Scholar Rock Holding Corporation Common Stock FDA announcement

I'm Laura Ekas, Vice President, Investor Relations at Scholar Rock. With me today are David Hallal, Chairman and Chief Executive Officer, Akshay Vaishnaw, President of R&D, R. Keith Woods, Chief Operating Officer, and Vikas Sinha, Chief Financial Officer. Before we begin, I'd like to remind you that during this call, we will 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 for our most up-to-date SEC statements and filings. With that, I'd like to turn the call over to David.

David? Thank you, Laura, and good morning.

Thank you all for joining us for what is an extraordinary day for the SMA community. On Friday, we reached a defining milestone, the FDA approval of ISEMBYLD, our novel, highly innovative myostatin inhibitor that is now the world's first and only muscle-targeted therapy for children and adults living with SMA. Over the past decade, SMN-targeted therapies have brought needed innovation to the SMA community by improving motor neuron health. Yet significant unmet need remained as treatment for muscle, the principal organ clinically affected by SMA had gone unaddressed. With the FDA approval of ISEMBYLD, we are now ushering in the next phase of innovation in SMA treatment, bringing the first and only therapy designed to directly target muscle to the SMA community and creating new possibilities for patients and families. I would note three important points with respect to this landmark FDA approval.

First, ISEMBYLD is indicated for all patients with SMA two years of age and older who are currently receiving an SMN2-targeted treatment. This broad label enables us to serve a significant population within the SMA community and advances our ambition that any patient who can benefit from ISEMBYLD should have access to ISEMBYLD. Second, the label reflects the compelling clinical benefits that ISEMBYLD can bring to children and adults with SMA. For patients receiving a chronic SMN2-targeted treatment in our global randomized double-blind placebo-controlled phase III SAPPHIRE study, ISEMBYLD changed the progression of SMA from a loss of motor function to a gain of motor function. Specifically, at the recommended dose of 10 milligrams per kilogram, ISEMBYLD delivered a robust, clinically meaningful 2.2 point improvement in motor function compared with patients receiving an SMN2-targeted treatment alone, as measured by the gold standard Hammersmith Functional Motor Scale.

Akshay will provide much more detail on the ISEMBYLD label and clinical data shortly. Finally, we are thrilled that our U.S. launch of ISEMBYLD is now underway. Our highly experienced U.S. team has worked with urgency on extensive disease education and awareness initiatives that have advanced the understanding of SMA as a disease of both the motor neuron and the muscle. Supported by a broad label, compelling efficacy, and a well-characterized safety profile, we are exceptionally well-positioned for a successful U.S. launch. We are poised to redefine the standard of care for people living with SMA as we begin to serve a steady and consistent number of new patients through the initial phase of the launch and for many years to come. Scholar Rock is operating from a position of strength as we enter a new chapter as a commercial organization.

From a financial perspective, we exited the second quarter with $492 million in cash equivalents, and marketable securities. Also, with access to an additional $150 million from our debt facility, a priority review voucher that we intend to monetize, and revenues that will now commence and grow, we are well positioned to fund our growth initiatives. They include the ISEMBYLD launch in the U.S., our global expansion to reach patients in Europe, Japan, and up to 50 countries around the world, and advance our robust clinical pipeline and innovative platform. With this strong balance sheet, we do not intend to raise cash through an equity offering at this time.

Looking forward, now that our U.S. launch has commenced, our opportunity with ISEMBYLD and SMA alone represents many years of sustainable growth as we begin to serve the estimated 35,000 people with SMA globally who are receiving an SMN targeted treatment. We are on our way to becoming the next global biotech powerhouse supported by bold science, innovative therapies, fully integrated global capabilities, and exceptional talent. Before I turn the call over to Akshay to further discuss the approval of ISEMBYLD, I want to express my gratitude to the FDA for their constructive and collaborative engagement throughout the review process, which helped bring us to this important moment. With that, I will turn the call over to Akshay.

Akshay? Thank you, David. I am delighted to be sharing news of the ISEMBYLD FDA approval with all of you today.

This is a momentous milestone for Scholar Rock. After nearly 30 years of failed efforts across the industry to drug myostatin, today, we are the first company to successfully develop and secure FDA approval for a myostatin inhibitor. With that, let me share details of the comprehensive clinical program that supported the ISEMBYLD approval and the resulting FDA-issued label. SMA is a rare severe neuromuscular disease resulting in irreversible loss of motor neurons and progressive muscle wasting, leading to motor function decline. Patients experience muscle wasting that impacts all aspects of mobility and daily life, including basic functions like breathing, eating, dressing, self-care, and walking. Affected children often require significant support, and for many, independent living in adulthood can be very challenging.

Despite progress over the last decade with SMN-targeted treatments, SMA remains a devastating disease for too many children, adults, and their families. The motor unit has two key components, motor neuron and muscle. Given that motor function depends not only on neuronal signaling but also on muscle responsiveness, approaches that target muscle from the start have been urgently needed. With that, let me share details of the comprehensive clinical program that supported the ISEMBYLD approval and the resulting FDA-issued label. We developed a rigorous program to study apitegromab, now known as ISEMBYLD, in children and adults living with SMA. This program includes our global randomized double-blind placebo-controlled Phase III SAPPHIRE study. In the positive SAPPHIRE study, we definitively demonstrated that in SMA patients on chronic background SMN2-targeted treatment, ISEMBYLD showed a gain in motor function, while placebo was associated with a loss in motor function.

The SAPPHIRE study also demonstrated that ISEMBYLD had a well-characterized safety profile. Turning now to the label, ISEMBYLD is indicated for the treatment of SMA in adults and children over 2 years who are currently receiving an SMN2-targeted treatment. The recommended dose is 10 mg per kilogram IV, administered every 4 weeks. At this dose, ISEMBYLD led to a robust, clinically meaningful improvement in motor function. Specifically, compared to patients on an SMN2-targeted treatment alone, ISEMBYLD demonstrated a 2.2-point improvement at one year with a nominal P value of 0.0121, as measured by the gold standard Hammersmith Functional Motor Scale. Importantly, 34.2% of patients receiving ISEMBYLD showed a three-point or greater increase in the Hammersmith scale compared to 13.5% of patients on placebo at one year. ISEMBYLD-treated patients were more than twice as likely as placebo-treated patients to demonstrate a clinically meaningful improvement, 34.2% versus 13.5%.

Indeed, they are almost three times as likely as placebo-treated patients to reach this level of motor function improvement. To support the long-term safety, tolerability, and clinical benefit of ISEMBYLD, a total of 246 SMA patients have been studied in our clinical program, and we have over 900 patient-years of data. The safety and tolerability of ISEMBYLD in children and adults with SMA is highlighted in this table. Underscoring that safety profile, a total of 99% of patients from the Phase II TOPAZ study and the Phase III SAPPHIRE study entered the ONYX long-term extension study, and 93% of those participants currently remain in the study, some for more than 7 years. Taken together, these data demonstrate that ISEMBYLD, the first and only muscle-targeted therapy for SMA, can deliver compelling benefits for children and adults with this disease.

The FDA approval of ISEMBYLD is an enormous milestone for the SMA community and for Scholar Rock. Before I hand the call over to Keith, I too want to take a moment to thank the patients, the families, and the clinical colleagues around the world whose support and commitment enabled ISEMBYLD to be developed. I would also like to recognize the Scholar Rock team, and in particular, my R&D colleagues and manufacturing colleagues who pursued a bold scientific vision with unwavering focus and determination, accomplishing something that has eluded the field for decades. My sincere congratulations to our team. At this point, I will turn the call over to Keith to discuss our U.S. launch.