Scholar Rock Holding Corporation (SRRK) Earnings Call Transcript & Summary

Good morning, and welcome to the Scholar Rock leadership update call, scaling for the next phase of growth. [Operator Instructions] Please note, this event is being recorded. Before we begin, I'd like to point out that we will be making various statements about Scholar Rock's expectations, plans and prospects that constitute forward 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 of any future date. I encourage you to go to the Investors & Media section of our website for 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 would now like to turn the conference over to Jay Backstrom of Scholar Rock. Please go ahead.

Well, thank you, operator. Good morning, everyone, and thank you for joining us. I've been reflecting a lot in my time at Scholar Rock in recent weeks. It all started with a cold call from David 3 years ago. And since that moment, it has been an incredible journey. Over the past 3 years, I had the rare opportunity to do something truly special, applying my 30 years of experience in R&D and work every day to deliver a life-changing medicine for people living with SMA. But more than that, I've had the privilege to lead an incredibly talented and dedicated team and to build a company focused on patients, an experience that has been both thrilling and deeply fulfilled. There are so many people to thank for this chapter. I'm grateful to the Board of Directors for placing their confidence and trust in me to bring us to this point and for the close partnership with David and Akshay. I'm especially grateful for the entire Scholar Rock team whose commitment and focus throughout my tenure has allowed us to consistently deliver on all of our key milestones. And to the executive team, my heartfelt and sincere thanks for your leadership and support. This moment, just after our BLA has been accepted under priority review and still 5 months ahead of our initial launch is the right time for today's leadership transition. Scholar Rock is rapidly entering a new phase, one that this expanded leadership team is exceptionally well equipped to navigate. As I told David back in 2022, I thought it could help move the company to the next inflection point and become a commercial stage company. Through our initial discussions 3 years ago, David convinced me that I was the right person to take Scholar Rock from where it was to where it is today. David, I thank you again for that phone call. Now in 2025, on the threshold of our first product launch and with the extraordinary growth that lies ahead, I'm fully convinced that David, you are the right leader to take this company forward. David has been instrumental in Scholar Rock's evolution over the past 8 years, helping guide the company's transformation from our preclinical private biotech to a public company with a robust pipeline and substantial commercial potential for many years to come. David has a proven track record of building global businesses, notably Alexion, where he established operations in over 50 countries to deliver life-transforming therapies for patients with devastating diseases. We all know and trust David's leadership, and we are very excited to now have him at the helm. David?

Thanks, Jay. We are so fortunate to have persuaded Jay to come out of retirement to leave Scholar Rock as our CEO. He has transformed our company. On behalf of the Board, we are deeply grateful to Jay for his leadership over the past 3 years, driving us through the highly successful apitegromab global Phase III program and now into the U.S. and European regulatory processes for marketing authorization. It has been my privilege working side-by-side with Jay throughout our journey and no doubt, Jay is one of the best hires I have ever made. As a great leader, he has brought sensational talent to Scholar Rock. Now as we prepare for the global launch of apitegromab in SMA, it's an ideal time for this planned leadership transition as we scale our operations to serve patients and families impacted with SMA in many countries around the world. Globally, nearly 35,000 patients with SMA have received SMN-targeted therapies. And at Scholar Rock, we are working with urgency to prepare for our global launch, which we anticipate will commence in the U.S. in Q3. We are also beginning to set the table to serve patients with SMA in Europe, Asia Pacific and Latin America. Our ambition is that any patient with SMA that can benefit from apitegromab should have access to apitegromab. I am confident that the global opportunity with apitegromab in SMA alone offers the potential for many years of sustainable growth that will power our company through the end of this decade and into the next. While we focus on our enormous opportunity to serve patients with SMA, I'd like to comment on our exploratory cardiometabolic program. We are the world leaders in myostatin biology and are well aware that GLP-1s have brought needed innovation to patients with obesity and cardiometabolic disorders. While benefits far outweigh the risks, muscle wasting or lean mass loss is something that the medical community is trying to address. We feel it is our obligation to understand how we can help these patients. The EMBRAZE study is our initial effort in the cardiometabolic area, and Akshay will touch upon this further in just a few moments. To underscore our commitment to patients with SMA, I am thrilled to begin my tenure with 3 exceptional leaders with an unparalleled track record of success. Today, we welcome Akshay, Keith and Vikas to Scholar Rock. Akshay was most recently President at Alnylam, where he was instrumental in developing the platform, which delivered 6 RNAi therapeutics globally. He is appointed to the newly created role as President of R&D. Keith was most recently the Chief Operating Officer at argenx, where he was the architect of the Vyvgart global launch. He joins us in the newly created role of COO and will oversee our operational build-out globally as we establish regional and country operations to reach all patients who can benefit from apitegromab. Vikas, who was previously CFO at Alexion and ElevateBio, joins us as CFO. He brings exceptional experience in corporate strategy, operations and capital markets. His leadership will be critical as we enter our next phase of growth and global expansion. These leadership additions significantly strengthen our organization and position Scholar Rock to execute as we advance our mission to deliver life-transforming therapies to patients around the world. Indeed, this is what we know well and what we do well. Now Akshay and I have worked together since 2017 to help Scholar Rock shape our scientific direction and long-term strategy. This long-standing relationship and shared vision are foundational as we move forward together. At this point, I'll turn the call over to Akshay. Akshay?

