Scholar Rock Holding Corporation

Ladies and gentlemen, thank you for standing by and welcome to Scholar Rock's first quarter financial results and business update call. At this time, all participants are in a listen-only mode. Following the presentation, we will conduct a question and answer session. To ask a question during the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Scholar Rock. Please go ahead.

Good morning. I'm Rashi Knopfinger, Vice President of Corporate Affairs and Investor Relations at Scholar Rock. With me today are David Halal, Chief Executive Officer, Akshay Vasnau, President of RMD, Keith Woods, Chief Operating Officer, and Vikas Sinha, Chief Financial Officer. For those of you participating via conference call, the accompanying slides can be accessed by going to the events section of the investors page on our website. During today's call, as outlined on slide two, David will provide introductory remarks and provide a general business update. Akshay will review our clinical and regulatory progress. Keith will provide an update on our commercial readiness activities. And Vikas will provide commentary on our company financials and a summary of our 2025 priorities. And then we will open the call for questions. 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?

Thanks, Rashmi, and good morning. Thanks to everyone for joining us on today's call. 2025 is off to a strong start at Scholarock. In the first quarter, we made significant progress against our top priority of bringing epinegrumab to patients and families living with and suffering from SMA in the US, Europe, and around the world. We were very pleased with the positive phase three SAPPHIRE trial, where we showed a statistically significant and clinically meaningful improvement in motor function as measured by the primary endpoint, the gold standard Hammersmith scale. And in Q1, to underscore the body of evidence for epitigromab for patients with SMA, we were gratified that our BLA was granted priority review by the FDA with a September 22nd PDUPA date. The team at Scholarock is working urgently to prepare for our U.S. commercial launch, which will be the first country in a series of launches over the coming years. I am confident under Keith's leadership we will assemble and deploy an experienced, talented, and patient-centric team committed to the SMA community. Along with Keith, Akshay, and Vikas, we now have the responsibility to bolster Scholaroc's capabilities as we advance our mission to deliver epidegromab to patients with SMA. This is what we know well and what we do well. We join Scholaroc at a time of great strength and opportunity as we scale for the next phase of growth to a commercial stage, fully integrated global biopharmaceutical company. Globally, nearly 35,000 patients with SMA have received SMN-targeted therapies, and at Scholarock, 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 at Scholarock is that any patient with SMA that can benefit from epidegromab should have access to epidegromab. I am confident that the global opportunity with epidegromab and 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 are very focused on our large opportunity to serve patients with SMA, we are continuing to evaluate expanding the study of epitigromab into other rare, severe, and debilitating neuromuscular disorders. Ache will touch upon this shortly. Now I'd like to turn to our exploratory cardiometabolic program, the EMBRAZE proof of concept study. Our effort here is to understand the role we may play in the treatment of obesity. We are the world leaders in myostatin biology and know well that GLP-1s have brought needed innovation to patients with obesity and cardiometabolic disorders. While the benefits outweigh the risks, muscle wasting and lean mass loss is something that the medical community is trying to address. The EMBRACE study is our initial effort in the cardiometabolic space and will provide insights that will guide us moving forward. We remain on track to share top-line results in June. Our achievements in 2025 to date underpin the opportunity before us to bring the potentially life-transforming benefits of epidegromab to patients and families with SMA. We are focused on delivering for patients with Akshay leading efforts in collaborating with U.S. and EU regulators. Key, applying a similar approach from Vivgar and MG to the commercial opportunity for epidechromab. And because, focused on disciplined capital allocation to fuel near and long-term growth. With that, I'll turn the call over to Akshay to provide a more detailed update on our R&D progress. Akshay?

