Andrew Parker, I'm a member of the Citi Biopharma Investment Banking team here. Very pleased to be joined this afternoon by David Hallal and Vikas Sinha of Scholar Rock, and so why don't we get into it with a little bit of Q&A around the company, your data, how to think about the path to commercial launch and beyond. Maybe just opening remarks, I'll open it up for you guys. A little bit on your background and how you got involved and what you saw at Scholar Rock to get you involved in your current executive roles would be good context, and then maybe some opening remarks, David, from you in terms of how investors should think about the positioning of Scholar Rock today.
Great. Thanks, Andrew. It's fantastic for Vikas and I to be here at the Citi Healthcare Conference in Miami. As you know, Andrew, this has been really a transformative sort of 12, 14 months for the company, really starting with the readout of our phase III trial in October of 2024, where we hit StatSig as the first ever muscle-targeted treatment to be used in children and adults with SMA, and then it's been quite a fun 14 months to get to this point today. Interestingly enough, as you know, in April of this year, we did announce that I was going to step into the CEO role in addition to my chairman role, which I've been holding since July of 2017.
But for me, given the opportunity that I see for Scholar Rock, which is to really build one of the next great global biotech powerhouses, much like the pattern recognition of some of us that we built together previously at places like Alexion and argenx and Alnylam, I thought it was important the day that I took over as CEO was to establish the foundation with a world-class executive team. And so on the same day that I was announced as stepping into the CEO role after eight-plus years as chairman, we announced my partner, Vikas Sinha, was assuming the role of CFO. My dear friend, Akshay Vaishnaw, who for 19 years led R&D for Alnylam, had been on the board with me at Scholar Rock, stepped into the role of President of R&D.
Then for the third time, I had an opportunity to hire Keith Woods as our Chief Operating Officer. Keith and I worked together at Amgen in the 1990s, again at Alexion in 2010 to 2017. Some of the best work that Keith has done was at argenx, where he was really the architect of the VYVGART launch and MG. The reason why I was so eager to not only step into the role when Jay Backstrom was resigning and retiring from the role, but to bring in this world-class leadership team is we sort of see the opportunity in front of us.
It's to build a dominant force in the rare neuromuscular space led by our first asset, apitegromab, with this opportunity that we have to serve patients globally with SMA, and then to follow that on with a series of clinical development programs for apitegromab and then some other myostatin inhibitors that we have at an earlier stage. And that provides us the opportunity, as I noted, not only to launch an extraordinary drug in the U.S., but much like we've done before, Vikas, turn our attention to Europe, Asia-Pacific, and Latin America and build a 50-country operating platform where we can make sure that we can serve patients in need wherever they reside around the world. And that is really what we have been focused on over these past seven, eight months. Vikas?
Thanks, David. Yes, when David invited us to come and join the Scholar Rock management team, it's just like going back to building once again the same way that we built Alexion Pharmaceuticals from zero to a $40 billion company. We are looking at this opportunity as a starting point and building it from here.
And Andrew, I'm going to go all the way back to after 11 years at Alexion. Why I accepted the role as board chairman of Scholar Rock is my own pattern recognition was the following. What was not novel at Alexion was that we were targeting complement to inhibit. What was novel at Alexion was that after years of pharma and biotech trying to effectively drug complement and being unable to do so, Lenny Bell and the scientists of Alexion had developed the ideal way both safely and effectively to inhibit complement. And that opened the door not only to the first-ever treatment for paroxysmal nocturnal hemoglobinuria, but it gave the company really a pipeline and a product for wherever complement was implicated in disease.
And so when I looked at Scholar Rock, for 20, 30 years, pharma had been focused on trying to drug myostatin, and every one of those trials failed. And we saw kind of the unique platform that we had at Scholar Rock to inhibit myostatin more uniquely than any other company had done before in a very novel way. And that is why even in a preclinical stage, I stepped in as board chairman because I thought we had the opportunity to do something really special. Now, eight, nine years later, we're the first company to ever have a successful phase III trial with a myostatin inhibitor. We did choose an indication that we think we can make a meaningful impact for patients and build the financial strength for our company for many years to come.
