UNITED STATES
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FORM
CURRENT REPORT
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| Item 7.01. | Regulation FD Disclosure. |
On October 11, 2023, Scholar Rock Holding Corporation (the “Company”) issued a press release announcing plans to expand into cardiometabolic disorders and advance its anti-myosatin program into cardiometabolic disorders and SRK-439, a novel investigational myostatin inhibitor, for the treatment of obesity towards the filing of an Investigational New Drug Application in 2025. A copy of the press release is attached hereto as Exhibit 99.1.
The information in this Item 7.01 of Form 8-K, including the accompanying Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liability of such section, nor shall such information be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, regardless of the general incorporation language of such filing, except as shall be expressly set forth by specific reference in such filing.
| Item 8.01. | Other Events. |
The Company has also made available a slide presentation relating to its cardiometabolic disorders program, a copy of which is attached as Exhibit 99.2 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 99.2.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
|
Exhibit No. |
Description |
| 99.1 | Press Release issued by the Company on October 11, 2023, furnished herewith. |
| 99.2 | Presentation Slide Deck |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) |
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.
| Scholar Rock Holding Corporation | ||
| Date: October 11, 2023 | By: | /s/ Junlin Ho |
| Junlin Ho | ||
| General Counsel and Corporate Secretary | ||
Exhibit 99.1
Scholar Rock TO ADVANCE ANTIMYOSTATIN PROGRAM to develop novel therapies for CARDIOMETABOLIC DISORDERS
| · | Company plans to expand into cardiometabolic disorders, leveraging its experience in myostatin inhibition |
| · | Preclinical data support advancing SRK-439, a novel investigational myostatin inhibitor for the treatment of cardiometabolic disorders, with an initial focus on obesity, towards an IND in 2025 |
| · | To inform the development of SRK-439, Company plans to initiate a Phase 2 proof-of-concept trial of apitegromab in obesity in 2024 with data readout expected in mid-2025 |
| · | Data from pivotal Phase 3 SAPPHIRE trial in SMA expected in Q4 2024 |
CAMBRIDGE, Mass., October 11, 2023 (BUSINESS WIRE) -- Scholar Rock (NASDAQ: SRRK), a Phase 3, clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, today announced it plans to advance SRK-439, a novel investigational myostatin inhibitor for the treatment of obesity towards an investigational new drug application (IND) in 2025. As part of the Company’s strategy to advance the development of SRK-439, it intends to initiate a Phase 2 proof-of-concept trial with apitegromab in combination with GLP-1 receptor agonist (GLP-1 RA) in 2024. Data from the clinical trial are expected in mid-2025 and will be used to inform further clinical development of SRK-439.
“As a long-standing leader in targeting myostatin with a highly selective antibody platform, we are excited to advance our cardiometabolic program. We have discovered multiple, highly selective myostatin inhibitors and see potential with SRK-439 to retain lean muscle mass, a concern that is commonly associated with weight loss strategies, including treatments currently on the market for obesity, a common, serious and costly public health issue affecting adults and children globally. As apitegromab has shown to date in spinal muscular atrophy (SMA), muscle-targeted therapies that are well tolerated have the potential to represent a new class of treatments across a wide range of diseases,” said Jay Backstrom, M.D., M.P.H., President and Chief Executive Officer of Scholar Rock. “While we continue to expand the development of our pipeline, our top priority remains advancing the apitegromab program in SMA. We recently completed full enrollment of the pivotal Phase 3 SAPPHIRE trial of apitegromab in SMA, for which we expect to read out topline data in Q4 2024.”
Cardiometabolic program
Muscle plays a key role in metabolic functions and energy homeostasis. Leveraging proven expertise in anti-myostatin and its effect on increasing muscle mass, the Company has been developing myostatin-selective inhibitors to address cardiometabolic disorders, including obesity. Scholar Rock’s platform has generated multiple antibody candidates, including apitegromab, that selectively target pro- and latent forms of myostatin. The Company believes the selectivity of these antibody candidates enables a favorable risk-benefit profile for patients with cardiometabolic disorders.
