PART I – FINANCIAL INFORMATION [Item 1. Financial Statements (Unaudited)](index=8&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) Presents unaudited consolidated financial statements, including balance sheets, statements of operations, equity, and cash flows, with detailed notes for Q1 2025 and FY 2024 [Consolidated Balance Sheets](index=8&type=section&id=Consolidated%20Balance%20Sheets%20as%20of%20March%2031%2C%202025%20and%20December%2031%2C%202024) The consolidated balance sheets show a decrease in total assets and stockholders' equity from December 31, 2024, to March 31, 2025, primarily driven by a reduction in cash, cash equivalents, and marketable securities Consolidated Balance Sheets (in thousands) | Metric | March 31, 2025 (in thousands) | December 31, 2024 (in thousands) | | :-------------------------------- | :----------------------------- | :----------------------------- | | Total assets | $407,553 | $474,922 | | Total liabilities | $95,220 | $106,288 | | Total stockholders' equity | $312,333 | $368,634 | | Cash and cash equivalents | $137,926 | $177,878 | | Marketable securities | $226,449 | $259,400 | [Consolidated Statements of Operations and Comprehensive Loss](index=9&type=section&id=Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss%20for%20the%20Three%20Months%20Ended%20March%2031%2C%202025%20and%202024) The company reported an increased net loss for the three months ended March 31, 2025, compared to the same period in 2024, primarily due to higher operating expenses, particularly in general and administrative costs and research and development Consolidated Statements of Operations and Comprehensive Loss (in thousands) | Metric | Three Months Ended March 31, 2025 (in thousands) | Three Months Ended March 31, 2024 (in thousands) | | :----------------------------------- | :--------------------------------------- | :--------------------------------------- | | Research and development | $48,678 | $43,094 | | General and administrative | $28,412 | $15,325 | | Total operating expenses | $77,090 | $58,419 | | Loss from operations | $(77,090) | $(58,419) | | Other income (expense), net | $2,367 | $1,566 | | Net loss | $(74,723) | $(56,853) | | Net loss per share, basic and diluted | $(0.67) | $(0.59) | - Net loss increased by **$17.87 million** (31.4%) from $56.85 million in Q1 2024 to $74.72 million in Q1 2025[15](index=15&type=chunk)[109](index=109&type=chunk) [Consolidated Statements of Stockholders' Equity](index=10&type=section&id=Consolidated%20Statements%20of%20Stockholders'%20Equity%20for%20the%20Three%20Months%20Ended%20March%2031%2C%202025%20and%202024) Stockholders' equity decreased from $368.6 million at December 31, 2024, to $312.3 million at March 31, 2025, primarily due to the net loss incurred during the period, partially offset by equity-based compensation expense and proceeds from stock option exercises Consolidated Statements of Stockholders' Equity (in thousands) | Metric | December 31, 2024 (in thousands) | March 31, 2025 (in thousands) | | :-------------------------------- | :----------------------------- | :----------------------------- | | Total Stockholders' Equity | $368,634 | $312,333 | | Net loss | $(74,723) | N/A | | Equity-based compensation expense | N/A | $13,413 | | Exercise of stock options | N/A | $5,038 | [Consolidated Statements of Cash Flows](index=11&type=section&id=Consolidated%20Statements%20of%20Cash%20Flows%20for%20the%20Three%20Months%20Ended%20March%2031%2C%202025%20and%202024) Net cash used in operating activities significantly increased in Q1 2025 compared to Q1 2024, while investing activities provided cash, mainly from marketable securities. Financing activities provided less cash in Q1 2025, influenced by debt refinancing and stock option exercises Consolidated Statements of Cash Flows (in thousands) | Cash Flow Activity | Three Months Ended March 31, 2025 (in thousands) | Three Months Ended March 31, 2024 (in thousands) | | :-------------------------------- | :--------------------------------------- | :--------------------------------------- | | Net cash used in operating activities | $(78,675) | $(49,785) | | Net cash provided by investing activities | $34,554 | $33,384 | | Net cash provided by financing activities | $4,169 | $6,525 | | Net decrease in cash, cash equivalents and restricted cash | $(39,952) | $(9,876) | | Cash, cash equivalents and restricted cash, end of period | $140,333 | $94,386 | - Net cash used in operating activities increased by **$28.89 million**, from $49.78 million in Q1 2024 to $78.67 million in Q1 2025[21](index=21&type=chunk)[123](index=123&type=chunk)[124](index=124&type=chunk) [Notes to Consolidated Financial Statements](index=12&type=section&id=Notes%20to%20Consolidated%20Financial%20Statements) Provides detailed disclosures on business, accounting policies, financial instruments, equity, debt, and other financial details, offering crucial context to the financial statements [1. Nature of the Business](index=12&type=section&id=1.%20Nature%20of%20the%20Business) Scholar Rock is a late-stage biopharmaceutical company focused on neuromuscular diseases, cardiometabolic disorders, and cancer, leveraging its TGFβ superfamily biology platform - Apitegromab for SMA: Positive top-line results from pivotal Phase 3 SAPPHIRE trial announced October 2024. U.S. BLA submitted January 2025 (priority review, PDUFA target action date September 22, 2025). EMA MAA submitted March 2025. Commercial launch in U.S. expected Q4 2025, Europe in 2026[23](index=23&type=chunk)[85](index=85&type=chunk) - SRK-439 for cardiometabolic disorders (including obesity): Preclinical data supports potential to increase lean mass with GLP-1 RA. IND submission planned Q3 2025. Phase 2 EMBRAZE proof-of-concept trial with apitegromab initiated May 2024, enrollment completed September 2024, top-line results expected Q2 2025[24](index=24&type=chunk)[88](index=88&type=chunk)[91](index=91&type=chunk) - SRK-181 for checkpoint inhibitor-resistant cancers: Phase 1 DRAGON trial enrollment completed December 2023. Safety, efficacy, and biomarker data presented June 2024 (ASCO) and November 2024 (SITC), showing encouraging responses in heavily pretreated patients[25](index=25&type=chunk)[26](index=26&type=chunk)[92](index=92&type=chunk) - The Company believes existing cash, cash equivalents, and marketable securities at March 31, 2025, will fund operations for **at least one year** from the financial statements' issuance date[31](index=31&type=chunk) [2. Summary of Significant Accounting Policies](index=14&type=section&id=2.