Thanks, David. I'm delighted to be here after six years on the board of Scholar Rock. As a physician scientist, I could not be more excited to have seen the concept of the Pitogramab, a highly innovative antimicrobial antibody, go from bench to bedside with our remarkable SAFIRE data. SAFIRE showed that the Pitogramab 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 as patients on placebo worsened. Importantly, patients treated with Pitogramab had an approximately three-fold higher chance of a three-point or greater increase in Hammersmith versus those on placebo. Along with the very encouraging safety profile, the SAFIRE data suggests that Pitogramab has great potential to provide clinically significant benefit patients with SMA, despite the use of background SMN-targeted therapies. Additionally, at the Muscular Dystrophy Association Conference in Dallas in March, the detailed data from the SAFIRE trial were presented for the first time. These data demonstrated that treatment with apidurumab achieved clinically meaningful and consistent benefit in motor function across pre-specified SMA patient subgroups, including the type of SMN-targeted therapy, age, age of initiation of SMN therapy, and geography. Efficacy was also supported by additional analyses of outcome measures of motor functions, such as the revised upper limb module and the World Health Organization Motor Development Index. As David mentioned, our BLA was accepted under priority review by the FDA, and the MA was validated by the EMA in Europe. Turning first to the FDA, we were gratified that our BLA for Ipidigrimab was granted priority review by the agency with a September 22nd PDUFA date. We feel the potential clinical benefits of Ipidigrimab, as demonstrated by a Phase III trial, are underscored by the FDA's priority review designation. By definition, a priority review designation by the agency conveys the capacity of Ipidigrimab to potentially impact unmet need in SMA by either being a treatment for a serious or life-threatening condition, or provide a significant improvement in safety or effectiveness over existing treatments. I'm excited that our team continues to work collaboratively with regulators and that we remain on track. With the success of Sapphire, we're just beginning to tap into the broader potential of our truly innovative MyStacken platform. There's much more we can do with the promise of the Pit of the Map and our platform by delivering advances in severe neuromuscular diseases, including the muscular dystrophies, such as DMD and FSHD. Additionally, we're advancing SRK439, a highly innovative and potent sub-Q anti-myostatin antibody to the clinic. Based on preclinical data, SRK439 has the potential to inhibit myostatin and increase muscle mass and create options for our pipeline. We remain on track to file the IND application for SRK439 to support the first in human study in Q3. Now earlier, David mentioned the potential role scolar rot can play in addressing lean mass in cardiometabolic diseases. As we all appreciate, whilst GLP-1s offer quantitative benefits in terms of weight loss, much more needs to be done from a qualitative perspective regarding preserving lean mass. Notably, a quarter to a third of the weight loss for GLP-1s is due to the loss of muscle. Looking forward, it will be important to preserve muscle from the viewpoint of the associated metabolic benefits and a healthier approach to weight loss. Our EMBRACE study is our ongoing phase two trial to investigate preliminarily the potential of further developing our highly selective antimicrobial approaches in patients with obesity with the goal of reducing the loss of lean mass. We look forward to the upcoming readout of our initial data from EMBRACE in June 2025. In summary, we remain focused and on track to deliver on our key priorities this year. We will, one, drive the U.S. approval of Epidigromab in Q3 2025 and advance the Eden Court approval in 2026. Two, initiate a study of Epidigromab for infants and toddlers with SMA under the age of two, starting in Q3. Three, file an IND for SRK429 in the third quarter. And finally, complete our clinical development plans for epitogramab in additional neuromuscular indications. With that, I'll turn it over to Keith to provide a commercial update. Keith.

Thanks, Akshay. And good morning, everyone. I'd first like to thank our colleagues from Research and Development for their focus and commitment over the years to make the September 22nd PDUFA date for epitogramab a reality. SMA is a disease impacted by both motor neuron degeneration and muscle atrophy. Today's therapies only address one piece of the puzzle, the motor neurons. Currently, there are no approved muscle-targeted therapeutics to treat muscle atrophy. With epitigrimab, we have the opportunity to usher in a new era for the treatment of patients with SMA. This is a progressive and devastating disease that leads to the loss of mobility, limited activities of daily living, and a lack of independence. Despite the advances made in treating SMA with SMN targeted therapies over the last decade, the contemporaneous natural history data shows that the majority of patients still experience progressive muscle degeneration over time. The bottom line, nearly all patients and families living with SMA are demanding a transformative new therapy. This is supported by a CURE SMA survey published last month, where 90% of patients identified that new SMA treatment options improving muscle strength is an important need. Our market research and interactions with healthcare professionals tell us that 80% of treating neurologists agree that preserving muscle should start as early as possible in treating patients living with SMA. Today, there are approximately 10,000 patients with SMA in the United States, and roughly two-thirds of them have received an SMN-targeted therapy. For these patients, as Akshay shared with our SAFIRE data, epitogrammab showed the potential to reverse the progression of SMA from a loss of motor function to a gain of motor function. Furthermore, Globally, there are approximately 35,000 individuals that have already received an SMN targeted therapy. Neurologists recognize that in the future, a treatment approach of dual modalities to target the motor neuron and the muscle will be necessary to treat SMA. At Scholarock, we have the opportunity to make a meaningful difference for both children and adults living with SMA, first starting in the US, then Europe, Asia Pacific, and Latin America. We are currently building on the momentum that has already been established for a successful U.S. launch. Last weekend, several of us at Scholar Rock had the opportunity to meet with patients and their families at the CURE SMA Walk and Roll in Boston. We continue our stakeholder engagement and SMA disease education. Life Takes Muscle is the first muscle-focused SMA disease awareness initiative Our fully staffed U.S. market access team is currently meeting with key U.S. commercial and federal payers. Our process of hiring and onboarding our customer facing team of roughly 50 sales, reimbursement, and patient support personnel is well underway. We expect to be fully staffed by mid 2025, well ahead of our potential launch in late September. Finally, we believe that apidigromab has the potential to be a first-in-class, best-in-class therapeutic to establish a new standard of care in SMA. Now, I will turn the call over to Vikas. Vikas?