SRK-439, a novel anti-myostatin antibody candidate developed by Scholar Rock, has attractive properties, including high in vitro affinity for pro- and latent myostatin, maintenance of myostatin specificity (i.e., no GDF11 or Activin-A binding), and robust in vivo efficacy in preclinical models. Studies in diet-induced obese mice showed that SRK-439 in combination with GLP-1 receptor agonist (GLP-1 RA) achieved:
| · | Dose-dependent reversal of lean mass loss during GLP-1-RA mediated weight loss; and |
| · | Enhancement of fat mass loss mediated by GLP-1 RA treatment. |
“Cardiometabolic disorders are creating growing global medical challenges and contribute to the development of serious health conditions, such as cardiovascular disease, Type 2 diabetes, and certain cancers,” said Mo Qatanani, Ph.D., Senior Vice President and Head of Research. “Leveraging our unique scientific platform, Scholar Rock has developed SRK-439 with a proposed mechanism of action that aims to safely maintain muscle mass, while enhancing body fat loss, thereby potentially enhancing metabolic health and potentially offering a unique opportunity to address a high unmet need in treating metabolic conditions, including obesity. We look forward to presenting preclinical data on this new asset from our pipeline at upcoming scientific conferences.”
About Scholar Rock
Scholar Rock is a clinical-stage biopharmaceutical company focused on the discovery and development of innovative medicines for the treatment of serious diseases in which signaling by protein growth factors plays a fundamental role. Scholar Rock is creating a pipeline of novel product candidates with the potential to transform the lives of patients suffering from a wide range of serious diseases, including neuromuscular disorders, cancer, and fibrosis. Scholar Rock’s approach to targeting the molecular mechanisms of growth factor activation enabled it to develop a proprietary platform for the discovery and development of monoclonal antibodies that locally and selectively target these signaling proteins at the cellular level. By developing product candidates that act in the disease microenvironment, Scholar Rock intends to avoid the historical challenges associated with inhibiting growth factors for therapeutic effect. Scholar Rock believes its focus on biologically validated growth factors may facilitate a more efficient development path.
Scholar Rock® is a registered trademark of Scholar Rock, Inc.
Forward-Looking Statements
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Scholar Rock’s future expectations, plans and prospects, including without limitation, any development plans, strategy and progress for apitegromab and SRK-439, the timing of its clinical trials, anticipated clinical data, and therapeutic benefits for apitegromab and SRK-439, and other product candidates and indication selection and development timing, the ability of any product candidate to perform in humans in a manner consistent with earlier nonclinical, preclinical or clinical trial data, and the potential of apitegromab, SRK-439 and its other product candidates and its proprietary platform. The use of words such as “may,” “might,” “could,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify such forward-looking statements. All such forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, without limitation, expectations regarding the therapeutic potential of SRK-439 for the treatment of obesity, planned timing for an IND submission for SRK-439, that preclinical and clinical data, including the results from the Phase 2 clinical trial of apitegromab and preclinical studies of SRK-439, are not predictive of, may be inconsistent with, or more favorable than, data generated from future clinical trials of the same product candidates, including, without limitation, the Phase 3 clinical trial of apitegromab in SMA and preclinical studies of SRK-439, Scholar Rock’s ability to provide the financial support, resources and expertise necessary to identify and develop product candidates on the expected timeline, the data generated from Scholar Rock’s SAPPHIRE Phase 3 clinical trial, information provided or decisions made by regulatory authorities, Scholar Rock’s dependence on third parties for development and manufacture of product candidates including, without limitation, to supply any clinical trials, as well as those risks more fully discussed in the section entitled "Risk Factors" in Scholar Rock’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, 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. All information in this press release is as of the date of the release, and Scholar Rock undertakes no duty to update this information unless required by law.
