Company Overview - Verrica Pharmaceuticals Inc. (NASDAQ:VRCA) is focused on developing and commercializing treatments for skin diseases, with its lead product candidate, VP-102, targeting molluscum contagiosum [1] Financial Performance - VRCA has a Return on Invested Capital (ROIC) of -166.93%, significantly lower than its Weighted Average Cost of Capital (WACC) of 17.69%, indicating inefficiencies in capital utilization [2][6] - The ROIC to WACC ratio for VRCA is -9.44, further emphasizing the challenge in generating sufficient returns to cover its cost of capital [2] Comparative Analysis - Y-mAbs Therapeutics (YMAB) has a ROIC of -27.64% and a WACC of 6.11%, resulting in a ROIC to WACC ratio of -4.53, making it the least inefficient among its peers [3][5] - Scholar Rock Holding Corporation (SRRK) shows a ROIC of -109.48% against a WACC of 5.32%, leading to a ROIC to WACC ratio of -20.57, indicating similar inefficiencies as VRCA [4] - Crinetics Pharmaceuticals (CRNX) and Kezar Life Sciences (KZR) also exhibit negative ROIC to WACC ratios of -6.99 and -10.94, respectively, highlighting broader challenges within the sector [4][5] Sector Insights - All companies analyzed, including VRCA, are currently operating at a loss relative to their cost of capital, with Y-mAbs Therapeutics managing its capital more effectively than its peers [5][6]

Group 1 - Scholar Rock (NASDAQ: SRRK) stock experienced a price increase of over 6% following the initiation of coverage by analyst Mani Foroohar from Leerink Partners, who rated the stock as an outperform with a price target of $51 per share, indicating a potential growth of more than 51% from its recent closing price [1][2] - The company's leading investigational drug, apitegromab, targets spinal muscular atrophy (SMA) and is currently under review for approval by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) [3][5] - Foroohar highlighted the strength of Scholar Rock's team, noting it as the most experienced in the commercialization of rare diseases among the healthcare stocks he covers [4] Group 2 - If Scholar Rock secures approval for apitegromab, it would be well-positioned for success, although effective rollout and marketing of the new medicine are crucial for achieving that success [5] - Despite the positive outlook, Scholar Rock was not included in a list of the top 10 stocks identified by The Motley Fool Stock Advisor, which suggests that there may be other investment opportunities with potentially higher returns [6][8]

Core Viewpoint - Scholar Rock Holding Corp. (NASDAQ:SRRK) is considered a promising multibagger stock, primarily driven by optimism surrounding its lead drug candidate, apitegromab, which has seen significant stock performance fluctuations as the company approaches a potential U.S. market launch in Q3 2025 [1] Group 1: Drug Candidate and Market Potential - Apitegromab is the first muscle-targeted therapy to show clinically meaningful and statistically significant functional improvement in spinal muscular atrophy (SMA), with a global market opportunity estimated to exceed $2 billion [2] - Analyst Amy Li from Jefferies initiated coverage with a Buy rating and a $50 price target, emphasizing the strong commercial opportunity for apitegromab, particularly if FDA approval includes patients aged two and older across SMA types 1-4 [3] - Risk-adjusted peak sales for apitegromab are modeled at $1.8 billion, with a 90% probability of success for patients over two years of age and 50% for those under two [4] Group 2: Pipeline and Future Potential - The company is also developing pipeline candidate SRK-439 for other neuromuscular conditions, including Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD), as well as exploring applications in obesity through external partnerships [5]

Summary of Earnings Call Records Industry Overview - **Industry**: Pharmaceuticals and Biotech Sectors - **Companies Discussed**: AbbVie, Biogen, Bristol Myers Squibb, Bio-Rad Laboratories, Neurocrine Biosciences, Takeda Pharmaceutical, Chugai Pharmaceutical, PeptiDream, Nxera Pharma Key Points by Company AbbVie - **Sales Performance**: Humira sales decreased by 58.1% year-over-year due to biosimilar competition, but this was offset by strong sales of Skyrizi, which increased by 62.2% to $4.4 billion, driven by market share growth in psoriasis and inflammatory bowel disease [1] - **Product Strategy**: Many patients switched from Humira to Skyrizi and Rinvoq instead of biosimilars. AbbVie plans to increase production capacity for Skyrizi in the long term [1] - **New Developments**: The obesity treatment ABBV-295 may address muscle and bone loss when used with other AbbVie drugs [1] Biogen - **Market Share**: Leqembi, an Alzheimer's treatment, maintains a 70% market share