Positive Ph2 EMBRAZE Trial Demonstrating Preservation of Lean Mass with Highly Selective Anti-Myostatin Inhibitor During Tirzepatide-Induced Weight Loss June 18, 2025 © 2025 Scholar Rock, Inc. All rights reserved. Today's Speakers David L. Hallal Chief Executive Officer Akshay Vaishnaw, M.D., Ph.D. President, Research & Development © 2025 Scholar Rock, Inc. All rights reserved. 2 Agenda | TOPIC | SPEAKER | | --- | --- | | Scholar Rock's Leading | David L. Hallal | | Anti-Myostatin Platform | Chief Executive ...

Scholar Rock Holding (SRRK) Update / Briefing June 18, 2025 08:00 AM ET Speaker0 Good morning, and welcome to ScholarRock's presentation of top line data from the Phase two EMPRAISE proof of concept trial. At this time, all lines are in listen only mode. Following the presentation, we will conduct a question and answer session. To ask a question, you may press star then 11 on your touch tone phone. To withdraw your question, please press then 11 again. This call is being recorded on Wednesday, 06/18/2025. I ...

Financial Data and Key Metrics Changes - The company is preparing for the PDUFA date of September 22 for apategromab in SMA, indicating a significant milestone in its financial outlook [11] - The management has emphasized a strong cash position, with a runway extending into early 2027, allowing for strategic investments without immediate equity issuance [42][44] Business Line Data and Key Metrics Changes - The company has seen robust clinical development for ipilimumab in SMA, with a Phase III SAFIRE trial enrolling 188 patients, demonstrating clinically meaningful benefits [12][13] - The obesity program is set to share Phase II data from the EMBRAZE trial, focusing on the preservation of lean mass in patients receiving tirzepatide [28][29] Market Data and Key Metrics Changes - The company is under review with the FDA and the European Medicines Agency, with plans for a substantial launch in the U.S. and thoughtful expansion into Europe and Asia Pacific [25][26] - There are approximately 35,000 patients worldwide who have received at least one SMN targeted therapy, highlighting a significant market opportunity for the company's products [26][40] Company Strategy and Development Direction - The company aims to scale its growth into global commercialization, focusing on the approval of ipilimumab in multiple countries [3][25] - The strategy includes leveraging existing assets while exploring new indications for ipilimumab and SRK-439 in rare neuromuscular disorders [9][38] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of ipilimumab to reverse the trend of motor function loss in SMA patients, positioning it as a new standard of care [15][19] - The company is committed to making a meaningful difference for patients and ensuring that no patient is left behind in accessing their therapies [27][44] Other Important Information - The company is considering the implications of pricing strategies based on the rarity and severity of diseases like SMA, as well as the clinical benefits demonstrated [39][40] - The management is cautious about the investment in cardiometabolic and obesity indications, focusing instead on rare severe neuromuscular disorders [33][44] Q&A Session Summary Question: What are the expectations for the label regarding apategromab in SMA? - Management expects a broad label based on the robust data from the Phase III SAFIRE trial and the consistency of results across patient subgroups [12][13] Question: How does the drug fit into the existing treatment paradigm for SMA? - The company believes ipilimumab can provide significant benefits beyond existing SMN targeted therapies, particularly for patients who have started to lose motor function again [14][15] Question: What is the company's strategy for the obesity program? - The company plans to present Phase II data from the EMBRAZE trial, focusing on the preservation of lean mass in patients receiving tirzepatide [28][29] Question: How does the company view the regulatory pathway for obesity treatments? - Management acknowledges the evolving view of the FDA and the need to demonstrate both weight loss and preservation of lean mass in future trials [32][33] Question: What is the current cash position and runway for the company? - The company has a strong cash position with a runway extending into early 2027, allowing for strategic investments without immediate equity issuance [42][44]