We're super excited about the future and discussing that in more detail with you over the course of our time together here.
Great. So you guys have clearly put together a world-class team around this to prosecute this opportunity. Maybe before we get to how to think about SMA and apitegromab's positioning in that marketplace, let's talk a little bit more about the approach to myostatin. And to your point, David, there's been a long list of attempts and failures. Just what's the secret sauce? How should investors think about what's differentiated here in terms of your approach to targeting myostatin?
So what I saw back in 2017 was that most companies that were targeting myostatin were doing it one of two ways, either by developing inhibition strategies to the mature form of myostatin or looking for a trap technology for the receptor. The problem with that is there are many other growth factors in the TGF-beta superfamily of growth factors that pharmacologically look and act very similarly to myostatin. And therefore, if you were to develop an antibody, for example, or a trap strategy, you are going to have off-target effects. You will inhibit other TGF-beta superfamily of growth factors, and that leads to either imperfect potency in inhibition and also some safety signals and safety challenges.
And so the secret sauce at Scholar Rock was when myostatin is such a powerful negative regulator of muscle growth that the body itself has a chemical cage around myostatin when it's released from the muscle, and that cage is what releases the mature myostatin into the body. What our scientific founders discovered was that it was that chemical cage or the latent form of myostatin that had a more pharmacologically unique chemical structure. And if we were to develop an antibody for that, we would have exquisite selectivity, only inhibit myostatin, not have any of those other off-target effects on things like activin. In that case, we could, we think, effectively drug this target that has been so elusive for pharma. And we think our eight-year development program has really proven that out.
Yeah. So with that selective approach, let's talk about the SMA opportunity. And how should investors think about just the SMA market with the SMN products that we have, three of them in the market today? And what's apitegromab's positioning as you think about launching this in the next couple of years?
It's a great question, Andrew. So as you noted, over the last decade, we've seen the introduction of SMN-targeted therapies that really focus on upregulating a protein which patients need for motor neuron survival. It's either SMN1 protein, which the gene therapy from Novartis' ZOLGENSMA focuses on, or SMN2 protein for which Biogen's SPINRAZA or Roche's Evrysdi really target those things, and it's actually brought very meaningful innovation to a community of children, adults, and families that desperately needed it. There were very significant mortality rates in the SMA population, and over these last 10 years, these three drugs have actually really improved the morbidities and mortality associated with SMA. At the same time, though, motor function is not just impacted by motor neuron survival. The motor unit is actually the motor neuron and the muscle, the organ of the muscle.
Those two things together is what provides motor function, which is what patients who are now surviving longer desperately need, and so our hypothesis, which has been proven out now in our phase II and phase III trials, is that anything that one can do with ZOLGENSMA, SPINRAZA and Evrysdi is going to help patients by upregulating either SMN1 or SMN2 protein and help with motor neuron survival, but we call this disease spinal muscular atrophy for a reason. Muscles deteriorate. There is irreversible muscle loss in these patients, and there has never been a muscle-targeted treatment to focus on muscle strength. It is the sum of muscle strength, muscle mass, muscle responsiveness with motor neuron survival that will provide the optimal benefit for motor function, which is what the community is really looking for.
We designed our phase II and phase III clinical trials largely to take patients who have been on one of these SMN-targeted therapies. They then receive apitegromab. What we have now seen over many years in clinical development is a statistically significant, clinically meaningful improvement in motor function when apitegromab is used with an SMN-targeted treatment versus an SMN-targeted treatment alone. In fact, in our phase III trial where we hit StatSig with a p-value of 0.01, what we actually saw was patients who had been on these SMN-targeted treatments over the long run started to once again progress to motor function loss after being on these therapies for quite some time.
