Scholar Rock Holding Corporation

Good morning, ladies and gentlemen, and welcome to this Caller Rocks Second Quarter 2025 Business Update Conference Call. At this time, all lines are in a listen-only mode. Following the presentation, we will conduct a question-and-answer session. If you would like to ask a question during this time, simply press star, followed by the number 1 on your telephone keypad. If you would like to withdraw your question, press star 1 again. This call is being recorded on Wednesday, August 6, 2025. I would like to turn the conference over to Scholar Rock. Please go ahead.

Good morning. I'm Rashmi Nofsinger, Vice President of Corporate Affairs and Investor Relations at Scholar Rock. With me today are David Hillal, Chairman and Chief Executive Officer, Akshay Vashnau, President of R&D, 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 for Opidigrimab, and Vikas will provide commentary on our financials. 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 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 our Q2 update call today. This is an exciting time of great strength and opportunity at Scholarock. We are scaling for the next phase of growth as a commercial stage, fully integrated global biopharmaceutical company. Our three core priorities drive our vision of becoming a global biotech powerhouse. First, epitogrammab regulatory approvals, and following those approvals, the U.S. launch of epitogrammab for children and adults with SMA, followed by a series of country launches in the coming years, starting in Europe with Germany next year. Second, expand epidigromab into additional rare, severe, and debilitating neuromuscular diseases. And third, disciplined capital allocation to support our high-value commercial and development initiatives. With respect to our ongoing regulatory processes, We are working collaboratively with the FDA and European Medicines Agency. We are also urgently preparing for our U.S. commercial launch as our BLA has been accepted under priority review with a target action date of September 22nd. As you are aware, GXP inspections are part of the standard FDA review process, including those relating to preapproval inspections, clinical trial site inspections, and manufacturing site inspections. These inspections often result in observations requiring responses within the review cycle. The FDA has conducted a full set of inspections and, as part of this process, noted observations at two of our CDMOs. On Friday, August 1, another pharmaceutical company disclosed observations as part of an FDA general site inspection at their filler, Catalan, Indiana, which was recently acquired by Novo Nordisk. Our fill finish for Opidigromab is conducted at the same site. The general site inspection of the facility was not specific to Opidigromab. Novo Nordisk submitted a robust and comprehensive response earlier this week to the observations noted by the FDA. For the other CDMO observations were received at the conclusion of a pre-licensing inspection and a comprehensive response will be submitted within the next week. We continue to work collaboratively with the agency. Importantly, the FDA recently completed our late cycle meeting following both site inspections. We are encouraged by the dialogue with the agency at the late cycle meeting where the FDA indicated that they are working towards completing the review of our BLA by our September 22nd PDUFA date. Earlier this year, we also filed our MAA for epidigremab in the EU and we continue to work with the European Medicines Agency and expect a potential approval near mid-2026. We are planning for Germany to be our first European country launch with an ambition to reach patients with SMA across all of Europe, followed by additional countries in Asia Pacific and Latin America over time. The global opportunity with Epidigromab and SMA alone offers the potential for many years of sustainable growth through the end of this decade and into the next. Along with Keith, Akshay, and Vikas, and the other leaders at the company, we have bolstered Scholaroc's capabilities as we advance our mission to deliver epitogromab to children and adults with SMA. This is, indeed, what we know well and what we do well. In addition to the large opportunity to serve patients with SMA, we will continue to expand our pipeline by planning additional opportunities for epitogromab for children and adults suffering with additional rare, severe, and debilitating neuromuscular disorders, which Akshay will discuss in more detail shortly. Importantly, to grow Scholarock, we are taking a thoughtful, deliberate approach to capital allocation by staging our investments along with our commercial progress in serving the SMA community. Q2 has been exceptionally productive. In the quarter, When Keith joined our team as our chief operating officer, he brought a proven track record of building and leading teams to deliver highly successful rare disease global launches in the neuromuscular therapeutic area, including most recently with VivGuard. Under Keith's leadership, we have assembled an exceptionally experienced, talented, and patient-centric field team committed to the SMA community. Impressively, over just a few months, the team is on board, trained, and deployed, and are ready to deliver apidigromab to the SMA community pending approval in September. Despite currently available treatments that have been approved over the past 10 years, we are acutely aware that muscle strength and motor function are among the top unmet needs in SMA, which we believe can be addressed with the potential approval of epitogramab, the world's first and only muscle targeted therapy to deliver statistically significant and clinically meaningful improvements in motor function in a pivotal phase three trial. I would like to now turn briefly to the readout of the positive phase two EMBRAZE proof of concept study in Q2. The goal of EMBRAZE was to understand the role of targeting myostatin in the treatment of patients with obesity. We are pleased that the EMBRACE study met the primary endpoint with patients on terzepatide. Epidigromab increased lean mass preservation by greater than 54% compared to terzepatide alone with a p-value equal to 0.001 with an encouraging safety profile. We are very pleased that the highly selective anti-myostatin approach from our innovative platform continues to deliver. While we remain focused on advancing epitagromab in clinical development for additional rare, severe, and debilitating neuromuscular disorders, EMBRAZE raises the exciting possibility to partner our potent and selective approach to targeting myostatin. As we communicated at EMBRAZE data readout, in addition to SRK439, we have a number of earlier stage research assets. both anti-myostatin antibodies and the fusion of those with GLPs, which we think have the potential to be meaningful therapeutic candidates in the future. As we look forward, we remain very focused on the nearly 35,000 patients with SMA globally that have received SMN targeted therapies. While we anticipate the global launch will commence in the U.S. in Q3, pending regulatory approvals, we are also making preparations to serve children and adults with SMA in Europe, Asia Pacific, and Latin America. Our ambition at Scholarock is that globally, any patient with SMA who can benefit from epitogramab should have access to epitogramab. At this point, I'll turn the call over to Akshay to provide a more detailed update on our R&D progress. Akshay?