Summary of Scholar Rock Holding (SRRK) Conference Call Company Overview - **Company**: Scholar Rock Holding (SRRK) - **Event**: 2025 Conference at Jefferies Healthcare Conference - **Date**: June 04, 2025 Key Points Management Transition - David, the new CEO, transitioned from chairman to CEO to lead the next growth phase of Scholar Rock, emphasizing his long-term commitment to the company [4][9] - Akshay, the President of R&D, returned from retirement to join Scholar Rock, highlighting the team's collective experience in biotech [6][18] Product Development and Pipeline - The company is focused on the development of **epitogromab**, a therapy for Spinal Muscular Atrophy (SMA), with a PDUFA date set for September 22, 2025 [37][42] - The EMBRAICE study, an exploratory phase two study, is expected to provide data on the preservation of lean mass in patients starting on tirzepatide with or without epitogromab [24][25] Market Position and Competition - Scholar Rock aims to differentiate itself in the myostatin inhibition space, addressing challenges faced by previous attempts to target myostatin [9][30] - The company acknowledges the competitive landscape, particularly with Regeneron's recent data on myostatin and obesity, which sets a benchmark for their own upcoming data [21][27] Safety and Efficacy - The management emphasized the importance of safety in their therapeutic approach, noting that their therapy has shown a favorable safety profile compared to competitors [25][30] - The company is optimistic about the efficacy of epitogromab across various age groups, including younger patients, based on their existing data [50][52] Launch Strategy - The launch of epitogromab is expected to be steady rather than explosive, with a focus on known patient populations already receiving treatment for SMA [65][69] - The reimbursement landscape is favorable, but the absence of a J code may pose challenges during the launch [67][68] Regulatory Interactions - Ongoing interactions with the FDA have been positive, with no indications of an Advisory Committee meeting required for the BLA review [42][43] - The company plans to submit safety updates as part of standard operating procedures [46] Future Outlook - Scholar Rock is preparing for a global launch of epitogromab, with plans to file for approval in Europe, expected around mid-2026 [74][76] - The management team believes that their combined experience in rare disease biotech will facilitate a successful launch and growth trajectory for the company [19][20] Additional Insights - The management discussed the evolving understanding of SMA as a single disease, which may influence treatment approaches and regulatory perspectives [60][62] - There is a recognition of the need to balance innovation in new therapeutic areas, such as obesity, while maintaining focus on core competencies in rare diseases [35][37]

Financial Data and Key Metrics Changes - Scholar Rock reported a strong start to 2025, with significant progress in bringing up epitigromab for SMA patients globally [6][9] - The company ended the quarter with $364.4 million in cash, and has an additional $100 million available under its debt facility to support the upcoming launch [25][26] Business Line Data and Key Metrics Changes - The phase three SAPPHIRE trial for epitigromab showed a statistically significant improvement in motor function, indicating its potential to reverse SMA progression [7][13] - The company is preparing for a U.S. commercial launch of epitigromab anticipated in Q3 2025, with plans to expand into Europe, Asia Pacific, and Latin America [9][20] Market Data and Key Metrics Changes - Approximately 10,000 SMA patients in the U.S. and around 35,000 globally have received SMN-targeted therapies, highlighting the market potential for epitigromab [21][22] - Market research indicates that 90% of SMA patients are seeking new treatment options that improve muscle strength, emphasizing the demand for epitigromab [20] Company Strategy and Development Direction - Scholar Rock aims to establish itself as a fully integrated global biopharmaceutical company, focusing on the launch of epitigromab and expanding its pipeline into other neuromuscular disorders [9][28] - The company is also exploring the EMBRAZE study to understand its role in treating obesity, indicating a diversification of its research focus [10][11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming U.S. launch and the potential for sustainable growth driven by epitigromab and its pipeline [9][28] - The management team is committed to ensuring that no patient with SMA is left behind, reflecting a strong patient-centric approach [29] Other Important Information - The BLA for epitigromab was granted priority review by the FDA, with a PDUFA date set for September 22, 2025 [8][15] - The company is actively engaging with U.S. payers and preparing for reimbursement discussions in Europe, indicating proactive market access strategies [30][35] Q&A Session Summary Question: How receptive are U.S. payers to coverage of combination therapy for SMA patients? - Management indicated that early discussions with U.S. payers have been positive, with a focus on the need for better therapeutic options for SMA patients [32][34] Question: Can you comment on interactions with the FDA regarding the upadacumab review? - Management reported that interactions with the FDA have been routine and constructive, with no issues anticipated for the September 22 PDUFA date [38][39] Question: What are the expectations for the EMBRAZE study data in June? - Management confirmed that the primary focus will be on the 24-week data, with additional follow-up information provided as necessary [42][43] Question: How are you evaluating the potential to secure a commercial partner for Europe? - Management stated that they do not prioritize finding a partner outside the U.S., as they feel well-equipped to serve patients directly [88][89] Question: What are the launch dynamics and early demand expectations for epitigromab? - Management expressed optimism about the launch, citing the 100% newborn screening for SMA in the U.S. and the concentration of patients in centers of excellence [69][70]