Thank you, Keith, and good morning, everyone. I'm pleased to provide a business update and provide insights into how we are thinking about resource allocation in the future. The opportunity with Apitigromab 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. We ended the quarter with $364.4 million. During the quarter, we continue to increase our investments in commercial readiness and inventory build out. As we look ahead, we are prioritizing the commercial launch and ongoing clinical programs. We have an additional $100 million under our debt facility that we can draw down this year to support the upcoming launch, bringing our anticipated runway into 2027. We are working on building a tighter financial plan and will share more details over the next few quarters. As we move forward, I will focus first on driving strong performance with financial discipline. Next, investing in capital-efficient commercial build-out and thoughtful capital allocation to advance our pipeline. With that, I will turn it back to David.

Thanks, Vikas. In closing, we are acutely focused on the key priorities that will enable us to build and scale Scalaroc into the next global biotech powerhouse. First, regulatory approvals and the upcoming U.S. launch of epitigromab for patients with SMA, followed by a series of country launches in the coming years. Next, develop epitigromab for additional rare, severe, and debilitating neuromuscular diseases. And finally, phase our capital allocation and investments thoughtfully to support our high-value commercial and development initiatives. On behalf of every member of the Scholarock team, we are deeply aware of our responsibility to patients and their families, and we'll work with urgency to ensure that no patient with SMA is left behind. With that, we'll now open the line for questions. Operator?

Thank you. As a reminder, to ask a question, please press Star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press Star 1-1 again. The first question comes from Allison Bretzel with Piper Sandler. Your line is now open.

Hey, good morning, team, and thanks for taking the questions. Just two from me. You know, ahead of Epidermab launch, could you just frame for us how your discussions with U.S. payers have gone? You know, how receptive are they to coverage of combination therapy for both an SMN targeting and a muscle targeting therapy in SMA patients? And can you also describe that feedback for ex-U.S. payers and governments as well? And then second, could you just characterize interactions with FDA on the Epidermab review Obviously, there's a lot of concern about the state of the agency right now. So, just want to know if you have anything to report on there. Thank you.

Thanks, Allie. So, why don't I just touch on pricing, then Keith will comment more specifically, and then Akshay will take on the regulatory update question. You know, one of the things that Keith and I have spent a long time sort of thinking about and sort of doing as it relates to, in general, you know, really what we're talking about is access for a potentially transformative therapy for a small population of patients. And, you know, we would sort of expect, you know, as we think about establishing access plans, that we consider sort of pricing for our therapies that would be reflective of the the rarity of the disease, the severity of the disease, and the value that our therapy would provide to patients, in this specific case, patients with SMA. And I think one of the other things that, you know, Keith and I think a lot about is also given the rarity of disease, we would expect that the budget impact, you know, to any one single payer in the U.S. or even globally would be very limited for the high value proposition. As it relates to sort of the engagement with payers, you know, largely in the U.S., I'll turn it over to Keith for some more commentary.

