Full Press Release Details
Patients 42nd ANNUAL J.P. MORGAN HEALTHCARE CONFERENCE JANUARY 9, 2024
Statements 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 preclinical studies 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 such 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 such 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 such 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 or Part B of the Phase 1 trial of SRK-181, are not predictive of, may be inconsistent with, or more favorable than,
data generated from future or ongoing clinical trials of the same product candidate, including the Phase 3 clinical trial of 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 authorities, 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
and 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 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, 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 risks 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 September 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. This presentation may also contain estimates and other statistical data made by independent 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 and SRK-181 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, SRK-181 and SRK-439 have not been established.
3 TGF =Transforming growth factor-beta. SMA=Spinal muscular atrophy *Christopher
is a participant in the TOPAZ and ONYX clinical trials. OUR MISSION To discover, develop, and deliver life-changing therapies by harnessing cutting-edge science to create new possibilities for people living with serious diseases We are a
4 Building a Fully Integrated Therapeutics Company SMA=Spinal muscular atrophy;
EMA=European Medicines Agency; FDA=United States Food and Drug Administration; R&D=research and development. Apitegromab in SMA Potential therapy in Ph 3 designed to improve motor function to help address remaining unmet need after
receipt of existing SMA therapies SRK- 439 in Obesity Novel antimyostatin antibody with the potential to support healthier weight management by preserving lean muscle SRK-181 in Immuno-Oncology In Ph 1 development to overcome resistance to
checkpoint inhibitors in multiple tumor types Revolutionary Scientific Platform Pioneers in unparalleled selective targeting of the latent forms of growth factors Robust pipeline of novel assets including two clinical programs and a
growing portfolio of preclinical programs Transformative Therapeutics in Development Experienced and Focused Seasoned team with track record of clinical and commercial success Deep rare disease, R&D, FDA/EMA approval & launch
Traditional Target "mature" active growth factor Scholar Rock's Target Latent
Growth Factor Our Approach S e l e c t i v i t y D r i v e s S u c c e s s Industry-leading antibody design and protein engineering to selectively target latent growth factors Optimized for efficacy and mitigates off-target effects Deep
Latent Myostatin SPINAL MUSCULAR ATROPHY Apitegromab CARDIOMETABOLIC
DISORDERS Apitegromab in Obesity* SRK-439 (novel antimyostatin antibody) Latent TGF -1 IMMUNO-ONCOLOGY SRK-181 (selective context-independent, anti-latent TGF -1) FIBROSIS Selective context-dependent (LTBP1 & LTBP3) anti-latent
TGF -1 RGMc ANEMIA Selective anti-RGMc TARGET DISCOVERY/ PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Potential to transform the lives of people living with a wide range of serious diseases, including neuromuscular disorders, cardiometabolic
disorders, oncology, and fibrosis Advancing a Robust Pipeline with Our Differentiated Platform * Subject to receipt of regulatory authority approval. We plan to utilize data from a previously completed Ph 1 study in healthy volunteers and
initiate a Ph 2 POC trial in 2024. LTBP1=Latent transforming growth factor beta binding protein 1; LTBP3=Latent transforming growth factor beta binding protein 3; POC=Proof of concept; RGMc=Repulsive guidance molecule C; TGF -1=Transforming
