Good afternoon. Thank you for joining us on the next session here at the 2024 Jefferies London Global Healthcare Conference. I know that I may stand between you and happy hour, but we have a packed room here to talk about Scholar Rock, and we are here with the CEO, Jay Backstrom. Jay, congrats. Seriously, congratulations on great results recently for your phase III apitegromab SMA results and tremendous work in the making, and I would love for you to just talk to the audience a bit about the results of this phase 3 SMA study, what it means for you, the timing of it, and what the opportunity could be, because once again, you're on the precipice of filing a new blockbuster drug.
Thank you. It's a pleasure to be here. Good afternoon, everyone. Mike, to your point, we've been in this journey to try to enhance care for those living with SMA for a number of years, starting with the proof of concept study with our lead program, apitegromab, which is highly selective, targeting myostatin. Myostatin regulates skeletal muscle. If you block it, you turn on the cellular machinery, you increase more muscle. Our proof of concept data suggested that we should improve function. For those with SMA, it's a neuromuscular disorder. Current available therapies are targeting the SMN protein, which is essential for the health of the motor neuron. With its deficiency, motor neuron dies, muscle atrophies, and weak. Current three approved therapies raise that protein level, but unfortunately, these children and young adults are still left with significant functional impairment.
Our strategy was to target the muscle and bring that on top of the standard of care to see if we can increase function. We had a very nice proof of concept data with Topaz, a very safe program. When we target myostatin, and this may come to follow on questions, and you knock that out, all that results in is more muscle and less fat. There's no additional biology that's perturbed by knocking out myostatin. So, it's a very clean target. It lends itself to chronic therapy. And our data from our phase III study, we designed Sapphire, which was the name of the trial, to study on top of either isdiplam or nusinersen as the background standard of care therapy, randomized to placebo or apitegromab. We did study two doses in that trial, but against apitegromab.
We used the gold standard measure of Hammersmith, which is a validated functional scale to assess for a functional improvement. Then we ran that study for a 52-week period of time. What was remarkable about our data is for the first time in any randomized controlled clinical trial studying myostatin, we showed functional improvement. I mean, of all the studies that took place over the last 20, 30 years, we're the first. What's important to that is when we looked at our data and what has been very clear with SMA, despite the innovation with the SMN therapies, because they really have changed practice, this is an inherently progressive disease.
And so, what we showed in our trial is when we add apitegromab to the best of care, at the end of that 52-week period, the standard of care lost function and apitegromab patients gained function, suggesting that we can change the arc of the trajectory of this disease. So, that was really striking. We've seen this data from the nusinersen long-term follow-up data. We really look like we can meaningfully change and really enhance. And then on top of that, we showed that there were three times more patients getting even greater benefit or three-point increase, which is substantial. So, we had clear win, very consistent data. Safety profile has really been very, very, very clean. And it really looks like we're setting the stage for becoming a new standard of care with those living with SMA.
So, you showed a statistically significant, clinically meaningful 1.8-point improvement in function. We'll get to that, but a clinically meaningful improvement in function. The Apitegromab patients went up in function. The control arm is declining. And so, you could be pausing, improving, but pausing and certainly improving these patients' life. And you are on the precipice of filing. Tell us about that and what are the timelines, because I think you could be a commercial drug company next year.
Yeah, it was our goal when we ran the study to be able to complete enrollment a year ago and report out these data, and we were planning for success. We had pretty good feel for it. Of course, you're never successful until you don't know for sure until you turn over the card, so we've been preparing for the regulatory applications over the past year, so we are on track. We're finishing the final pieces to that, and we've announced publicly that we're on plan to get in Q1 . We'll submit the application in the U.S., and in the same quarter, we'll submit to Europe in the MAA, so the BLA and MAA going in Q1.
Okay. And then analyst estimates, but I think you wouldn't totally disagree. If you do get a Priority Review, you should have approval by the end of the year.
Yeah, very much so. We're going to take advantage of the expedited regulatory path. We'll request Priority Review in the U.S. And under that review, we would be available on these timelines by the end of the year. Equally, we have PRIME designation in Europe. The innovation and the need was recognized by the European Medicines Agency. We have PRIME designation. And that affords us an accelerated assessment in Europe. We're going to apply for both of those expedited or accelerated pathways.
Now, since it's a financial audience, we've been trying to figure out where the sales of this drug could be. You could give me some patient numbers. You could give me your estimates. But people look at the current SMN corrector drugs since these patients are out there, they're identified, they're under care, they're getting drugs, the fundamental underlying drug, the SMN corrector. And I think Spinraza is doing about $2 billion or so, $1.8 billion. And Evrysdi is doing $1 billion something and going to $2 billion. So, that's about $4 billion across the world. How would your drug fit on that? Would most people get this drug? So, maybe your drug could be somewhere in that range. Is this a $1 billion drug, $2 billion drug? What are you thinking?