Thank you, David, and good morning, everybody. I'm delighted to be here at Scholar Rock. It's been so gratifying to see our early translational work mature into the positive Phase III SMA study for apitegromab. SAPPHIRE showed that apitegromab has the potential to reverse the progression of SMA from a loss of motor function to a gain of motor function. Specifically, the study demonstrated a statistically significant improvement in Hammersmith whilst patients on placebo worsened. Most importantly, patients treated with apitegromab had an almost threefold higher chance of increase in Hammersmith versus those on placebo. Along with the very encouraging safety profile, the SAPPHIRE data suggests that apitegromab has great potential to provide clinically significant benefit to patients with SMA despite the use of background SMN target therapies. With the success of SAPPHIRE, we're just beginning to tap into the broader potential of our truly innovative myostatin platform. There's much more we can do with the promise of apitegromab and our platform by delivering advances in severe neuromuscular diseases such as the muscular dystrophies, including DMD and FSHD. Additionally, we're advancing our franchise with SRK-439, a highly innovative and potent subcu anti-myostatin antibody to the clinic. With that in mind, let me describe for you the 4 areas we remain focused on and on track to deliver. We will, number one, drive the U.S. approval of apitegromab in Q3 2025 and the EU approval in 2026. Number two, initiate a study of apitegromab for infants and toddlers with SMA under the age of 2 starting Q3 this year. Number three, file an IND for SRK-439 in Q3 '25. And finally, finalize our plans -- clinical development plans for apitegromab in additional neuromuscular indications. Now David mentioned the potential role Scholar Rock can play in addressing lean mass in cardiometabolic disorders. As we all appreciate, whilst GLP-1s offer great quantitative benefits in terms of weight loss, much more needs to be done from a qualitative perspective with regard to preserving muscle. This is important, particularly from the viewpoint of metabolic benefits and a healthier approach to weight loss. Our EMBRAZE study is our ongoing Phase II trial to investigate preliminarily the potential of further developing our highly selective anti-myostatin approaches, including SRK-439 in patients with obesity. We look forward to reporting initial data in Q2 2025. Finally, as an R&D professional, the most gratifying thing for me is to see our pipeline advances reach patients in the real world. I'm therefore delighted to be partnering with Keith to achieve that goal. Now let me turn over the call to Keith. Keith?