in Spinal Muscular Atrophy
8 Hallmarks of SMA Motor Neuron Loss and Muscle Atrophy Leads to Progressive
Muscle Weakness SMA=Spinal muscular atrophy; SMN=Survival motor neuron. Hua Y, et al. Nature. 2011;478(7367):123-6. Figure adapted from: SMA Foundation Overview. http://www.smafoundation.org/wp-content/uploads/2012/03/SMA-Overview.pdf.;
Accessed April 18, 2021. S P I N A L M U S C U L A R A T R O P H Y SMN therapies slow further degeneration of motor neurons1 ...but do not directly address muscle atrophy Motor neuron degeneration2 Muscle fiber atrophy Spinal Muscular
Atrophy Motor neuron impairment and loss due to SMN genetic deficiency leads to muscle atrophy and weakness There is further potential to regain vital muscle function by also addressing the progressive muscle atrophy and associated weakness
SMA Leads to Deterioration in Essential Muscle Function Quotes are from patient
advocates who participated in 2022 Cure SMA FDA Patient-Led Listening Session and not from the pictured individuals. Summary of the listening session can be found on the FDA website at
https://www.curesma.org/cure-sma-holds-patient-led-listening-session-with-fda/ 9 S P I N A L M U S C U L A R A T R O P H Y Despite significant advancements, progressive muscle weakness remains an unmet need in SMA Small tasks are huge
success in my life. If I could lift that 1L bottle of water at work instead of having to find a graduate student to move it for me things don't take a ton more muscle, but they are all muscle I still don't have. What may seem like minimal
gains in strength actually translate to exponential gains in functional abilities. I often have to choose between taking a shower and doing homework because I don't have the energy to do both. Muscle weakness can lead to deterioration in
10 SMA Today: More Patients Screened and Treated CHF=Swiss franc; LTM=last
twelve months; SMA=Spinal muscular atrophy; SMN=Survival motor neuron; WW=worldwide. Cure SMA 2022 Report: 9042022_State-of-SMA_vweb.pdf (curesma.org) Lally et al. Indirect estimation of the prevalence of spinal muscular atrophy Type I, II,
and III in the United States. Orphanet J Rare Dis. 2017 Nov 28;12(1):175. doi: 10.1186/s13023-017-0724-z. Revenue as of Biogen 3Q23 financial update; includes patients treated worldwide in post-marketing setting, expanded access program, and
clinical trials as of May 2022. Revenue as of Roche 3Q23 financial update; includes patients treated worldwide as of July 2023. S P I N A L M U S C U L A R A T R O P H Y GLOBAL DISEASE: >20,000 affected in US and Europe1, 2 Three
treatments to address SMN loss >13,000 patients treated WW $1.8 billion annual revenue (LTM)3 > 11,000 patients treated WW ~CHF1.4 billion annual revenue (LTM)4 > 3,500 patients treated WW ~$1.2 billion in revenues
(LTM)5 Established market dynamics support Scholar Rock's first potential commercial launch 5. Revenue as of Novartis 3Q23 financial update; includes patients treated worldwide including clinical trials, commercially, and managed access
11 Muscle-Targeted Therapy: A New Treatment Frontier *Percentages represent
percent of patients who named these unmet needs when asked, "What are your most significant current unmet needs that you hope new therapies would address?" HFMSE=Hammersmith Functional Motor Scale-Expanded. 1. Mercuri E et al.; N Engl J Med
2018; 378:625-635; DOI: 10.1056/NEJMoa1710504; cherish trial results; 2. 2022 Community Update Survey, Cure SMA. S P I N A L M U S C U L A R A T R O P H Y 0 Mean improvement in HFMSE experienced by patients in nusinersen Phase 3 CHERISH
trial1 20 40 60 80 3.9-point increase in HFMSE from nusinersen (4.9 point increase relative to sham control) HFMSE Score at Month 15 Total Possible HFMSE Score of 66 Unmet need remains substantial Patients and caregivers want new
therapies to address the following unmet needs2 : INCREASE muscle strength 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. 2024 Scholar
12 Apitegromab Offers Significant Potential to Address Unmet Needs * Based on