Thanks, David, and good morning, everyone. SMA is a rare, severe neuromuscular disease resulting in irreversible loss of motor neurons and progressive muscle wasting that causes continuous motor function decline throughout life, diminishing the independence of both children and adults. There's been progress over the last decade with new therapies for SMA. However, despite the chronic use of these SMN correctors, SMA remains a devastating disease for children, adults, and their families living with the disorder. Patients experience muscle wasting that impacts all aspects of mobility, basic activities of daily living, like eating, washing, and dressing, and the ability to live independently. The motor unit has two key components, the motor neuron itself and muscle. SMN target therapies are aimed at preventing motor neuron loss, but muscle, the principal organ effect in SMA, has not been directly addressed. Given that motor function depends not only on neuronal signaling, but also on muscle responsiveness. Approaches that target muscle from the start are urgently needed. Our SAFIRE trial showed that in those receiving chronic ongoing SMN targeted therapies, apidigramab 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 motor function as measured by the gold standard Hammersmith motor function scale, while patients on placebo worsened. Importantly, patients treated with the Pitogramab had an approximately three-fold higher chance of a three-point or greater increase in Hammersmith versus those on placebo. In addition, there was a consistent 1.8-point improvement in Hammersmith across all ages in our Phase III trial. Along with the encouraging safety profile, The SAFIRE data suggests that epidogramab has great potential to provide clinically significant benefit to patients with SMA, despite the chronic use of SMN-targeted therapies. As David mentioned, a BLA was accepted under priority review, which recognizes the potential of epidogramab to be a treatment for a serious or life-threatening condition or to provide a significant improvement in safety or effectiveness over existing treatments. I'm excited that our team continues to work collaboratively with regulators towards the September 22nd PDUFA date. With respect to Europe, the EMA was validated by EMA, and we look forward to further review and the approval of PIRGMAB in Europe in 2026. Turning to the next slide, I'm pleased to report that we're on track to initiate the phase two OPAL trial in children under the age of two. The study is evaluating two different doses over the course of 48 weeks and will assess PK, PD, efficacy, and safety. The enrollment criteria are broad, and infants and toddlers may be enrolled with any approved SMN-targeted therapy, including gene therapy. Early intervention with the Pitigramab in the OPAL study could support muscle during a critical early developmental phase, complementing SMN-targeted therapies that aim to preserve motor neurons. By promoting muscle growth, when both motor neurons and muscle are still forming, epitogramab has a unique opportunity to improve motor outcomes in babies and toddlers with SMA. Turning to our plans for the study of epitogramab in additional rare and severe neuromuscular disease, at the outset, let me state that the potential to prevent muscle loss and enhance muscle growth by blocking myostatin holds great potential across a wide array of diseases. Here you see just two examples of that potential in mouse models of the severe debilitating disorders Duchenne muscular dystrophy, or DMD, and fascioscapulohumeral dystrophy, or FSHD. In the DMD model on the left, the inclusion of an anti-myostatin antibody in mice receiving an exon skipping oligo is associated with a dramatic increase the level of dystrophin and a resulting increase in muscle force. FSHD is a neuromuscular disease resulting in patchy changes with affected and unaffected motor fibers. In the FSHD model on the right, treatment with an anti-myostatin antibody results in hypertrophy of unaffected motor units and once again an impressive gain in motor function. We continue our evaluations of an anti-myostatin approach in DMD and FSHD as well as in other models of disease, and will initiate the study of epigramab in an additional neuromuscular indication by the end of 2025. In June, we were gratified to announce the exciting results from our EMBRACE proof-of-concept study. David has covered those findings, including that the study met the primary endpoint with an encouraging safety profile. These findings are important as preservation of lean mass during GLP-1-mediated weight loss has the potential to enhance both cardiometabolic and musculoskeletal health. Next, we continue to advance our world-leading anti-myostatin platform beyond a pilgrim map. Further to our commitment to neuromuscular disease, SRK439 builds on the validated approach that delivered a pilgrim map. There's great potential for SRK439 to be an infrequent, potent, subcutaneous anti-myostatin antibody, and we look forward to exploring its potential as another innovative Scholar Rock therapy for patients suffering with severe neuromuscular disorders. We remain on track to file the I&D application for SRK439 to support the first in human study later this year. I'd like to conclude by reiterating our key priorities. Number one, drive the U.S. approval of epinephrine in Q3 2025 and advance the EU toward approval in 2026. Number two, initiate a study of apitogramab for infants and toddlers with SMA under the age of two in Q3-25. Number three, initiate clinical development of apitogramab in at least one additional neuromuscular indication by the end of 25. And finally, file an IND for SRK439 in the second half of 25. With that, I'll turn the call over to Keith to provide a commercial update.

