Scholar Rock Holding Corporation

Good morning and welcome to Scholar Rock's fourth quarter of financial results and business update call. All participants will be in listen-only mode. After the company's prepared remarks, call participants will have the opportunity to ask questions. To ask a question, you may press star then 1-1 on your touchtone phone. To withdraw your question, please press star 1-1 again. Please note this event is being recorded. Before we begin, I'd like to point out that we'll be making various statements about Scholar Rock's expectations, plans, and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date. I encourage you to go to the Investors and Media section of our website to find our most up-to-date SEC statements and filings. A recording of today's event will also be available on our website should you want to rewatch at a later date. I will now turn the conference over to Jay Backstrom, President and CEO of ScholarRock. Jay, please go ahead.

Well, thank you, Operator. Good morning and welcome, everyone, and thank you for joining our fourth quarter 2024 business update. We had an outstanding year in 2024, and we're off to a great start to 2025. For today's call, I'll start by providing a review of the Sapphire results and our progress toward our regulatory milestones. Tracy Sacco, our Chief Commercial Officer, will share the terrific progress we're making with our commercial preparation and our planning for a 2025 launch. as we're working with a sense of urgency to serve those living with SMA globally, starting with the U.S. And then I'll follow with a review of our innovative Myostatin platform and our ambition to transform the current GLP-1 treatment paradigm for weight management. Following our prepared remarks, Tracy and I will be joined by Ted Miles, Chief Operating Officer and Chief Financial Officer, and Mo Katanani, our Chief Scientific Officer, for the Q&A portion of today's call. Moving to slide four. With our success in 2024, the stage is set for what will be a transformative year for ScholarO. And as I said, we are working with a sense of urgency to bring EpidogramMap to those living with SMA, and we continue to hit our milestones on time or ahead of schedule. Starting with the regulatory applications for EpidogramMap and SMA, we submitted the BLA in the US in January, and we remain on track to submit the MAA in the EU in March. We look forward to sharing the SAFIRE data at the Muscular Dystrophy Association's annual meeting in Dallas on March 19th, where this data will be featured as an oral presentation. We will also be sharing our work with the murine version of epitogrammab in a non-clinical model of BMD, setting the stage for us to expand the development of epitogrammab into other neuromuscular indications. We also continue to make progress on our goal to expand treatment to even the youngest of those with SMA, and we're on track to open the OPAL study for those under two years of age in the third quarter. For our cardiometabolic program, we remain on track to share the top line data from EMBRACE and Q2 with the filing of the IMD for SRK439, our highly selective anti-myostatin designed for cardiometabolic indications in the third quarter. Turning to slide five. Before I hand over to Tracy, I want to review the positive top line results for Sapphire our registration study with epitogrammab, the only muscle-targeted therapy with clinical success in a pivotal study in SMA, which has the potential to transform the standard of care. Epitogrammab plus standard of care delivered gains of 1.8 points improvement compared to placebo plus standard of care, as measured by the gold standard SMA-specific Hammersmith functional motor scale at week 52, gains that were both clinically meaningful and statistically significant. Importantly, there was consistency across age groups 2 through 21 in a broad SMA population. In addition, 30% achieved an additional 3-pointer greater improvement in their Hammersmith scores when compared to placebo plus an SMM therapy, where only 12.5% achieved the same high bar. Further, as shown in the graph displaying motor function over the 52-week treatment period, those receiving epitidermab achieved a gain in function. while those receiving an SMN therapy alone lost function over this 52-week period. With respect to safety, the safety was consistent with the TOPAS data, with over 95% rolling over and remaining in the long-term follow-up study, adding to our experience in over 200 patients, and we remain the only muscle-targeted therapy that has over four years of clinical experience in SMA. Together, the data support an overall favorable benefit-risk with the potential to shift the treatment paradigm and usher in a new standard of care to include epidermab, a muscle-targeted therapy, with an SMN-directed therapy as part of the treatment regimen for SMA. I will now turn the call over to Tracy, our Chief Commercial Officer, to provide an update on our commercial preparations. Tracy?

Thank you, Jay. Moving to slide seven. Despite successes in treating the motor neuron over the past eight years, progressive muscle weakness continues to be a critical unmet need in SMA. And there's currently no approved muscle targeted therapy to treat this muscle neuromuscular disease. Patients and caregivers have described to us the debilitating impacts of progressive muscle weakness and how it significantly detracts from their independence and their ability to perform basic daily activities like eating, dressing, getting in and out of bed or their car, brushing teeth, climbing stairs, and using the bathroom. This is why 97% of patients surveyed by Cure SMA identified improving muscle strength as an important need that they want to see from a new SMA treatment. From our own market research, we know that more than 80% of treating neurologists agree that preserving muscle should start as early as possible in SMA. The SMA community is collectively calling for more to treat this relentless progression of muscle weakness and improve motor function in SMA. Next slide. Today, roughly two-thirds of the 10,000 people living with SMA in the U.S. and 35,000 individuals globally have already received an SMN targeted therapy. Yet we see from the data that Jay just presented that despite these effective therapies, progressive muscle weakness still robs these individuals of their ability to function over time. This is why 74% of neurologists recognize that in the future, a combination of modalities to target the motor neuron and the muscle will be necessary to treat SMA. The future of SMA will be to directly treat both the muscle and the motor neuron to provide the best outcomes for patients. Epidogramab is the potential first approved muscle targeted therapy in SMA is leading the transformation of SMA care. Next slide. Scholarock has been at the forefront of preparing the market for this potential new treatment paradigm in SMA. Last year, we introduced Life Takes Muscle, the first muscle-focused SMA disease education campaign that amplifies what we've been hearing from patients and caregivers for years about the devastating impacts of progressive muscle weakness. Life Takes Muscle has resonated with both the patient and HCP communities and led to continued strong engagement with Scholarock. Additionally, our MSL team has also been meeting with the leading cure SMA centers and engaging with top treating neurologists and care teams to educate on our phase three SAFIRE top line data. And Scholar continues to partner and learn from our patient advocacy partners who have been so effective already in helping to bring new treatments to the SMA community. Next slide. We're doing all this with a team of experienced professionals with deep rare disease and launch experience, including prior SMA launches, and we're continuing to be a magnet to attract top commercial talent as we build out our team. Next slide. 2025 is an important year for Scholarock, and we are positioned for a successful launch. We'll continue to build on our stakeholder engagement and education, and this quarter have initiated outreach to top US commercial and federal payers ahead of our potential Q4 launch. We will also be scaling our customer-facing team of roughly 50 sales, reimbursement, and patient support personnel in late Q2 and early Q3 to be hired and onboarded ahead of our potential launch. And finally, Scholarock is building out our patient services offering and preparing to offer home infusion as an option at launch to provide excellent support and optionality to patients and treaters alike. We have been laying the groundwork for years, and now we're putting the broader team and infrastructure in place for a successful U.S. launch to meet a critical need in the fight to continue to improve the lives of those living with SMA. I'll now turn the call back to Jay.