Animal Model Data; 1. Long KK, et al. Hum Mol Genet. 2019;28(7):1077-1088; 2. Pirruccello-Straub M, et al. Sci Reports. 2018;8(1):2292. doi:10.1038/s41598-018-20524-9 3. S P I N A L M U S C U L A R A T R O P H Y Apitegromab is a selective
MUSCLE-TARGETED APPROACH designed to improve motor function*1,2 Myostatin is a negative modulator of muscle growth Strong clinical and preclinical evidence indicates upstream targeting of structurally differentiated pro- and latent myostatin
avoids undesirable off-target effects Apitegromab specifically and only inhibits myostatin and has the potential to build muscle and strength to improve patient outcomes Apitegromab Muscle fiber atrophy Motor neuron degeneration3 Figure
observations N = 35; Baseline mean age=7.3 |Time on SMN Rx=24.1m PRO=patient reported outcomes; HFMSE=Hammersmith Functional Motor Scale Expanded; OC=observed case; PEDI-CAT=Pediatric Evaluation of Disability Inventory Computer Adaptive Test;
PROMIS=Patient Reported Outcome Measurement Information System; RULM=Revised upper limb module; SE=standard error of the mean. Pooled nonambulatory patients, age 2-21, all doses. Crawford et al., Cure SMA 2023 32 32 31 27 27 27 Change
from baseline ( SE) Year 1 IMPROVEMENT 8 7 6 5 4 3 2 1 0 -1 -2 0 136 156 Year 1 IMPROVEMENT 2 1 0 -1 -2 -3 -4 -5 -6 -7 -8 0 PROMIS Fatigue (Proxy) Year 2 Year 3 IMPROVEMENT 28 27 Change from baseline
( SE) 5 4 3 2 1 0 -1 -2 0 Time (weeks) 0 8 16 24 32 40 52 68 84 104 120 136 156 0 8 16 24 32 40 52 68 84 104 120 136 156 No. of observations 31 29 30 21 23 25 25 27 22 23 16 15 17 25 23 22 19 19 22 16 18 19 19 16 14 14 0 8 16 24 32
40 52 68 84 104 120 35 35 34 29 28 29 32 32 32 29 27 PEDI-CAT Daily Activities Year 1 Year 2 Year 3 Year 3 Year 2 Year 3 Year 1 Year 2 -2 -1 0 1 2 3 4 0 0 8 16 24 32 40 52 34 34 34 28 27 29 31 68 84
104 120 136 156 IMPROVEMENT HFMSE RULM 13 S P I N A L M U S C U L A R A T R O P H Y TOPAZ Over 36 Months Sustained Functional and PRO Improvements Beyond SMN Treatment
14 TOPAZ Over 36 Months Well Tolerated Safety Profile & Low Discontinuation
Rate S P I N A L M U S C U L A R A T R O P H Y RIGHT TIME L a t e n t F o r m M y o s t a t i n RIGHT TARGE T Crawford et al., Cure SMA 2023 * Excludes patients on monotherapy >90% of patients on combination therapy remained in
extension study* Treatment-emergent adverse events (TEAEs) were consistent with previous reports with no new findings after 198 patient- years of exposure - Most frequently reported TEAEs included headache, pyrexia, COVID-19,
nasopharyngitis, & upper respiratory tract infection - TEAEs were mostly mild to moderate and generally consistent with the underlying patient population and nusinersen therapy No treatment-related serious AEs or hypersensitivity
15 SAPPHIRE Phase 3 Design is Optimized by Insights from TOPAZ HFMSE=Hammersmith
Functional Motor Scale Expanded. TOPAZ Learnings SAPPHIRE Design Elements Phase 3 SAPPHIRE Trial Registrational trial with topline 12-month data readout expected in Q4 2024 S T U D Y P O P U L A T I O N Substantial HFMSE gains observed in
the nonambulatory Type 2/3 SMA cohorts A G E Exploratory age 2-12 analysis in nonambulatory Type 2/3 showed transformative potential D U R A T I O N HFMSE gains substantial by 12 months of treatment D O S E Dose response seen (greater
effect observed with 20 mg/kg over 2 mg/kg) S T U D Y P O P U L A T I O N Nonambulatory Type 2/3 SMA Primary efficacy endpoint: HFMSE A G E Age 2-12 main efficacy population Age 13-21 exploratory population D U R A T I O N 12-month
16 Apitegromab: Potential to Maximize Outcomes for People Living with Spinal
Muscular Atrophy (SMA) Apitegromab is an investigational drug candidate being evaluated for the treatment of spinal muscular atrophy (SMA). Apitegromab has not been approved for any use by the FDA or any other regulatory agency, and its safety