Yeah, so I agree with your assessment of the current market size. Between all therapies, it's about $4-$4.5 billion, and I think as we think about how this would be fit into practice and then in turn how that would generate sort of the revenues we're anticipating, we do expect to have a broad label that would be for the treatment of pediatric and adult, with the exception of maybe the under two we haven't studied. So, a broad label, and as we look at the data that we've generated, we anticipate that we should become part of that treatment paradigm in the majority of those patients already on treatment, so our estimates of the $4.5 billion market size, we consider that this is a $1 billion plus opportunity, to be honest.
I think as we generate the value and we understand the treatment paradigm, we've been socializing this with not only our experts that helped us get to this place, but other physicians. And as they see the safety is extraordinarily clean. So, from a risk perspective, this really lends itself to chronic care. The efficacy for those in need is obvious. To your point, it was statistically significant, but absolutely clinically meaningful. And we're seeing this in a way that if we put this on to the patients early in their journey, we could potentially shape and bend this curve to their advantage. And that additional benefit on top of standard of care, where there's such room for improvement, I think is just enormous opportunity for us to improve outcomes, but I think also then to create a revenue opportunity for us that is substantial.
So, this was a huge win for, I think, for the community, but certainly for us as a company.
So, the class of current therapies, which you would be adding on top of and showed statistically significant, clinically meaningful improvements on top of, I think that those drugs are around $500,000 a year U.S. Is that kind of the range? And analyst estimates for pricing of just traditionally an antibody like yours are much lower. But is that kind of the range? And is that you don't disagree with that and where you are also adding on top of?
Yeah, so I think we've done some payer interaction leading up to this. That's been part of our background assessment. Now that we have data in hand, we're going to continue to refine that further. We're not in the position to kind of really indicate pricing at this juncture. But what I can say to you from our preliminary information is it's very clear that payers understand the value proposition of enhancing and improving lives for those with SMA. We've got a nice opportunity to do that. Currently, what we're seeing, which is interesting, is that there's a willingness for paying for gene therapy, for example. And then, unfortunately, if that is not effective, then the follow-on care for nusinersen or risdiplam as well. So, there's clear evidence that the payers are already understanding that there's a need and opportunity to then have more than one therapy at a time.
And I think from our perspective, again, if we continue to showcase data, we just showed the top line data, we'll have more to come. I mean, I really do think this is a practice-changing opportunity. We've engaged so heavily with the SMA community. They are ready for this care. They're anticipating it. They've been asking for additional therapies. We're really deeply involved in engagement and socializing. So, I think, Mike, I think we have a really good opportunity to turn this into a...
Well, look, it's a fairly tight-knit community. These patients are identified. They're known. They have been seeking out and getting therapy already. And obviously, they're ready for the next drug to add on to that, to add further benefit. Now, if I may add to the formula is that you're not the only one. There is another program from Biohaven specifically, who is here at the conference. And they are about to read out their phase III myostatin-related program. And their phase III is coming soon. Can you tell us about when that result comes? Are there differences in that? How should we look at those two programs? They are weekly sub-Q. You are monthly IV. But look, how do we compare those? Because there could be another agent. There's actually a couple more, but we'll start with just that one.
Yeah. So, just to start, I mean, we're anticipating, because we were in this space before we ran the trial, that there's others running. And so, our expectation on the commercial landscape took into consideration competition. And I think to your starting question, which I think is a really important one, Mike, is that the current three therapies are $4.5 billion together, each generating $1 billion plus revenue. So, there's clear evidence that with choice, that there's room for more than a single treatment.
Speaking about that, right, so there's one that's basically an injection through spinal tap. One is an oral. One is gene therapy. They're all different things. And yet, each one of them are blockbuster products.
Yes, without question. So, we're anticipating, even in the space of competition, the numbers that I were quoting, I think, considers that there's more than one of us in this space. So, I think that's the first thing. I think secondly, and again, I think the beauty of Scholar Rock, for those that don't understand us fully, we were founded on the understanding of how to very selectively target the growth factors as part of the TGF-beta family of growth factors, which is really important. The biology is complicated, and the field is littered with efforts that are not so selective because of toxicities. So, I say that to you because we have an elegant solution to blocking myostatin. It only hits myostatin. The profile is very clean. The other approach is the approach that the competitor is not as clean.
It doesn't hit it as early in the course. And so, there's some different mechanistically. But, you know, at the end of the day, I think if, in fact, it's successful, I think commercially we're in a good place. But as I think about our profile, we've got long-standing safety data, very clean. Monthly infusion, once a month dosing, I think, is an advantage. And in fact, we're really working deeply with the community to be able to have home infusion where it makes sense to make this as convenient as possible for patients. And I think against our efficacy, what we are hearing, the community wants to gain function, maintain function, and they want to be able to fit this in to keep doing their life, living it as fully as they can. I think our efficacy data will speak for itself. We'll see.
