concerns
8 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 9: Guiding Principles for Neuromuscular Indication Selection
9 Scholar Rock’s Guiding Principles for Neuromuscular Indication Selection Key Characteristics of Spinal Muscular Atrophy (SMA) Younger population Genetic disorder with onset in childhood A t least partially intact innervation and no structural muscle abnormalities Partial neural connectivity and a
Slide 10: Significant Unmet Need Remains Despite Current Therapies
10 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 11: Review of Preclinical Data in SMNΔ7 Mouse Models
11 Review of Preclinical Data in SMN Δ7 Mouse Models *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 Models of SMA Therapy
Slide 12: Phase 1 Trial Design
12 SRK - 015 Phase 1 Trial Design SINGLE - ASCENDING DOSE (SAD) MULTIPLE - ASCENDING DOSE (MAD) Design Subjects Dosing Double - blind, placebo - controlled 3:1 randomization 40 Adult healthy v olunteers (Ages 18 - 55) Double - blind, placebo - controlled 3:1 randomization Single doses at: 1, 3, 10,
Slide 13: Phase 1 Interim Safety Results Support Advancing to Phase 2
13 Phase 1 Interim Safety Results Support Advancing to Phase 2 Trial • SRK - 015 was well - tolerated with no apparent safety signals • No dose - limiting toxicities identified up to highest evaluated dose of 30 mg/kg - No discontinuations due to a treatment - related AE - No treatment - related SAE
Slide 14: PK Data Support Infrequent Dosing
14 PK Data Support Infrequent Dosing Displayed Well - Behaved PK Profile • Consistent with that commonly observed with monoclonal antibodies • Dose - proportional serum drug exposure Half - Life S upports I nfrequent D osing • Serum half - life of 23 - 33 days across the SRK - 015 dose groups • Supp
Slide 15: PD Data Demonstrate Robust and Sustained Target Engagement
15 PD Data Demonstrate R obust and Sustained Target Engagement Robust Target Engagement Observed • Marked increases in serum concentrations of latent myostatin following a single dose of SRK - 015 • No meaningful change observed with placebo Evidence Supports Durable Target Saturation • Peak latent
Slide 16: Evidence to Date and Target Profile in SMA
16 EVIDENCE TO DATE Effectively increase motor function to drive clinically meaningful outcomes x Translational/preclinical data support myostatin as a drug target in SMA x Preclinical data demonstrate potential for substantial increases in muscle strength x Interim Phase 1 PD data demonstrate SRK -
Slide 17: Opportunity in Spinal Muscular Atrophy
17 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 Relative Prevalence Among Patients Living Wit
Slide 18: Overview of Phase 2 TOPAZ Trial in SMA
18 Overview of Phase 2 TOPAZ Trial in SMA • 3 cohorts ; total of 50 - 60 patients • 12 - month treatment period • SRK - 015 IV every 4 weeks (Q4W) Design Subjects Key Objectives Timeline • Type 3 ambulatory SMA (monotherapy or in conjunction with approved SMN upregulator) • Type 2 and Type 3 non - a
Slide 19: Path to Top-Line Results in SMA
19 SRK - 015: Path to Top - Line Results in SMA End of 2019 1H 2020 4Q20 - 1Q21 2Q19 1 Q19 Initiate trial - Start - up activities, including contracts and IRB submissions with trial sites Commence patient dosing - Provide additional details of Phase 2 trial design Preliminary PK/PD data from subset
Slide 20: TGFβ1: Significant Opportunities in Oncology/Immuno-oncology and Fibrosis
TGFβ1: Significant Opportunities in Oncology/Immuno - oncology and Fibrosis
Slide 21: TGFβ1 Plays Central Role in Multiple Diseases with Unmet Need