Scholar Rock:
Investors
Rushmie Nofsinger
Scholar Rock
rnofsinger@scholarrock.com
ir@scholarrock.com
857-259-5573
Media
Molly MacLeod
Scholar Rock
mmcleod@scholarrock.com
media@scholarrock.com
802-579-5995
###
Exhibit 99.2
| CONFIDENTIAL AND PROPRIETARY Introduction of Scholar Rock’s Cardiometabolic Disorders Program Optimizing weight loss by preserving and increasing lean muscle mass with a highly selective myostatin inhibitor
© Scholar Rock, Inc. All rights reserved. 2023. Forward - Looking Statements Various statements in this presentation concerning the future expectations, plans and prospects of Scholar Rock, Inc. (“Schol ar 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 re sul ts from its preclinical and clinical trials for SRK - 439, apitegromab , SRK - 181, and other product candidates and indication selection and development timing, its cash runway, the ability of any product candidate to perform in humans in a manner consistent with earlier nonclinical, preclinical or clinical trial data, and the potential of its product candidates and proprietary platform. The use of words su ch as “may,” “could,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify su ch forward - looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. All such forward - looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by su ch forward - looking statements. These risks and uncertainties include, without limitation, that preclinical and clinical data, including the results from the Phase 2 trial of apitegromab or Part A of the Phase 1 trial of SRK - 181, are not predictive of, may be inconsistent with, or more favorable than, data generated from future clinical trials of the same product candidate, including the Phase 3 clinical tria l o f apitegromab in SMA and Part B of the Phase 1 clinical trial of SRK - 181, respectively, Scholar Rock’s ability to provide the financial support, resources and expertise necessary to identify and develop product candidates on the expected timeline, the data generated from Scholar Rock’s nonclinical and preclinical studies and clinical trials, information provided or decisions made by regulatory aut horities, competition from third parties that are developing products for similar uses, Scholar Rock’s ability to obtain, maintain and protect its intellectual property, the success of Scholar Rock’s current an d potential future collaborations, Scholar Rock’s dependence on third parties for development and manufacture of product candidates including, without limitation, to supply any clinical trials, Scholar R ock ’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, and the impacts of current macroeconomic and geopolitical events, hostilities in Ukraine, increasing rates of inflation and rising interest rates, on business operations and expectations, as well as those r isk s more fully discussed in the section entitled "Risk Factors" in Scholar Rock’s Form 10 - K for the year ended December 31, 2022, and Quarterly Report on Form 10 - Q for the quarter ended June 30 , 2023, 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 repres ent Scholar Rock’s views only as of today and should not be relied upon as representing its views as of any subsequent date. All information in this press release is as of the date of the release, and Scholar Rock und ertakes no duty to update this information unless required by law. This presentation and the accompanying oral presentation may also contain estimates and other statistical data made by indepe nde nt parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we compete are necessarily subject to a high degree of uncertainty and risk. Apitegromab , SRK - 181 and SRK - 439 are investigational drug candidates under evaluation. Apitegromab , SRK - 181 and SRK - 439 have not been approved for any use by the FDA or any other regulatory agency and the safety and efficacy of apitegromab and SRK - 181 have not been established.