despite competition from Eli Lilly's Kisunla [3] - **Testing Growth**: Monthly PET testing for Alzheimer's has increased fivefold, and blood-based biomarker testing has tripled in the past year [3] - **Future Expectations**: Biogen anticipates interim data readout for the AHEAD 3-45 study in 2028 [3] Bristol Myers Squibb - **Sales Growth**: Sales of Opdivo's subcutaneous formulation increased by 7% year-over-year to $30 million, while the intravenous formulation rose to $2.56 billion [6] - **New Product Launch**: Cobenfy, a schizophrenia treatment, generated $35 million in sales with over 2,000 weekly prescriptions [6] - **Direct-to-Patient Model**: The company plans to sell Eliquis directly to patients at a discount of over 50% below the list price [6] Bio-Rad Laboratories - **Sales Performance**: Reported sales of $652 million, up 2% year-over-year, but operating profits fell by 24% to $77 million due to weak demand in biotech and academic research markets [8] - **Market Challenges**: The demand for instruments has been particularly weak, impacting overall sales [8] Neurocrine Biosciences - **Sales Growth**: Total sales reached $688 million, up 16% year-over-year, with operating profits flat at $146 million [10] - **Future Studies**: Plans to initiate a Phase 2 study of NBI-570 in H2 2025, with Phase 1 data readouts expected for NBI-567 and NBI-569 [10] - **Market Positioning**: Neurocrine is exploring differentiation opportunities in muscarinic receptor agonists, which may be better suited for elderly patients [10] Implications for Japanese Companies - **Takeda Pharmaceutical**: Entyvio retains a top share among first-line therapies for ulcerative colitis but is losing market share in second-line settings due to competition [2] - **Chugai Pharmaceutical and PeptiDream**: Both companies are developing myostatin inhibitors to counteract muscle mass loss associated with long-term GLP-1 receptor agonist use [2] - **Nxera Pharma**: The company is positioned positively due to its licensing of muscarinic receptor agonists to Neurocrine, although earnings contributions may not be reflected in share prices until Phase 3 study results are available [11] Additional Insights - **Market Trends**: The aggressive advertising by competitors is impacting market shares of established products like Entyvio [2] - **Direct Sales Models**: There is a growing trend among overseas pharmaceutical companies to adopt direct-to-patient sales models, which Japanese companies have yet to fully embrace [7] This summary encapsulates the key insights and data from the earnings calls of the discussed companies, highlighting their performance, strategies, and implications for the broader industry.

Financial Data and Key Metrics Changes - The company ended the quarter with $295 million in cash, with an additional $50 million available under a debt facility for the year [29] - The company anticipates receiving approximately $16 million from the exercise of outstanding common warrants by year-end, extending its financial runway into 2027 [30] Business Line Data and Key Metrics Changes - The company is preparing for the U.S. launch of epitigramab, pending regulatory approval, with a target action date of September 22 [7][9] - Epitigramab has shown statistically significant improvements in motor function in clinical trials, with a pivotal Phase III trial demonstrating a threefold higher chance of improvement compared to placebo [17] Market Data and Key Metrics Changes - Approximately 10,000 patients in the U.S. are currently living with SMA, with about two-thirds having received SMN-targeted therapies [26] - Globally, around 35,000 patients have received SMN-targeted therapies, indicating a significant market opportunity for epitigramab [27] Company Strategy and Development Direction - The company aims to become a global biotech powerhouse by focusing on regulatory approvals for epitigramab, expanding its use in additional neuromuscular diseases, and maintaining disciplined capital allocation [6][31] - The first European launch of epitigramab is planned for Germany in 2026, with ambitions to reach patients across Europe, Asia Pacific, and Latin America [10][14] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing dialogue with the FDA, indicating a collaborative approach towards the review of the BLA [9][35] - The company is committed to ensuring that no patient with SMA is left behind, emphasizing the urgency of delivering epitigramab to the SMA community [32] Other Important Information - The company is preparing for a global launch of epitigramab, with a focus on addressing the unmet needs in muscle strength and motor function for SMA patients [12][24] - The EMBRAZE study demonstrated that epitigramab increased lean mass preservation by