Keith? Thanks, Akshay. And good morning, everyone. With epitigromab advancing through the regulatory processes in the U.S. and Europe, we are preparing to usher in a new era for the treatment of children and adults with SMA. This is a progressive and devastating disease that leads to loss of mobility, limited activities of daily living, and a lack of independence. If muscle is left untreated, it can result in irreversible atrophy. we are excited about epitogrammab's potential as the first and only muscle-targeted treatment to show clinically meaningful and statistically significant motor function improvements in children and adults living with SMA. The SMA community is calling for a treatment to address progressive muscle degeneration and motor function loss. To underscore this, a 2025 CURE-SMA survey showed that 90% of patients report that their greatest unmet need is to gain muscle strength. 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. 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. We are on track with the preparation of the global launch of epitogramab starting with the U.S. Based on our September 22nd PDUFA date, we will execute our commercial launch of epitogramab immediately following our FDA approval. In Europe, our MAA is under review by the European Medicines Agency, and we are preparing to launch upon approval in 2026. I'm excited to announce that as of today, under the leadership of our U.S. General Manager and Chief Brand Officer, Rebecca McLeod, our U.S. customer-facing team is fully on board, trained, and now deployed in the field. Our team is currently engaging with the SMA treatment centers, key opinion leaders, and both public and private payers. We are impressed by the talent, the extensive rare disease experience, and the passion to serve patients that our new team members bring. The team is comprised of many professionals that have substantial experience in serving the SMA community or the broader neuromuscular disease community, and we are united by a commitment to serving these patients. Today in the U.S., there are approximately 10,000 patients living with SMA, and roughly two-thirds of them have received an SMN-targeted therapy. These investments we are making position us to reach these patients with epitogramab and will provide a blueprint for our global rollout. Globally, there are approximately 35 patients with SMA that have already received an SMM-targeted therapy, and we have an enormous opportunity to make a meaningful difference with epitigromab with the potential to reverse progression of SMA from a loss of motor function to a gain of motor function. The entire Scholarock team is ready to serve the SMA community, and we will move with a sense of urgency to deliver a Pitagor map to them following approval. Now I will turn the call over to Vikas. Vikas?