© 2023 Scholar Rock, Inc. All rights reserved. Scholar Rock: Transforming Patient Lives, Addressing High Unmet Medical Need 3 • Global leader in TGF β superfamily biology • Targeting the latent forms of growth factors • Exquisite selectivity to deliver differentiated therapies Revolutionary Platform • Phase 3 SAPPHIRE study underway, enrollment completed in Q3 2023; data readout expected in Q4 2024 • Phase 1 proof - of - concept DRAGON trial in immuno - oncology: enrollment expected to be completed in Dec 2023 • Advance Ca rdiometabolic Program: • Plan to initiate proof of concept trial in obesity with apitegromab in combination with GLP - 1 RA in 2024 • Plan to concurrently advance SRK - 439, a novel investigational anti - myostatin antibody towards IND submission in 2025 Neuromuscular and Beyond • Compelling proof - of - concept TOPAZ data with apitegromab in spinal muscular atrophy (SMA) informed Phase 3 SAPPHIRE trial design • Seasoned leadership team with track record of clinical and commercial success Positioned for Success
© 2023 Scholar Rock, Inc. All rights reserved. Revolutionary Approach to Regulating TGF β Superfamily Implicated in Devastating Diseases 4 Scholar Rock’s R&D Platform Goals Aiming to Transform Medical Practice • Selectively target the latent form of growth factors in the microenvironment of cells and tissues with uniquely designed antibodies • Overcome the challenges that plague traditional approaches that target the “mature” active growth factor or its receptors, which are difficult to differentiate and lead to unintended negative effects Scholar Rock’s Target Latent G rowth Factor Traditional Target “mature” active growth factor TGF β Superfamily: Highly Sought - After Targets Dysregulation plays a role in devastating diseases that have a high unmet need, including: • Neuromuscular disorders • Fibrosis • Oncology Recognized by the industry as important targets given their fundamental roles in regulating a variety of biological processes
© 2023 Scholar Rock, Inc. All rights reserved. Differentiated Expertise Developing Muscle - Targeted Therapies 5 Next Frontier in Antimyostatin Leveraging Our R&D Platform to Expand into Cardiometabolic Disorders • Pioneered unique approach to develop antibodies that bind to pro - and latent forms of myostatin with exquisite selectivity and inhibit its activation • Apitegromab is being developed as a highly selective inhibitor of latent myostatin activation, to enhance muscle growth and function in neuromuscular disorders • To date apitegromab has been evaluated in approximately 250 patients ages 2 to 21 living with spinal muscular atrophy (SMA), showing sustained benefit over 36 months, a well tolerated profile and low discontinuation rate • Discovered multiple additional anti - pro/latent myostatin inhibitory antibodies including: • SRK - 439: Being developed as a novel, highly potent and selective antibody tailored for cardiometabolic disorders Myostatin is a member of the TGF β superfamily known to be a negative regulator of muscle mass and promotes muscle catabolism
© 2023 Scholar Rock, Inc. All rights reserved. Potential to transform the lives of people living with a wide range of serious diseases, including neuromuscular disorders, cardiometabolic, oncology, and fibrosis TARGET DISCOVERY/ PRECLINICAL PHASE 1 PHASE 2 PHASE 3 ANTICIPATED KEY MILESTONES Latent Myostatin SPINAL MUSCULAR ATROPHY Apitegromab SAPPHIRE Data Readout 2024 Commercial Launch 2025* CARDIOMETABOLIC DISORDERS Apitegromab in Obesity** File IND Initiate Ph 2 POC trial in 2024 SRK - 439 (novel antimyostatin antibody) IND - enabling studies in 2024 File IND in 2025 Latent TGF β - 1 IMMUNO - ONCOLOGY SRK - 181 (selective context - independent, anti - latent TGF β - 1) Rolling clinical data updates FIBROSIS Selective context - dependent (LTBP1 & LTBP3) anti - latent TGF β - 1 IND - enabling studies RGMc ANEMIA Selective anti - RGMc IND - enabling studies Robust Pipeline of Novel Product Candidates 6 LTBP3=latent transforming growth factor beta binding protein 3; LTBP1=Latent Transforming Growth Factor Beta Binding Protein 1; RGM=Repulsive guidance molecule; TGF β - 1 =Transforming Growth Factor Beta - 1 ; IND = Investigational New Drug; POC = Proof of Concept * Contingent upon receipt of regulatory approval; ** Ph1 studies in healthy volunteers have been completed.