%20Summary%20of%20Significant%20Accounting%20Policies) Significant accounting policies remain consistent with 2024 Annual Report; recent ASUs are noted, with no material impact from ASU 2023-07 - No material changes to significant accounting policies from the 2024 Annual Report on Form 10-K[32](index=32&type=chunk) - ASU 2023-07 (Segment Reporting) adopted, **no material impact** on financial position or results of operations[37](index=37&type=chunk) - ASU 2023-09 (Income Tax Disclosures) effective January 1, 2025, not early adopted, impact on disclosures being evaluated[38](index=38&type=chunk) - ASU 2024-03 (Expense Disaggregation) effective after December 15, 2026, impact on disclosures being evaluated[39](index=39&type=chunk) [3. Fair Value of Financial Assets and Liabilities](index=17&type=section&id=3.%20Fair%20Value%20of%20Financial%20Assets%20and%20Liabilities) Financial assets measured at fair value are primarily Level 1, with no transfers between levels; debt carrying value approximates fair value Fair Value of Financial Assets (in thousands) | Asset Category | March 31, 2025 (in thousands) | December 31, 2024 (in thousands) | | :------------------------------------------------- | :----------------------------- | :----------------------------- | | Money market funds (Level 1) | $87,071 | $97,290 | | U.S. treasury obligations (Level 1) | $31,907 | $63,171 | | Marketable securities (U.S. treasury & government agency securities) (Level 1) | $226,449 | $259,400 | | Total assets at fair value | $345,427 | $419,861 | - All financial assets measured at fair value are categorized as **Level 1**, indicating valuation using quoted market prices[40](index=40&type=chunk) [4. Marketable Securities](index=17&type=section&id=4.%20Marketable%20Securities) Marketable securities, classified as available-for-sale, include U.S. treasury and government agency securities, with some unrealized losses considered temporary Marketable Securities (in thousands) | Metric | March 31, 2025 (in thousands) | December 31, 2024 (in thousands) | | :------------------------------------------------- | :----------------------------- | :----------------------------- | | Estimated Fair Value of Marketable Securities | $226,449 | $259,400 | | Aggregate Fair Value of Securities with Unrealized Losses | $51,000 | $23,900 | | Number of Investments with Unrealized Losses | 11 | 12 | - Unrealized losses are considered temporary, and the company has the ability and intent to hold these investments until recovery of amortized cost or maturity[43](index=43&type=chunk) [5. Prepaid Expenses and Other Assets](index=18&type=section&id=5.%20Prepaid%20Expenses%20and%20Other%20Assets) Prepaid expenses and other current assets significantly increased from December 2024 to March 2025, mainly due to prepaid external R&D expenses Prepaid Expenses and Other Assets (in thousands) | Category | March 31, 2025 (in thousands) | December 31, 2024 (in thousands) | | :------------------------------------ | :----------------------------- | :----------------------------- | | Prepaid external R&D expenses | $13,739 | $7,716 | | Total prepaid expenses and other current assets | $20,872 | $13,887 | | Total other long-term assets | $2,857 | $2,945 | [6. Accrued Expenses](index=19&type=section&id=6.%20Accrued%20Expenses) Accrued expenses decreased from December 2024 to March 2025, primarily due to lower accrued payroll, partially offset by increased professional services and R&D Accrued Expenses (in thousands) | Category | March 31, 2025 (in thousands) | December 31, 2024 (in thousands) | | :------------------------------------ | :----------------------------- | :----------------------------- | | Accrued external R&D expense | $12,853 | $12,116 | | Accrued payroll and related expenses | $8,386 | $14,776 | | Accrued professional services expense | $5,652 | $3,296 | | Total accrued expenses | $27,640 | $31,067 | [7. Common Stock](index=19&type=section&id=7.%20Common%20Stock) Authorized common stock increased to 300 million shares; a public offering raised $324.4 million net, and 26.04 million warrants remain outstanding - Authorized common stock increased from 150 million to **300 million shares** in June 2024[47](index=47&type=chunk) - October 2024 public offering: Issued 10,265,488 common shares and pre-funded warrants for 353,983 shares, raising approximately **$324.4 million net**[48](index=48&type=chunk) - ATM program: Sold 619,290 shares for **$5.2 million net proceeds** as of March 31, 2025; no sales in Q1 2025[49](index=49&type=chunk) Outstanding Warrants as of March 31, 2025 | Warrants | Outstanding as of March 31, 2025 | | :----------------- | :----------------------------- | | Pre-funded warrants | 17,362,147 | | Common warrants | 8,678,664 | [8. Equity-Based Compensation](index=20&type=section&id=8.%20Equity-Based%20Compensation) Equity-based compensation expense significantly increased in Q1 2025 due to headcount and award modifications, with $134.95 million unrecognized expense remaining Equity-Based Compensation Expense (in thousands) | Expense Category | Three Months Ended March 31, 2025 (in thousands) | Three Months Ended March 31, 2024 (in thousands) | | :-------------------------------- | :--------------------------------------- | :--------------------------------------- | | Research and development expense | $4,035 | $3,531 | | General and administrative expense | $9,378 | $4,633 | | Total equity-based compensation | $13,413 | $8,164 | Unrecognized Equity-Based Compensation Expense (in thousands) | Award Type | Unrecognized Expense (in thousands) | Weighted Average Remaining Period of Recognition (years) | | :---------------- | :-------------------------------- | :------------------------------------------------------- | | RSUs | $63,427 | 2.7 | | Stock options | $71,527 | 2.6 | | Total | $134,954 | N/A | - Total fair value of RSUs vested during Q1 2025 was **$28.3 million**[53](index=53&type=chunk) [9. Commitments and Contingencies](index=21&type=section&id=9.