Thanks, David. So, Ali, what we know in speaking with payers is that, you know, with SMM targeted therapies alone, patients can still have progressive motor function loss. And at the MDA in Dallas in March, we heard that a proportion of patients are already receiving more than one SMM therapy. So SMN targeted therapy. So right now, it's not uncommon that you'll see a payer pay for more than one of these therapies. As you know with our data, when we go in addition to an SMN targeted therapy, we see improvement consistent across all age groups of 2 to 21. And so with that in mind, these patients need a better therapeutic, and our early discussions with payers have proven to be positive and we'll continue those discussions. As for Europe, we plan to, as you know, we filed and we're going through the regulatory process right now. We will be preparing to go into reimbursement discussions. Let's remember that we are going to sequence through Europe and we will start with Germany in 2026. And then we will roll out over time how we will sequence through the remainder of the countries in Europe. Thanks for the question. And maybe a closer look

Sure. Thanks, David. So, thanks, Alex, for the question on FDA interactions. Look, it's a time of evolution and change at the FDA. We all recognize that. But what I'm delighted by is that the pace and the collaborative conversations we've had with the FDA are all going as per routine, and we continue to guide that we're focused on working with the FDA and delivering on that September 22nd PDUFA date. So, really, we're seeing no issues in specific to PIDDRAMAB and the SMA approval. And we're also delighted that FDA Commissioner Martin Macri actually made a point that with all the changes, one of the main areas of focus continues to be rare disease and delivering on what patients need for rare disease. So it's all systems go here and we continue to work productively with regulators here and in Europe.

And our next question comes from Michael Yee with Jefferies. Your line is open.

Hey, guys. Good morning. Maybe just two questions on obesity coming up in June. Given that it's towards the end of the second quarter, but also that there's two different endpoints, I think 24 and 32 weeks, are you thinking about providing more data to be a more complete package of information to help people out? in terms of longer-term follow-up data on some of the metabolic parameters that could come out in June. Have you thought about that? And then just holistically, the prior CEO, Jay, has mentioned a 20% to 40% reduction of muscle loss would be great, but I think people are still sort of trying to grasp what you think a good result is and what is exciting. Can you give some color on that? Thanks.

Yeah, great questions, Mike. As Akshay and I noted, this is our first effort at really understanding what role we may be able to play in this space. We know that there is a need that the medical community is trying to address. And I'll turn it over to Akshay for sort of a closer look at what one might expect in terms of, you know, as you were saying, the 24-week endpoint, but then the eight-week sort of withdrawal of the therapies as well. Akshay?

Yeah, thanks, Mike. So, you know, the core of it will be providing the 24-week data. That's the main study. We'll certainly provide any necessary follow-up information that we have that helps us understand and helps everybody else understand the potential of an anti-myostatin approach in the obesity space. We're excited to test this hypothesis preliminarily. It's an important one. I think we all appreciate that loss of muscle is almost certainly not a good thing as people lose weight, especially when it's a quarter to a third of the weight loss is due to muscle. And so The primary focus will be the 24-week data, changing lean mass, the safety, and helping us understand the path forward. So I'll leave it at that, but it's not so long to wait now until we get the data.

And the next question comes from Tess Romero with JP Morgan. Your line is open.

Hey, David and team. Thanks so much for taking our questions this morning. So in the U.S., you noted collaboration with regulators and that you remain on track here. Can you confirm or not if you have completed your mid-cycle meeting? And if so, can you comment on any high-level discussions you have had around labeling? And at this time, what has the agency said about the need or lack thereof for an adcom? Thank you.

Thanks, Tess. As Akshay and I both noted in the call today, we remain on track, and maybe for a closer look on just kind of where we are, Akshay can provide a little bit more detail.

Yeah, I mean, there's not much more to provide other than the conversations have been extremely constructive and right on track, I would say. As for the detail of when and how the various interactions occur, I don't really think this is the time or space, but I do want to reassure everybody that Our ability today to guide on the call that we're heading for that September 22 PDUFA date is based on a series of very constructive conversations. So I'll leave it at that and more news as we get it.

And the next question will come from David Nearinggarten with Wedbush. Your line is open.

Hey, thanks for taking the question. I just had one on the additional potential indications for Pitocramab. As I recall, there's a lot of exploration in preclinical models, at least, of DMD and related disorders. Is there any, you know, particular, you know, new development or, you know, new treatments that you think, you know, are particularly attractive to you'll bring epinegrumab forward into, you know, one of the other muscular, neuromuscular indications, you know, to just kind of help us out with thinking about the expansion plans. Thanks.

Thanks very much, David. Akshay?

Yeah.

