Deep Insights Advancing Impactful Medicines Company Overview | January 2025 © 2025 Scholar Rock, Inc. All rights reserved. Forward-Looking Statements Various statements in this presentation concerning the future expectations, plans and prospects of Scholar Rock Holding Corporation and Scholar Rock, Inc. (collectively, "Scholar Rock"), including without limitation, Scholar Rock's expectations regarding its strategy, its product candidate selection and development timing, including timing for the initiation o ...

Financial Data and Key Metrics Changes - Scholar Rock reported an outstanding year in 2024, with significant progress towards regulatory milestones for apitegromab, including the submission of the BLA in the U.S. in January and the upcoming MAA submission in the EU in March [6][36]. - The company anticipates a transformative year in 2025, with plans for a potential launch of apitegromab in the U.S. in Q4 2025 and in the EU in 2026 [37]. Business Line Data and Key Metrics Changes - The SAPPHIRE study demonstrated that apitegromab plus standard-of-care resulted in a 1.8% improvement in the Hammersmith Functional Motor scale compared to placebo, with 30% of patients achieving a 3-point or greater improvement [9][10]. - The cardiometabolic program is on track to share top-line data from the EMBRAZE study in Q2, with the IND filing for SRK-439 planned for Q3 [8][35]. Market Data and Key Metrics Changes - Approximately two-thirds of the 10,000 individuals living with SMA in the U.S. and 35,000 globally have received SMA-targeted therapy, indicating a significant market opportunity for apitegromab as a muscle-targeted therapy [14][15]. - The current market for GLP-1 receptor agonists is projected to generate over $100 billion in sales, highlighting the potential impact of Scholar Rock's cardiometabolic programs [22]. Company Strategy and Development Direction - Scholar Rock aims to establish a neuromuscular franchise starting with SMA, with plans to expand treatment to other neuromuscular disorders [37]. - The company is focused on building a strong commercial team and infrastructure to support the launch of apitegromab, including outreach to payers and scaling the customer-facing team [19][20]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of apitegromab to transform the standard of care for SMA, emphasizing the importance of addressing progressive muscle weakness [12][15]. - The company is optimistic about the EMBRAZE study and the potential for SRK-439 to enhance weight management therapies by preserving lean muscle mass [35][36]. Other Important Information - Scholar Rock has initiated a disease education campaign called "Life Takes Muscle" to raise awareness about the impacts of muscle weakness in SMA [16][17]. - The company is preparing to offer home infusion services at launch to enhance patient support [19]. Q&A Session Summary Question: Discussion on SAPPHIRE data presentation - Management highlighted the importance of presenting additional data points at the MDA conference, focusing on the consistency and impact across age groups and endpoints [42][43]. Question: Insights on obesity and lean mass preservation - Management clarified that a 20% to 40% improvement in lean mass is considered clinically meaningful, and they are looking for trends in the EMBRAZE study to inform the development of SRK-439 [41][47]. Question: Exploration of additional neuromuscular indications - Management is actively engaging experts to explore adjacent neuromuscular indications and is assessing the unmet need and technical success probability for potential studies [60][63]. Question: Implications of FDA guidance on obesity trials - Management noted that the FDA's guidance reinforces the importance of assessing lean mass loss and that they will continue to follow this closely while developing SRK-439 [69][71]. Question: Comparison of SRK-439 and apitegromab - Management expressed confidence in the profile of SRK-439, indicating it may have greater affinity for the target and could potentially offer advantages in dosing and efficacy [80][82]. Question: Initial payer discussions and pricing strategy - Payers have shown receptiveness to Scholar Rock's innovation, and management expects access to be reflective of the value apitegromab brings to SMA treatment [85][86]. Pricing details are not yet disclosed but are expected to align with other SMA treatments [89].

