UNITED
STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM
8-K
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CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event Reported): May 26, 2021
(Exact Name of Registrant as Specified in Charter)
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(State or Other Jurisdiction of Incorporation)
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(Commission File Number)
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(I.R.S. Employer Identification Number)
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(857 ) 259-3860
(Registrant’s telephone number, including area code)
(Registrant’s telephone number, including area code)
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Securities registered pursuant to Section 12(b) of the Act:
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Title of each class
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Trading Symbol(s)
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Name of each exchange on which registered
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2). Emerging growth company
☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange
Act. ☒
Item 8.01. Other Events.
The Company from time to time provides business updates to members of the investment community and other parties. A copy of the Company’s current corporate
slide presentation is being filed herewith as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit
99.1.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits
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Exhibit
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Description
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SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the
undersigned hereunto duly authorized.
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Scholar Rock Holding Corporation
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Date: May 26, 2021
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By:
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/s/ Junlin Ho
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Junlin Ho
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General Counsel and Corporate Secretary
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Exhibit 99.1
Deep Insights,Impactful Medicines May 2021
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 timing for the initiation of and reporting
results from its clinical trials for its product candidates, its disease indication selection and timing for such selection, the ability of apitegromab (SRK-015) to affect the treatment of patients suffering from Spinal Muscular Atrophy (SMA)
either as a monotherapy or in conjunction with the current standard of care, and the ability of SRK-181 to affect the treatment of cancer patients in a manner consistent with preclinical data constitute forward-looking statements for the
purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. The use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “target,” “project,” “intend,”
“future,” “potential,” or “continue,” and other similar expressions are intended to identify such forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various
important factors, including, without limitation, preclinical and clinical data, including the 12-month top-line results from the Phase 2 trial of apitegromab, are not predictive of, are inconsistent with, or more favorable than, data generated
from future clinical trials of the same product candidate, including the planned Phase 3 trial of apitegromab in SMA, Scholar Rock’s ability to provide the financial support, resources and expertise necessary to identify and develop product
candidates on the expected timeline, information provided or decisions made by regulatory authorities differ from the company’s expectations, competition from third parties that are developing products for similar uses, Scholar Rock’s ability
to identify and develop multiple product candidates on the expected timeline, the impacts of the COVID-19 pandemic, Scholar Rock’s ability to obtain, maintain and protect its intellectual property, Scholar Rock’s dependence on third parties for
development and manufacture of product candidates including to supply any clinical trials, and Scholar Rock’s ability to manage expenses and to obtain additional funding when needed to support its business activities and establish and maintain
strategic business alliances and new business initiatives as well as those risks more fully discussed in the section entitled "Risk Factors" in the Quarterly Report on Form 10-Q for the quarter ended March 31, 2021, which is on file with
the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors in Scholar Rock’s subsequent filings with the Securities and Exchange Commission. Any forward-looking statements
represent Scholar Rock’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Scholar Rock explicitly disclaims any obligation to update any forward-looking statements unless required by law.
© Scholar Rock, Inc. All rights reserved. May 2021.
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 Another Transformative
