Joining us, I'm Selvine Richter, biotechnology analyst at Goldman Sachs, and it's a pleasure to have with us David Hallal, the CEO of Scholar Rock. David, to start here, you recently took over as the CEO of Scholar Rock after serving as the Chairman of the Board of Directors since 2017, and you were previously the CEO of Alexion. Can you discuss your decision to step into this role and your vision for the company, including this team that you've put together?
Thanks, Selvine, and it's great to be here with you and great to be in Miami here at the Goldman Conference. As you noted, while I'm rounding out my first month as the CEO of Scholar Rock, I'm commencing my ninth year as Board Chairman. Over that time, I've had an opportunity to work with a few tremendous CEOs at Scholar Rock who took us through each phase of our evolution. Nagesh Mahanthappa was the founding CEO and somebody I enjoyed working with, and he took us up through the proof of concept study for apitegromab in SMA, the TOPAZ phase II trial.
I personally went out and recruited Jay Backstrom, who was an extraordinary drug developer, where he was last the Executive Vice President of R&D at Acceleron and, of course, had a long storied history at Celgene as their Chief Medical Officer, to take us from the promise of Topaz to the confirmed results of phase III Sapphire. Now we are at this moment in time where there is this opportunity for Scholar Rock to really scale its growth into the next phase, which is global commercialization. This was a moment in time for me and for us, with just a handful of months before the PDUFA date, which I know we will talk about shortly, to really position the company not only for an approval in the U.S. in Europe, but sort of thinking about bringing apitegromab to patients with SMA and upwards to 50 countries around the world.
You noted the team, and that's a big part of it for me. Akshay and I had an opportunity to work together. A lot of people do not know this. Back at Biogen in 2002, he was a member of the Scholar Rock Scientific Advisory Board in 2014. When I joined as Board Chair in 2017, he was my first recruit to the Board of Directors in 2019. He and I are not the board members that have shown up from time to time, but really have been actively involved with management over our entire duration of eight to ten years at the company.
There is not anybody better to be the President of Research and Development at Scholar Rock than Akshay, who did it better than anybody else at Alnylam for 19 years as the President of R&D. Of course, Vikas who's here with us, we're starting our third consecutive decade together, and nobody did it better for 12 years at Alexion, where we really launched multiple products and scaled the business globally. Keith Woods, many folks may or may not know, it's my third time having the honor and privilege of hiring Keith Woods, who worked with me at Amgen, also Alexion, and then his best work yet was as the Chief Operating Officer at argenx, where he was really the architect of the Vyvgart launch.
For him to join us here at Scholar Rock as the Chief Operating Officer, it gives the four of us an opportunity to do something and really maximize the opportunity that's in front of us, which I know we'll turn to now here at Scholar Rock for many years to come.
Maybe if I could just delve into one of the points you made. When you say that you're looking to really, sorry, it's been a long morning, but when you're looking here with regard to your strategy to further develop this company, how much of that strategy is driven by taking the assets you have in hand and pushing them through on the commercial front and development front versus also serving as drug hunters per se and kind of building this whole rare disease outfit?
One of the similarities to Alexion that I saw in Scholar Rock when I made this choice back in 2017 to become Board Chair is it's not the novelty of trying to develop a drug for a target, but it's being able to drug a target like no other company can in the world. As you know, what made Alexion special after years of pharma and biotech trying to drug complement effectively, Alexion did it. When I looked at Scholar Rock, the ability to drug myostatin so cleanly, so neatly, and so effectively, even in the preclinical stage, is what got me so excited. I feel like our vision and strategy for the company is that we have an incredible capability in R&D, one that Akshay knows quite well and is now leading on a day-to-day basis.
We think what we've seen with apitegromab in SMA alone provides us, from an opportunity perspective, a chance to grow this company for many years to come, very much like many successful rare disease companies first maximize the opportunity of the first drug and the first indication. We also do see a pipeline and a product. We see other rare, severe, debilitating neuromuscular disorders for which apitegromab and/or SRK-439 could be developed for, and we think that provides us, Selvine, many years of opportunity with our organic pipeline to grow our business. Of course, we'll always be thoughtful.
I think one of the things Vikas and I, and we've spent time with you on this, Selvine, once we build a 50-country operating platform, there is the opportunity to then monetize those operations with perhaps even things that are brought in through licensing or acquisition and brought onto that platform, and we'll always be thoughtful about that.
Starting with apitegromab and SMA, where you have a PDUFA date of September 22, help us understand what your expectations are for the label in terms of age, ambulatory status, and disease type, just based on the dataset.