Regulatory Approval and Compliance - The company is preparing for the potential commercialization of apitegromab in the U.S. and Europe, investing significant resources in compliance, medical affairs, and commercial organizations[339]. - The company anticipates submitting a Biologics License Application (BLA) for apitegromab in January 2025, which requires extensive preclinical and clinical data[336]. - The company is seeking priority review for apitegromab, which could shorten the FDA's review time to six months if granted[346][349]. - The regulatory approval process for product candidates is lengthy and unpredictable, with potential delays impacting commercialization[330][336]. - Changes or disruptions at the FDA and other regulatory agencies could negatively impact the timely review and approval of the company's applications[343][344]. - The company must comply with Good Clinical Practice (GCP) requirements, and any non-compliance could delay regulatory approval[372]. - Regulatory approvals may come with limitations on approved uses and requirements for costly post-market testing, including Phase 4 clinical trials[395]. - Regulatory approval in one jurisdiction does not guarantee approval in others, and failures in one region may negatively impact the approval process elsewhere[389]. - The company is subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expenses and penalties for non-compliance[393]. - The company may not be able to realize the benefits associated with Orphan Drug designation if it fails to meet regulatory requirements or if the designation is revoked[379]. Financial Performance and Capital Needs - The company has incurred net losses every year since inception and expects to continue incurring losses, necessitating additional capital for operations[335]. - The company expects to rely on third-party manufacturers for commercial supplies of apitegromab, with no long-term supply agreements in place, which may lead to delays in clinical trials or commercialization if new manufacturers are needed[414]. - The company may face substantial civil and criminal penalties for failing to comply with international business laws, which could hinder government contracting opportunities[457]. - The company may struggle to obtain adequate product liability insurance, which could inhibit the commercialization of developed products[462]. Clinical Development and Trials - The Phase 2 TOPAZ trial for apitegromab showed sustained clinical benefit over 48 months, with a retention rate of over 90% in nonambulatory Types 2 and 3 SMA patients[362]. - The Phase 3 SAPPHIRE trial for apitegromab announced positive top-line data in October 2024, indicating efficacy and safety[362]. - The company initiated the Phase 2 EMBRAZE trial of apitegromab in obesity in May 2024, with top-line results expected in Q2 2025[362]. - Delays in clinical trials may arise from various factors, including regulatory agreements and site negotiations, potentially leading to denial of regulatory approval[352]. - Access to approved therapies is critical for ongoing trials; any limitations could necessitate pausing or stopping clinical studies[359]. - The company anticipates that clinical trial delays could shorten exclusive commercialization periods, allowing competitors to enter the market sooner[358]. - The company may face difficulties in patient enrollment for clinical trials due to the small size of the SMA patient population and competition with other trials[367]. - Delays in patient enrollment could result in increased costs and affect the timing or outcome of future clinical trials, potentially hindering the development of product candidates[368]. - The company relies on third parties for conducting clinical trials, and any failure by these parties to meet contractual obligations could materially harm the business[369]. Market and Competitive Landscape - Market acceptance of product candidates is uncertain and depends on factors such as efficacy, safety, and competitive pricing[400]. - The biopharmaceutical industry is highly competitive, with many companies potentially developing similar products, which could affect market share[405]. - The company may seek collaborations for product candidates like apitegromab, SRK-181, and SRK-439, but failure to secure successful collaborations could adversely affect business[477]. - Collaborations pose risks such as collaborators not performing obligations satisfactorily or failing to pursue development of product candidates[480]. - The company faces significant competition in seeking appropriate partners for product candidates, and the negotiation process is complex and time-consuming[484]. Intellectual Property and Legal Risks - The ability to protect intellectual property is crucial for commercial success, and challenges in securing patent protection could adversely affect the commercialization of product candidates[486]. - The patenting process is expensive and time-consuming, and failure to maintain compliance with patent requirements could result in loss of patent rights[492]. - The company depends on intellectual property licensed from third parties, and failure to comply with obligations under these licenses could result in significant rights loss[498]. - The company may have limited control over the maintenance and prosecution of in-licensed patents and patent applications, which could affect the validity and enforceability of these rights[499]. - Disputes may arise regarding intellectual property subject to license agreements, potentially impairing the ability to develop and commercialize product