over 54% compared to tirzepatide alone, highlighting its potential in treating obesity [13] Q&A Session Summary Question: Can you tell us more about the specific observations at the two sites? - Management acknowledged the observations were not surprising and emphasized their commitment to addressing them within the review cycle [34][35] Question: What feedback have you received from the FDA regarding the review of epitigramab? - Management reported a constructive late cycle meeting with the FDA, expressing optimism about the review process and potential labeling [41][44] Question: How are discussions with U.S. payers progressing? - The payer outreach has been positive, with discussions focusing on the durability of response and the unmet medical need for dual modality therapies [45][46] Question: What is the expected timeline for the OPAL trial enrollment? - Enrollment for the OPAL trial is set to begin in Q3, with further guidance on completion timelines to follow [80] Question: How does the company plan to address the budget impact of dual SMA therapies? - Management indicated that the rarity and severity of SMA, along with the compelling clinical benefits of epitigramab, will be considered in pricing discussions [68][70]

Financial Data and Key Metrics Changes - The company ended the quarter with $295 million in cash [28] - The company anticipates receiving approximately $16 million from the exercise of outstanding common warrants by year-end, extending its financial runway into 2027 [29] - The company has an additional $50 million available under its debt facility post-approval to support the upcoming launch [29] Business Line Data and Key Metrics Changes - The company is preparing for the U.S. launch of epitigramab, with a BLA accepted under priority review and a target action date of September 22, 2025 [6][8] - The company plans to expand epitigramab into additional rare, severe, and debilitating neuromuscular diseases [5][10] - The EMBRAZE study met its primary endpoint, showing that epitigramab increased lean mass preservation by over 54% compared to tirzepatide alone [11] Market Data and Key Metrics Changes - Approximately 10,000 patients in the U.S. are currently living with SMA, with about two-thirds having received SMN-targeted therapy [26] - Globally, around 35,000 patients have received SMN-targeted therapies, indicating a significant market opportunity for epitigramab [27] Company Strategy and Development Direction - The company aims to become a global biotech powerhouse by focusing on regulatory approvals for epitigramab, expanding into additional neuromuscular diseases, and disciplined capital allocation [5][31] - The first European launch of epitigramab is planned for Germany in 2026, with ambitions to reach patients across Europe, Asia Pacific, and Latin America [9][13] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing dialogue with the FDA and the collaborative nature of the late cycle meeting, indicating a positive outlook for the BLA review [8][35] - The company is committed to ensuring that no patient with SMA is left behind, emphasizing the urgency of delivering epitigramab to the SMA community [31] Other Important Information - The company is working collaboratively with the FDA and European Medicines Agency to prepare for the commercial launch of epitigramab [6][9] - The company has assembled a highly experienced field team to support the launch of epitigramab [10] Q&A Session Summary Question: Can you tell us more about the specific observations at the two sites? - The company acknowledged that GMP inspections are standard and noted that they were disappointed but not surprised by the observations at two CDMO sites [34][35] Question: What is the current status of the two facilities in terms of product release? - Both facilities continue to operate and manufacture products, with the supply chain having produced over 600 patient years of experience through clinical trials [37][38] Question: How are discussions with FDA regarding the epitigramab review going? - The company reported constructive feedback from the late cycle meeting with the FDA and is working towards the September 22 PDUFA date [44][45] Question: What is the expected enrollment timeline for the OPAL trial? - Enrollment for the OPAL trial is expected to start in Q3 2025, with further guidance on completion timelines to be provided as momentum builds [78] Question: How does the company plan to address the budget impact of dual SMA therapies? - The company is considering the rarity and severity of SMA, along with the compelling clinical benefits of epitigramab, in discussions with payers [70][72]