Yeah, so it's a good question and something we spend a lot of time thinking about. We've had a robust seven-year, no shortcut clinical development program for apitegromab in SMA, starting with approximately 60 patients, both ambulatory and non-ambulatory, in the phase II TOPAZ study, aged up to 21 years old. Of course, the phase III SAPPHIRE trial, where we enrolled 188 patients, also on background SMN-targeted therapy across a wide range of patients aged 2 to 21. The consistency of the results that we have seen across really the gold standard in measuring improvement from a drug therapy in SMA, which is the Hammersmith Functional Motor Scale, we saw clinically meaningful and statistically significant benefits in our primary endpoint in the SAPPHIRE trial.
Given the strength and the robustness of the 188 phase III SAPPHIRE trial, along with the phase II TOPAZ study, and the way the FDA has, in general, looked at SMA as one disease, we think there is precedent for a fairly broad label. We also think the way that myostatin biologically works and the value of inhibiting it, there's no reason to believe it's any different by, let's just say, age or ambulatory status. Again, I think what is most important for us is we think the consistency of our data that we've seen in almost any patient subgroup that we've studied over the last seven years.
Where do you see the drug fitting in in the treatment paradigm, just given the existing assets out there?
Yeah, so again, the existing assets really ushering in a new standard of care for SMA back when Biogen had this incredible approval for Spinraza and then launched in 2017, followed then by Novartis and Zolgensma, and then followed by Roche, Genentech, and Evrysdi. What they have really represented is an opportunity for patients for the first time to really sort of get to the underlying cause or the root cause of the disease by having these SMN-targeted therapies to preserve the motor neuron. What we have seen over these 10 years is, as highly innovative as these therapies are, patients really need more.
In fact, what we've seen in some of the long-term data is that over time, patients will revert, and we saw this in some of those registration trials where you followed the patients for a long period of time, and then even our phase III SAPPHIRE trial, that despite an initial uptick in motor function, patients may peak, plateau, and then revert to the progressive form of SMA where you're losing motor function year on year. Given that as a backdrop, what we have seen in our phase III trial is that we are able to reverse that trend, where there is a move from loss of motor function to a gain of motor function, where we saw a threefold, nearly a threefold increase in a Hammersmith improvement of three points or more.
There can be a dramatic effect by being able to have the first ever muscle-directed, muscle-targeted therapy. When we think about where we might see the use, they're certainly late. That is, patients that have received those SMN-targeted therapies that have started to lose motor function again. We've also seen a lot of data where we are dosed early, just after the SMN-targeted therapy has been administered, and what you see is some dramatic effects in treatment and long durability of effect. We have reported out from our phase II trial now, patients out four years, and they don't give up that typical reduction that you once again see in motor function. We do not see that in our long-term data. We think there's a wide range of patients that will be able to benefit from apitegromab treatment.
What about combinatorial therapy? How do you think about that?
It's a great question. We think, as I said, there's a new standard of care. It is these SMN-targeted therapies. They've gotten us so far. Akshay and I have been even talking about the experience in other rare diseases where two therapies can really make a difference for patients. ATTR is one of those examples today, as we're seeing with Tafamidis and Amvuttra. I think as it relates to SMA, first and foremost, nearly a fifth of patients already are receiving more than one SMN-targeted therapy, either sequentially or together. We think that underscores a lot that patients and families are looking for more. The medical community wants those patients to get more, and the payers are actually supporting patients in that ambition to get a better outcome.
Now you bring a completely new mechanism of action in with the robustness of our phase II and phase III clinical program, and we think there'll be a strong underpinning for apitegromab to really be the new standard of care for all of the patients, 35,000 worldwide that have been receiving SMN-targeted therapies.
How much education do you think is required here on the disease at this point, recognizing there are three therapies out there?
It's a great question, and one that is rooted in Selvine's great knowledge of our history, Vikas, back at Alexion, where whether or not it was PNH or AHUS, these were diseases the medical community was not even really aware of. We invested quite a bit of time in disease awareness and even diagnostic initiatives, like how do you uncover these patients that are living with a rare disease, but you don't know that they have them. In this case, SMA, as you know, is well recognized. These patients are under the care of leading key opinion leaders, large treatment centers, and so it is a disease where a lot of and very strong patient advocacy groups. It's a disease that is well recognized. There may not be that same level of intensity as it relates to disease awareness and diagnostics.
On the other hand, we're still learning about, sort of because we're in these first 10 years of this new standard of care, still learning about now the new natural history of patients and what happens to them on one or more of these SMN-targeted therapies. Now we're launching. This is where I think the disease awareness and therapeutic education is required. What happens with the first-in-class, best-in-class muscle-directed therapy of apitegromab for these patients initially and then over time? I think that that will be an important element of our educational initiatives.
Is there anything you want to touch on before we move on to the other asset with regard to ex-U.S. strategy versus U.S. strategy commercially?