Thanks, David. So, look, I think with epinegrumab and our really unique and potent antimicrobial platform, we have an incredible opportunity to not just help in FMA across the spectrum of disease there, but well beyond that into other neuromuscular disorders, many of which are very severe and life-threatening. As you said, we've certainly spoken about and done a lot of good work on DMD and FSHD models, two very important muscular dystrophies. We've shared those data. People are very excited about them. And the fact that we've validated epidogrammab as having the ability to put on the degree of muscle that it can in such a serious disease as SMA obviously bodes well in these other neuromuscular disorders. There are other indications beyond DMD and FSHD. ALS is one that we can talk about as well, and we've got some thinking there. And there'll be more beyond that. But I think at the current time, we're very encouraged by the model data, both from DMD and FSHD. We're working through details of exactly how to begin to study in those disorders, and we'll share more details around that later in the year. But there's no question that an agent that is as strong as a pituitary gland clearly has to be investigating additional indications.

Thanks. And our next question comes from Gary Natchman with Raymond James. Your line is open.

Thanks, and good morning. So if you get the SMA approval on the PDUFA, how quickly will you be able to launch? Will everything be completely in place already on the sales and marketing side, including with access and patient support programs? And how much commercial supply will you have at launch, you know, just in terms of meeting the demand? And then also, if the proof of concept data in obesity are positive, just talk about the likely next steps with 439 after you file the IND. You know, what type of phase one study will you run and how long before it can potentially move into a phase two? Thanks.

Yeah, thank you. And as Keith noted on the call, he's working with urgency here by midyear to have the team in place for more commentary on like readiness you know, to serve patients that approval key?

Yeah, Gary, thanks for the question. I mean, I think the first thing that I want to call out is that the team here has already been at work and has already been building, preparing for this launch for some time. We are fully staffed when it comes to our marketing team and, as I mentioned, our market access team. We have also, we're fully staffed in our leadership team for our patient support programs. We will, as I mentioned in the prepared remarks, we will have the entire commercial team fully staffed by mid-2025, so we should have a couple of months prior to launch. In regard to how soon will we launch after a September 22nd date, we're going to be prepared to be out there the next day. I know that the supply chain team is working so that we can have product available to patients as soon as possible. And then I think the last thing that you had asked was in regard to supply. And I want to assure you that we have ample supply to be able to have a very successful launch.

Thanks, Keith. And regarding, like, sort of the embrace study, the proof of concept, and I think, Gary, as you noted, you know, how do we think about 439? As Akshay mentioned, we're moving forward with an anticipated IMD for SRK 439 and Q3, no matter what. We see this as just another indication for us that we are the world leaders in myostatin biology, and we're very excited to move this into first in human studies. The beautiful thing about SRK439 is we have optionality. It can support our ambition in SMA and other additional rare, severe, and debilitating neuromuscular disorders, or depending upon the you know, sort of results that we see with EMBRACE, you know, depending upon, you know, our thoughts about further study there and how we might approach it, 439, as I think was previously noted by our team, could have some optionality for us in a different space, that being cardiometabolic disorders and obesity. So, we'll be guided by the data. We absolutely will sort of focus on what we see in this first exploratory readout in the EMBRACE study, and then we'll provide you all here in the coming month or two further plans for SRK 439.

All right, great. Thank you.

And our next question comes from Kripa Devrakonda with Truist. Your line is open.

Good morning, team. Thank you so much for taking our question today. Given that we're getting close to the Purdue for Day, just a follow-up question from one of the prior analysts. Would you be able to provide any kind of metrics or guidance once the drug is approved or any color on how you see the early demand? And not sure how much you expect the recent executive order on drug pricing to have an impact on orphan disease area, but In light of that executive order, any comments on how you think about pricing in the U.S. versus ex-U.S.? I know it's early to give us exact numbers, but just qualitatively.

Kripa, two great questions. Why don't I take sort of the president's executive order first, and then Keith can comment a little bit about launch dynamics and kinetics. As you know, and I think you just noted it in your question, It's very early to really comment on the President's executive order on MFN pricing. However, it really does not change in any way our plans to commercialize epitogramab, not only in the U.S., but in Europe, Asia Pacific, and Latin America. We do believe, should any elements of the executive order be implemented, be implementable, it would obviously be better to have not yet established pricing for a therapy versus, let's just say, products that are already out there with established pricing. In all countries, we would expect that, you know, the price of a Pitigromab will be reflective of the rarity of SMA, the severity of SMA, despite the use of all sort of SMN-targeted therapies. As we noted, still a loss of motor function despite the use of those over time. And then, of course, the strong value proposition that epitogramab may be able to provide to patients and families with SMA. And then, as I also noted a bit earlier, We think that given the rarity of the disease, epitagromab would not really impact, you know, tremendously any real budget of any magnitude of any single payer, let's just say in the U.S. or in any country around the world. So we think no matter what happens with the president's executive order for MFN, we think we're going to be in a position of strength when we think about the launch of epitagromab globally. for the 35,000 patients in the world that have received an SMN targeted therapy. For a closer look at sort of your first part of your question on launch dynamics and kinetics, I'll ask Keith to comment.