And what we were able to show and demonstrate in our phase III trial, a return of motor function improvement or motor function gain rather than the patients on SMN-targeted treatments alone having motor function loss. Also underscoring the benefit is there was a near four times greater likelihood in our phase III trial of patients having the most significant improvement of motor function, which is a three-point improvement in the Hammersmith motor function score for SMA compared to an SMN-targeted treatment alone. We thought that that was quite profound. And it is really in that 188-patient placebo-controlled global clinical trial has really been the basis of, to this point, a very successful review cycle with the FDA to get to a point where we are on the near doorstep of an approval and bringing this to patients in the U.S. living with SMA.
So as you think about, and I think the data that you guys have published and presented and made public is quite profound to your point of motor function improvement, maybe paint the picture of relative to the current market of patients that are on SMN-targeted therapies, how should we think about apitegromab's opportunity here in conjunction with patients that are currently on therapy? Maybe just size the market for us.
It's a great question, so in the U.S., there are approximately 7,000 patients who have received at least one SMN-targeted treatment, and globally, there are about 35,000 patients inclusive of the 7,000 in the U.S., and that actually, Vikas, follows very much the global footprint that we saw in other rare diseases at companies like Alexion, so we would see maybe a third of the opportunity in the U.S., a third of the opportunity in Europe, and a third of the opportunity rest of world, and certainly, that seems to be playing out when we look at the sales and the revenues of those other three programs. In aggregate, those other three drugs are delivering year-on-year continued growth a decade after the first one was introduced by Biogen, SPINRAZA and in aggregate, they're doing $5 billion a year in annual revenues, and it continues to grow.
For us, we think whatever SMN-targeted therapy is used, what the patient community really needs is the first-ever muscle-targeted treatment to provide the optimal benefit for motor function improvement. And so that we see this as our opportunity in the U.S. is these 7,000 patients that have received one or more of these SMN-targeted therapies and 35,000 patients globally. We think that's quite, it's almost the perfect size. It's a small enough rare disease community where the budget impact is not so great that it will really trip off the system, but it's a really meaningful number of patients that we think provides sustainable revenue growth through the end of this decade and well into the next for Scholar Rock as we grow what we believe is a multi-billion dollar opportunity for apitegromab and SMA alone.
And then I'm sure Andrew will talk about our plans to enter the clinic for other rare neuromuscular disorders as we've been able to develop this very strong body of evidence starting in SMA. But together, we see in the U.S. a tremendous opportunity and globally probably more than $2 billion in annual revenue for apitegromab and SMA alone.
And let's talk about two follow-up questions there, David. One is I think it's important to understand the commercial preparedness and how you plan on executing on that opportunity not only in the U.S., but globally. Obviously, you and members of your team have very successfully done that in the rare disease space a couple of times before. So where does Scholar Rock stand, and how do you think about, as you think about the patient opportunity outside of the U.S. in particular, how you tackle that relative to the current competition with SMN-targeted therapies? And then let's talk about really the opportunity to build a global leader beyond this is not just an SMA play, right?
As you think about neuromuscular more broadly, let's talk about where you think this approach to myostatin and your world-leading expertise in biology there is applicable to really build a pipeline and a pill type of opportunity here.
Thanks, Andrew. I guess first off, what I would say is I view Biogen, Roche, and Novartis as definitely not competitors, and the reason for that is they focus on a key part of the motor unit, which is motor neuron survival. But there is no doubt that patients and physicians, and we hear this on a daily basis, really do believe that motor function is the sum of motor neuron survival and muscle strength. And there is nothing to address muscle strength in SMA. So we really see what apitegromab is, is like we're kind of like the Switzerland in this marketplace where no matter what one or in many cases, what we see in the U.S. is upwards to a third of patients are receiving more than one of these SMN-targeted treatments at the same time because the patient community is really looking for more.
No matter which one or more of those therapies you choose to use, no matter what the background or foundational treatment really ought to be, apitegromab, so one can address the muscle component of this disease and address the muscle atrophy. We feel like we're well positioned where we're really competing with ourselves. We don't really see any near-term competitors over the next three to five years. We think most other programs have just not matured or delivered favorable phase III results. I think we're still upwards to a year away from even the first proof of concepts study being done with a muscle-targeted treatment behind us. Then there's years to then plan and enroll a phase III trial. We think we're in a really, really good position.