Yeah, yeah. As you know, Selvine, we're under review with the FDA with a PDUFA of September 22. This will follow the form of our prior experience where the initial launch of many country launches and the most substantial launch will happen in the United States later this year. We are also under review with the European Medicines Agency. We would expect that timeline to take us into the middle part of next year. Germany is typically going to be the first country of Europe that we would launch into. We are also being thoughtful about Asia Pacific, Latin America.
As you note, with 35,000 patients having received at least one SMN-targeted therapy in 50-100 countries around the world, we'll just be very thoughtful and deliberate about our global expansion plans, but in a capital-efficient way, so we do not really ding ourselves from an SG&A perspective. We feel like we have a lot of experience in how to do this. We're excited, just as I closed the conversation about apitegromab and SMA. We're excited about the opportunity in front of us. We have strong conviction for ourselves to make a meaningful difference for patients. We really want to leave no patient behind. The 35,000 that reside worldwide that have received these SMN-targeted therapies deserve the benefit of apitegromab, and we will not rest until we reach those patients.
Maybe we'll pivot over to the obesity program here. You plan to share phase II data this month from that program. Can you discuss expectations for the data and where you intend to present it?
It's a great question. It's something that is, I felt like coming in as CEO, I thought there might have been a disproportionate focus on this dataset, for good reason, by the way. That is, there's a lot of excitement about the very large and evolving landscape with GLP-1s, GIPs, and now something that Akshay and I have been spending a lot of time with management about when we were on the board, which is a third of weight loss is from tissue that you actually want to preserve, which is your muscle. As the world leaders in myostatin biology, what role can we play in helping patients with cardiometabolic disorders and obesity preserve lean mass? That's been on our mind for quite some time. You're right, Selvine.
Later this month, we'll have a look at our EMBRACE trial, which, as a reminder, is a 100-patient phase II exploratory study, which looks at apitegromab. This will be one and done for apitegromab in the cardiometabolic obesity setting. We wanted to see what role that we could play on patients who were newly administered tirzepatide, and they were randomized to receive tirzepatide alone or tirzepatide along with apitegromab. We will have a look at 24-week data, and we will look at the primary endpoint, which is the preservation of lean mass. That we feel like is probably the most important metric. Then secondarily, because of the large patient population, one is only going to accept an extremely clean safety profile in these patients. We will have a look at safety.
So far, apitegromab and our platform in general has panned out to be an extremely safe way of inhibiting myostatin. I think given the data last week, it's very important, and one needs to be mindful of that. Now, what I want to recognize is that just like we saw very encouraging results from Regeneron last week, how much can we really learn from 24-26 week data? I think what we'll learn is how much muscle mass can we preserve? What is the clinically meaningful outcome that one might find with that? I think we need more patients and more time. The muscle is an important metabolic organ in the body, and I think that you could have meaningful differences over time in patients, let's just say from a hemoglobin A1C perspective. We know that older patients lose muscle mass naturally year on year.
The last thing you're going to want to have is patients losing a third of their weight from lean mass. You would think over time there could be some benefits from a physical function perspective. Lastly, one thing that I would not turn my back on is the aesthetics of losing muscle. We all know, folks who are on GLPs, that there are remarkable benefits, but there can also be some aesthetic differences, and preserving muscle may be very helpful in that also. I think that will take quite a bit of time to see, and I think our Embrace trial is limited in terms of what we will see.
We look forward to having a look at them for the first time and sharing them with the community, probably by a press release, given the urgency of folks wanting to know what that data looks like later this month.
Recognizing Regeneron presented data, as you noted, what do you view as the bar for success here, but also what do you see as the regulatory pathway? Because it does seem right now that one needs to show weight loss in addition to benefit on the muscle wasting side.
Yeah, I mean, we do think the FDA will have an evolving view as more is known. For sure, I think the opaqueness of a long-term clinical development and regulatory strategy is what also gives me pause that there may be a massive role Scholar Rock could play in this space. Is it Scholar Rock themselves? Is this the best use of our time and our money when we're building what we believe is the world's leading rare, severe, debilitating neuromuscular capability, starting with SMA and then thinking about other neuromuscular disorders? That feels like, for us, sticking to our knitting and being very thoughtful of building a high-value company, the best use of our time and our money and our assets. Let's come back to the Regeneron data. I think what we saw is, I think at least numerically, meaningful preservation of lean mass.
I think it underscored a few things that we've been saying at Scholar Rock for a long period of time. One is obviously the problem. What we saw in the semaglutide patients is a third of their weight loss was indeed due to lean mass loss. That's not what patients want to lose. The question you raise is a good one. When you're preserving 50% of lean mass in the myostatin-only arms and then upwards to 80% of lean mass preservation when you actually combined it with Akshay Vaishnaw, that seems like an important numerical number. Is the FDA going to want overall weight loss? Is this about quality of weight loss? Is it about quantity of weight loss? Is it some combination of those things? Do those endpoints, what do they look like? Is it a hemoglobin A1C endpoint? Is it a composite endpoint?