Financial Data and Key Metrics Changes - Scholar Rock reported a strong start to 2025, with significant progress in bringing up epitigromab for SMA patients globally [6][9] - The company ended the quarter with $364.4 million in cash, indicating a solid financial position to support upcoming initiatives [25] Business Line Data and Key Metrics Changes - The phase three SAPPHIRE trial for epitigromab showed statistically significant improvement in motor function, with patients treated having a threefold higher chance of a three-point or greater increase in Hammersmith Scale compared to placebo [7][13] - The company is preparing for a U.S. commercial launch of epitigromab anticipated in Q3 2025, with plans to expand into Europe, Asia Pacific, and Latin America [9][22] Market Data and Key Metrics Changes - Approximately 10,000 SMA patients in the U.S. and around 35,000 globally have received SMN-targeted therapies, highlighting the market potential for epitigromab [21] - The company is focusing on the dual modality treatment approach for SMA, combining SMN-targeted therapies with muscle-targeting therapies [20] Company Strategy and Development Direction - Scholar Rock aims to establish itself as a fully integrated global biopharmaceutical company, with a focus on SMA and potential expansion into other neuromuscular disorders [9][27] - The company is also exploring the EMBRAZE study to understand its role in treating obesity, indicating a diversification of its research focus [10][11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming U.S. launch of epitigromab and the potential for sustainable growth through the end of the decade [9][27] - The company is committed to ensuring that no patient with SMA is left behind, emphasizing its responsibility to patients and families [28] Other Important Information - The BLA for epitigromab was granted priority review by the FDA, with a PDUFA date set for September 22, 2025 [8][15] - The company has an additional $100 million under its debt facility to support the upcoming launch, extending its financial runway into 2027 [25][26] Q&A Session Summary Question: How have discussions with U.S. payers gone regarding coverage for combination therapy? - Management indicated that early discussions with payers have been positive, with a focus on the need for better therapeutic options for SMA patients [31][34] Question: Can you provide an update on interactions with the FDA regarding the upadacumab review? - Management reported that interactions with the FDA have been routine and constructive, with no issues anticipated for the September 22 PDUFA date [36][37] Question: What are the expectations for the EMBRAZE study data in June? - Management confirmed that the primary focus will be on the 24-week data, with additional follow-up information provided as necessary [41][42] Question: How do you evaluate the potential to secure a commercial partner for Europe? - Management stated that they do not prioritize seeking a partner outside the U.S., feeling confident in their ability to serve patients directly [86] Question: What are the expectations for launch dynamics and early demand post-approval? - Management noted that while they will not provide specific guidance, they are optimistic due to the existing infrastructure and patient population [68][70]

Financial Data and Key Metrics Changes - The company ended the quarter with $364.4 million in cash [25] - The company has an additional $100 million under its debt facility that can be drawn down this year to support the upcoming launch, extending its anticipated runway into 2027 [26] Business Line Data and Key Metrics Changes - The company is focused on the commercial launch of epitigromab for SMA, with a PDUFA date set for September 22, 2025 [6][13] - The company is preparing for a global launch, starting in the US in Q3 2025, and is also evaluating expanding the study of upitigramab into other rare neuromuscular disorders [7][8] Market Data and Key Metrics Changes - Approximately 10,000 patients with SMA are in the US, with about two-thirds having received SMN-targeted therapies [20] - Globally, around 35,000 patients have received SMN-targeted therapies, indicating a significant market opportunity for epitigromab [20] Company Strategy and Development Direction - The company aims to establish itself as a fully integrated global biopharmaceutical company, focusing on SMA and exploring additional indications for its therapies [7][14] - The company is committed to ensuring that any patient with SMA who can benefit from epitigromab has access to it, indicating a patient-centric approach [7] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming launch and the potential of epitigromab to transform the treatment landscape for SMA [19] - The company is aware of the competitive landscape and the need for dual modalities to address both motor neuron and muscle degeneration in SMA patients [20] Other Important Information - The EMBRAZE proof of concept study is ongoing, focusing on the role of the company in treating obesity and preserving lean mass [9][10] - The company is on track to share top-line results from the EMBRAZE study in June 2025 [10] Q&A Session Summary Question: How have discussions with U.S. payers gone regarding coverage for combination therapy? - Management indicated that early discussions with payers have been positive, and they expect that the budget impact for any single payer will be limited due to the rarity of the disease [31][34] Question: Can you comment on interactions with the FDA regarding the upadacumab review? - Management reported that interactions with the FDA have been routine and constructive, with no issues anticipated for the September 22 PDUFA date [38] Question: What are the expectations for the EMBRAZE study data in June? - Management confirmed that they will provide the 24-week data as the main study outcome and will include any necessary follow-up information [43] Question: How quickly will the company be able to launch after the PDUFA date? - The company is prepared to launch the day after the PDUFA date, with ample supply to meet demand [60] Question: How is the company evaluating the potential to secure a commercial partner for Europe? - Management stated that they do not prioritize finding a partner outside the U.S. and feel well-equipped to serve patients directly [86]

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE QUARTERLY PERIOD ENDED March 31, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD FROM _ TO _ COMMISSION FILE NUMBER 001-38501 ______________________________________________ SCHOLAR ROCK HOLDING CORPORATION (Exact name of registrant as sp ...

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 ...