Year TOPAZ extension Continue to discover and advance preclinical programs Multiple opportunities for additional myostatin-related indications beyond SMA and muscular dystrophies Multiple additional opportunities: 1) SRK-181 in
oncology; 2) latent TGFβ1 immune cell in IO; 3) latent TGFβ1 immune cell in oncology Gilead Fibrosis collaboration 2022 and Beyond 2021 Q3 Q4 Q2 Latent TGFβ1 Immune Cell Immuno-Oncology and Oncology 3 DRAGON Part B to initiate
mid-year: multiple tumor typesMelanomaNSCLCUrothelial CarcinomaOther Solid Tumor Types ApitegromabOther Indications Multiple opportunities in muscular dystrophies, including Becker Muscular Dystrophy
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 drugApply revolutionary approach to
tough targetsLeverage deep insights into structure and function Engineer antibodies to deliver differentiated therapeutic profiles(i.e. exquisite selectivity) TOPAZ demonstrated the therapeutic potential of inhibiting the latent forms of
growth factors
Apitegromab: Transformative Potential Demonstrated in TOPAZ Phase 2 Trial for Patients with Type 2 and 3
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 needed to complement the disease stabilizing
effects of SMN upregulatorsApitegromab demonstrated transformative potential in SMA through the TOPAZ Phase 2 trial, especially in non-ambulatory Type 2 and 3 patientsPatients 2-6 years of age: +7.1-point increase in HFMSE and 63% attained a
≥3-point increase with 20 mg/kg dosePatients 8-19 years of age: +1.2-point* increase in HFMSE and 31% attained a ≥3-point increaseNon-ambulatory Type 2 and 3 patients represent ~2/3 of overall populationTOPAZ results offer exciting path forward
for investigating apitegromab in a rational, targeted, and efficient Phase 3 trial in non-ambulatory Type 2 and 3 patients *Per-protocol: excludes patient with concomitant exposure to an acetylcholinesterase inhibitor not permitted per the
TOPAZ protocol
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-month results demonstrated
transformative efficacy in non-ambulatory Type 2 and 3 patients Represents ~2/3 of overall patient population Motor neuron impairment and loss due to SMN genetic deficiency, leading to muscle atrophy and weakness *TOPAZ Phase 2 trial
evaluated patients with Type 2 and 3 SMA (did not include Type 1)
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 activation Apitegromab is a muscle-directed
approach aimed at improving motor function Apitegromab SMN upregulators prevent further degeneration of motor neurons...but do not directly address muscle atrophy Motor neurondegeneration Muscle fiber atrophy
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 financial update on 4/21/21; includes
patients treated worldwide between clinical trials, commercial, and compassionate use program.***As of 1Q21 financial update on 4/27/21; commercially, via managed access programs and in clinical trials Persistent Need Non-ambulatory Type
2/32-12 years of agePrimary endpoint: Mean change from baseline in HFMSE at 15 months >11,000* patients treated WW$2+ billion in revenues (LTM) ~1,200*** patients treated WW~$1.1 billion in revenues (LTM) ~3,000** patients treated
WW~CHF135 million in revenues (LTM) Type 1, 2, and 3 SMA in pediatric and adult patients Type 1, 2, 3 SMA in patients 2 months of age and older Approved for SMA less than 2 years of age Non-ambulatory Type 2/3 2-25 years of agePrimary
endpoint: Mean change from baseline in MFM-32 at 12 months Infantile-onset Type 1<6 months of agePrimary endpoints: Ability to sit independently and event-free survival Major functional deficits remainIncreases in MFM-32 primarily limited
to youngest patientsHFMSE effects not as pronounced Limited data and eligibility for use beyond very young patients Major functional deficits remainHFMSE improvements only in younger patients and rapidly plateaus
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 and is not intended to convey or
imply a comparison to the TOPAZ clinical trial results. Mean improvement in HFMSE score experienced by patients withnon-ambulatory Type 2/3 SMA in the Phase 3 CHERISH clinical trial of nusinersen HFMSE increase from nusinersen HFMSE Score
at Month 15 Total Possible HFMSE Score of 66 Treated patients still experience major functional deficits… TOPAZ Therapeutic Hypothesis: Apitegromab may improve outcomes in patients with SMA on chronic maintenance nusinersen.
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 background only and is not
intended to convey or imply a comparison to the TOPAZ clinical trial results. Initial treatmentCHERISH Chronic maintenance phaseSHINE Most nusinersen-treated patients in CHERISH were <5 years at therapy initiation +3.9-points Mean (+
SE) Change in HFMSETotal Score From Baseline Analysis Visit, d 1 92 169 253 350 450 690 930 1170 1410 1650 -1-2-3-4 8765 43210 Nusinersen CHERISH trial showed mean HFMSE increase of +3.9 points in first 15 monthsImprovement largely
observed in younger patientsMajority of older children (initiate treatment >5 years of age) do not improve +3.9-points
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 provided for background only and is not intended to