%20Commitments%20and%20Contingencies) The company's primary commitment is an amended operating lease for its Cambridge headquarters, with no material legal proceedings during the period - Lease for corporate headquarters extended in May 2024 for approximately **two years**, with an option for a **five-year extension**[57](index=57&type=chunk) Lease Metrics (in thousands) | Lease Metric | Three Months Ended March 31, 2025 | | :------------------------------------ | :-------------------------------- | | Operating lease cost | $1,714 (in thousands) | | Variable lease cost | $392 (in thousands) | | Total lease cost | $2,106 (in thousands) | | Weighted average remaining lease term | 2.4 years | | Weighted average incremental borrowing rate | 13.1% | - No material legal proceedings during the three months ended March 31, 2025 and 2024[59](index=59&type=chunk) [10. Debt](index=22&type=section&id=10.%20Debt) An Amended and Restated Loan and Security Agreement with Oxford Finance LLC provides up to $200.0 million, extending interest-only payments through March 2029 - Amended and Restated Loan and Security Agreement with Oxford Finance LLC provides up to **$200.0 million** in term loans[69](index=69&type=chunk) - Interest-only payment period extended through **March 2029**, with principal payments commencing **April 2029**[69](index=69&type=chunk) - Annual interest rate is the greater of (i) 1-Month CME Term SOFR (min **3%**) plus (b) **5.5%**[70](index=70&type=chunk) [11. Net Loss per Share](index=24&type=section&id=11.%20Net%20Loss%20per%20Share) Basic and diluted net loss per share are identical due to the net loss, rendering 21.67 million common stock equivalents anti-dilutive - Basic and diluted net loss per share are the same because the company incurred a net loss, making potentially dilutive securities anti-dilutive[71](index=71&type=chunk)[72](index=72&type=chunk) Common Stock Equivalents Excluded from Diluted EPS Calculation | Common Stock Equivalents | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :----------------------- | :-------------------------------- | :-------------------------------- | | RSUs | 3,701,687 | 3,089,689 | | Stock options | 9,287,577 | 9,048,138 | | Warrants | 8,678,664 | 9,157,496 | | Total | 21,667,928 | 21,295,323 | [12. Segment Reporting](index=26&type=section&id=12.%20Segment%20Reporting) The company operates as a single segment, with CODM reviewing consolidated financials; operating expenses increased, particularly for SMA and cardiometabolic/obesity R&D - The company operates as a **single segment**, with the CODM reviewing consolidated financial information[74](index=74&type=chunk) Operating Expense Categories (in thousands) | Operating Expense Category | Three Months Ended March 31, 2025 (in thousands) | Three Months Ended March 31, 2024 (in thousands) | | :------------------------------------ | :--------------------------------------- | :--------------------------------------- | | Employee related expense | $22,938 | $16,080 | | External R&D expense - SMA | $17,074 | $16,201 | | External R&D expense - oncology | $1,110 | $2,747 | | External R&D expense - cardiometabolic/obesity | $6,348 | $4,032 | | External expense - G&A | $8,942 | $5,001 | | Employee related equity-based compensation expense | $13,413 | $8,164 | | Net loss | $74,723 | $56,853 | [13. Subsequent Events](index=27&type=section&id=13.%20Subsequent%20Events) Effective April 27, 2025, new CEO, President of R&D, COO, and CFO were appointed, receiving new equity awards - David Hallal appointed CEO, Akshay Vaishnaw as President of Research and Development, R. Keith Woods as COO, and Vikas Sinha as CFO, effective **April 27, 2025**[76](index=76&type=chunk) - New executives received stock options, RSUs, and PSUs as part of their appointments[76](index=76&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=28&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management's discussion and analysis covers financial condition, operational results, biopharmaceutical focus, recent developments, operating expenses, liquidity, capital resources, and critical accounting estimates [Overview](index=28&type=section&id=Overview) Scholar Rock is a late-stage biopharmaceutical company developing treatments for neuromuscular diseases, cardiometabolic disorders, and cancer, expecting continued operating losses - Scholar Rock is a late-stage biopharmaceutical company focused on neuromuscular diseases, cardiometabolic disorders, and other serious diseases, utilizing a proprietary platform for monoclonal antibodies targeting latent growth factors[82](index=82&type=chunk) - Key product candidates: Apitegromab (SMA, potential in other neuromuscular disorders and obesity), SRK-439 (cardiometabolic disorders), SRK-181 (checkpoint inhibitor-resistant cancers), SRK-373 (fibrotic diseases), SRK-256 (iron-restricted anemias)[83](index=83&type=chunk)[89](index=89&type=chunk) - The company has incurred significant operating losses since inception, with a net loss of **$74.7 million** for Q1 2025 and an accumulated deficit of **$997.4 million** as of March 31, 2025. Expects continued significant losses[94](index=94&type=chunk) [Recent Developments](index=34&type=section&id=Recent%20Developments) The company amended its Loan and Security Agreement, increasing borrowing capacity and extending interest-only payments, alongside a significant management transition - Amended and