Thank you, Keith, and good morning, everyone. I'm pleased to provide our Q2 business update and provide insights into how we are thinking about resource allocation in the future. The opportunity with Apidigromab 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 $295 million. During the quarter, we continue to increase our investment in infrastructure to support commercial readiness and our supply of epidigromab to support the launch. As we look ahead, we are prioritizing the commercial launch and our ongoing clinical programs. We have an additional $50 million under our debt facility that we can draw down this year, and we also anticipate receiving approximately $16 million from exercise of outstanding common warrants by year end, bringing our anticipated runway into 2027. Additionally, $50 million is available under our debt facility post-approval to support the upcoming launch. We also anticipate monetizing our priority review voucher following approval. We continue to operate with a tight financial plan and will share more details over the next few quarters. As a reminder, we will continue to focus 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. David? Thanks, Vikas.

In closing, we are committed to successfully executing on these key priorities, which position us to transform Scholarock into a premier global biotech leader. First, epitogrammab regulatory approvals, and following those approvals, the U.S. launch of epitogrammab for children and adults with SMA, followed by a series of country launches in the coming years, starting in Europe with Germany next year. Second, expand epidegromab into additional rare, severe, and debilitating neuromuscular diseases. And finally, disciplined capital allocation to support our high-value commercial and development initiatives. On behalf of every member of the Scholarock team, I want to emphasize our unwavering commitment to more than 35,000 patients and their families. Our mission is to move 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. We will now begin the question and answer session. At this time, I would like to remind everyone, in order to ask a question, press star, then the number one on your telephone keypad. And your first question comes from the line of Eric Schmidt with Cantor. Your line is open.

Well, thanks, and good morning, Scalaroc team. Appreciate the transparency around your CDMO issues. Can you tell us a little bit more about the specific observation at those two sites, whether you expect that a re-inspection is going to be required prior to epitagromab approval, and whether the two facilities right now are currently able to release other pharmaceutical products? Thank you.

Yeah, thanks very much, Eric, and it's great to be working with you. First, I think as you know, Eric, GMP inspections are super standard as part of the FDA review process. And in fact, in 2024, based on FDA's inspection data dashboard, actually more than 70% of drug quality assurance inspections resulted in observations noted by the FDA. So as I noted in the call, we you know, look, we're disappointed, but we weren't surprised to learn that two of our sites received observations. I think the benefit for us is those observations were, you know, were presented well within our review cycle that allow for a response and obviously a green light. It's always like very difficult to sort of read the tea leaves and try to understand what the FDA, with those observations, may want to do. Would they want a reinspection or not? At this moment in time, given the very constructive late cycle meeting that, again, was held after these site inspections and after these observations were provided, again, the tone and tenor and collaborative nature of that late cycle meeting certainly indicated to us that the agency is very much working toward completing their review of our BLA by the September 22nd to do for date. I would also just note that we're obviously working on multiple levels with our CDMO partners. We're a skilled team. We're an experienced team. We understand how best to work through situations like this, which we are prepared to do.

And, David, do you know whether the two facilities are releasing any product currently?

Very good question. The two facilities continue to operate. Of course, the one that, you know, given the disclosure on August 1st, it's not common practice in the industry nor our common practice to name facilities. But in the case of Catalan, Indiana, now owned and operated by Novo Nordisk, certainly, as you know, Eric, that's – That's an important filler across the board for a number of very important products across the industry, and we know they continue to be very active. And the other facility continues to manufacture product as well. I think I would also note, and I think this is probably important for our entire audience, our supply chain has produced the epitomab drug supply that has now accumulated over you know, over 600 patient years of experience through multiple years of clinical trials, including our PIVITAL trial, the most recent EMBRAZE trial. And I think importantly, I'd like to note that our launch supply and beyond is manufactured, viled, and ready to go.

Thank you very much.

Your next question comes from the line of Allison Bradsell with Piper Sounder. Your line is open.

Hey, good morning, team, and thanks for taking the questions. First, could you just further characterize any interactions with FDA on the epigrammab review outside of the observations at CDMOs you just discussed? Any feedback on your overall confidence in receiving a broad label would be particularly helpful. And then I think you talked about expansion of payer outreach, so could you just frame for us how your discussions with U.S. payers are going and just overall receptiveness to coverage of epitogramab on top of SMN targeting therapy. Thank you.

Yeah, no, thanks, Allison. And, yes, as we noted earlier, You know, we were very encouraged by our late cycle meeting that we recently had, and Akshay can provide a little bit more context on that. And then, as I noted, and Keith did as well, he's just recently deployed a sensational team, and he can comment on some of those payer interactions. Related to the label and the interactions with the FDA, Akshay?