Thanks, Akshay. I am honored to be here and have the opportunity to be a part of the Scholar Rock team. I have been fortunate to help build and lead teams dedicated to delivering highly innovative therapies for people living with serious and devastating diseases. At argenx, in just a 6-year period, we scaled from an 80-person Belgian-based R&D company to a global organization. We transformed a scientific vision into a worldwide commercial success. Vyvgart has become a blockbuster drug in the neuromuscular space impacting patients around the globe. When I look at the opportunity with apitegromab, I see some common themes I also saw with Vyvgart, the potential for a first-in-class, best-in-class therapy, elements of a pipeline and a product and a therapy for a rare neuromuscular disease with the opportunity to get close to the patient community. As I turn my attention to the upcoming global launch with apitegromab in SMA, beginning with the U.S., Scholar Rock is applying similar principles that we did at argenx, and those include attract and deploy top talent, focus on disease awareness and patient education, communicate the compelling clinical benefit of therapy; and finally, develop patient support programs to ensure reliability and predictable access to therapy. At Scholar Rock, we have the opportunity to make a meaningful difference for both children and adults living with SMA in the U.S. and beyond. I'm thrilled to be here and energized to help drive this mission forward, beginning in the U.S., then Europe, Asia Pacific and Latin America. Building and leading global businesses to serve patients around the world isn't only what I know well and do well, it's what I love to do. Finally, I'm very much looking forward to working once again with Vikas. During his tenure at Alexion, Vikas played a pivotal role in transforming the company from a pre-commercial organization into a leading global biotech. His experience and strategic mindset will be invaluable as we shape Scholar Rock's future and scale our global operations with capital efficiency and executing our commercial build. I will now turn the call over to Vikas. Vikas?

Thank you, Keith. I look forward to bringing the strong collaborative partnership that Keith and I built at Alexion to our work now at Scholar Rock. What excites me about this opportunity is to work with the great team here at Scholar Rock and the chance to leverage our collective experience, skills and relationships to build a global foundation to serve patients with rare diseases. As we move forward, I will focus first on: driving strong performance with financial discipline; next, investing in a capital-efficient commercial build-out; and thoughtful capital allocation to advance our pipeline. Indeed, the opportunity with apitegromab in SMA alone offers the potential for many years of sustainable growth and will enable strategic, thoughtful investment in our pipeline to develop new indications and new therapies for an increasing number of patients. These pipeline investments will be aligned to our commercial success. I'm truly honored to be joining this exceptional team. I'm excited for what's ahead and energized to help lead Scholar Rock through this next phase of growth. Back to David.

Thank you, Vikas. In closing, I want to acknowledge again Jay's tremendous leadership. The remarkable team he attracted and led has established a powerful foundation and is setting the stage for extraordinary growth ahead. Akshay, Keith, Vikas and I are humbled to step into leadership roles at this pivotal time and to work alongside the incredibly talented and committed team at Scholar Rock. We will build on the progress to date and carry the mission forward. No matter our accomplishments over these past years, our best years are in front of us, and we are confident that we will build and scale Scholar Rock into the next global biotech powerhouse. On behalf of every member of the Scholar Rock team, we are deeply aware of our responsibility to patients and their families, and we will work with urgency to ensure that no patient is left behind in the U.S. or in the many countries around the world where patients with SMA are counting on us. With that, I'll now open up the line for questions. Operator?

[Operator Instructions] And our first question will be coming from Michael Yee of Jefferies.

Surprised by the news, but perhaps you could talk to 2 things. Obviously, a number of people joining the team from 3 very successful companies. So just trying to understand, is the game plan here to completely build a whole commercial global company and completely build the pipeline, and that's what we should be expecting? And how does obesity play into that given that the data is literally right around the corner. So I guess I'm just scratching my head around the timing of the announcement. And then the second thing relates to, obviously, the balance sheet and how you think about the balance sheet going into the end of the year and into 2026 and what types of different scenarios are you thinking about?

Michael, thank you. This is David. Yes, I think the way to think about it is, as I noted in the call and as Jay and the team have noted previously, like with the contours of many rare disease blockbuster therapies, they don't follow sort of typical patterns where the majority of the revenue opportunity is simply in the U.S. And all of our experiences, we've oftentimes seen the majority of the opportunity to serve patients is outside of the U.S. I think in the last quarter call, Jay and the team referred to the 35,000 patients in the world that have received SMN-targeted therapies and somewhere near 25% to 33% of those were in the U.S. We feel like it's our obligation. We feel like it's what we know well and do well to reach patients in all of the countries in which they reside in. And we will be very thoughtful as we were previously at other organizations in allocating capital to build out a commercial infrastructure and platform to reach these patients who need apitegromab. As it relates to obesity, as we noted in the call, we feel like as the world leaders in myostatin biology and really the company that is building the deepest and widest array of anti-myostatin therapies in our pipeline, we just felt like given what we are seeing with the remarkable innovation of GLPs, we're seeing that one blemish is obviously muscle wasting and lean mass loss. And we feel like as those world leaders, it's really our obligation to understand what role we can play. And so EMBRAZE is important to us. It's the first initial trial that will help us understand how our capabilities and our highly innovative approach to myostatin may be able to help patients who are living with obesity and cardiometabolic disorders. As it relates to how to think about the balance sheet -- and Vikas, do you want to comment?