Restated Loan and Security Agreement with Oxford Finance LLC on **February 10, 2025**, for up to **$200.0 million**, extending interest-only payments through **March 2029**[97](index=97&type=chunk) - Effective **April 27, 2025**, David Hallal appointed CEO, Akshay Vaishnaw as President of Research & Development, R. Keith Woods as COO, and Vikas Sinha as CFO[98](index=98&type=chunk) [Financial Operations Overview](index=34&type=section&id=Financial%20Operations%20Overview) Outlines R&D, G&A, and Other Income (Expense), Net; R&D costs are expensed as incurred, G&A expected to rise for commercialization, and other income is primarily interest [Research and Development](index=34&type=section&id=Research%20and%20Development) R&D expenses, including employee costs and third-party activities, are expensed as incurred and are expected to remain substantial as product candidates advance - R&D expenses are expensed as incurred and include employee costs, third-party research, clinical trials, manufacturing, and regulatory compliance[99](index=99&type=chunk)[100](index=100&type=chunk) - R&D costs are expected to remain substantial due to ongoing development of apitegromab (SMA, obesity), SRK-439, and pipeline expansion[103](index=103&type=chunk)[112](index=112&type=chunk) [General and Administrative](index=36&type=section&id=General%20and%20Administrative) G&A expenses cover employee-related costs, facility, legal, and professional services, projected to increase with apitegromab's commercialization infrastructure build-out - G&A expenses include employee-related costs (salaries, benefits, equity-based compensation), facility costs, legal fees, and professional services[106](index=106&type=chunk) - G&A expenses are expected to increase as the company invests in commercialization infrastructure for apitegromab[106](index=106&type=chunk)[113](index=113&type=chunk) [Other Income (Expense), Net](index=37&type=section&id=Other%20Income%20(Expense)%2C%20Net) Other income (expense), net, primarily reflects interest income from cash, cash equivalents, and marketable securities, offset by interest expense on debt - Other income (expense), net, is mainly interest income from cash, cash equivalents, and marketable securities, offset by interest expense on debt[108](index=108&type=chunk) [Results of Operations](index=37&type=section&id=Results%20of%20Operations) Total operating expenses increased by 32.0%, leading to a 31.4% higher net loss in Q1 2025, driven by significant increases in R&D and G&A expenses Summary of Results of Operations (in thousands) | Metric | Three Months Ended March 31, 2025 (in thousands) | Three Months Ended March 31, 2024 (in thousands) | Change ($) | Change (%) | | :-------------------------- | :--------------------------------------- | :--------------------------------------- | :--------- | :--------- | | Total operating expenses | $77,090 | $58,419 | $18,671 | 32.0% | | Loss from operations | $(77,090) | $(58,419) | $(18,671) | 32.0% | | Other income (expense), net | $2,367 | $1,566 | $801 | 51.1% | | Net loss | $(74,723) | $(56,853) | $(17,870) | 31.4% | [Research and Development Expenses](index=37&type=section&id=Research%20and%20Development%20Expenses) R&D expense increased by 13.0% to $48.7 million in Q1 2025, driven by higher external costs for apitegromab and SRK-439, and increased employee-related costs Research and Development Expenses (in thousands) | R&D Expense Category | Three Months Ended March 31, 2025 (in thousands) | Three Months Ended March 31, 2024 (in thousands) | Change ($) | Change (%) | | :------------------------------------ | :--------------------------------------- | :--------------------------------------- | :--------- | :--------- | | Apitegromab | $19,301 | $18,248 | $1,053 | 5.8% | | SRK-181 | $1,110 | $2,747 | $(1,637) | (59.6)% | | SRK-439 | $4,279 | $1,985 | $2,294 | 115.6% | | Other early programs and unallocated costs | $1,455 | $741 | $714 | 96.4% | | Total external costs | $26,145 | $23,721 | $2,424 | 10.2% | | Employee compensation and benefits | $18,110 | $14,928 | $3,182 | 21.3% | | Total R&D expense | $48,678 | $43,094 | $5,584 | 13.0% | - Increase in apitegromab costs primarily due to drug supply manufacturing, partially offset by decreased clinical trial costs for TOPAZ and SAPPHIRE[110](index=110&type=chunk) - SRK-439 preclinical and manufacturing development costs increased by **115.6%**[110](index=110&type=chunk) - SRK-181 costs decreased by **59.6%** as Phase 1 DRAGON trial enrollment completed[110](index=110&type=chunk)[112](index=112&type=chunk) [General and Administrative Expenses](index=39&type=section&id=General%20and%20Administrative%20Expenses) G&A expense surged by 85.4% to $28.4 million in Q1 2025, driven by increased employee-related costs, equity-based compensation, and professional service fees - General and administrative expense increased by **$13.1 million** (**85.4%**) to **$28.4 million** in Q1 2025[109](index=109&type=chunk)[113](index=113&type=chunk) - Key drivers: **$4.2 million** increase in employee-related costs, **$4.7 million** increase in non-cash equity-based compensation, and **$4.0 million** increase in professional service fees[113](index=113&type=chunk) [Other Income (Expense), Net](index=39&type=section&id=Other%20Income%20(Expense)%2C%20Net) Other income (expense), net, increased by $0.8 million (51.1%) in Q1 2025, primarily due to higher interest income from increased cash balances - Other income (expense), net, increased by **$0.8 million** (**51.1%**) to **$2.37 million** in Q1 2025, driven by higher interest income[109](index=109&type=chunk)[114](index=114&type=chunk) [Liquidity and Capital Resources](index=39&type=section&id=Liquidity%20and%20Capital%20Resources) Liquidity decreased in Q1 2025, with $364.4 million in cash, cash equivalents, and marketable securities; additional financing will be required for full development and commercialization [Sources of Liquidity](index=39&type=section&id=Sources%20of%20Liquidity) The