Now, commercially, how we're approaching this, and Andrew, as you and others at Citi came to know Vikas and I previously, in the multi-billion dollar businesses we've had to build before, those were rare diseases where the patients had the disease, but they were not yet diagnosed. These were such rare diseases that most doctors didn't even know what they were, never even thought of them, PNH, AHUS. In the case of SMA, these patients are diagnosed. In the case of SMA, these patients have either private or public funding for rare disease therapies because they are already on either ZOLGENSMA, SPINRAZA or Evrysdi, so it means they're residing in a country in which there is support for rare disease therapies, and that probably helps us in terms of the timing of being able to identify and treat these patients.
We think that that's quite a nice setup for us. The patients are known to us. The patients are known to the medical community. They're now gaining a greater and greater appreciation for how important a safe and potent muscle-targeted therapy will be for their overall sort of outcomes over the long run. We think we are well positioned to sort of really take advantage of this unique dynamic in the marketplace. We also think, and I think this is important, I've been asked, how do we feel about apitegromab now being reimbursed in addition to the current SMN-targeted treatment that a patient is on? I think if one looks at many rare diseases, both the patient numbers can be higher and even the price of a single drug could be higher.
We think there is plenty of room for the combination of apitegromab with those SMN-targeted therapies where there will be limited budget impact and really optimal sort of outcomes for patients by receiving apitegromab and their current SMN-targeted treatment. So it sets up very, very well for us to kind of follow the market that's been created over these last 10 years.
Yeah.
To come to your next question, so the way I think about the growth at Scholar Rock and Vikas is really helping us build that balance sheet and then build, he will oversee along with Keith Woods kind of the global build-out very much like we've done at Alexion before. We'll start in the U.S., we'll move to Europe, we'll then add on Japan, other key markets in Asia-Pacific, and also then Latin America, and these are not massive operational builds.
These are generally very tight, small organizations, country by country. And we see over the next 10-15 years just consistent growth year on year as we add new countries and add new patients with SMA on apitegromab over the course of a 10- to 15-year period of time. And so that will be kind of our very methodical march to building a multi-billion-dollar business in SMA alone. But then you asked another important question, Andrew. We're not going to stop there.
We'll announce early in 2026 the next indication with an IND that has been cleared so that we can move into the next rare neuromuscular disorder that we believe we can then follow the same pattern as SMA, really address the needs of the marketplace, do a robust phase II trial to demonstrate safety and efficacy in that next rare neuromuscular disorder, and then follow that into phase III. And the air will not be thin there. We've talked about FSHD. We've talked about DMD. There's a number of other indications we are assessing right now, and we look forward to sharing more light on that in the near term.
But very much like you've seen at our argenx more recently, Alexion dating back over the last 20 years, we think that pipeline and a product strategy is a very efficient way to build an extremely valuable company that's really focused on the service of patients with rare diseases.
Great. I'm sure we all look forward to hearing more about that in 2026 as you roll out that next leg of how you're thinking about the pipeline in rare neuromuscular. Maybe to come back to the SMA opportunity, I know you face a lot of questions of what's the state of FDA interactions post-CRL? Maybe bring us up to speed on what you're able to share on interactions with the FDA and how to think about timeline to potential launch.
First of all, it's refreshing to talk about something not related to manufacturing. But this is also the thing we're obviously thinking about quite a bit because it's the one thing in the way of bringing a revolutionary new treatment option to children and adults with SMA. To bring us back to the story, we were, as I noted at the beginning in my opening remarks, we were thrilled after a seven, eight-year development program to have a positive phase III trial, which we announced in October of 2024. We then submitted our BLA in January of 2025.
And then just before the announcement of Vikas, Akshay, and Keith joining me on the executive team, just a few weeks before that in April of 2025, we announced that the FDA had accepted our BLA under priority review, which then provided us an accelerated review period with an action date of September 22nd. During the course of that, we obviously had all the necessary inspections focused on clinical GCP standards and all of our clinical trial sites, on-site inspections at Scholar Rock, on-site inspections at those clinical trial sites, but then also inspections at our drug substance and drug product manufacturers.