21 TGF β1 Plays Central Role in Multiple Diseases with Unmet Need Oncology Fibrosis Immuno - Oncology Tumor - Directed Therapy Myeloproliferative Disorders
Slide 22: Inhibition of TGFβ1: Multipronged Approach for Immuno-Oncology
22 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 23: TGFβ is the Predominant Isoform in Most Human Tumors
23 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 24: TGFβ Blockade Renders Preclinical Bladder Tumors Susceptible to Anti-PD1
24 TGF β 1 Blockade with SRK - 181 - mIgG1 Renders Preclinical Bladder Tumors Susceptible to Anti - PD1 Therapy Dosing initiated when tumors reached 30 - 80 mm 3 Treatment with RMP1 - 14 anti - PD1 (5mg/kg twice weekly) and/or SRK - 181 - mIgG1 (once weekly at indicated dose) Days after treatment in
Slide 25: Anti-TGFβ1 Combination with PD-1 Blockade Effective in Melanoma Model
25 Days after treatment initiation Tumor volume (mm3) Control Anti - PD - 1 Anti - PD - 1/ SRK - 181 - mIgG1 ( 10 mg/kg ) Anti - PD - 1/ SRK - 181 - mIgG1 ( 3 mg/kg ) SRK - 181 - mIgG1* (30 mg/kg) Anti - PD - 1/ SRK - 181 - mIgG1 ( 30 mg/kg ) Endpoint Responders 0/11 0/12 2/12 10/12 7/9 8/11 Anti -
Slide 26: Combination with Anti-PD1 Leads to Significant Survival Benefit
26 Cloudman S91 Melanoma Model 0 10 20 30 40 0 25 50 75 100 Days after treatment initiation Survival (%) SRK - 181 - mIgG1 Combined with Anti - PD1 Therapy Leads to Significant Survival Benefit in Preclinical Tumor Models MBT - 2 Bladder Cancer Model Days after treatment initiation Survival (%) 0 7
Slide 27: Combination Therapy Enables Infiltration and Expansion of CD8+ T cells
27 200 µm Control Anti - PD - 1/ SRK - 181 - mIgG1 ( 10 mg/kg) SRK - 181 - mIgG1 * Anti - PD - 1 SRK - 181 - mIgG1 Combination Therapy Enables Infiltration and Expansion of CD8 + T cells in Preclinical Tumor Model IHC of MBT - 2 tumors at day 10 • Marked increase in frequency of CD8 + T cells within
Slide 28: TGFβ1 Isoform Specificity Results in Improved Preclinical Toxicity Profile
28 TGFβ1 Isoform Specificity of SRK - 181 Results in Improved Preclinical Toxicity Profile • Animals dosed with pan - TGF β inhibitors, LY2109761 (inhibitor of ALK5, common TGF β receptor kinase) or pan - TGF β antibody, exhibited expected cardiac findings based on published data • Exposure as asses
Slide 29: SRK-181: Advancing Development for Cancers Resistant to Checkpoint Blockade
29 SRK - 181: Advancing Development for Treatment of Cancers Resistant t o Checkpoint Blockade Therapies (CBTs) SRK - 181 is a fully human antibody designed to bind to, and prevent the activation of, latent TGFβ1 with high affinity and high selectivity TGF β signaling Implicated as a culprit in prim
Slide 30: Highlights of Strategic Fibrosis Collaboration with Gilead
30 Highlights of Strategic Fibrosis Collaboration with Gilead Upon option exercise, responsible for preclinical and clinical development and commercialization Upfront cash and equity investment: $80 million* One - time preclinical milestone: $25 million Additional development, regulatory, and commer
Slide 31: Upcoming Key R&D Milestones
31 Upcoming Key R&D Milestones SRK - 01 5 o Initiate Phase 2 SMA proof - of - concept trial by the end of 1Q19 o Commence patient dosing in Phase 2 SMA proof - of - concept trial in 2Q19 o Present full Phase 1 results at a scientific conference in 2019 o Continue to evaluate selective inhibitors of
Slide 32: Building Value in All Dimensions
32 Building Value in All Dimensions Executing Strategic Collaboration Advancing Clinical Development Growing Innovative Pipeline Leveraging Strong Financial Foundation
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