Michael, great talking to you again. We reported around $437.5 million of cash at the end of last year. And we are -- I've just joined -- it's just probably my first day here right now. And we need a little bit time to go through all the analysis and look at how best to take it forward. But what I also see here is another $100 million can be drawn down in our current loan agreement. So I feel very good coming into the company with a very strong balance sheet.

Yes. And Mike, just to add to that, right? So we're finishing out the quarter. So we're going to be having our quarterly filing soon, and we're closing that out. So you'll have a better granularity on it. I think to what we just heard though, we do have access to that vehicle. In addition, as you know, we are pediatric designation. We're coming under priority review. And assuming all that goes forward, then we have access then potentially to monetize a priority review voucher. So I think you're going to find we're in a good position closing out the year. Our guidance for cash runway is well into Q4 of 2026. And more to come with that, but I feel like we're in a good position with everything that we've just heard.

One moment for our next question, which will be coming from Allison Bratzel of Piper Sandler.

Best of luck to Jay. 2 questions from me. First, can you just talk about your sense of how to maximize the opportunity and reach for apitegromab across multiple musculoskeletal disorders in addition to SMA? I know post MDA, there's quite a bit of interest in DMD, perhaps Becker and FSHD. So I would just love to get your sense of how to execute on that in coming years. And then turning to EMBRAZE ahead of that readout this quarter, can you just clarify for us what will be included in that top line readout? Should we expect to see any exploratory functional data and/or 8-week off-treatment data at the time of the top line readout? And it would just be great to get your sense on the value of continued investment in 439 without a partner.

Thanks, Ally. I'll just make a couple of comments and then bring in Jay and Akshay. As you know, as Jay referred to back in 2022, I specifically targeted Jay because I felt like he was the best leader to take this company forward. And over the last 3 years, he's done a remarkable job with the SMA program, but he's also been thinking quite a bit about a pipeline and a product with apitegromab and thinking about other severe neuromuscular disorders. And importantly, as I will be starting my ninth year at Scholar Rock next month, Akshay Vaishnaw joined Scholar Rock on the SAB in 2014, joined our Board in 2019 and has been partnering with Jay every step of the way as a member of our Board's Scientific Technology and Innovation Committee. So Jay, maybe a few comments and then from Akshay, just how you guys are thinking about the other diseases, the other neuromuscular disorders. Jay?

Yes, Ally, as you know, we really do see the opportunity beyond SMA. And as I've said earlier, we're working diligently to really walk through kind of the next step and which indication to expand. And to David's point, the beauty of this transition is that Akshay and the team, we've been collaborating consistently over this period of time to really put -- make sure we got the clear scientific rationale to proceed and the highest probability of success. So that's continuing. Maybe, Akshay, you want to kind of add to that?