What we announced in our Q2 earnings call on August 6th, I believe, was that the FDA, when doing a PLI inspection at our drug substance manufacturer and then at a general site inspection at our drug product manufacturer, issued a Form 483 with multiple observations in those facilities. And I think the thing that obviously was a bit of a concern was that in the drug product manufacturing facility known as Catalent, Indiana, now owned by Novo Nordisk, these were repeat observations dating back to prior inspections for when Catalent had owned that facility.
We did feel like at that time between August 6th and September 22nd, there was enough time for those manufacturing facilities to adequately respond to the Form 483 observations with a robust remediation plan and try to get to be done with as much as possible so that we could be approved on time on September 22nd. In fact, we had a great late-cycle meeting with the FDA. Everybody was lined up to try to get there by the 22nd of September. Given the tone and the tenor and the nature of the review, we expected when we woke up on Monday, September 22nd, given what we were doing with the FDA on the 18th and 19th of September, we expected we were getting approved. Unfortunately, we then received a CRL after five o'clock, six o'clock or so on the 22nd.
What was outlined in that CRL is that the one remaining issue that led to the CRL was the drug product manufacturer, Catalent, Indiana, owned and operated by Novo Nordisk. In fact, the Form 483 observations at the drug substance facility had been adequately resolved. And look, both facilities had completed a similar percentage of their remediation plan. I think the difference was the historic observations and issues with GMP practices at the drug product manufacturer, and the FDA wanted to see more from them. This obviously followed Regeneron getting tripped up with their own timelines because they were at the same facility. So the CRL was issued on September 22nd. We felt like Novo was really committed to remediating the plant.
Then in October, right around Columbus Day weekend, we then learned from Novo Nordisk that the classification of the facility became OAI, Official Action Indicated, which kind of made us feel like we were heading toward a little bit longer of a remediation process than we would have hoped for. That obviously was all issued before our Type A meeting. Our Type A meeting we requested shortly after our CRL, and we held that on November 12th. What was important about that Type A meeting, Andrew, it was going to be the first time with Novo being at that meeting with us that they were able to present.
They had been sending the FDA updates on their remediation plan, but they were able in person to present their progress on their remediation plan and state to the FDA that they would be reinspection ready by the end of 2025, by the end of December. And we had a very constructive and collaborative in-person meeting with the FDA. They don't do a lot of in-person meetings. We think that underscored their commitment to want to learn about what was happening and sort of hold hands and agree that there was shared urgency to get this very important first and only drug for patients with SMA targeting the muscle to patients as quickly as possible. We walked out of that Type A meeting feeling like there was going to be more urgency to resolve the remediation plan at the facility.
In fact, we expect the next step would be some level of correspondence that the FDA would have with Novo, and then that would trigger whatever needed to be done before the reinspection. In fact, a week after our Type A meeting, and we just disclosed this yesterday via 8K, that correspondence came in the form of a warning letter that is not yet even published on the FDA website. That warning letter is pretty consistent with the Form 483 observations. Novo is committed to responding to that warning letter within 15 days. And that should then lead to the necessary next steps. Within a month after responding to that warning letter, we would hope that Novo and the FDA would be working together to then agree on whatever is left to be done and then sort of start to indicate when the reinspection could occur in 2026.
And we expect this to all be handled expeditiously by both Novo and the FDA. And we'll continue to work with both parties in a very collaborative fashion because this is the only issue remaining in the way of apitegromab finally being approved for children and adults with SMA. Hopefully, that's helpful.
It is. Yeah. Thank you for going back through that. I'm sure there's been no shortage of questions about that over the last couple of months. Maybe to shift gears, I'd love to come back to the pipeline and SRK-439 and maybe put in a context how that next-gen anti-myostatin, which is sub-Q, fits into the portfolio and the broader rare neuromuscular opportunity that you outlined for us.