company funds operations through equity, collaborations, and debt; total cash, cash equivalents, and marketable securities decreased by $72.9 million in Q1 2025 - Primary funding sources: equity financings, research collaborations, and debt facilities[115](index=115&type=chunk) Cash, Cash Equivalents, and Marketable Securities (in thousands) | Metric | March 31, 2025 (in thousands) | December 31, 2024 (in thousands) | | :------------------------------------ | :----------------------------- | :----------------------------- | | Cash and cash equivalents | $137,926 | $177,878 | | Marketable securities | $226,449 | $259,400 | | Total cash, cash equivalents and marketable securities | $364,375 | $437,278 | - Total cash, cash equivalents, and marketable securities decreased by **$72.9 million** in Q1 2025, primarily due to cash used in operations[116](index=116&type=chunk) - Amended and Restated Loan and Security Agreement with Oxford provides up to **$200 million** in borrowing capacity[120](index=120&type=chunk) [Cash Flows](index=41&type=section&id=Cash%20Flows) Net cash used in operating activities significantly increased to $78.7 million in Q1 2025, while investing activities provided cash, and financing activities provided less cash Cash Flow Activities (in thousands) | Cash Flow Activity | Three Months Ended March 31, 2025 (in thousands) | Three Months Ended March 31, 2024 (in thousands) | | :-------------------------------- | :--------------------------------------- | :--------------------------------------- | | Net cash used in operating activities | $(78,675) | $(49,785) | | Net cash provided by investing activities | $34,554 | $33,384 | | Net cash provided by financing activities | $4,169 | $6,525 | | Net decrease in cash, cash equivalents and restricted cash | $(39,952) | $(9,876) | - Net cash used in operating activities increased by **$28.89 million** YoY, driven by higher net loss and changes in operating assets/liabilities[123](index=123&type=chunk)[124](index=124&type=chunk) - Net cash provided by financing activities in Q1 2025 was primarily from stock option exercises and debt refinancing, partially offset by debt extinguishment[126](index=126&type=chunk) [Funding Requirements](index=43&type=section&id=Funding%20Requirements) Existing capital is expected to fund operations into 2027, but substantial additional capital is required for full development and commercialization, to be sought through various financing methods - Existing cash, cash equivalents, and marketable securities are expected to fund operations into **2027**[128](index=128&type=chunk) - Additional capital is required to complete clinical development and commercialization for current programs[128](index=128&type=chunk) - Future funding requirements are highly uncertain and depend on factors like clinical trial costs, manufacturing, regulatory review, and commercialization activities[128](index=128&type=chunk)[129](index=129&type=chunk)[376](index=376&type=chunk)[378](index=378&type=chunk) - Plans to finance future cash needs through equity offerings, debt financings, collaborations, strategic alliances, and licensing arrangements[131](index=131&type=chunk)[377](index=377&type=chunk) [Critical Accounting Estimates](index=45&type=section&id=Critical%20Accounting%20Estimates) No material changes to critical accounting estimates from the 2024 Annual Report on Form 10-K were reported - No material changes to critical accounting estimates from the 2024 Annual Report on Form 10-K[134](index=134&type=chunk) [Off-Balance Sheet Arrangements](index=45&type=section&id=Off-Balance%20Sheet%20Arrangements) The company did not have any off-balance sheet arrangements during the periods presented or currently - No off-balance sheet arrangements during the periods presented or currently[135](index=135&type=chunk) [Recent Accounting Pronouncements](index=45&type=section&id=Recent%20Accounting%20Pronouncements) Reviewed recently issued accounting standards; no material impact on financial statements other than as disclosed in Note 2 - Reviewed all recently issued standards; no material impact on financial statements other than as disclosed in Note 2[136](index=136&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=45&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, Scholar Rock Holding Corporation is not required to provide quantitative and qualitative disclosures about market risk - The company is a smaller reporting company and is not required to provide quantitative and qualitative disclosures about market risk[137](index=137&type=chunk) [Item 4. Controls and Procedures](index=47&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded disclosure controls and procedures were effective as of March 31, 2025, with no material changes to internal controls over financial reporting - Disclosure controls and procedures were effective at the reasonable assurance level as of **March 31, 2025**[139](index=139&type=chunk) - No material changes in internal controls over financial reporting occurred during the three months ended March 31, 2025[140](index=140&type=chunk) PART II. OTHER INFORMATION [Item 1. Legal Proceedings](index=47&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently subject to any material legal proceedings or claims that are reasonably expected to have a material adverse effect on its business - No material legal proceedings or claims that would individually or in aggregate have a material adverse effect on the business[141](index=141&type=chunk) [Item 1A. Risk Factors](index=48&type=section&id=Item%201A.