convey or imply a comparison to the TOPAZ clinical trial results. Most nusinersen-treated patients in CHERISH were <5 years at therapy initiation Mean (+ SE) Change in HFMSETotal Score From Baseline Analysis Visit, days 1 92 169 253 350
450 690 930 1170 1410 1650 -1-2-3-4 8765 43210 Nusinersen observed plateauing of improvement during chronic maintenance phase… <1-point increase in HFMSE after first 15 months of treatment +3.9-points +4.6-points Unmet Need for
Motor Function Gains Initial treatmentCHERISH Chronic maintenance phaseSHINE
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 nusinersen (initiated <5 years of
age)Apitegromab 2 mg/kg and 20 mg/kg IV Q4W + nusinersen Key objectives: HFMSE and safety at 12 months Non-ambulatory Type 2/3 patients (ages 5-21) on chronic maintenance nusinersen (initiated ≥5 years of age) Apitegromab 20 mg/kg IV Q4W +
nusinersen Key objectives: HFMSE and safety at 12 months 57 patients* completed 12-month TOPAZ trial All Elected to Opt Into Extension Period Patients on background SMN therapy were in chronic maintenance phase of nusinersen (~5
mean maintenance doses at baseline) *Excludes one patient from Cohort 1 that discontinued from the trial
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 (min, max) 3.8 (2, 6) 4.1 (2, 6) 4.0 (2, 6) 11.7 (8, 19) 12.1 (7, 19) 13.1 (7, 21) 12.6 (7, 21) Mean RHS score (min, max) 47.6 (26, 63) 51.3 (43, 62) 49.6 (26, 63) Mean HFMSE score
(min, max) 23.5 (14, 42) 26.1 (12, 44) 24.8 (12, 44) 22.7 (13, 39) Mean # of nusinersen maintenance doses (min, max) 5.4 (3, 8) 5.5 (2, 9) 5.5 (2, 9) 5.1 (2, 9) N/A 5.6 (2, 8) N/A SMN2 Gene Copy* (#, %) 2 1
(10%) 1 (10%) 2 (10%) 1 (9%) 0 (0%) 1 (4%) 3 8 (80%) 8 (80%) 16 (80%) 11 (73%) 4 (36%) 9 (75%) 13 (57%) 4 0 (0%) 1 (10%) 1 (5%) 2 (13%) 4 (36%) 1 (8%) 5 (22%) Discontinuation(s) 0 0 0 0 0 1** 1** *Data not
available for all patients**Patient who discontinued study for reasons unrelated to study drugHFMSE=Hammersmith Functional Motor Scale Expanded; RHS=Revised Hammersmith Scale Data on file. Scholar Rock, Inc. Cambridge, MA
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, 12.2) +6.2 (2.2, 10.1) # (%) patients
achieving ≥1-pt increase in HFMSE 7/8 (88%) 7/9 (78%) 14/17 (82%) # (%) patients achieving ≥3-pt increase in HFMSE 5/8 (63%) 5/9 (56%) 10/17 (59%) # (%) patients achieving ≥5-pt increase in HFMSE 5/8 (63%) 5/9 (56%) 10/17 (59%) 35%
(6/17) with >10-point increase in HFMSEUp to 20-point increases in HFMSE observedSizable, dose-dependent increases in HFMSE observed in patients already on chronic maintenance nusinersenDurable and continuous improvements observed through
12-monthsCHERISH and SHINE nusinersen studies suggest substantial HFMSE increases do not occur in younger patients following first year of treatment Data on file. Scholar Rock, Inc. Cambridge, MA
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) +1.2 (-0.5, 2.9) +0.6 (-1.4, 2.7) # (%)
patients achieving ≥1-pt increase in HFMSE 9/13 (69%) 9/14 (64%) # (%) patients achieving ≥3-pt increase in HFMSE 4/13 (31%) 4/14 (29%) # (%) patients achieving ≥5-pt increase in HFMSE 2/13 (15%) 2/14 (14%) 16 Majority of patients
attained increases in HFMSE~30% achieved ≥3-point increase in HFMSEDurability of effect observed through 12-monthsImprovements not seen with other therapies in this older patient populationPatients already on chronic maintenance
nusinersenCHERISH data suggest older patients on average observe declines and rarely observe a 3-point increase in HFMSE *Patient had concomitant exposure to an acetylcholinesterase inhibitor, which is not permitted per the TOPAZ trial
protocol Data on file. Scholar Rock, Inc. Cambridge, MA
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%) Any TEAE leading to study
drug discontinuation 0 (0.0%) 1 (2.1%) 1 (1.7%) Any Grade 3 (severe) or higher TEAE 0 (0.0%) 3 (6.2%) 3 (5.2%) Treatment-emergent adverse events (TEAEs) are defined as AEs that start after the first dose of study drug or start prior to
the administration of study drug and worsen in severity/grade or relationship to investigational medication after the administration of study drug.*TEAE rates are across all patients in TOPAZ trialData on file. Scholar Rock, Inc. Cambridge,
MA Five most frequently reported TEAEs*: Headache (24%), pyrexia (22%), upper respiratory tract infection (22%), cough (22%), and nasopharyngitis (21%).SAEs, Grade 3 AEs and AE leading to early study discontinuation were all assessed by
investigators as unrelated to study drugAnti-drug antibodies (ADA) were present at low titers following apitegromab treatment in 3 out of 58 enrolled patients. No apparent impact on drug exposure was observed and was not associated with any
hypersensitivity reactions. No safety signals identified as of the TOPAZ 12-month top-line analysis. Incidence and severity of AEs were consistent with the underlying patient population and background therapy
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 benefits of SMN regulators not
well-establishedTOPAZ suggests potential clinical benefit in a subset of patients 3 Type 1 patients, including those treated with gene therapy Highest incidence population and growing prevalence due to SMN upregulator treatmentTOPAZ showed