Yeah, thanks, David. We had an exceptionally constructive conversation. late cycle meeting recently with the FDA. All the different disciplines that needed to be there were there. We talked through the different aspects of the BLA. I think we were very pleased with the feedback we had. And so, you know, we're working with them, as David said, in his prepared statement towards September 22, and look forward to the rest of the BLA review being completed and, you know, We appear to be doing just that right now.

Yeah, Allison, and as far as the payers, as we've noted before, we have a fully staffed payer team. Our outreach has been progressing to be able to be ready for our September 22nd PDUFA date. The meetings have been going positive as we've been going through some of the epitogram app data and overall response. But importantly, the durability of response is something that payers have found quite impressive. Lastly, to your other question about paying for another therapy for SMA, I would say that you already have better than 20% of patients that are receiving more than one SMA therapy that is being paid for by payers at this time. So, although the question has come up, the unmet medical need is there, and therefore, all I can say is the discussions are going positively.

Thank you.

Your next question comes from the line of David Nearing-Garten with Wetbush Securities. Your line is open.

Hey, thanks for taking my questions. I just had one on the labeling. Have you had labeling discussions with FDA and, you know, able to discuss labeling you know, possible labels with payers or is that to be discussed with the, you know, with the PDUFA date or as we approach the PDUFA date? And then the second one is if there is unfortunately a delay in the PDUFA, does that possibly put the PRP at risk if, you know, if there are different changes in the budget that starts, you know, on October 1st of the fiscal year?

Thanks. Yeah, maybe I'll take that second or last question, David, first. There would be no change in PRV, and I think you've all come to know us, this group of management team. We think about everything. We're a measured twice, cut once type of crowd, and we would think through Any scenarios, even before, as we mentioned, we weren't totally surprised by observations, only because three-quarters of the time they happened. And so we would have been thinking through all of this, and there'd be no impact on the PRB at all, which is important and very good news. Regarding just the constructive nature of the dialogue and the label, I'll have Akshay comment.

Yeah, so with respect to that topic, again, we had a very good late cycle meeting, and as you can expect at the late cycle meeting, all the different aspects of the BLA leading to a potential approval are discussed, including labeling and the timings around who can expect what. We've had those types of interactions. I can't get into more detail than that right now, but we were reassured that everyone is working towards September 22nd.

Next question comes from the line of Tess Romero with JP Morgan. Your line is open.

Hi. Good morning, team. So, just double-clicking back on some of the earlier comments you've made, you know, what is the right way to think about the next step following these observations given proximity to your goal date? How likely do you think that the outcome of the review will be positive in light of these findings and remain on time? And then my second question is, what does an ideal label look like for a pentagram app? And at this point, what do you believe the indication statement should be? Thanks.

Thank you, Tess. Great questions. So just kind of letting you into our kitchen a little bit, what you might expect us to be doing is working very closely with our CDMO partners. So in other words, like being well aware of the observations, having input on the responses to those observations, and then having levels of transparency, both with the CDMOs and their communication, with the agency as well as our own continued dialogue with the agency through the final stages of our review process. And so I would just say that we have substantial talent internally. We would always take a no stone left unturned approach to external experts to help us and help our CDMO partners think through The very best way to respond to observations, as I noted, we're confident that Novo submitted, and we actually have access to those responses that they made earlier this week. and the same will hold true for the responses that are going in within the week related to the other CDMOs. So we'll have a great visibility into this and then multiple lines of communication through our CDMO partners as well as the FDA directly. Related to the ideal label, I'd turn over to Akshay and Keith. One of the things we've worked very hard on by taking a no-shortcut approach to the development program is the robustness of our phase two and then phase three trial. And so obviously when we think about children and adults with SMA, we think about aligning with our partners at CURE-SMA, really for the best interest of the community, a broad label is quite important so that all patients who can benefit from epidigromab will have access to epidigromab. For more comments on the label, I'll hand it over to Akshay.

Yeah, thanks, David. So with respect to that topic, SAFIRE itself studied individuals two years and older to the age of 21. The primary endpoint was for the group that was two to 12-year-old. We obviously hit that primary endpoint. We relayed the data again today. The important thing is that the data in the 13 to 21 were also entirely consistent with what we saw in the two to 12 group. And so I think we can expect that those under two that were not studied may not be in the label, but certainly above two, we would like to see those in the label given the very exciting findings from SAFIRE all the way up into adulthood. And if a patient in SAFIRE is 21 years old and is experiencing benefit, they're not going to suddenly stop getting benefit when they're 22. So I think from a logic perspective, two years and older is a way to think about the group that would be eligible. But again, we cannot give any final information on that until the FDA has finished their deliberations.