%20Risk%20Factors) Outlines significant risks that could materially and adversely affect Scholar Rock's business, financial condition, and results of operations, spanning development, regulatory, commercial, operational, IP, financial, and stock volatility [Summary of the Material Risks Associated with Our Business](index=48&type=section&id=Summary%20of%20the%20Material%20Risks%20Associated%20with%20Our%20Business) The company faces numerous material risks, including unpredictable regulatory approval, commercialization challenges, development uncertainties, reliance on third parties, IP protection issues, ongoing net losses, and stock price volatility - Regulatory approval process is lengthy, time-consuming, and unpredictable, potentially delaying or preventing approval of product candidates[144](index=144&type=chunk) - Lack of prior commercialization experience and challenges in building commercial infrastructure for apitegromab could negatively impact business[144](index=144&type=chunk) - Reliance on third-party manufacturers and clinical trial conductors poses risks of supply limitations, interruptions, or quality issues[150](index=150&type=chunk) - Difficulty in protecting intellectual property rights and potential infringement claims from third parties could harm business[150](index=150&type=chunk) - History of net losses and future capital requirements necessitate additional financing, which may not be available on acceptable terms[150](index=150&type=chunk) [Risks Related to Product Development, Regulatory Approval and Commercialization](index=51&type=section&id=Risks%20Related%20to%20Product%20Development%2C%20Regulatory%20Approval%20and%20Commercialization) Substantial risks include lengthy regulatory approval, commercialization challenges, clinical trial delays, unpredictable early-stage results, reliance on third parties, limited benefits of special designations, and market acceptance issues - Regulatory approval process is lengthy, time-consuming, and inherently unpredictable; failure to obtain or delays in approval for apitegromab, SRK-181, SRK-439, and future candidates are significant risks[151](index=151&type=chunk) - The company has no prior commercialization experience and is building sales, marketing, and distribution capabilities for apitegromab, which, if unsuccessful, could negatively impact its launch[154](index=154&type=chunk)[155](index=155&type=chunk) - Product development is expensive and uncertain; delays in clinical trials due to various factors (e.g., trial design, enrollment, safety issues, regulatory requirements) could increase costs and jeopardize commercialization[163](index=163&type=chunk)[165](index=165&type=chunk)[171](index=171&type=chunk) - Preclinical and early-stage clinical trial results may not be predictive of future outcomes, and interim data are subject to change, potentially leading to setbacks in later stages[173](index=173&type=chunk)[176](index=176&type=chunk)[177](index=177&type=chunk) - Reliance on third parties (CROs, manufacturers) for clinical trials and preclinical studies introduces risks if they fail to meet contractual duties, deadlines, or regulatory requirements[181](index=181&type=chunk)[187](index=187&type=chunk) - Orphan Drug, Rare Pediatric Disease, Fast Track, and PRIME designations do not guarantee faster development, approval, or market exclusivity, and their benefits may be limited or revoked[189](index=189&type=chunk)[190](index=190&type=chunk)[193](index=193&type=chunk)[197](index=197&type=chunk)[200](index=200&type=chunk) - Even if approved, product candidates may fail to achieve market acceptance due to factors like efficacy, safety, pricing, reimbursement, and competition[214](index=214&type=chunk) [Risks Related to Our Business and Operations](index=76&type=section&id=Risks%20Related%20to%20Our%20Business%20and%20Operations) Operational risks include reliance on third-party manufacturers, scaling challenges, supply chain disruptions, managing growth, retaining personnel, regulatory compliance, cybersecurity, product liability, and business interruptions - Reliance on a limited number of third-party contract manufacturers for all product supplies (clinical and commercial) creates risks of supply limitations, interruptions, or quality issues[227](index=227&type=chunk) - Scaling manufacturing processes for commercial supply is a challenge, and failure to do so in a timely or cost-effective manner could delay development and commercialization[233](index=233&type=chunk)[235](index=235&type=chunk) - Economic uncertainty, geopolitical instability, high inflation, and tariffs could adversely impact supply chains, development, and financial results[237](index=237&type=chunk)[239](index=239&type=chunk) - Challenges in managing organizational growth, recruiting, and retaining highly skilled personnel, especially during management transitions, could impair development and commercialization efforts[240](index=240&type=chunk)[243](index=243&type=chunk)[244](index=244&type=chunk)[246](index=246&type=chunk) - Internal computer systems and those of third-party contractors are vulnerable to security breaches, incidents, or compromises, risking data loss, operational disruption, and legal liability[247](index=247&type=chunk)[248](index=248&type=chunk) - Misconduct by employees or third parties, including noncompliance with regulatory standards (e.g., FDA, EMA, anti-kickback, fraud and abuse laws), could lead to significant penalties, reputational harm, and operational restrictions[249](index=249&type=chunk)[251](index=251&type=chunk) - Ongoing healthcare legislative and regulatory reforms, including pricing and reimbursement changes, could adversely affect market demand, pricing, and profitability of products[252](index=252&type=chunk)[295](index=295&type=chunk)[298](index=298&type=chunk) - Failure to comply with health care privacy and data protection laws (e.g., HIPAA, EU GDPR, UK GDPR, CCPA) could result in enforcement actions, litigation, and adverse publicity[256](index=256&type=chunk)[258](index=258&type=chunk)[260](index=260&type=chunk)[261](index=261&type=chunk)[264](index=264&type=chunk)[267](index=267&type=chunk) - The use of artificial intelligence (AI) presents risks including security risks to confidential information, intellectual property infringement, and increased regulatory burden (e.g., EU AI