candidates[500]. - Changes in patent law in the U.S. and other jurisdictions could diminish the value of patents, impairing the ability to protect products[508]. - Recent U.S. Supreme Court rulings have narrowed the scope of patent protection, creating uncertainty regarding the value of patents once obtained[510]. - Third-party claims of intellectual property infringement may delay product discovery and development efforts, leading to potential litigation costs[514]. Operational and Management Challenges - Future growth will require hiring additional personnel across various functions, which may pose challenges in managing this growth effectively[422]. - The company is dependent on third parties for critical services, and any failure to manage these relationships could delay regulatory approvals and hinder business advancement[423]. - Attracting and retaining qualified personnel in the competitive biopharmaceutical space is crucial, and failure to do so may impede the company's ability to develop and commercialize its product candidates[424]. - Management transitions or loss of key personnel could disrupt the company's strategy and operational execution, negatively affecting business performance[425]. - Cybersecurity risks and potential breaches of IT systems could disrupt operations and delay development programs, impacting the company's overall business[429]. Compliance and Regulatory Costs - The EU General Data Protection Regulation (GDPR) imposes fines of up to €20 million or 4% of total worldwide annual turnover for serious offenses, highlighting the financial risks associated with non-compliance[438]. - The UK GDPR allows for monetary penalties of up to £17.5 million or 4% of worldwide revenue, whichever is higher, indicating significant compliance costs[439]. - The company is subject to various healthcare laws and regulations that could expose it to civil penalties and reputational harm, affecting future earnings[434]. - The introduction of the EU's Artificial Intelligence Act may require the company to implement costly compliance measures, impacting research and development budgets[450]. - Compliance with state privacy laws, such as California's CCPA, may necessitate operational changes and increase overall compliance costs[445]. - The adequacy decision for the EU-U.S. Data Privacy Framework allows for safe data transfers but carries risks of future challenges, increasing regulatory complexity[442]. - The evolving regulatory landscape for artificial intelligence may require substantial resources to ensure compliance and mitigate risks associated with new technologies[450]. Product Liability and Market Risks - Product liability lawsuits pose a significant risk, potentially resulting in substantial liabilities and limiting the commercialization of product candidates[460]. - Global events, such as health crises and geopolitical instability, could adversely impact business operations and financial results[466]. - Coverage and reimbursement from third-party payors are critical for the success of product candidates, with significant uncertainty regarding future approvals[468]. - Changes in healthcare legislation may limit reimbursement amounts, resulting in reduced demand for pharmaceutical products[471]. - Increasing scrutiny on drug pricing practices may lead to pricing pressures for the company's product candidates[472]. - The company's disaster recovery and business continuity plans may prove inadequate in the event of significant disruptions, impacting operations[467]. - In the EU, the proposed pricing for a drug must be approved before lawful marketing, and pricing negotiations can take considerable time after receiving marketing approval[476]. - Historical data indicates that products launched in the EU generally have significantly lower prices compared to the U.S., which may negatively affect revenue and profitability[476].

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT (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: Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event Reported): February 27, 2025 Scholar Rock Holding Corporation (Exact Nam ...

Core Insights - Scholar Rock Holding Corporation is focusing on the development of apitegromab for spinal muscular atrophy (SMA), with discussions at the J.P. Morgan Healthcare Conference highlighting its potential market and adoption factors [1][4]. Group 1: Product Development and Trials - The company plans to submit U.S. and European marketing applications for apitegromab in Q1 2025, targeting a U.S. launch in Q4 2025 and a subsequent European launch [7]. - Upcoming results from the Phase 2 EMBRAZE trial, evaluating apitegromab in combination with tirzepatide or semaglutide for overweight or obese adults, are expected in Q2 2025 [3]. - Detailed results from the Phase 3 SAPPHIRE trial, involving non-ambulatory type 2/3 SMA patients, will be presented at medical meetings in 2025 [7]. Group 2: Market Potential and Financial Projections - The current SMA market is estimated at approximately $4.5 billion across three SMN-targeted therapies, primarily for the 2-21 age group [7]. - Scholar Rock expects apitegromab to generate over $2 billion in global revenue, an increase from previous estimates of $1 billion, due to strong data and a favorable competitive landscape [7]. - JP Morgan maintains a positive outlook on Scholar Rock, anticipating a strong product launch and further value if cardiometabolic data is favorable, with initial results expected in Q2 2025 [4]. Group 3: Stock Performance - Scholar Rock's stock (SRRK) has seen an increase of 4.89%, reaching $43.56 [5].