Yeah, Kripa, thank you for the question. First of all, in regard to guidance, we are not going to be providing guidance at this time. I can give you some aspects that from working in rare disease for now two decades, One thing that I'm very excited about the SMA marketplace is that, you know, 100% of newborn screening in the U.S. And as we noted in the prepared statements that, you know, we know of the two-thirds of SMA patients of the 10,000 in the U.S. that have already had an SMN targeted therapy. These are good aspects to begin in a launch. Also, the fact that we have the centers of excellence with the, you know, it's highly concentrated because of the cure SMA model. All of these things give me optimism. Now, think about this. These centers of excellence are also going to be many at your academic hospitals. So we will be going through formulary processes and such. And some of them are quite timely. They're not just set based on our launch date, but when the academic centers and other centers are going through it. So we expect that between that as well as applying for a J-code that we would receive sometime six plus months later. that will prepare for a consistent and steady launch.

Thank you so much.

Thanks, Kripa. The next question comes from Mark Fromm with TV Cohen. Your line is open.

Hi, thanks for taking my question. Maybe just following up a little bit on Kripa's question before, just on launch trajectory, as you mentioned, the SMA population now has 100% newborn screening in the U.S. They've gotten very concentrated into these centers of excellence to receive SMA therapy. Those would seem to be tailwinds to the launch relative to prior SMA launches, but then while there's certainly unmet need, maybe it's not quite as dramatic as it was before the original SMA correctors launched, which would maybe be a headwind. Do you think those net out and this we should look at prior SMA launches as a good proxy for the trajectory that epitagroma might have. And I guess to the extent that you don't think those are good proxies, is there other launches out there in the rare disease space that you think maybe are more analogous to what we should expect with epitagroma?

It's a great question, Mark. I think, first of all, one of the things that our team is always focused on as opposed to looking at other sort of proxies or other launches, we just kind of look in the mirror and try to compete with ourselves and think about the best way that we can serve patients immediately and then over time. And so you're right, there's probably some headwinds, there's probably some tailwinds, but I think, you know, a couple of things that I would just underscore. SMN targeted therapies in and of themselves with longer term data that's been presented absent of Scholarock have shown that there can be a return to the progressive motor function loss of the disease. despite what happens, you know, earlier when treatment is initiated. And then we ourselves showed in the SAFIRE study, obviously, at the time in which, you know, we were capturing patients and enrolling them in the study, there was overall loss of motor function rather than what we demonstrated with our primary endpoint, the gold standard Hammersmith scale, again, a motor function. So, we do think that there's a lot of urgency still for patients. And I think Keith even commented on how that was underscored at the last month's presentation by Gear SMA of what, you know, patients and families were looking for. At the same time, we really want to play the long game. You know, independent of sort of launch trajectory, we want to build a team and a model to serve patients immediately and then over time for sort of a steady, consistent growth of our business by serving patients in a very meaningful way. I don't know if Keith would like to add a little bit more onto that as well.

Keith? Yeah, I mean, you bring up the point of the launch compared to other SMN targeted therapies when there was nothing else available. Okay, so they truly had no other treatment. So I think this sense to urgency to be able to get to that product was great. As we take a look at the information, you know, we find that patients that are on SMN targeted therapies most of them see their doctor on average two times per year. So it's not like September 22nd happens and they have an appointment the next week. So I just want to guide you on that. I agree with your statement that, you know, the fact that we know where these patients are is an advantage. However, there are going to be some headwinds, as David mentioned. Thanks.

And our next question will come from Evan Sigerman with BMO Capital. Your line is open.