I think we just don't know for now. I think it will take time. It will take money because I think these are longer trials with a lot of patients. I do believe there's a role to play, but I don't know if that's the best use of our time and money to understand what role we can play. The last thing I will note is safety does matter. We did see that in the triplet arm, when one moved out to maybe more ability to preserve lean mass, there were some adverse events that just don't look like that profile would be fit for a large population of patients with cardiometabolic disorders.
That looks potentially active and driven, maybe more than myostatin.
Yes.
What else in your pipeline would you like to highlight?
Yeah, what I would note is, and Akshay has been spending a lot of time with the team, we did present some preclinical data recently at the MDA conference in Dallas in March. This was our own preclinical data in studying apitegromab with exon skipping technology in an animal model for DMD. Obviously, we want to be very thoughtful, like we were with SMA, the types of patients that might be the most appropriate to study, thinking about the types of corrector therapies that one might be using in, let's just say, the DMD space. And then what we might want to be looking at from either a biochemical, anatomic, or clinical outcome perspective in kind of thinking about, and by the way, this isn't just for DMD. This is just thinking about more broadly rare neuromuscular disorders. How do we think about each one of those?
How do we think about doing the right sort of analysis on whether or not a proof of concept study is a good investment of time and money? When we have a better feel for that, Akshay will be the first one to share it with the community about our efforts there. We are committed to, when we do believe there is a pipeline and a product strategy with apitegromab, and by the way, with SRK-439, which is absolutely not a high-potency, high-affinity subcutaneous myostatin inhibitor that is only allocated to the cardiometabolic setting. We actually think that can be very powerful in the rare, severe neuromuscular disease setting as well. Akshay will be updating the community later this year on our plans, not only in Duchenne Muscular Dystrophy, but more broadly thinking about other neuromuscular disorders for further investigation.
For apitegromab, if you're going into multiple indications and you have this pipeline and product dynamic, how do you price this drug?
Yeah, so Selvine has known me and us for a long time, and I know this won't be the first time she's heard this. The considerations for us when we think about establishing a price, which today in June of 2025 is probably too early to really comment on price, and we haven't made any pricing decisions, but at least to shed light on the considerations that we will be thinking about. First and foremost, the rarity of any disease, and in this case, SMA, which would be the only indication that we would be launching into as a first-in-class, best-in-class therapeutic. The rarity of SMA, the severity of SMA, despite the use of all known best standard of care treatments like these SMN targeted therapies.
I think what we've seen is the patients are reverting back to a progressive form of SMA despite the use of these products. We will look at the totality of our clinical data and the compelling clinical benefits that we can offer individual patients and a population of patients. Those three factors we will use in establishing a pricing decision. I do think we need to be thoughtful that over time, if we serve greater and greater numbers of patients because we are introducing years later new indications, I think we'll want to be thoughtful about what impact that might have on the pricing of apitegromab as well.
A final question for me. Where do you stand currently from a cash perspective on your balance sheet, and what does this runway look like in the context of these launches and program readouts?
The first thing we might have, you might have imagined when Vikas came in as our CFO, Selvine, is like, and we talked about this, is let's look at our current capital allocation. We think our investors have actually supported us. Some of our largest investors have been with us now for seven, eight years. The first thing we want to be mindful of is dilution if we do not really have an exact plan for every dollar that we are going to spend. The first thing that we did is we looked at things that are nice to-dos, not need to-dos, and maybe phased those investments over time.
Vikas, through his good work with Akshay, with Keith, with myself, and the rest of the management team, we were able to actually soften some of our investments that were expected by the prior management team in 2025, 2026. That is what really allowed us to be able to provide a runway into early 2027 versus the end of 2026. That was the first thing that we did. We have also looked at a number of different ways that we can continue to have access to working capital to fund these launches in the U.S. and beyond. First and foremost, we have $100 million on a debt facility that is still in front of us that we can pull down. That is something that we will be thinking about. We also know that we qualify for a rare disease priority review voucher.
Having a PRV, as you know, most recently they've been monetized somewhere around $150 million. There's also interest in us should we have one of those. We'll be thoughtful about that as well. There's just the overall operating performance as an organization. We'll also share later this month the Embrace data and what our plans are. I lean toward being thoughtful about investment into rare severe neuromuscular disorders as opposed to opening up a large-scale trial in cardiometabolic and obesity indications. Given all of that, we're in a very, very nice cash position where we don't really feel the need to come back to the market to issue equity. We'll continue to update you and the community on our cash balance and the use of our proceeds to fund our operations.
Great. Thank you so much, David.
Great to be with you again, Selvine. Thank you.
Take care.