Apitegromab in SMA - Positive Phase 3 trial data showed a 18 point improvement versus placebo in Hammersmith Functional Motor Scale-Expanded (HFMSE) in SMA patients[23] - 30% of apitegromab patients achieved ≥3-point improvement in HFMSE compared to 125% of placebo patients[23] - FDA accepted BLA under Priority Review with a target action date of September 22, 2025[25] - MAA Validated with anticipated EU approval in 2026[14] - The company is initiating Phase 2 OPAL Trial in Q3 to study apitegromab in patients under 2 years old[14, 27] Pipeline Expansion - EMBRAZE trial achieved primary endpoint with positive Phase 2 proof-of-concept in obesity[14] - Apitegromab combined with tirzepatide resulted in a 549% reduction in lean mass loss versus tirzepatide alone[36] - The company is on track to file IND for SRK-439 in 2H 2025[14, 39, 43] Financial Status - The company had $295 million cash as of June 30, 2025[14]

PART I [Item 1. Financial Statements (Unaudited)](index=8&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) Presents unaudited condensed consolidated financial statements and notes on financial position and performance [Condensed Consolidated Balance Sheets](index=8&type=section&id=Condensed%20Consolidated%20Balance%20Sheets%20as%20of%20June%2030,%202025%20and%20December%2031,%202024) Presents the company's financial position at specific dates, detailing assets, liabilities, and equity | Metric | June 30, 2025 (in thousands) | December 31, 2024 (in thousands) | Change (in thousands) | | :----- | :--------------------------- | :------------------------------- | :-------------------- | | Cash and cash equivalents | $152,925 | $177,878 | $(24,953) | | Marketable securities | $142,088 | $259,400 | $(117,312) | | Total current assets | $319,126 | $451,165 | $(132,039) | | Total assets | $340,045 | $474,922 | $(134,877) | | Total liabilities | $106,752 | $106,288 | $464 | | Total stockholders' equity | $233,293 | $368,634 | $(135,341) | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss%20for%20the%20Three%20and%20Six%20Months%20Ended%20June%2030,%202025%20and%202024) Details the company's revenues, expenses, and net loss over specified three and six-month periods | Metric (in thousands) | 3 Months Ended June 30, 2025 | 3 Months Ended June 30, 2024 | Change ($) | Change (%) | | :-------------------- | :--------------------------- | :--------------------------- | :--------- | :--------- | | Research and development | $62,401 | $42,373 | $20,028 | 47.3% | | General and administrative | $49,708 | $17,125 | $32,583 | 190.3% | | Total operating expenses | $112,109 | $59,498 | $52,611 | 88.4% | | Net loss | $(110,031) | $(58,508) | $(51,523) | 88.1% | | Metric (in thousands) | 6 Months Ended June 30, 2025 | 6 Months Ended June 30, 2024 | Change ($) | Change (%) | | :-------------------- | :--------------------------- | :--------------------------- | :--------- | :--------- | | Research and development | $111,079 | $85,466 | $25,613 | 30.0% | | General and administrative | $78,120 | $32,451 | $45,669 | 140.7% | | Total operating expenses | $189,199 | $117,917 | $71,282 | 60.5% | | Net loss | $(184,754) | $(115,361) | $(69,393) | 60.2% | [Condensed Consolidated Statements of Stockholders' Equity](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders'%20Equity%20for%20the%20Six%20Months%20Ended%20June%2030,%202025%20and%202024) Tracks changes in the company's equity over the six months, including net loss and equity compensation | Metric (in thousands) | Balance at Dec 31, 2024 | Balance at June 30, 2025 | Change | | :-------------------- | :---------------------- | :----------------------- | :----- | | Total Stockholders' Equity | $368,634 | $233,293 | $(135,341) | | Net loss (6 months) | N/A | $(184,754) | N/A | | Equity-based compensation expense (6 months) | N/A | $37,846 | N/A | | Exercise of stock options (6 months) | N/A | $8,126 | N/A | [Condensed Consolidated Statements of Cash Flows](index=11&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows%20for%20the%20Six%20Months%20Ended%20June%2030,%202025%20and%202024) Summarizes cash inflows and outflows from operating, investing, and financing activities over six months | Metric (in thousands) | 6 Months Ended June 30, 2025 | 6 Months Ended June 30, 2024 | Change | | :-------------------- | :--------------------------- | :--------------------------- | :----- | | Net cash used in operating activities | $(155,616) | $(98,981) | $(56,635) | | Net cash provided by investing activities | $120,020 | $84,006 | $36,014 | | Net cash provided by financing activities | $10,643 | $6,492 | $4,151 | | Net decrease in cash, cash equivalents and restricted cash | $(24,953) | $(8,483) | $(16,470) | [Notes to Condensed Consolidated Financial Statements](index=12&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) Provides detailed explanations and additional information supporting the consolidated financial statements [1. Nature of the Business](index=12&type=section&id=1.