Act)[268](index=268&type=chunk)[269](index=269&type=chunk)[270](index=270&type=chunk)[273](index=273&type=chunk) - Non-compliance with international laws (e.g., FCPA, export control) could lead to substantial penalties and restrict global operations[274](index=274&type=chunk)[277](index=277&type=chunk) - Failure to comply with environmental, health, and safety laws could result in fines, penalties, or costly clean-up liabilities[278](index=278&type=chunk)[280](index=280&type=chunk) - Product liability lawsuits, if brought against the company, could result in substantial liabilities, limit commercialization, and exhaust insurance/capital resources[282](index=282&type=chunk)[283](index=283&type=chunk)[285](index=285&type=chunk) - Concentration of laboratory operations in one location and reliance on third parties for clinical trials and manufacturing facilities expose the company to business interruptions from natural disasters or other unforeseen events[286](index=286&type=chunk)[287](index=287&type=chunk)[289](index=289&type=chunk) - Coverage and reimbursement for product candidates, if approved, may be limited or unavailable, making it difficult to sell profitably and impacting revenue[290](index=290&type=chunk)[294](index=294&type=chunk)[302](index=302&type=chunk) - Inability to enter into or maintain successful collaborations with third parties could adversely affect product discovery, development, and commercialization[303](index=303&type=chunk)[304](index=304&type=chunk)[306](index=306&type=chunk)[308](index=308&type=chunk) [Risks Related to Intellectual Property](index=106&type=section&id=Risks%20Related%20to%20Intellectual%20Property) Success relies on protecting IP; challenges include costly patenting, infringement claims, licensing difficulties, evolving patent laws, and inadequate trade secret protection - Commercial success depends on obtaining and maintaining patent, trademark, and trade secret protection for proprietary technologies and product candidates[310](index=310&type=chunk) - Patenting is expensive, time-consuming, and uncertain; patent applications may not result in issued patents, or issued patents may be challenged, narrowed, or invalidated[313](index=313&type=chunk)[314](index=314&type=chunk) - Third-party claims of intellectual property infringement could lead to expensive litigation, substantial damages, injunctions, or the need to obtain costly licenses[337](index=337&type=chunk)[338](index=338&type=chunk)[342](index=342&type=chunk) - Dependence on in-licensed intellectual property means failure to comply with license obligations or termination of licenses could result in loss of significant rights[322](index=322&type=chunk) - Inability to obtain or maintain necessary rights to develop future product candidates on acceptable terms could hinder business growth[327](index=327&type=chunk)[328](index=328&type=chunk)[329](index=329&type=chunk) - Changes in patent law (e.g., America Invents Act, Supreme Court rulings) could diminish the value of patents, increasing uncertainty and costs[331](index=331&type=chunk)[332](index=332&type=chunk)[335](index=335&type=chunk)[336](index=336&type=chunk) - Inadequate protection of trade secrets, including through disclosure or independent development by competitors, would harm competitive position[364](index=364&type=chunk)[366](index=366&type=chunk) - Limited foreign intellectual property rights mean inability to protect inventions globally, potentially allowing competitors to use technologies in other jurisdictions[356](index=356&type=chunk) - Patent terms may be inadequate, and inability to obtain patent term extensions or data exclusivity could allow competitors to enter the market sooner[361](index=361&type=chunk)[363](index=363&type=chunk) [Risks Related to Our Financial Condition and Capital Requirements](index=127&type=section&id=Risks%20Related%20to%20Our%20Financial%20Condition%20and%20Capital%20Requirements) The company expects continued net losses, requiring substantial additional capital; NOL carryforwards may be limited, and financial services industry risks and loan restrictions impact flexibility - The company has incurred net losses since inception (**$74.7 million** in Q1 2025, accumulated deficit of **$997.4 million** as of March 31, 2025) and anticipates continued losses[371](index=371&type=chunk) - Substantial additional capital is required to fund operations, complete product development, and commercialization, beyond existing cash, cash equivalents, and marketable securities (expected to last into **2027**)[374](index=374&type=chunk)[375](index=375&type=chunk) - Ability to use net operating loss carryforwards (**$512.6 million** federal, **$498.8 million** state as of Dec 31, 2024) and tax credit carryforwards may be limited by ownership changes under Section 382 of the Code[381](index=381&type=chunk) - Adverse developments in the financial services industry (e.g., bank failures, liquidity problems) could impair access to funding sources and negatively impact financial condition[382](index=382&type=chunk)[385](index=385&type=chunk)[386](index=386&type=chunk) - Potential for losses on marketable securities due to interest rate increases or deteriorating economic conditions, despite a focus on capital preservation[389](index=389&type=chunk)[390](index=390&type=chunk) - Terms of the Amended and Restated Loan and Security Agreement place restrictions on operating and financial flexibility; default could accelerate repayment obligations[391](index=391&type=chunk)[392](index=392&type=chunk)[393](index=393&type=chunk) [Risks Related to Our Common Stock](index=136&type=section&id=Risks%20Related%20to%20Our%20Common%20Stock) Stock price is highly volatile, no dividends are planned, significant insider ownership exists, scaled disclosures may reduce investor appeal, public company costs are high, and potential dilution from warrants and ATM sales is a risk - The price of common stock is volatile, subject to fluctuations from operating results, acquisitions, collaborations, accounting changes, and