But yeah. And one last thing I'd comment on in our, you know, very strong partnership with Cure SMA, they've actually advocated, you know, with the FDA for many years, the importance of sometimes a narrower clinical trial, but a broader label. recognizing the biology of the disease isn't necessarily, you know, different as patients get older. We were gratified that our most recent study in adults, over 100 adults, showed the biology of myostatin again held up. That, of course, was with the EMBRACE trial. But it has been common practice that there can be a slightly narrower patient population in a pivotal trial, but then an acceptance of a broader label. And that's what we're working toward. The ideal label, as Akshay said, would be the, you know, patients at two years of age and older would have access to the therapy.

Thank you. And our next question comes from the line of Mark Pham with TD Cowan. Your line is open.

Thanks for taking my questions. Maybe first to push a little bit on the pricing discussion that you're having with payers. Just, you know, I think we are encouraged that, you know, 20 plus percent of patients are getting clinical combination therapy today, you know, even without phase three data supporting that. But maybe the ask on the payers is a little bit different with that, right? Because most of that is one time gene therapy costs that may have already occurred. And then on an annual budget basis, just one therapy, just keep through how they're kind of thinking through the budget impact of maybe two SMA type pricing drugs in individual patients happening on a concurrent and ongoing basis. And then maybe from the R&D side, starting a new indication later this year, should we view that as like one pilot outside of SMA or is that just the first of many and we should expect as we go into 26, you know, additional indications to continue to be added to the pipeline?

Mark, thanks. Very thoughtful questions. On the pricing side, I would note, of course, as I have in the past, that we'll consider a number of things when establishing the price. Certainly, the rarity of SMA, and you talk about budget impact as an individual patient, we obviously think about just how rare SMA is. The severity of the disease, despite the use of, over the past 10 years of SMN targeted therapies, where They have shown in some of their long-term data, and we then again underscored in our Phase III trial, that patients eventually move to a progressive state of motor function loss and how severe SMA is despite the use of best-known standard of care. And then, of course, the compelling clinical benefits that we can provide, and some of those were underscored by Akshay earlier. And so You know, we'll think about those things. We'll think about the budget impact. And one of the things we also have a lot of experience with is looking at even sort of pricing corridors for rare disease therapies, monotherapies in different settings and sort of thinking about sort of where the starting point is today. We definitely do not think the error has been in terms of payers' willingness to support of both physician interest as well as patient interest and accessing, and Keith will comment in a moment, on the importance of dual modality therapy for this devastating disorder. Keith?

Yeah, thanks, David. Mark, one of the things is, you know, you mentioned that this is using two agents as just post-sologensma, and I just want to call out that we actually have met with patients and physicians that have tried both Rizdiflan and Spinraza simultaneous, so they're paying for two current agents at the same time. So it's not just post gene therapy. The bottom line is that over time, these patients on these SMN targeted therapies, many of them plateau and then they begin to decline and payers are realizing that there is a great deal of unmet medical need that's left. If I think about the fact, as David mentioned, treating with dual modality and targeting the muscle directly as well as the motor neuron, It gives you an opportunity to potentially not only increase your response, as we've shown from the SAFIRE data, but then also have a durability of response over time. And so that is a meaningful impact that is valuable to payers.

And then, Mark, regarding the other, you know, sort of the pipeline and a product strategy that Ache is so skillfully leading, I'll have him comment.

Yeah, thanks, Mark. So, you know, we see enormous opportunities for antagonizing myostatin in a whole array of neuromuscular disorders. And so, yes, there'll be many opportunities that you'll see us studying. We'll begin with one by the end of the year, but I think we'll add to that in quick succession over time.

So much more to come on that. Thank you.

And your next question comes from the line of Martin Oster with Raymond James. Your line is open.

All right. Hey, good morning. This is Thomas on for Marty. Thanks for taking our question. Maybe just one on the OPAL trial here. Anything you can say about expected enrollment timelines there? And maybe just frame for us how to think about the significance of that expansion opportunity if we envision an initial label for epitagrimab in patients two years and older. Thank you.

Yeah, thank you very much. And consistent with our ambition and mission at the company that no patient would ever be left behind, including, you know, babies and toddlers, this is an important study for us. And as Akshay noted, so I'll have him comment a little bit further on the study and expected timelines.