It's going to be hard to do cross-trial comparisons. We're not doing a head-to-head comparison. But I think our profile, I really like our profile. And we're often running to really bring this to as many patients as we can.
First of all, they presented yesterday. They said that they're still analyzing or they're just taking time to clean it all and get it together. So, it's coming, but they don't view it as late. I know some investors thought that. But they are working through that. And they also are going to do a subgroup of looking at just the non-ambulatory, which is 70%. So, they will take a look at that and try to also see if that group works. So, there's a bunch of different things they're working on there. I did want to ask, because the endpoint is different, when people look at this, just to clarify that you think it's not one for one because it's a different endpoint. So, you want to clarify that?
Yeah, very clear. I mean, there are two validated scales, so to be clear. And the one that's being incorporated into the Biohaven study was used for the Risdiplam approval. So, MFM-32 is a validated measure. We used Hammersmith. Hammersmith is also validated, but it was designed specifically for SMA. It's an SMA tool that has been validated, used by Nusinersen for their approval. The differences are it's a three-point scale for the Hammersmith, a four-point scale for motor function measures. And so, if you look at that, it's a little bit more sensitive maybe on the MFM-32, which means there might be more noise in the system. We have a higher bar to clear. The best way to think about how you could compare those two scales probably comes from recent notes that you might want to take a look at.
But I think Mike is very thoughtful of trying to understand this space. Within the Risdiplam initial approval data, they studied MFM-32 as their primary measure, their primary endpoint. But they also included Hammersmith as a secondary endpoint. So, within the same trial, you have some idea of how these scales compare. And to take a look at it, we had a 1.8 change in our mean delta over time. To be comparable in MFM-32, you probably need a 4.8, just under five-point difference. So, just think about those scales.
Using the same scale that Roche reported on.
Yes.
They showed both, and they did both. And if you take a look at that ratio, applying that ratio to yours, four or five points.
Right. But to be clear, that's doing cross-trial comparison. But if you're trying to get some understanding of how those tools compare, that's probably a reasonable reference to look at.
This is a different endpoint.
Right.
Maybe just shifting gears, obviously, you are looking at, might I have to say, obesity. That is important. That is extremely relevant because of the $100 billion class that is expected over the next 10 years. You could also here add the anti-myostatin approach to significantly benefit obesity patients. Can you talk briefly about it and then describe the phase II study you're running? Because data will be coming mid-year.
Yeah. So, Scholar Rock has been deep into myostatin and muscle biology almost from its inception. So, the idea of going into cardiometabolic is not a new one for us. We'd consider this maybe in 2019. But you can imagine companies feeling where to deploy capital going after SMA, a company our size was the right answer. However, in the last two years, we've continued to invest and understand that from a research perspective. And so, we believe we have an elegant solution to preserving lean muscle. Our view of this is that it's really that sustainable, healthy weight loss management, given the role that muscle plays in metabolism, basal metabolic rate, glucose uptake, insulin metabolism, insulin sensitivity. So, it's a clear need, it seems. And there's many in this field now. I think what I would go back to is we started about our selectivity.
If you look at all of those in the space, we only hit myostatin. I think we have a differentiated approach to safety and tolerability, and I think we'll have equal efficacy. We've shown that in non-clinical data, so it's a good place for us to be in the phase II, well, we took full advantage of. We have two programs for those that are kind of getting familiar with us. The Apitegromab targeting myostatin, as you know, we've talked about in SMA. Because it's a clinical program, we opened up another IND to do a proof of concept study in combination with either tirzepatide or semaglutide to look on Apitegromab added to that placebo, so randomized phase II controlled proof of concept data to demonstrate at week 24, if by DEXA scan, we can preserve lean mass, lean muscle mass. That's kind of the main proof of concept idea.
Because our entry into this space is we think we could add, enhance, if you will, the profile of these highly effective weight loss drugs. So, that's program one. We'll read that out in Q2, and I'll give a bit more of what to expect from that. Simultaneously, we have another separate program. We have a family portfolio of anti-myostatin ones called SRK-439. This was geared and designed for cardiometabolic. It's its own IP, same target, but enables us to go into a low volume sub-Q right out of the gate. That's working toward IND mid-year. So, Apitegromab will stop, and 439 will open up.
Is that 439 a second-generation, highly potent, remind me, like 20-fold more potent to the epitope?
Yeah, it has higher affinity for the target. And so, it really allows us to be 10-fold at the very least. And we've shown higher potency compared to a bimagrumab equivalent that I didn't induce more.
Right. So that you can put this into a sub-Q, which is particularly convenient in the space.
Absolutely.