%20Nature%20of%20the%20Business) Describes Scholar Rock's focus as a late-stage biopharmaceutical company and its key product candidates - Scholar Rock is a late-stage biopharmaceutical company focused on developing and commercializing apitegromab for spinal muscular atrophy (SMA) and other neuromuscular diseases, utilizing a proprietary platform targeting the TGFβ superfamily[22](index=22&type=chunk)[79](index=79&type=chunk) - Apitegromab achieved its primary endpoint in the pivotal Phase 3 SAPPHIRE trial for non-ambulatory SMA, is under FDA priority review with a PDUFA target action date of **September 22, 2025**, and received EMA MAA validation. A U.S. commercial launch is expected in **Q4 2025**, with Europe to follow in **2026**, if approved[23](index=23&type=chunk)[82](index=82&type=chunk) - The company is expanding its anti-myostatin program with SRK-439, a novel, fully human anti-myostatin monoclonal antibody, with an investigational new drug (IND) application planned for the **second half of 2025**[24](index=24&type=chunk)[85](index=85&type=chunk) - SRK-181, a highly selective inhibitor of latent TGFβ1 activation for checkpoint inhibitor-resistant cancers, completed its Phase 1 DRAGON trial in **June 2025**, showing encouraging responses[25](index=25&type=chunk)[88](index=88&type=chunk) [2. Summary of Significant Accounting Policies](index=14&type=section&id=2.%20Summary%20of%20Significant%20Accounting%20Policies) Outlines the company's accounting policies and the impact of recent and future accounting pronouncements - The company's significant accounting policies remain materially unchanged from those disclosed in its Annual Report on Form 10-K for the year ended December 31, 2024[31](index=31&type=chunk) - ASU 2023-07 (Segment Reporting) was adopted and did not have a material impact on the condensed consolidated financial position and results of operations[35](index=35&type=chunk) - The company is evaluating the impact of ASU 2023-09 (Income Taxes) and ASU 2024-03 (Expense Disaggregation) on future disclosures, with effective dates in **2025** and **2026/2027**, respectively[36](index=36&type=chunk)[37](index=37&type=chunk) [3. Fair Value of Financial Assets and Liabilities](index=17&type=section&id=3.%20Fair%20Value%20of%20Financial%20Assets%20and%20Liabilities) Details fair value measurements of financial assets, primarily marketable securities and cash equivalents | Asset Category (in thousands) | June 30, 2025 (Total Fair Value) | December 31, 2024 (Total Fair Value) | | :---------------------------- | :------------------------------- | :----------------------------------- | | Money market funds | $132,321 | $97,290 | | U.S. treasury obligations (cash & cash equivalents) | $12,963 | $63,171 | | Marketable securities (U.S. treasury & government agency) | $142,088 | $259,400 | | **Total assets at fair value** | **$287,372** | **$419,861** | - All financial assets measured at fair value on a recurring basis (money market funds, U.S. treasury obligations, and government agency securities) are categorized as **Level 1**, indicating valuation using quoted market prices[38](index=38&type=chunk) [4. Marketable Securities](index=17&type=section&id=4.%20Marketable%20Securities)

[Filing Details](index=1&type=section&id=Filing%20Details) This section provides fundamental information regarding the Form 8-K filing, including registrant details and securities information [General Information](index=1&type=section&id=General%20Information) This section provides the foundational details of the Form 8-K filing, identifying Scholar Rock Holding Corporation as the registrant, the filing date, and its corporate contact information General Information Details | Detail | Information | | :--- | :--- | | **Registrant** | Scholar Rock Holding Corporation | | **Filing Type** | Form 8-K | | **Date of Report** | August 6, 2025 | | **Jurisdiction** | Delaware | | **Commission File Number** | 001-38501 | | **Address** | 301 Binney Street, 3rd Floor, Cambridge, MA 02142 | | **Telephone** | (857) 259-3860 | [Securities Information](index=1&type=section&id=Securities%20Information) This part details the company's registered securities and its status regarding emerging growth company provisions Registered Securities | Title of each class | Trading Symbol(s) | Name of each exchange on which registered | | :--- | :--- | :--- | | Common Stock, par value $0.001 per share | SRRK | The Nasdaq Global Select Market | - The registrant is **not an emerging growth company** as defined in Rule 405 of the Securities Act of 1933 or Rule 12b-2 of the Securities Exchange Act of 1934[3](index=3&type=chunk) [Report Items](index=2&type=section&id=Report%20Items) This section outlines specific disclosures required by Form 8-K, including financial results, Regulation FD disclosures, and a list of exhibits [Item 2.02. Results of Operations and Financial Condition](index=2&type=section&id=Item%202.02.