Yes. Thanks, Jay. 3 things I'd say. First of all, I think apitegromab and the whole myostatin approach here at Scholar Rock affords enormous opportunities, not just in SMA, but well beyond in other neuromuscular disorders. And in SMA itself, obviously, we've got to get apitegromab to approval, get to patients. We've got to get to infants and toddlers. We outlined today how we're working urgently to do that. Then we want to build on that by expanding the approach in broader neuromuscular disorders. And you're absolutely right. I think the opportunity in DMD and FSHD is real. The 2 decades of mouse data that suggests that myostatin blockade can help in those settings. Now we also keep in mind that there have been any number of failed human trials in DMD with anti-myostatin approaches. And we're learning from those. For example, we know that DMD, when it's in older individuals, the myostatin levels aren't the same as in younger individuals. So age selection is an important criteria to think about. So all these factors are going to have to be worked through before we finalize and share our clinical development plans in DMD and FSHD with you later in the year. And then finally, EMBRAZE, I think, is a very exciting preliminary study to look at the potential for the impact of myostatin blockade with apitegromab in obesity. Muscle loss is not good for patients when we're trying to lose weight. We all agree with that. There's a metabolic impact there that's not helpful. And beyond that, we know that long term, particularly in older patients, there could be an impact on mobility and other factors as well as the fact that when GLP-1s are withdrawn there's rapid weight rebound. So anti-myostatin approaches can help with all 3 of those issues, we think. We continue to guide that we're getting the data in and we'll report our top line at the end of Q2 '25. So more news then. But even beyond EMBRAZE, in the core mission in SMA itself and neuromuscular disease, enormous opportunity to do good with the anti-myostatin approach.

Our next question will be coming from Tess Romero of JPMorgan.

Jay, it's been such a pleasure to work with you and David and team look forward to the next chapter here. Big picture, David, how does your vision for the company shift, if at all, as you think about the overall priorities for Scholar Rock over the near and also long term? And on the commercial side, what gives you confidence that you will be ready to deliver a strong launch by the time of key approvals starting later this year? And when will we know more precisely about the commercial vision?

Thanks, Tess. Really, we're building on the strength of the foundation that Jay and his team have established here at Scholar Rock. And as I noted in the call, Tess, Akshay and I have had the true pleasure and benefit of working with Jay every step of the way over his last 3 years. So when you look at our strategy as an organization, it's a strategy that we've been completely aligned with Jay on as a Board of Directors and obviously, Akshay and I as operators at heart. So our vision for the company is, as I noted in the call, we see this enormous opportunity to serve patients with SMA around the world as a strong foundation to deliver sustainable growth through the end of this decade and into the next. With a large opportunity to serve patients globally, nearly 35,000 patients who have received SMN-targeted therapies, we feel like this is our first, second and third priority. We owe that to patients. And then I think as Vikas had highlighted, through that commercial success that we have, starting first in the U.S. in Q3 and then in other regions and countries around the world, we'll also be very thoughtful in terms of capital allocation to support the global launch while we also support the pipeline initiatives. But I think we all have experienced that the most successful global biotech powerhouses focus on their first commercial opportunity and make sure that no patients are left behind. As it relates to how prepared are we for the U.S. launch, Jay and Tracey had an opportunity to provide an update in last quarter's call on that progress. And Keith was reflecting on some of his experiences more recently at argenx and Vyvgart. And Keith, do you want to comment on how you're thinking about the U.S. and beyond?

Yes. Thanks, David. Tess, I mean, first of all, Jay and Tracey had shared that they are -- they have currently been building an experienced team that has rare disease experience, launching of SMA products in the past. They've already been working with patient communities and with the top key opinion leaders and have hired the entire payer team to begin to work with both commercial and federal payers. So the proper steps have already been in place. We are now going to be at kind of a warp speed ramp-up with the PDUFA date being September 22. So we will be prepared to launch after the PDUFA date. As far as the commercial vision, I think David has already summed it up well. What it boils down to is we believe apitegromab has too much value to patients, to this organization and then to shareholders that we want to put a commercial vision out there wherever you are in the globe, if you can benefit from apitegromab, we're going to be able to get you access to it. That's our vision. That's our goal and what we'll strive for.

Our next question will be coming from Gary Nachman of Raymond James.

Great. Congrats, Dave and team on the transition and best of luck to you, Jay. So first, what are your views specifically on partnerships to maximize the value, either for SMA or for obesity? Or would you prefer to do those on your own depending on the different regions? It sounds like definitely in the U.S. to do it on your own, but not sure how you're thinking about that ex U.S. with obesity -- yes, just one follow-up. With obesity, just talk about how you think of the competitive dynamics in that market. It's getting a lot more crowded. And when you say you have an obligation to explore it, it could be quite costly over time. So would you be more likely to look for a partner there as well to take that program forward?