© 2023 Scholar Rock, Inc. All rights reserved. Next Horizon: Cardiometabolic Disorders
8 Obesity is a common, serious, and costly chronic disease affecting adults and children worldwide Obesity is Recognized as a Top Global Public Health Issue By 2030, obesity will affect > 1 billion adults and >250 million children and adolescents 1 In the US, 1 in 5 children and more than 1 in 3 adults are obese Obesity can increase the risk of comorbidities, such as some cancers, heart disease, and type 2 diabetes 1 The World Obesity Foundation, World Obesity Atlas 2022; 2 Centers for Disease Control and Prevention (CDC) Obesity Facts, www.cdc.gov/obesity/about - obesity, accessed August 30, 2023; 3 Ward ZJ, Bleich SN, Long MW, Gortmaker SL (2021) Association of body mass index with health care expenditures in the United States by age and sex. PLoS ONE 16(3): e0247307 Adult obesity associated with more than $170 billion in excess costs annually in the U.S. 3
9 Loss of Lean Muscle Is Significant with GLP - 1 RA Therapies Lean muscle is essential to healthy metabolic function & body composition Situation • Significant challenges with current weight loss strategies (dietary/behavioral, pharmacological, surgical), including tolerability, lack of durability and significant muscle loss 1,2,3 • Recently approved GLP - 1 receptor agonists (GLP - 1 RAs) are highly effective in weight loss & experiencing rapid uptake • However, 25% - 40% of total body weight loss mediated by GLP - 1 RA therapy may be attributed to loss of lean muscle mass 2,3 • Preserving lean muscle mass is important to promote long - term metabolic benefits, sustainable weight management and health outcomes 4,5,6,7 Significant proportion of weight loss due to loss of lean muscle mass 1 Muller TD, et al Anti - obesity drug discovery: advances and challenges. Nature Reviews Drug Discovery 2022; 21, 201 – 223 ; 2 Wil ding JPH, Batterham RL, Calanna S, et al. Once - Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989 - 1002; 3 Jastreboff AM, et al Tirzepatide Once Weekly for the Treatment of Obesity. NEJM 2022; 387 (3): 205 - 216 ; 4 Cava et al. Preserving healthy muscle during weight loss. Adv Nutr 2017;8:511 - 19. ; 5 Lundgren JR et al. Healthy Weight Loss Maintenance with Exercise, Liraglutide or Both Combined. NEJM 2021;384:1719 - 30. ; 6 Beal JW et al. Dietary weight loss - induced improvements in metabolic function are enhanced by exercise in people with obesity and prediabetes. Nat Metab . 2022;5(7):1221 - 1235 ; 7 Dulloo AG, et al How dieting makes some fatter: from a perspective of human body composition autoregulation. Proc Nutr Soc. 2012 Aug;71(3):379 - 89 GLP - 1: glucagon - like peptide - 1
10 Obesity Landscape is Evolving & Growing: Estimated $70 - $100B Annual Revenues by 2035 1 1. Seigerman , ED, et al. “Obesity Exceptionalism: It’s different this time.” BMO Capital Markets: September 2023 retatrutide 2010 2014 2017 2021 2023 2025 2022
11 Recent KOL Interviews: Select Physicians See Value and Benefit in Muscle Maintenance During Weight Loss » Some key opinion leaders (KOLs) see a lack of standard of care (SOC) in obesity which leads to significant unmet need in large patient population » KOLs see the potential for additional benefit to patients as sustained results stem from exercise, proper diet and treatment » Combination therapy with other weight loss drugs (GLP - 1 RA) may have a synergistic effect on weight loss and benefit overall patient health » Patients may experience prolonged weight - loss and sustained results through the addition of muscle - targeted therapy Key Opportunities “There isn’t a set SOC right now for obesity and there clearly needs to be something out there that is standard and addresses the entire scope of the disease. If a company could address both weight loss and muscle maintenance, I think this could improve SOC significantly.” - KOL , PCP “I do see the importance of muscle mass, and this is something that if I could add to my patient’s program, I would in a heartbeat and really think it would make an impact. I have a lot of patients that would benefit from something like this.” - KOL , Endocrinologist Source : Clarion 2022 Analysis, Clarion KOL interviews