Hi, I'm Mack Moffman on for Evan. Thank you for taking our question. Recently, we had noted some stronger rebound and spend rise of sales to start 2025, and we're hoping to get your updated thoughts on long-term changes that may occur in the SMA market, specifically with Epidemromab being used in conjunction with SpinRisa. Are you Internally expecting any longer-term growth from Spinrazi that may benefit epinegrumab upon launch? Thanks for sharing.

No, it's a great question. I think, you know, one of the things that we would note is that, as Akshay shared earlier, in the SAFIRE study, really in a pre-specified way, depending upon which SMN-targeted therapy, you know, a patient were, you know, received, You know, we feel like we can help all patients, independent of whether or not they receive Spinraza or Rizdiplam. We'll continue to sort of assess the nearly $5 billion annual market across the three different SMN-targeted therapies, whether or not it's the highly innovative gene therapy, Zolgensma, or the other highly innovative SMN-targeted therapies like Spinraza and Rizdiplam. And we would just expect to follow those dynamics but recognize with the SAFIRE data, and then as Akshay noted earlier in today's call, the upcoming under-2 study, the OPAL study, where we would expect more experience for epitogromab for patients who have received solgensma. You know, we think we're going to be in a position of strength to really help and provide potential transformational benefits for all patients that have received SMN-targeted therapies over time. Thank you for your question. Appreciate it. Thanks.

Our next question comes from Andres Maldonado with HC Wainwright. Your line is open.

Hi, everyone. Thanks for taking my question. Just a quick one from me. Given the progress towards U.S. launch and your ongoing readiness in Europe, I guess, how are you evaluating the potential to secure a commercial partner for Europe? And in this context, obviously, you want to fire on all cylinders across the pipeline, but how would you prioritize the additional indications for PIDMOTE or GROMAB in this situation? Thank you.

Yeah, thank you. I think we noted this just a few weeks ago on our April 28th call. Given the experience that you know, this collective team has had, you know, between Alexion and Myelomargenics, we feel like there is nobody better suited to serve patients globally than us directly. So, it is not a priority of ours to think about a partner outside of the U.S. We feel like this is something that we know well and, in fact, do well, and we'll continue to run a playbook that Not only do we know the playbook, we feel like we wrote that playbook. As it relates to other indications, as Akshay noted, we'll be data-driven. The team's been doing some wonderful work in looking preclinically at additional rare, severe, and debilitating neuromuscular diseases. And Akshay will be providing further guidance on that toward the end of this year and into next. Thank you.

And the next question comes from Dennis Kennedy with LifeSci Capital. Your line is open.

Thanks for taking the question. As we look towards the embraced data in June, could you just help frame expectations for the terzapatide monotherapy arm? Specifically, you know, how much of the lean mass loss that we'd expect at one year with terzapatide do you think typically occurs by week 24? And related to that, do you think eight weeks of follow-up post-treatment is sufficient time to demonstrate a weight regain in patients in the TIRS epitide monotherapy arm?

Yeah, Dennis, these are great questions. And in fact, I think within your questions, you sort of highlight some of the limitations for us in sort of a, you know, 24-week endpoint and then eight weeks following. But nonetheless, as Akshay and I have noted, We feel like it's important to understand for a first time if there is a role that we can play. Akshay?

Yeah, thanks. So, Dennis, I mean, Tazepatide consistently has shown loss of lean mass, as have the other GLP-1. That mass is symmetrical to the overall loss in body mass. And so you can expect that at week 24, you know, about 25 to 30, 30% of the weight loss that will have occurred in the tazeptide alone arm will be due to loss of muscle. We're projecting that based on historical data. There's no reason to believe that it would be any different in the context of this study. Now, will that be the maximal amount of lean mass loss at week 24? I don't think so, because in the pivotal studies, you know, diseptide was studied for much longer, and overall, the impact on muscle mass is even greater, obviously, as the therapy continues and patients lose more weight. But within the context of embrace, quarter to a third of weight loss at week 24 will be lean mass loss, we expect. Your other point about is eight weeks of follow-up sufficient? Well, look, you know, this study was an exploratory study to understand the potential of epidigromab in a pure, clean, safe, potent anti-myostatin approach in the context of obesity. I don't think the eight-week follow-up answers the whole question, but you can anticipate that there'll be some weight regain during that period, and the trajectory of that would be quite important to monitor between the two arms.

Great. Thank you. Thanks, Jess.

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Thanks for everybody joining the call today, and we'll look forward to continuing to update you and keeping you apprised of our progress as an organization. Thank you.

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