Financial Data and Key Metrics Changes - Scholar Rock reported a successful quarter with a cash balance of approximately $463 million following a $345 million follow-on offering, enabling the company to focus on key priorities [27][28] - The SAPPHIRE study met its primary endpoint with a statistically significant improvement of 1.8 points in the Hammersmith Functional Motor Scale for patients receiving apitegromab compared to placebo [11][39] Business Line Data and Key Metrics Changes - The apitegromab program is on track for regulatory submissions in Q1 2025, with a commercial launch anticipated in the U.S. by Q4 2025 [7][21] - The EMBRAZE Phase 2 proof-of-concept study for apitegromab in obesity completed enrollment ahead of schedule, with top-line results expected in Q2 2025 [8][29] Market Data and Key Metrics Changes - The current treatment landscape for spinal muscular atrophy (SMA) is valued at $4.5 billion and is growing, with apitegromab positioned to address the muscle component of the disease [35] - The company anticipates a total revenue potential of greater than $1 billion for apitegromab, assuming a competitive market for muscle-targeted therapies in SMA [36] Company Strategy and Development Direction - Scholar Rock aims to expand its anti-myostatin platform and prepare for the commercialization of apitegromab, focusing on building relationships with healthcare providers and patient communities [30][31] - The company is also working on the IND submission for SRK-439, targeting mid-2025, to preserve lean muscle mass in obesity treatments [23][24] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of apitegromab to transform the standard of care in SMA, highlighting the favorable safety profile and efficacy data [39][40] - The company is committed to ensuring an excellent treatment experience for patients and is actively preparing for a successful launch of apitegromab [33][34] Other Important Information - The addition of Beth Shafer as Chief Business Officer is expected to enhance investment decisions and partnering opportunities [9] - The company launched the "Life Takes Muscle" campaign to raise awareness about SMA and the need for more effective treatments [32] Q&A Session Summary Question: Differences in trial design and context against apitegromab - Management discussed the EMBRAZE trial's focus on lean muscle mass as the primary endpoint, contrasting it with Lilly's trial design [42][43] Question: OPAL study considerations and obesity data parameters - Management emphasized the importance of PK/PD data in guiding dosing for the OPAL study and the significance of preserving muscle mass in obesity treatments [47][48] Question: Approval for different doses and age range - The company plans to seek approval for the 10 mg/kg dose only, confident in the data supporting its efficacy across the entire age range [52][53] Question: Initial payer discussions and pricing considerations - Early payer discussions have been positive, with management optimistic about the value proposition of apitegromab based on the SAPPHIRE data [57][58] Question: Broader labeling chances and regulatory interactions - Management anticipates a broad label for apitegromab, similar to existing SMA treatments, based on the strength of the data [62][63]

Financial Performance - The company reported a net loss of $179.8 million for the nine months ended September 30, 2024, with an accumulated deficit of $856.3 million[84]. - The net loss for Q3 2024 was $64.48 million, reflecting a 52.2% increase from a net loss of $42.36 million in Q3 2023[109]. - The company reported a net loss of $179.8 million for the nine months ended September 30, 2024, which is a $60.2 million increase or 50.3% from a net loss of $119.7 million in the same period of 2023[117]. - Total operating expenses for Q3 2024 were $64.78 million, a 48.3% increase from $43.67 million in Q3 2023[109]. - Total operating expenses