benefits of early treatment suggesting potential in Type 1 patients 2 Represents 2/3 of overall patientsMany patients already treated with or are eligible for SMN upregulator therapyImprovements in motor function on top of SMN upregulators
observed in TOPAZ Anticipated Focus of Phase 3 Trial
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 nusinersen or
risdiplamTOPAZ data support investigation of 20 mg/kg dose Registrational trial design subject to regulator interactions and feedback
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 SMN regulators not well-establishedTOPAZ
suggests potential clinical benefit in a subset of patients 3 Type 1 patients, including those treated with gene therapy Highest incidence population and growing prevalence due to SMN upregulator treatmentTOPAZ showed benefits of early
treatment suggesting potential in Type 1 patients 2 Represents 2/3 of overall patientsPatients already treated with or eligible for SMN upregulator therapyImprovements in motor function on top of SMN upregulators observed in TOPAZ
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 (-2.0, 1.4) -0.3 (-2.1, 1.4) # (%)
patients achieving ≥0-pt increase in RHS 6/11 (55%) 7/12 (58%) 13/23 (57%) # (%) patients achieving ≥1-pt increase in RHS 4/11 (36%) 5/12 (42%) 9/23 (39%) # (%) patients achieving ≥3-pt increase in RHS 3/11 (27%) 2/12 (17%) 5/23
(22%) Data on file. Scholar Rock, Inc. Cambridge, MA Majority of patients maintained or improved57% (13/23) with ≥0-point increase in RHS39% (9/23) with ≥1-point increase in RHSIncreases of up to 8-points observedPotential signal for
therapeutic benefit observed in this population
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 months 57 patients* completed 12-month
TOPAZ trial All Elected to Opt Into Extension Period *Excludes one patient from Cohort 1 that discontinued from the trial TOPAZ trial enrolled in ~8 months
23 SRK-181: Potential Transformative Backbone for a New Era ofCancer Immunotherapy
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/ s41571-020-0403-1 February 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”€300 million upfront and up to €3.7 billion total June 2019: “Merck to
Acquire Tilos Therapeutics: Merck Gains Portfolio of Investigational Antibodies Modulating TGFβ”$773 million total potential deal value 24 August 2020: “Bristol Myers Squibb Enters Agreement to Acquire Forbius TGF-beta Program”
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 Pathway in Cancers 25 †Priti H, et
al. Top 10 challenges in cancer immunotherapy. Immunity. 2020 Jan 14:52(1):17-35. https://doi.org/10.1016/j.immuni.2019.12.011.*Source: National Cancer Institute - Cancer Genome Atlas Program.
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 associated with non-selective TGFβ
inhibitionTherapeutic flexibility - pair with any CPI and optimize dosing of each component of combination therapy Scholar Rock’s Target SRK-181: Latent TGFβ1 Inhibitor Traditional target:“Mature” growth factor
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 SRK-181 80 mg
(n=1) SRK-181 240 mg (n=1) SRK-181 1600 mg (n=3) SRK-181 800 mg (n=3) SRK-181 2400 mg (n=3) SRK-181 3000 mg (n=3) SRK-181 240 mg (n=3) SRK-181 800 mg (n=3) SRK-181 1600 mg (n=3) SRK-181 2400 mg (n=3) Different dose
regimen if needed (n=3) SRK-181 + anti-PD-(L)1; non-responders to prior anti-PD-(L)1n=up to 40/cohort Cohort B: urothelial carcinoma (UC) Cohort C: cutaneous melanoma Cohort D: Other solid tumor types SRK-181 + pembrolizumab SRK-181 +
pembrolizumab SRK-181 + pembrolizumab SRK-181 + any anti-PD-(L)1 As of March 9, 2021: Part A1: 3000 mg Q3W dose being evaluated Part A2: 1600 mg Q3W dose being evaluatedPart B initiation planned mid-yearInitial clinical response and
safety data anticipated by year-end 2021
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 Another Transformative
Year TOPAZ extension Continue to discover and advance preclinical programs Multiple opportunities for additional myostatin-related indications beyond SMA and muscular dystrophies Multiple additional opportunities: 1) SRK-181 in
oncology; 2) latent TGFβ1 immune cell in IO; 3) latent TGFβ1 immune cell in oncology Gilead Fibrosis collaboration 2022 and Beyond 2021 Q3 Q4 Q2 Latent TGFβ1 Immune Cell Immuno-Oncology and Oncology 28 DRAGON Part B to initiate
mid-year: multiple tumor typesMelanomaNSCLCUrothelial CarcinomaOther Solid Tumor Types ApitegromabOther Indications Multiple opportunities in muscular dystrophies, including Becker Muscular Dystrophy
Appendix
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 atrophied muscles that largely retain
structural integrity Need for increase in fast-twitch muscle fibers Substantial deficit in fast-twitch fibers Clinical trial endpoint driven by fast-twitch fiber function Fast-twitch fiber function has a prominent role in SMA outcome
measures 30 Apitegromab: Pairing the latent form with important translational insights
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 dose offers relatively
higher magnitude of target engagement than 2 mg/kg dose High levels of target engagement achieved by both doses, with relatively higher absolute levels with high dose 31 *Starting at day 28, measures are pre-dose trough levelsData on file.