So, to clarify, A, what are you looking for in the results? I think you were going to talk about that coming in Q2. Thank you. Not mid-year, but Q2. What are you looking for when added on to GLP-1 versus GLP-1 alone? Are you looking for additional weight loss? Are you looking for the GLP-1 arm to predictably lose lean muscle? And your arm shows a statistically significant improvement in retaining lean muscle. What are you looking for?
Yeah. So, the primary endpoint is looking at, can we, the primary question is, can we preserve lean muscle mass in the setting of these highly effective weight loss drugs? Not looking for additive weight loss, but looking for preservation of lean mass. And we'll do that by DEXA scans. And to your point, what we would expect to see in the weight loss curve and the lean mass curve for the standard of care arm, that we would change that. We would preserve and maintain that lean mass. So, that's what we're looking at week 24. We have a follow-on measure eight weeks after that where we stop therapy and then reassess the DEXA scan. Because, you know, if you follow the field, when you stop the GLP-1 drugs, you tend to get rebound of the weight, return of fat mass.
And we'll check to see if, in fact, we can attenuate that. We've shown that in our non-clinical models. So, that's the primary. The other thing that's really important, because a question we've been fielding a lot as we've got into this space, is what about safety and tolerability? We do not touch activin pathways at all. We don't have any perturbation of activin. And that has a host of potential toxicities. So, we'll also be able to demonstrate in this randomized data set the safety profile of the standard of care arm, plus or minus Apitegromab, to show that, in fact, the safety is not really adversely affected. At least that would be the stated goal.
Right. So, this is important because, look, it's first plausible you could see some additional weight loss. But importantly, the clinically meaningful part here is to prevent 30%, 40% of the weight loss is basically lean muscle.
Right.
And so, if you can prevent the decline in lean muscle, could be flattish, that would be important. Now, that appears to have been clearly de-risked by the fact that Lilly acquired Bimagrumab, i.e., Versanis. Versanis had run and shown statistically significant weight loss and lean muscle improvements versus a placebo. And they have gone on to run now multiple phase II studies. So, that would suggest that Lilly has seen something. However, those approaches may be safety questions because they hit activin. And in fact, that publication shows that. There are some questions. So, you believe that your program, particularly de-risked through the SMA study you just ran, should be pretty safe. And that's important in this market.
Yeah, without question. I mean, that was one of the reasons we took into consideration. Benefit risk really matters in almost any indication. You know, in oncology, you can tolerate more risk given the benefit. In this setting, you really have to, in our opinion, need to be very, very clean. We've seen that in the SMA program. We expect that because it's on target. All we're hitting is myostatin, blocking it. That's all you get is more muscle, less fat. So, we're advantaged by the biology. We're advantaged by our selectivity. And I think to your point, with Lilly's acquisition of Versanis, I think there are other major companies in this space that are going after the same. Roche is considering a strategy. Lean mass is a real issue. It's a real issue. How it manifests and how you show benefit, it's a real issue. First step for us is that.
We've built into it additional kind of exploratory endpoints within this proof of concept study where we look for ways to see how we affect the metabolic profile, for example, hemoglobin A1C and an influence on that. Because we think at the end of the day, muscle's role is so critical that we can maintain and sustain that we can really improve outcomes.
My last question in the last minute. Obviously, obesity and orphan diseases remains a big area of focus for large pharmaceutical companies. Like I may add, Lilly did an acquisition in the space. Regeneron is running stuff here. Roche has now begun this. So, big companies are playing in this space. And there's others that care about obesity and orphan diseases. To what extent are you planning to launch commercial a product in orphan? Would you partner it? Would you partner the obesity side? How would you strategically think about things? Because I wouldn't think you're going to do obesity by yourself.
No. So, to start, I think SMA is the perfect first commercial opportunity for our company. And so, we're intending to commercialize on our own in the U.S. and thoughtfully here in Europe with a staged approach given reimbursement and timing. We'll be very careful and thoughtful about that. I think we can do that as well as anybody because it's set up for we know the patients, we know the centers. That really lends itself. Obesity is a different story. We certainly need, I think, as we continue this journey, there's interest in this space. There's strategic interest in it. And I think long-term story for us to create real clear value. We can't do it all our own. We need strategic partners in certain areas. Cardiometabolic obesity would be one of those places where it would be very nice to have a strategic partner. We have clear interest.
But in the meantime, I think what has been very good is we've delivered on everything we said we're going to deliver on. And in fact, we're ahead of schedule on the EMBRAZE trial. So, we can run to IND. We can do this proof of concept. As we continue to get interest, we'll continue to keep the world advised. But I think for us as a commercial company, SMA is a very first good place for us to start.
Fantastic. Well, thank you very much. I appreciate it. Congrats on the recent data.
Yeah, thank you.
I look forward to the obesity results coming up.
Indeed. Thank you.
Thank you very much.