No, those are really good questions. Look, we have an ambition and an obligation to children and adults with SMA. We demonstrated in SAPPHIRE the potentially transformative benefits that we can deliver to them and their families. And I think that this team has had a very strong, long track record of success in building global organizations, recognizing that in the rare disease environment, typically about 1/3 of revenues for rare disease therapies tend to be in the U.S., another 1/3 in Europe and another 1/3 rest of world. So as we really think about partnerships in this space, we think we're well equipped with a very strong team with a tremendous track record of success and a lot of experience in being able to do this in a very thoughtful way, a very capital-efficient way, we would expect to be leaning in on this global launch for apitegromab in SMA. As it relates to obesity, I've heard a lot about, boy, it's crowded and there's a lot of GLPs in it. What we do see is that this is a very large marketplace. I think as it relates to muscle wasting or lean mass loss, Jay, myself, Akshay, we just don't see it as a -- there's a winner-take-all environment here in this market. We think we're better than anybody else in the world at developing therapeutics to target myostatin. And so we want to see and we look forward to seeing the first indication of what our expertise and our innovation can show in this initial exploratory EMBRAZE study. And I think that will really guide our direction from that point moving forward. And we'll be looking forward to sharing that data with you all later in Q2.

Our next question will be coming from Marc Frahm of TD Cowen.

First to start, congrats, Jay, to a great tenure at the head of Scholar Rock. And then maybe for the incoming team, obviously, you've built some amazing franchises before. Those were often launching into spaces where there was really no global presence and you had to build the market absolutely everywhere. No one had done it before. But why is that -- it sounds like that's kind of strategy you want to push forward here with apitegromab. Why is that the right strategy than maybe leveraging some partners given that SMA and some of these other diseases you'd like to go after? Do you already have major global players offering other types of therapies in some of those diseases?

Thank you. Well, first of all, the reason why is nobody in the world can do it better than us. We think our track record demonstrates that. Secondly, I don't know of a single partner that really overlays and meets the needs of every single patient with SMA that can benefit from apitegromab. I'm not sure that I would even see a partner that would make sure that apitegromab, which will overlay all of the patients that have received SMN-targeted therapies have access to what now will be a new era in the treatment of patients with SMA. Apitegromab can help all of these patients. So that's why we would take that approach. Nobody can do it better than us, and nobody will have a more holistic view on serving all patients who can benefit from apitegromab than the team here at Scholar Rock.

Okay. That's helpful. And then maybe to be a little more granular, can you walk through some of the timing that you'd expect for how quickly you can start pivoting into some of those other territories beyond the U.S. for SMA?

Beyond the U.S., as Jay has noted and the team has noted and Akshay underscored today, we are in the European regulatory process for MAA, and we would expect approval in 2026. And thereafter, we've certainly got a lot of experience with country-by-country market introductions to reach patients. And then as noted in this call, there's a variety of different paths and access in other regions of the world, including Asia Pacific and Latin America, where we've also had a tremendous amount of experience and success.

Our next question will come from Kripa Devarakonda of Truist Securities.

Congrats to the team on this transition. Look forward to working with you. And Jay, thank you so much for all the amazing interactions over the last few years. Best of luck to you. As investors are digging deeper into the commercial opportunity for SMA and the launch, we've been getting questions around a couple of things. One is reimbursement for apitegromab as an add-on and how that might influence how you price the drug. I understand you can't talk about pricing right now, but any color that you can provide on how you're thinking about it? Any prior benchmarks that can help us better understand the reimbursement environment? And the other question has been around the likelihood of getting a broad label. With the new commissioner and the recent commentary from the new commissioner on rare diseases, do you see that as a positive for apitegromab?