for the nine months ended September 30, 2024, were $182.7 million, an increase of $59.4 million or 48.2% compared to $123.3 million in the same period of 2023[117]. - Cash, cash equivalents, and marketable securities decreased by $140.9 million during the nine months ended September 30, 2024, primarily due to operating expenses[126]. - Net cash used in operating activities for the nine months ended September 30, 2024, was $151.4 million, compared to $107.9 million for the same period in 2023, reflecting an increase in net loss from $119.7 million to $179.8 million[137][140]. - The net decrease in cash, cash equivalents, and restricted cash for the nine months ended September 30, 2024, was $25.5 million, an improvement from a decrease of $35.6 million in the same period of 2023[138]. Research and Development - The Phase 3 SAPPHIRE trial for apitegromab enrolled 156 patients aged 2-12, achieving a statistically significant improvement in motor function with a mean difference of 1.8 points in HFMSE compared to placebo (p=0.0192)[88]. - 30.4% of patients receiving apitegromab in the main efficacy population had a ≥3 point improvement in HFMSE versus 12.5% of patients on placebo[91]. - The company plans to submit a U.S. Biologics License Application and a European Union marketing authorization application for apitegromab in Q1 2025, with a potential commercial launch in 2025[76]. - SRK-439, a novel anti-myostatin monoclonal antibody, is being developed for cardiometabolic disorders, with an IND submission targeted for 2025[78]. - The DRAGON trial for SRK-181, an inhibitor for cancers resistant to anti-PD-(L)1 therapies, completed enrollment in December 2023 and is ongoing[80]. - The company is advancing multiple antibody profiles toward product candidate selection, including those targeting latent TGFβ1 for fibrotic diseases[75]. - The company expects substantial ongoing research and development expenses driven by clinical stage programs, particularly for apitegromab and SRK-439[121]. - The external costs associated with apitegromab increased by $12.5 million in Q3 2024, primarily due to clinical trial costs[110]. - The company completed enrollment of the Phase 1 DRAGON clinical trial for SRK-181 in December 2023, with expected costs for this program to decrease[121]. Regulatory and Designations - The company has received multiple designations for apitegromab, including Fast Track and Orphan Drug designations from the FDA[77]. - The FDA has granted multiple designations for apitegromab, with plans to submit a Biologics License Application in Q1 2025 and a commercial launch expected in Q4 2025[100]. Adverse Events - The most common adverse events in the main efficacy population were pyrexia (29.2%), nasopharyngitis (24.5%), and cough (24.5%)[97]. - Serious adverse events were consistent with the underlying disease, with no SAEs assessed as related to apitegromab[97]. Capital and Financing - The company raised approximately $324.4 million from a follow-on offering, including the exercise of an option for additional shares[101]. - Approximately $324.4 million in net proceeds from a follow-on offering completed in October 2024 is expected to fund operating expenses and capital expenditures into Q4 2026[144]. - The company anticipates requiring additional capital to complete clinical development and commercialization for its current programs, with future capital requirements dependent on various factors including clinical trial costs and regulatory reviews[144][145]. - Net cash provided by financing activities was $6.7 million for the nine months ended September 30, 2024, compared to $6.0 million for the same period in 2023, primarily from warrant exercises[142]. - The company continues to rely on additional financing to achieve its business objectives, with potential dilution of common stockholder ownership interests if additional capital is raised through equity offerings[146][147].