litigation[395](index=395&type=chunk)[396](index=396&type=chunk) - No intention to pay dividends; returns are limited to stock appreciation, and debt facility restricts dividend payments[397](index=397&type=chunk) - Executive officers, directors, and affiliates own approximately **9%** of outstanding voting stock, allowing significant influence over stockholder approval matters[398](index=398&type=chunk) - As a 'smaller reporting company,' the company uses scaled disclosures, which may make its common stock less attractive to some investors and increase price volatility[399](index=399&type=chunk)[402](index=402&type=chunk) - Operating as a public company incurs significant legal, accounting, and compliance costs, diverting management time[403](index=403&type=chunk) - Failure to maintain effective internal control over financial reporting could lead to inaccurate financial reports, fraud, and loss of investor confidence[405](index=405&type=chunk) - Broad discretion in the use of cash, cash equivalents, and marketable securities may not always increase investment value[408](index=408&type=chunk) - Anti-takeover provisions in charter documents and Delaware law could delay or prevent a change of control, limiting stock price and hindering stockholder actions[409](index=409&type=chunk)[410](index=410&type=chunk) - Securities litigation is expensive and could divert management attention, harming business and stock price[414](index=414&type=chunk) - Exclusive forum provisions in bylaws could limit stockholders' ability to choose a favorable judicial forum for disputes[415](index=415&type=chunk) - Substantial number of outstanding warrants and equity awards (**17.36 million** pre-funded warrants, **8.68 million** common warrants, **12.99 million** stock options/RSUs) could result in significant dilution[416](index=416&type=chunk) - Sales of a substantial number of common stock shares, including through the ATM program, could cause the stock price to fall[419](index=419&type=chunk)[420](index=420&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=144&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reported no unregistered sales of equity securities during the period - No unregistered sales of equity securities during the three months ended March 31, 2025[422](index=422&type=chunk) [Item 3. Defaults Upon Senior Securities](index=144&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reported no defaults upon senior securities during the period - No defaults upon senior securities during the three months ended March 31, 2025[424](index=424&type=chunk) [Item 4. Mine Safety Disclosures](index=144&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) The company reported no mine safety disclosures during the period - No mine safety disclosures during the three months ended March 31, 2025[424](index=424&type=chunk) [Item 5. Other Information](index=145&type=section&id=Item%205.%20Other%20Information) Details Rule 10b5-1 trading plans adopted or terminated by directors and officers in Q1 2025 for stock sales and tax obligations - Several directors and officers adopted Rule 10b5-1 trading plans in **February and March 2025** for the sale of common stock[425](index=425&type=chunk) - Plans are intended to satisfy tax obligations upon RSU vesting or for general stock sales[426](index=426&type=chunk)[427](index=427&type=chunk) - Former COO and CFO, Ted Myles, terminated his trading plan in **March 2025**[425](index=425&type=chunk) [Item 6. Exhibits](index=147&type=section&id=Item%206.%20Exhibits) Lists all exhibits filed with Form 10-Q, including corporate documents, loan agreements, employment agreements, equity plans, and certifications - Includes Amended and Restated Certificate of Incorporation, Amended and Restated Loan and Security Agreement, Separation Agreement, and Equity Plan amendments[429](index=429&type=chunk) - Certifications of Principal Executive Officer and Principal Financial Officer are filed herewith[429](index=429&type=chunk)[430](index=430&type=chunk)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT (857) 259-3860 (Registrant's telephone number, including area code) Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event Reported): May 14, 2025 Scholar Rock Holding Corporation (Exact Name of Registrant as Specified in Charter) (State or Other Jurisdiction of Incorporation) Delaware 001-38501 82-3750435 (Commission File Number) (I.R.S. Employer Identificat ...

Although there are many examples throughout history of positive changes in top company management teams, important personnel moves tend to unsettle investors. They get worried that significant changes could reflect instability, indecision, or both in a company's decision-making. That seemed to be very much the case Monday with biotech Scholar Rock (SRRK -3.35%). Its stock closed almost 4% lower in price on a day when the S&P 500 index basically traded flat. A quartet of new executive appointments Scholar Ro ...

Core Insights - Scholar Rock's stock saw a nearly 3% increase following a positive analyst note, outperforming the S&P 500 index which rose by 1.7% [1] Company Overview - Scholar Rock focuses on rare disorders with limited treatment options, with its lead drug candidate, apitegromab, aimed at preserving muscle mass in patients with spinal muscular atrophy (SMA) [2] Analyst Perspective - Analyst Allison Bratzel from Piper Sandler believes that the market has not fully priced in the potential of apitegromab, suggesting that a positive reception could significantly increase the stock price, which she considers undervalued. She maintains an overweight recommendation with a price target of $42 per share [3] Drug Potential - There is currently no cure for SMA, but treatments that address the disorder's symptoms could perform well. Apitegromab has shown promising results in clinical trials, positioning it as a potential key treatment for muscle mass preservation in SMA patients [4]

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]