Yes. Kripa, thank you. And I know how much -- and Jay and I had an opportunity to sit with you earlier, and I know how much Jay has also enjoyed the working relationship with you over these past years. The first thing, I guess, I would note is my difference of opinion really for apitegromab being an add-on therapy. I feel like SMN-targeted therapies were introduced to the world about a decade ago, and they have clearly made a meaningful difference for patients. At the same time, now nearly 10 years later from the first introduction, what we demonstrated with the SAPPHIRE study is despite the use of background SMN-targeted therapies, patients were actually on the decline years later and losing motor function. And what we were able to demonstrate with apitegromab is we turned a loss of motor function into a gain of motor function. We believe that is transformational. And now we have more than 230 patients who have received our therapy, and we have a growing body of evidence. So the way we see it is really the SMN-targeted therapies have ushered in an important new standard of care for patients and families suffering with SMA. And now what apitegromab represents is a new standard of care for those patients in need. You're absolutely right that as it relates to price, it might be a little bit early to talk about it, but this team will really be anchored on the key tenets that we've always used when we think about pricing and reimbursement, and that is we think about the rarity of the disease, we think about the severity of the disease, and we also think about the compelling clinical benefits that we potentially can deliver to patients. And all of those things are factors when we think about making sure that any patient with SMA in the world who can benefit from apitegromab would have access to apitegromab. And those will be anchors that we think about moving forward. As it relates to sort of the regulatory process, Akshay?

Yes. So let me just begin with the issue of how to think about anti-myostatin approach to SMA. I totally agree with you, David. The important thing is the SMN corrector treatments have provided significant help for these patients, but the muscle has been left unattended. And we know both from animal work and now from our human data that the combination is what these patients need. And as David said, patients on SMN therapies were declining, we were actually able to reverse the course and show an increase in motor function, which is so powerful and hopefully will be very helpful to patients. As far as the label is concerned, it's very early to comment on all of that. We generally don't want to get into the regulatory discussions that go back and forth. The BLA is on track. PDUFA date is on track. We're under review. Target date is September 22, '25. And closer to the time, I'm sure we'll be having more discussions. But important to note that SAPPHIRE unequivocally, in our opinion, showed benefit in terms of an increase in Hammersmith in patients 2 to 12. That was the primary endpoint. Patients declined in the placebo group. And secondarily, the 13 to 21 group, we also saw consistent changes in terms of increase in motor function. So the dialogue with the FDA will continue, but we look forward to working productively with them.

And then I would just note, Kripa, importantly, Jay is going to continue to work very closely with us over these coming months and right through the regulatory process and beyond here in the U.S., which we -- Akshay and I are very gratified for that ongoing partnership.

And Kripa, it has been fun working with you, right.

Our next question will be coming from Dennis Kennedy of LifeSci Capital.

Congrats on the new appointments. Could you maybe just walk us through the OPAL study design you plan to initiate midyear and what the time lines could look like for a potential label expansion for patients under 2 years old? And then just kind of curious if there's interest in expanding into kind of older SMA patients over 21 or those previously treated with Zolgensma?

Yes. This is Jay. Just to start. So the OPAL study, we're gearing up to get that posted on ClinicalTrials.gov. So there'll be more granularity around that trial. So you'll be able to get to see it more specifically. But just as a highlight, for that under 2, what we need to be able to do is define a dose to guide the clinicians to how to dose that age group. So we certainly needed the SAPPHIRE PK/PD data. And so principally, that trial will be a way to identify the right dose for children, and so we can be able to move that forward with PK/PD data quicker than perhaps we could with just clinical functional endpoints. But more to come on that. And your second question was?

Label expansion.

Yes, looking at the older group. So there's a complete sort of evidence generation plan that both the medical affairs team are going through right now. I think there's a lot of opportunity to expand that and support that use. I think what Akshay highlighted, which we were very, very delighted to see when we reported out SAPPHIRE is we have a consistent effect across all age groups from 2 to 21. And so you think about that 21-year-old that basically it's an adult -- young adult group. So there'll be an opportunity for us to kind of expand use in that setting, but looking forward to be able to share more of those plans later.

So I think that -- thank you very much. I think we're going to wrap up the call here. I really appreciate the time of all who joined us this morning, and we're going to get back to work. Our team with Jay, with the amazing team here at Scholar Rock because as I noted on the call, we have a responsibility to patients and families and to work urgently to reach them as fast as we can wherever they are with apitegromab. So thank you very much. We look forward to our future communications and interactions with you. Thank you.

And this concludes today's conference call. Thank you for participating. You may now disconnect.