and efficacy have not been established. S P I N A L M U S C U L A R A T R O P H Y Phase 2 TOPAZ Trial Demonstrated substantial and sustained functional improvements in Type 2 and nonambulatory Type 3 SMA patients First and only
Open-Label Extension Study Evaluating the long-term safety and efficacy of apitegromab in patients who have completed TOPAZ or SAPPHIRE Transformative Potential to Change the Standard of Care
17 Expanding to Benefit More People Living with SMA *Subject to regulatory
approval. SMA=Spinal muscular atrophy; Sub-Q=Subcutaneous S P I N A L M U S C U L A R A T R O P H Y WHERE WE ARE WHERE WE WERE WHERE WE ARE GOING P H A S E 2 12-Month COMPLETE 24-Month EXTENSION COMPLETE 36-Month EXTENSION
COMPLETE 12-Month Q4 2024 data P H A S E 3 Scale for Commercial Launch (2025)* Under 2 Years of Age (including those treated with gene therapy) Ambulatory Population Sub-Q Formulation Long-term EXTENSION for TOPAZ and SAPPHIRE
Program: Cardiometabolic Disorders
Obesity is Recognized as a Top Global Public Health Issue 1. The World Obesity
Foundation, World Obesity Atlas 2022; 2. 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. BY 2030, OBESITY WILL
AFFECT: >1 BILLION adults >250 MILLION children and adolescents1 Obesity can increase the risk of comorbidities, such as some cancers, heart disease, and type 2 diabetes Adult obesity associated with more than $170 billion in
excess costs annually in the U.S.2 In the US, 1 in 5 children and more than 1 in 3 adults are obese Obesity is a common, serious, and costly chronic disease affecting adults and children worldwide 19 O B E S I T Y 2024 Scholar Rock,
20 Loss of Lean Muscle Significant with GLP-1 RA Therapy Lean muscle is
essential to healthy metabolic function GLP-1 RA=Glucagon-like peptide-1 receptor agonists. 1. Muller TD, et al Anti-obesity drug discovery: advances and challenges. Nature Reviews Drug Discovery 2022; 21, 201-223; 2. Wilding 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. O B E S I T Y Significant proportion of weight loss due to loss of lean muscle mass Recently approved GLP-1 RAs are highly effective in weight loss & experiencing rapid uptake But 25%-40% of
total body weight loss mediated by GLP-1 RA therapy may be attributed to loss of lean muscle mass2,3 Preserving lean muscle mass is important to promote long-term metabolic benefits, sustainable weight management and health
21 Maintaining Muscle is Important for Healthy Weight Loss GLP-1
RA=Glucagon-like peptide-1 receptor agonist. 1. Aristizabal JC, Freidenreich DJ, Volk BM, et al. Effect of resistance training on resting metabolic rate and its estimation by a dual-energy X-ray absorptiometry metabolic map. Eur J Clin
Nutr.2015; 69, 831-836. https://doi.org/10.1038/ejcn.2014.216; 2. Lindegaard B, Hansen T, Hvid T, et al. The effect of strength and endurance training on insulin sensitivity and fat distribution in human immunodeficiency virus-infected patients
with lipodystrophy. J Clin Endocrinol Metab. 2008; 93:3860-9; 3. Srikanthan P, Karlamangla AS. Relative muscle mass is inversely associated with insulin resistance and prediabetes. Findings from the third National Health and Nutrition
Examination Survey. J Clin Endocrinol Metab. 2011; 96:2898-903. doi: 10.1210/jc.2011-0435; 4. Wewege MA, Desai I, Honey C, et al. The effect of resistance training in healthy adults on Body fat percentage, fat mass and visceral fat: A
systematic review and meta-analysis. Sports Med. 2022(Feb);52(2):287-300. doi: 10.1007/s40279-021-01562-2; 5. Zurlo, F., Larson, K., Bogardus, C., et al. Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin
Invest. 1990;86(5), 1423-1427; 6. Fukushima Y, Kurose S, Shinno H, et al. Importance of lean muscle maintenance to improve insulin resistance by body weight reduction in female patients with obesity. Diabetes Metab J. 2016;40: 147-153; 7. Roh
E, Choi KM. Health consequences The preservation of lean mass has many benefits for overall health: Improved strength Improved insulin sensitivity Increased basal metabolic rate Improved metabolic profile Reduced total body fat O B E S I