12 We believe Therapeutic Strategy for Safe, Durable Weight Loss Could Include a Highly Selective Antimyostatin to Retain Lean Muscle Opportunity • Inhibition of myostatin has demonstrated important physical (increased muscle mass) and beneficial metabolic effects (insulin sensitivity, basal metabolic rate, reduction in fat mass) in preclinical models 1 • Strong evidence has indicated upstream targeting of structurally differentiated pro - and latent myostatin leads to exquisite selectivity and avoids undesirable off - target effects 2 - 4 • Inhibition of myostatin in combination with GLP - 1 RA - driven weight loss may lead to retention of lean muscle mass and combat the counter - regulatory metabolic effects of weight loss 1 Yang M et al. Myostatin: A potential therapeutic target for metabolic syndrome. Frontiers in Endocrinology 2023;14:1181913 ; 2 Pirruccello - Straub M et al. Blocking extracellular activation of myostatin as a strategy for treating muscle wasting. Sci Reports 2017;8:2922; 3 Welsh BT et al. Preclinical safety assessment and toxicokinetics of apitegromab, an antibody targeting proforms of myostatin for the treatment of muscle - atrophying disease. Int J Tox 2021;40(4):322 - 336. ; 4 Barrett D et al. A randomized phase 1 safety, pharmacokinetic and pharmacodynamic study of a novel myostatin inhibitor apitegromab (SRK - 015): A potential treatment for spinal muscular atrophy. Adv Ther 2021;38:3203 - 3222. SRRK’s antimyostatin antibody
13 Scholar Rock Antibodies Selectively Inhibit Activation of Myostatin Selective Targeting of Proforms of Myostatin SRRK antibodies do not bind to mature myostatin or any form of GDF11, Activin A, or other TGF - β family members Selectivity is critical to avoid safety concerns ▪ Mature myostatin and mature GDF11 have 90% sequence conservation ▪ Most prior myostatin approaches bind/inhibit both myostatin and GDF11 ▪ GDF11 loss leads to embryonic lethality, skeletal and kidney formation defects 1 ▪ GDF11 signaling inhibition may have negative impacts on bone 2 Broad inhibition of ActRIIb signaling may be problematic ▪ ActRIIB knockout animals die shortly after birth with developmental defects in respiratory and cardiac organs 3 ▪ Activins are critical in reproductive biology and inhibition was shown to reduce FSH levels in women 4 13 1.McPherron AC et al Nat Genet 1999, 22(3):260 - 264.; 2. Joonho Suha et al Proc Natl Acad Sci U S A . 2020 Mar 3;117(9):4910 - 4920 ; 3. Oh SP & Li E. Genes Dev . 1997 Jul 15;11(14):1812 - 26; 4. Garito T, et al. Clin Endocrinol (Oxf) . 2018 Jun;88(6):908 - 919 GDF11: Growth and Differentiation factor 11 ; ActRIIB : Activin Receptor IIB Apitegromab SRK - 439 Pro - GDF - 11 Proactivin Myostatin GDF - 11 Activin A Promyostatin ActRIIB
© 2023 Scholar Rock, Inc. All rights reserved. SRK - 439 Preclinical Data 14