Yeah. Thanks. So, you know, with respect to timelines, you know, we are going to start enrollment in Q3, as I said on the prepared remarks. My usual practice is let's get that going. And then in the coming quarter or two, as we see momentum build, we'll be able to guide further on the exact completion date of the study. And, you know, with respect to zero to two-year-old children with SMA and the label, We didn't study under the age of two in the SAFIRE study. We've initiated this study to understand the impact of the drug in that population safety, PKPD efficacy. And as David said, no child should be left behind with this disease. And we think Pidigromab can have an impact across the entire age range here. I think in terms of trying to do good with this drug and helping as many kids as possible, one thing I would note is that the the prevalent population is much, much larger than the incident population. And so, you know, if the zero to two are the new children being born with SMA, that's dwarfed by the 35,000 or greater who currently have SMA or are on treatments and we believe could be helped by a drug like a pedigree map. So there's a lot for us to do whilst we get OPAL done and start helping under two, and we'll begin with two years and hold it.

Thank you.

And our next question comes from the line of Srikripa Devarakonda with Truist Securities. Your line is open. Hey, guys. Thank you so much for taking my question.

I just want to go back to the CDMO site inspections. Now, if there is a need for another inspection, do you have a sense of timelines as to when you will get to know that by? And given the CRLs that we've seen with one of the peers involved, what are typical timelines for potential resolution of these issues? Thank you.

Yeah, thanks, Kripa. Again, it's hard to predict what the FDA will do. I mean, I think you all do this for a living, and as do we. And the best we can do, like you, is assess what has happened from time to time in the industry and what could be some of the different scenarios. But I can tell you that from all of our experience and that of our expert advisors that we are working with along with our CDMOs, the very best thing to do initially is have a robust response to those observations. And that is what we've been spending a lot of time on. the robustness of those responses obviously can have an impact on whether or not any reinspection would be required. And so that's where our effort is being placed. And then again, I think, as I noted, we would be gathering information both through our CDMO partners, but then also directly with the review division. And we'll keep you apprised at that. But right now, given the fact that following these site inspections and following the presentation of those observations, we held our late cycle meeting. The FDA completed that late cycle meeting. The dialogue, the tone, the content of the discussion was very encouraging with a commitment to move forward toward our PDUFA date under priority review of September 22nd. And we will certainly keep you and all of our stakeholders apprised on that progress.

Great. Thank you so much.

And our next question comes from the line of Evan Seegerman with BMO Capital Markets. Your line is open.

All right, two questions from me. Can you provide more color, characterize the, you know, the interactions from your late cycle review meetings? Did they at all talk about just the difference in efficacy we saw between the 20 milligram and the 10 milligram doses? And then also, Vikas, one for you, as we think about kind of modeling, you know, the asset post-launch, how should we think about the cadence in the back half of this year into next year? Thank you, guys.

Yeah, Evan, great question. Regarding the combined dose analysis, I'll have Akshay comment on that, which obviously, as you know, there's been extensive clinical work done with the 10 and the 20. Most recently embraced was 10.

Akshay? Yeah. So the late cycle interaction was indeed very constructive and positive. So we have discussed the file fully, including the combined dose analyses. with all of you before, and we've had very constructive discussions with regulators around that as well. As you know, we hit the primary endpoint. The important thing is both 10 and 20 have an almost identical pharmacodynamic effect, and so it's unsurprising that both showed a positive outcome with efficacy, and combining the two groups increased statistical power to be able to see the difference versus placebo, and obviously we saw a gain in motor function with the Pigramab versus a decline. And our expectation is that given that the regulatory practice always do approve the lowest dose that's efficacious, and given that both have equivalent pharmacodynamic impact, we would request that 10 milligram per kilogram is the approved dose. I'll leave it at that.

And on the financial side, we have still to do the 2026 budget planning session, but As I mentioned in my call, I'm going to be very thoughtful about how we go into next year. Some of the expenses in the clinical side is going to drop out next year, and then we'll replace it with the prioritization as Akshay was laying out in his section with moving 439 and some of the pipeline forward. So that's other indications for us. So that's our key priority in keeping our overall spending in check. We do expect it to be in similar lines like what we spent this year.

Thank you, ladies and gentlemen. This concludes the Q&A session and concludes today's call.

Thank you all for joining.