%20Results%20of%20Operations%20and%20Financial%20Condition) Scholar Rock Holding Corporation issued a press release on August 6, 2025, announcing its financial and operating results for the fiscal quarter ended June 30, 2025. This press release is furnished as Exhibit 99.1 and is not considered 'filed' for certain legal purposes - Scholar Rock Holding Corporation issued a press release on **August 6, 2025**, announcing financial and operating results for the fiscal quarter ended **June 30, 2025**[4](index=4&type=chunk) - The press release is furnished as **Exhibit 99.1** to this Report on Form 8-K[4](index=4&type=chunk) - Information in this report and Exhibit 99.1 is furnished, not deemed 'filed' for Section 18 of the Exchange Act, and not incorporated by reference unless expressly stated[5](index=5&type=chunk) [Item 7.01. Regulation FD Disclosure](index=2&type=section&id=Item%207.01.%20Regulation%20FD%20Disclosure) The Company will host a conference call on August 6, 2025, at 8:00 am ET to discuss its Q2 2025 financial and operating results and provide a business update, utilizing presentation slides furnished as Exhibit 99.2. Similar to Item 2.02, this information is furnished, not filed - A conference call is scheduled for **8:00 am ET on August 6, 2025**, to discuss Q2 2025 financial results and provide a business update[6](index=6&type=chunk) - Presentation slides for the conference call are furnished as **Exhibit 99.2** to this Current Report on Form 8-K[6](index=6&type=chunk) - Information in this report and Exhibits 99.1 and 99.2 is furnished, not deemed 'filed' for Section 18 of the Exchange Act, and not incorporated by reference unless expressly stated[7](index=7&type=chunk) [Item 9.01. Financial Statements and Exhibits](index=2&type=section&id=Item%209.01.%20Financial%20Statements%20and%20Exhibits) This section lists all exhibits included with the Form 8-K filing, which comprise the press release, conference call presentation slides, and the interactive data file List of Exhibits | Exhibit No. | Description | | :--- | :--- | | 99.1 | Press Release issued by the Company on August 6, 2025, furnished hereto | | 99.2 | Presentation Slides for August 6, 2025 Conference Call, furnished hereto | | 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | [Signature](index=3&type=section&id=Signature) This section confirms the official signing of the Form 8-K report by an authorized corporate officer - The report was signed on behalf of **Scholar Rock Holding Corporation** by **Junlin Ho, General Counsel & Corporate Secretary**, on **August 6, 2025**[10](index=10&type=chunk)[12](index=12&type=chunk)

Business Overview - Scholar Rock's strategy focuses on selectivity in targeting latent growth factors to develop therapeutics across multiple disease areas[12, 15, 17, 19] - The company is advancing a pipeline of product candidates in neuromuscular disorders, cardiometabolic disorders, immuno-oncology, fibrosis, and anemia[20, 23] - Scholar Rock anticipates transformative execution in the next 12-24 months, driven by upcoming milestones and commercialization efforts[12] Apitegromab (Spinal Muscular Atrophy) - Topline readout from the Phase 3 SAPPHIRE trial in SMA is expected in Q4 2024, with a potential SMA launch in Q4 2025 if successful and approved[30] - 48-month data from the TOPAZ clinical trial showed substantial and sustained improvements in motor function outcomes in pooled nonambulatory SMA patients[39, 46, 52] - In the TOPAZ trial, pooled nonambulatory patients showed mean change from baseline in HFMSE of 2.8 at 6 months, 3.6 at 12 months, 4.2 at 24 months, 4.0 at 36 months, and 5.3 at 48 months[40] - In the TOPAZ trial, pooled nonambulatory patients showed mean change from baseline in RULM of 0.6 at 6 months, 1.3 at 12 months, 2.3 at 24 months, 2.4 at 36 months, and 3.6 at 48 months[47] Apitegromab (Obesity) & SRK-439 - A Phase 2 proof-of-concept EMBRAZE study of apitegromab in obesity is enrolling, with topline data expected in Q2 2025[23, 30, 60, 63] - SRK-439, a novel anti-myostatin antibody, is being advanced to IND submission, with preclinical data showing potential for healthier weight loss in combination with GLP-1 receptor agonists[23, 30, 75] - Preclinical data showed that SRK-439 increased lean mass and attenuated regain of fat mass after GLP-1 RA withdrawal in an obesity mouse model[78] - In preclinical studies, SRK-439 demonstrated greater potency than an anti-ActRII antibody at maintaining lean mass during GLP-1 RA-induced weight loss[77, 88]