15 SRK - 439: New Preclinical Myostatin Inhibitor Candidate Represents Opportunity to Address Cardiometabolic Patient Population Antibody/ Variant mTLL2 IC 50 ( nM ) mAb K D ( nM ) SRK - 439 0.145 0.579 • SRK - 439 , a novel antimyostatin antibody being developed by SRRK, has attractive properties and potential to address muscle loss associated with weight loss ▪ High in vitro affinity for pro - and latent myostatin ▪ Maintained myostatin specificity (No GDF11 or Activin - A binding) ▪ Maintained good developability profile • Amenable to subcutaneous formulation and dosing ▪ High concentrations achieved with unoptimized standard buffer Several lead candidates identified 150nM 0.24nM 0 1 2 3 Campaign Screening High Conc Low Conc A b s ( 4 5 0 n m ) 150nM 0.24nM L o w e r t h e A b s ( 4 5 0 n M ) G r e a t e r A c t i v i t y mTLL2 IC 50 : Inhibitory concentration at 50% as measure of in vitro potency of the antibody in its ability to inhibit the activation of lat ent myostatin by its activating enzyme mammalian tolloid like protease 2 | K D : Equilibrium dissociation constant as a measure of binding affinity of the antibody to latent myostatin. Represents highest activity of existing SRRK antimyostatin antibody at the time of initiation of the new discovery campaign Selection of new leads with activities ≥ previous antibodies that were advanced for further testing
16 SRK - 439 Maintained Lean Mass in Mouse Diet Induced Obesity (DIO) Model When Combined with GLP - 1 RA Therapy -80 -60 -40 -20 0 20 40 60 80 % Change Fat Mass from Baseline (qNMR) % C h a n g e IgG IgG 3 1 0.3 0.06mg/kg Lira SRK-439 ▪ Improved fat mass loss vs GLP - 1 RA alone -20 -10 0 10 20 % Change Lean Mass from Baseline (qNMR) % C h a n g e IgG IgG 3 1 0.3 0.06mg/kg Lira SRK-439 **** **** **** ▪ Increased lean mass gain vs GLP - 1 RA alone One - way ANOVA * P< 0.05 ** P< 0.005 *** P< 0.0005 **** P< 0.0001 Figure shows the effects of increasing doses of SRK - 439 in combination with liraglutide on fat mass (left panel) and lean mass (right panel) in a 28 - day DIO mouse model as measured by qNMR ; statistical analysis was done using one - way ANOVA (Dunnett’s multiple comparison test).
17 SRK - 439 Dose - Dependently Reversed Lean Mass Loss in Mouse DIO and Enhanced Fat Mass Loss Induced by Semaglutide Treatment -80 -60 -40 -20 0 20 % Change - Fat Mass (qNMR) % C h a n g e IgG S R K - 4 3 9 IgG 0.1 0.3 1.0 3.0 SRK-439 (mg/kg) Semaglutide 0.04 mg/kg -20 -10 0 10 20 % Change - Lean Mass (qNMR) % C h a n g e IgG S R K - 4 3 9 IgG 0.1 0.3 1.0 3.0 SRK-439 (mg/kg) Semaglutide 0.04 mg/kg ✱ ✱✱✱✱ One - way ANOVA * P< 0.05 ** P< 0.005 *** P< 0.0005 **** P< 0.0001 Figure showed the effects of increasing doses of SRK - 439 in combination with liraglutide on fat mass (left panel) and lean mass (right panel) in DIO mouse model as measured by qNMR ; statistical analysis was done using one - way ANOVA (Dunnett’s multiple comparison test). ▪ Additional fat mass loss vs semaglutide alone ▪ Dose - dependent preservation of lean mass with effects seen as low as 0.3mg/kg
18 ▪ Preclinical data suggests mechanism of action that could safely reduce body fat while maintaining muscle , thereby enhancing metabolic health ▪ Studies in DIO mice on the effects of GLP - 1 receptor agonist (GLP - 1 RA) in combination with a myostatin - selective inhibitor showed: – Dose - dependent reversal of lean mass loss mediated by GLP - 1 RA treatment – Enhancement of fat mass loss mediated by GLP - 1 RA treatment ▪ Initial preclinical data for SRK - 439 , a novel myostatin selective inhibitor, supports an overall profile for a differentiated molecule designed to address cardiometabolic patient population – Potentially suitable for subcutaneous administration ▪ Filed composition of matter patent for SRK - 439 with projected expiry of 2043 SRRK Selective Myostatin Inhibitors Represent an Opportunity to Address High Unmet Need in Cardiometabolic Disorders DIO: Diet Induced Obesity / GLP - 1: glucagon - like peptide 1