Clinical Trials and Data - Reported positive topline data from the pivotal Phase 3 SAPPHIRE trial, achieving a statistically significant mean difference of 1.8 points in HFMSE for apitegromab versus placebo in patients aged 2-12[4] - Completed enrollment of the Phase 2 EMBRAZE trial for apitegromab in obesity, with topline data expected in 2Q 2025[6] - The ONYX open-label extension study is ongoing, with over 90% of patients from the TOPAZ trial completing 4 years of treatment[4] - New data from the Phase 1 DRAGON trial of SRK-181 showed a 23.3% overall response rate in the clear cell renal cell cohort[8] - SRK-439, a novel myostatin inhibitor for obesity, is in preclinical development, with an IND filing planned for 2025[5] Financial Performance - Reported a net loss of $64.5 million or $0.66 per share for Q3 2024, compared to a net loss of $42.4 million or $0.53 per share for Q3 2023[11] - Total operating expenses for the three months ended September 30, 2023, were $43,672,000, compared to $123,263,000 for the nine months ended September 30, 2023[20] - Net loss for the three months ended September 30, 2023, was $42,359,000, resulting in a net loss per share of $0.53[20] - Research and development expenses increased to $48.7 million in Q3 2024 from $30.3 million in Q3 2023, primarily due to costs associated with ONYX and EMBRAZE trials[12] - Research and development expenses for the three months ended September 30, 2023, were $30,337,000[20] - General and administrative expenses for the three months ended September 30, 2023, were $13,335,000[20] Cash and Assets - As of September 30, 2024, cash, cash equivalents, and marketable securities totaled approximately $139.1 million, with a proforma amount of $463.5 million including the recent equity offering[12] - Total assets decreased from $311,035,000 as of December 31, 2023, to $179,133,000 as of September 30, 2024[21] - Cash, cash equivalents, and marketable securities decreased from $279,938,000 to $139,065,000[21] - Total stockholders' equity decreased from $225,218,000 to $79,196,000[21] Liabilities - Total liabilities increased from $85,817,000 to $99,937,000 during the same period[21] Future Plans - Plans to submit a U.S. Biologics License Application (BLA) and European Union marketing authorisation application (MAA) in 1Q 2025[2] - Raised $345 million in an upsized public offering to fund the commercial launch of apitegromab and advance priority programs[10]

Core Insights - Scholar Rock Holding Corporation (SRRK) is showing potential as a technical investment due to a recent "golden cross" formation, where the 50-day simple moving average has crossed above the 200-day simple moving average, indicating a possible bullish breakout [1] - Over the past four weeks, SRRK has experienced a significant price increase of 225.4%, and currently holds a 3 (Hold) rating on the Zacks Rank, suggesting further breakout potential [2] - The positive earnings outlook for SRRK, with no downward revisions in earnings estimates and two upward revisions in the past two months, strengthens the bullish case for the stock [2] Technical Analysis - The golden cross pattern consists of three stages: a downtrend that bottoms out, a crossover of the shorter moving average above the longer moving average, and a continuation of upward momentum [1] - As of October 18, 2024, SRRK's 50-day simple moving average is at 12.789, while the 200-day simple moving average is at 12.743, indicating a strong technical position [2] - The volume of trading for SRRK is reported at 146.97, which may reflect increased investor interest [2]

Core Viewpoint - Scholar Rock's stock surged 364% following positive clinical trial results for its lead candidate, apitegromab, which is being tested for spinal muscular atrophy (SMA) treatment [1][2]. Company Overview - Scholar Rock is a clinical-stage drugmaker focusing on therapies for muscle-wasting diseases, with apitegromab as its primary candidate [3][4]. Clinical Trial Results - Apitegromab is an antibody targeting myostatin, tested in the phase 3 Sapphire trial involving 156 nonambulatory SMA patients aged 2 to 12 [3][4]. - The trial showed that adding apitegromab to standard care improved patient scores on the expanded Hammersmith functional motor scale (HFMSE) by an average of 1.8 points [5]. - After 12 months, 30.4% of patients improved by three or more points compared to 12.5% in the placebo group, indicating significant efficacy [5]. Market Potential - Apitegromab could generate over $1 billion in annual sales at peak, as it serves as a companion therapy for SMA alongside existing treatments like Spinraza and Evrysdi [7]. - Analysts are optimistic about apitegromab's potential beyond SMA, particularly in combination with anti-obesity medications like tirzepatide, which has seen rapid sales growth [8][9]. Future Developments - Scholar Rock plans to submit marketing authorization applications for apitegromab to the FDA and European Medicines Agency in Q1 2025 [10]. - If accepted, the fast-track designation could reduce the review period from 10 months to 6, potentially allowing sales to begin by the end of next year [11]. - The company expects to report top-line data from the phase 2 Embraze trial in Q2 2025, which could further influence stock performance [12][13]. Valuation - Scholar Rock currently has a market cap of $2.5 billion, reflecting its potential for SMA treatment approval [14].