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]

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 10-Q (Exact name of registrant as specified in its charter) Delaware 82-3750435 (State or other jurisdiction of incorporation or organization) 301 Binney Street, 3rd Floor Cambridge, Massachusetts (Address of principal executive offices) (Zip Code) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE QUARTERLY PERIOD ENDED JUNE 30, 2025 OR ☐ TRANSITION REPORT PURSUANT T ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event Reported): August 6, 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 Identification Number) 301 Binney Street, 3rd Floor, Cambridge, MA 02142 (Add ...

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]

Apitegromab in SMA - Positive Phase 3 SAPPHIRE data was presented at MDA, showing that 30% of apitegromab patients achieved ≥3-point improvement in HFMSE compared to 12.5% on placebo[19] - Apitegromab demonstrated a 1.8 point improvement (p=0.0192) in HFMSE versus placebo[19] - The FDA has accepted the BLA for Apitegromab under Priority Review, with a PDUFA date of September 22[22] - The company anticipates a commercial launch of Apitegromab in Q3, pending regulatory approval[37] - The company anticipates EU approval in 2026[10] Pipeline Development - The company plans to file the IND application for SRK-439 in Q3[26] - An exploratory Phase 2 EMBRAZE POC study in Obesity readout is on track for June[10] - The company plans to initiate Ph 2 OPAL Trial in Q3 2025 for SMA patients <2 years old[32] Financial Status - The company reported $364.4 million in cash as of March 31, 2025[10]

Core Insights - Scholar Rock Holding's shares increased by 13.7% following positive phase 2 trial results for its weight-loss therapy [1] - The trial demonstrated that the combination of Scholar Rock's apitegromab with Eli Lilly's tirzepatide significantly reduced lean mass loss compared to tirzepatide alone [2] - The therapy is well tolerated and has the potential to support healthier weight loss by preserving lean mass for patients on GLP therapies [3] Market Potential - The GLP-1 drug market, including Eli Lilly's Mounjaro and Novo Nordisk's Ozempic, was valued at $53.5 billion in 2024 and is projected to triple by 2030 [5] - Given the public's preference for fat loss over muscle loss, Scholar Rock's apitegromab could capture a significant share of this expanding market [5]

Core Insights - Scholar Rock's Phase 2 EMBRAZE trial results indicate that apitegromab combined with tirzepatide can significantly preserve lean mass during weight loss, with a notable reduction in lean mass loss compared to tirzepatide alone [1][2][3] Group 1: Trial Results - The trial showed that 30% of the weight loss from tirzepatide was attributed to lean mass loss, while the addition of apitegromab reduced this to 14.6% [3][4] - Patients receiving the apitegromab-tirzepatide combination lost 12.3% of their body weight, compared to 13.4% for those on tirzepatide with placebo [4] - The combination therapy resulted in a higher quality of weight loss, with patients losing 85% fat and 15% lean mass, compared to 70% fat and 30% lean mass in the placebo group [4] Group 2: Market Reaction - Following the positive trial results, Scholar Rock's stock price increased by 18%, reaching $36.77 [6]