Scholar Rock's Q4 2024: Navigating Contradictions in SMA Dosing, Obesity Strategies, and FDA Guidance

These are the key contradictions discussed in Scholar Rock Holding Corporation's latest 2024Q4 earnings call, specifically including: SMA dosing and target population, implications of FDA's draft guidance on obesity clinical trials, focus on potential differences in SMA treatment effects, strategy for addressing obesity, expected weight loss in the obesity readout, and timing of IND filing for apitegromab in obesity:



SMA Program Milestones and Data:
- Scholar Rock Holding Corporation submitted the BLA for apitegromab in the U.S. in January and is on track to submit the MAA in the EU in March.
- The SAPPHIRE study results showed that apitegromab plus standard-of-care delivered gains of 1.8 points improvement in the Hammersmith Functional Motor scale at week 52, both clinically meaningful and statistically significant.
- The positive top-line results and regulatory milestones are driven by the success of apitegromab as the only muscle targeted therapy with clinical success in a pivotal study in SMA.

Cardiometabolic Program and EMBRAZE Study:
- Scholar Rock is preparing to share top-line data from the EMBRAZE study in Q2, with the filing of the IND for SRK-439 planned for the third quarter.
- The EMBRAZE study aims to assess the impact of adding SRK-439 to Tirzepatide regarding lean muscle mass preservation, with expectations to show a reduction of 1 kg to 2 kg of lean mass loss.
- The study aligns with the company's strategy to address the loss of lean mass associated with weight loss therapies, enhancing GLP-1 receptor agonists' profiles without introducing additional toxicities.

Commercial Preparation and Payer Engagement:
- Scholar Rock has initiated outreach to top U.S. commercial and federal payers ahead of its potential Q4 launch of apitegromab.
- Payers have been receptive to Scholar Rock's innovations as the first muscle targeted therapy in SMA, with more than 80% of treating neurologists agreeing that preserving muscle should start as early as possible.
- These efforts are crucial for securing access and reimbursement for apitegromab, reflecting its potential value and unmet need in SMA.

Neuromuscular Expansion and Strategic Investment:
- Scholar Rock is exploring expanding its reach to other rare neuromuscular disorders beyond SMA, with a focus on indications like DMD, FSHD, Becker's, and even ALS.
- The company is actively engaging experts in these fields to assess the unmet need and potential impact of its therapies, with an eye on technical success and opportunity for meaningful benefit.
- The strategic investment in these indications is part of a broader effort to build a multimillion-dollar neuromuscular franchise, leveraging the success of its SMA program.