And I should say, Andrew, on November 14th, after the Type A meeting, recognizing that a correspondence was likely coming from the FDA to Novo, it would either be an untitled letter or a warning letter, the content of which would likely be the same. We actually shared guidance that we expect to resubmit and launch in the U.S. in 2026, and that guidance remains unchanged. That's what we're expecting. We know that's a wide time window, and we're not ready to narrow that time window just yet until Novo and FDA sort of have a couple of more meetings about kind of where they are with their remediation plan. Coming back to SRK-439 and our confidence that we will be launching next year, we continue to move forward with our pipeline. As I noted, we'll highlight our next indication for apitegromab and phase II trial early in 2026.
And then we are starting to dose healthy volunteers with SRK439 this month. This is a really important drug for us. SRK439 is not a next-gen apitegromab. It's a completely independent molecule. It's a very potent, high affinity, low frequency sub-Q presentation of a myostatin inhibitor based off of our very same platform of inhibiting latent myostatin. When I had become the CEO of the company, it was generally thought that this would be the cardiometabolic or obesity program for Scholar Rock. But I kind of took a step back and I said, "Given all of my experience, we're going to build a multi-billion dollar business with apitegromab. It's going to be an SMA and a variety of other rare neuromuscular disorders.
Given the power of SRK-439, wouldn't it be great if it was going to be something to help us defend and grow this rare neuromuscular franchise that we are building? And that's why we've just tamped down the brakes in sort of determining that this is going to be something not for rare neuromuscular. I think we want to get through our healthy volunteer studies. It's got its own IP. It's got composition of matter well into the 2040s. By the way, apitegromab has composition of matter well into the 2030s and late 2030s. We feel really good about that. But we think this is going to be a very, very important asset for us.
We think the healthy volunteer data, which we'll disclose in 2026, will be important because if you can safely and potently inhibit myostatin, there's going to be a pretty clear read-through that this will be a very effective therapeutic that we'll be able to bring into clinical trials, and we look forward to updating the world on that next year.
Great. So you guys have had a very eventful 2025 and 2024 as well too. We're looking forward to all the progress that you'll make in 2026 with a launch, the next indication, 439. Maybe in closing, and then I'll open it up for questions to the extent there are any here from folks in the room. Anything we haven't covered that you want to cover in closing remarks?
I would like to cover the balance sheet because we took some steps with the CRL, but I think the one thing about the CRL, there was kind of a little bit of strength behind our stock, which is not common with a CRL, but I think there was a lot de-risked with a CRL. I've often said like a CRL served us better than a major amendment. If we got a major amendment, there still would have been questions around, "Have you met the bar for safety and efficacy with the FDA? Was your drug substance manufacturing facility cleared or not cleared?" We wouldn't have known that with a major amendment. The CRL actually helped to illuminate we have one issue and it's solvable, and our approval is not a matter of if, but when.
But what we wanted to do in the strength of sort of how we were continuing to perform is tighten up the balance sheet so we can continue to build a great company. And I'd love for Vikas to just share those steps that we took, our current cash balance, and how we look at being able to finance our operations right through the approval next year and U.S. launch and beyond. Vikas.
Thanks, David. And thanks, Andrew, for hosting us today. In our Q3 call, we talked about $369 million in our balance sheet, which takes us into 2027 in, right? The first role I see as a CFO to play here is how do you control the cost? And with the leadership and the company all behind me, we've gated a lot of expenses that we would only release it once the approval comes. So that helps us give us a little time. And the second one is try to avail as much as we can the antidilutive ways. So we are currently looking at expanding our loan facility. So we have currently withdrawn $100 million, add another $100 into that, and try and create at approval another $150 million. What was very intriguing yesterday that the House also passed the extension of PRVs, right?
So we should be able to, they'll help us monetize the PRV whenever the approval comes. That adds a good chunk of cash also into the balance sheet. So we feel fairly comfortable right now that the launch will have enough dollars for us to take us through.
Great. Well, thank you both, gentlemen. Really enjoyed the conversation. Maybe I'll open it up with the remaining few minutes we have to the extent that anybody has questions here in the crowd. On that note, thank you, David and Vikas. Appreciate your time.