Scholar Rock, Inc. Cambridge, MA Pharmacokinetics* (PK) Pharmacodynamics (PD)
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 determinant of
primary resistance to anti-PD-(L)1 therapy TGFβ1 creates ‘immune excluded’ tumor microenvironment
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) model: Combination treatment led to
tumor regression and survival benefit Anti-PD1/SRK-181-mIgG1 (10 mg/kg QW) Anti-PD1/SRK-181-mIgG1 (30 mg/kg QW) 4/9 8/11 SRK-181-mIgG1 (30 mg/kg QW) 3/12 Anti-PD1 (10 mg/kg BIW) *P<0.01. †P<0.05 Log-rank (Mantel-Cox test) vs
anti-PD1. **† Tumor Regression: Monotherapy Tumor Regression: Combination Therapy Days after treatment initiation Days after treatment initiation Days after treatment initiation Survival Benefit Anti-PD1/ SRK-181-mIgG1 led to influx of
CD8+ cells in preclinical bladder tumor model Anti-PD1 Overcoming immune exclusion Tumor volume (mm3) Responders 0/12
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 CJ, et al. Sci Transl Med. 2020 Mar
25;12(536):eaay8456. https://scholarrock.com/platform/publications/.*SRK-181-mIgG1 is the murine version of SRK-181; responder defined as tumor size <25% endpoint volume at study end. Bladder Cancer Breast Cancer (TGFβ1/3
co-expressing) Responders SRK-181-mIgG1* (10 mg/kg QW) 0/13 Anti-PD1 (10 mg/kg BIW) 0/12 0/10 SRK-181-mIgG1* (10 mg/kg QW) Anti-PD1/SRK-181-mIgG1(10 mg/kg QW) 5/10 Responders 0/9 Control 0/9 Anti-PD1 (10 mg/kg BIW) 34
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. Toxicol Pathol. 2011;39: 916-924.; and Stauber
AJ, et al. Nonclinical safety evaluation of a transforming growth factor β Receptor I kinase inhibitor in Fischer 344 rats and beagle dogs. J Clin Pract. 2014: 4:3. Selectivity of SRK-181 offers potential to overcome toxicity and dose-limiting
challenges of non-selective TGFβ pathway approaches Microscopic observations in heart Valvulopathy Atrium—Mixed cell infiltrate Myocardium—Degeneration/necrosis Myocardium—Hemorrhage Myocardium—Mixed cell infiltrate, base Coronary
artery—Necrosis with inflammation Cardiomyocyte—Necrosis/inflammatory cell infiltrate Control Vehicle iv, qwk x 4 LY2109761 300
mg/kg po, qd x 8 PanTGFβAb 30 mg/kg Iv, 1 dose 10
mg/kg iv, qwk x 4 30 mg/kg iv, qwk x 4 100 mg/kg iv, qwk x
4 SRK-181 LEGEND UnremarkableMinimalSlightModerate Repeat dose pilot toxicology study in adult female Sprague Dawley rats:Cardiac findings were exhibited
in animals dosed with a pan-TGFβ antibody or LY2109761 (inhibitor of ALK5, common TGFβ receptor kinase) as expected based on published data†No cardiotoxicities (valvulopathy) were noted with SRK-181 NOAEL for SRK-181 was the highest dose
evaluated of 100 mg/kg QW 4-week GLP toxicology studies: Rats: NOAEL for SRK-181 was up to highest evaluated dose of 200 mg/kg QWNon-human primates: NOAEL for SRK-181 was up to highest evaluated dose of 300 mg/kg QW 35