19 Plan to Expedite Cardiometabolic Program with Phase 2 Proof of Concept Study of Apitegromab in Obesity SRK - 439 Rapid Proof of Concept Phase 2 Study with A pitegromab in combination with GLP - 1 APITEGROMAB While a dvanc ing investigational SRK - 439 for cardiometabolic indication 2023 2024 2025 Apitegromab (SMA) Apitegromab POC ( Cardiomet ) Pipeline: SRK - 439 Enrollment Completed Q3 SAPPHIRE Topline Q4* POC study start * POC data readout * DC candidacy * IND * Potential Commercial Launch * Expanding antimyostatin programs creates additional potential milestones in next 18 - 24 months * Anticipated milestones
© 2023 Scholar Rock, Inc. All rights reserved. 20 • Preclinical data suggests selective mechanism of action that can maintain muscle mass while enhancing fat mass loss, thereby improving metabolic function • SRK - 439: Preclinical data supports the overall target candidate profile to address the cardiometabolic patient population • Represents a potential new class of treatment Differentiation • Strong pre - clinical evidence indicates maintenance or increase in lean muscle mass & enhancement of fat loss when a myostatin selective inhibitor is combined with GLP - 1 receptor agonist (GLP - 1 RA) • Scholar Rock has the potential to lead the next frontier in anti - myostatin therapies with pioneered unique approach and differentiated expertise Strong Scientific Rationale • Expanded investments in pipeline, including to accelerate and advance cardiometabolic program Investment Opportunity • Obesity is a growing global epidemic leading to chronic health problems and 4.7M premature deaths annually 1 • Clinical and commercial landscape evolving quickly amid high unmet need • Muscle - targeted approach represents a new potential class of treatments High Unmet Medical Need & Significant Commercial Opportunity Cardiometabolic Program Summary 1 www.who.int/news - room/fact - sheets/detail/obesity - and - overweight
© 2023 Scholar Rock, Inc. All rights reserved. THANK YOU 21
© 2023 Scholar Rock, Inc. All rights reserved. APPENDIX 22
© 2023 Scholar Rock, Inc. All rights reserved. Ongoing SAPPHIRE Phase 3 Trial Overview 23 Randomized, double - blind, placebo - controlled, parallel arm design (n=204) Enrolling patients who are on SMN - directed therapy ( nusinersen or risdiplam ) Anticipate completing enrollment in 3Q 2023 TREATMENT (52 weeks) Apitegromab (20 mg/kg IV q4w) + SMN - directed therapy Apitegromab (10 mg/kg IV q4w) + SMN - directed therapy Placebo (IV q4w) + SMN - directed therapy SCREENING MAIN POPULATION (n=156) Ages 2 - 12 With nonambulatory Types 2 and 3 SMA N=52 N=52 N=52 R Stratified to ensure balanced allocation across the three arms: 1. Age at SMN therapy initiation (age < 5 vs age ≥ 5) 2. SMN therapy ( nusinersen vs. risdiplam ) ENDPOINTS Primary Efficacy: Mean HFMSE change from baseline at 12 months Additional Efficacy Measures: RULM, WHO, other outcome measures Safety, PK/PD, ADA Additional Data Opportunities Exploratory population (age 13 - 21), in patients using SMN therapy Focused upon safety & exploratory efficacy (n=48; 2:1 randomization between apitegromab 20 mg/kg vs placebo) Separate open - label extension study (after patients complete 12 - month treatment period) Focused upon safety & exploratory long - term efficacy ClinicalTrials.gov Identifier: NCT05156320 HFMSE=Hammersmith Functional Motor Scale Expanded; RULM=Revised Upper Limb Module; R=randomization; SMA=spinal muscular atrop hy; SMN=survival motor neuron.
© 2023 Scholar Rock, Inc. All rights reserved. Executing on the Promise: Apitegromab SMA Trials 24 SMA=Spinal Muscular Atrophy *Subject to regulatory approval WHERE WE ARE Phase 3 12 - Month IN PROCESS Long - term EXTENSION 2023 enrollment completed Q4 2024 data 2025 launch* ANTICIPATED MILESTONES WHERE WE WERE Phase 2 12 - Month COMPLETE 24 - Mont h EXTENSION COMPLETE 36 - Month EXTENSION COMPLETE WHERE WE PLAN TO GO Ambulatory patients Under 2 Years of Age (including those treated with gene therapy)