Pleasure to be here at the Goldman Sachs conference, sharing with you all the progress we've made as a company. These are my disclaimers. I will be making forward-looking statements. I suggest you refer to this slide as well as to our quarterly filings, as well as the annual filings for more detailed review of our risks. At Scholar Rock, we're a global leader in harnessing the life-changing potential of TGF-β biology, with a mission to try to create new possibilities for people living with serious diseases, starting with those living with spinal muscular atrophy. We're now on a journey toward commercialization, and from my remarks today, I'd like you to leave with three things in mind. When it comes to managing TGF-β biology, selectivity is the key.
It is the hallmark of our differentiated platform, that we are entering into two areas of large unmet need, with both SMA and obesity representing significant potential revenue opportunities. We're positioned for success. We have a very experienced team. We've been extraordinarily focused on driving against our strategy and goals, and over the next 12-24 months will be transformative for us as a company. What I'd like to share with you today is a review of our pipeline, how we're focusing on building out the muscle-targeted franchise, and a view of the road ahead. It starts with our approach, and it starts with selectivity, which is the key, we believe, to safely managing and harnessing TGF-β biology.
The traditional approaches to targeting the active or mature form has been littered with failures, unfortunately, because of the challenge to do it selectively and avoid the toxicities that can occur, given the structural similarities across the growth factors. A leading example is that of bleeding, which has occurred with many programs. The foundation of the company was the structural insight, as reflected on the slide with the figure in the middle, which is showing that the precursor form of the growth factors are encaged. They're not active. There are two proteolytic steps that cleave them to form the active growth factor. By understanding that structure, our scientists could then target very specifically with a monoclonal antibody, to target and block the growth factor without interfering with the other biology associated with hitting the other growth factors.
So it's the right target, and we're hitting that at the right time in the latent or precursor form before it's activated. So as a result, we lock it, block it, the growth factor never even engages with the receptor. We've taken that strategy, and we're applying it to myostatin. Myostatin is a very interesting target because its job is to regulate skeletal muscle, and when you block it, you end up with more muscle, less fat, but no other consequences. It's a very specific target. And as we've shown, and I'll talk more about it in our SMA program, by taking that strategy in SMA, we've been the first to demonstrate functional improvement by targeting myostatin, as we've seen in the SMA program, and we're getting exactly as expected, a very nice safety profile, given the specificity of our target. So selectivity really matters in this space.
We've taken that strategy, and we've built out a very robust pipeline of highly selective targets across very high-value therapeutic areas. Our lead program is blocking anti-myostatin, as we look at that in SMA. We also have two programs targeting TGF-β1. TGF-β1 plays a very significant role in creating an immuno suppressive environment, and we have a study we just shared at ASCO, where we're able to overcome resistance to checkpoint inhibitors, as well as it's a driver for fibrosis. So we have a very nice pipeline. But over the last 12-18 months, we've expanded that pipeline. I'm going to talk today about SRK-439. It's a newest entry of our anti-myostatin programs focused on cardiometabolic disease. And we also have another program that we're moving toward development candidate in the neuromuscular space. Considering upon success with apitegromab, we will be establishing ourselves as a neuromuscular franchise.
So we've built the pipeline, we've expanded the pipeline, but importantly, in our business, we've advanced the pipeline. It's critical that we drive further on the developmental milestones, and we've done that across our portfolio of programs. I'm going to talk today about SAPPHIRE, our phase III study, that's going to read out soon, the EMBRAZE protocol we've opened up in cardiometabolic disease, and we've done that across our portfolio. So built it, expanded it, and advanced it. But we focused over the last 12 months on our anti-myostatin program. I believe we have the industry-leading approach, very established science around how we target myostatin, and we have two distinct programs. Apitegromab, as we're driving forward in SMA, clear unmet need, which I'll share with you later in the presentation. The current market size is $4.5 billion.
We believe there's significant opportunity for us to create value as we go into this area, and we believe, and I'll talk further about it, that this is the right opportunity for us to commercialize on our own. At the same time, we're now moving SRK-439 forward. We also believe that we have a very nice opportunity to enhance the profile of the current GLP-1 receptor agonist, the weight loss programs, as we can restore and preserve lean muscle and create a healthier weight loss management. We're driving that forward to clinic. As you know, that's a market size at $20 billion. It seems to change by the day, estimated to be $100 billion by 2030. So obviously, significant revenue opportunities there. But given the size, scale, and scope of that program, this is clearly something we look for with a partner to help us advance.
But we certainly can drive to value inflection points, such as proof of concept, which we're doing. So our view of our pipeline is where it makes sense for us, we commercialize on our own, and otherwise, we look for strategic partnerships. And what that's bringing us to today is we've got the powerful building blocks for a scientific platform that I believe is world-class, an experienced team. We're established markets of unmet need. We have a global, global rights across our portfolio, so good IP protection. And we're coming on some very significant inflection points for us with a phase III readout, a proof of concept in the cardiometabolic space, and that positions us to move forward to potentially become a commercial company. So the building blocks that could set the stage for transformative period of time for our company over the next 18 months.
That's my introduction to the company. Now let me focus on our lead program in spinal muscular atrophy. To start, just a brief review of spinal muscular atrophy. This is a neuromuscular disorder. The primary defect in spinal muscular atrophy is associated with the motor neuron. It's a heritable disease. There's a deficiency in a protein that's essential for the motor neuron's health, the SMN protein. And in the absence of that protein, the motor neurons degenerate, and that degeneration leads to muscle atrophy and ultimately weakness and potentially paralysis. So it's a problem initially, fundamentally within the motor neuron. The current available therapies all target the SMN protein in various fashions, and they have been meaningfully transformative for these patients with or those living with SMA, but they don't target the muscle itself.
What's important to understand is the muscle is healthy, with the exception of the motor neuron degeneration results in atrophy. So if you can preserve the motor neuron, it leaves significant opportunity to target the muscle to further improve function. And so what kind of functional improvement has been associated with nusinersen and risdiplam? And what the graph I'm displaying shows, these are from the data from the CHERISH and SHINE study, and also data from the risdiplam programs in their initial studies. And what it's representing is a validated functional score called the Hammersmith score. It measures function. It's a 66-point scale, and it measures the ability of children to roll over, sit, hold your head, raise their hand, stand, and walk. So it's a variety of functional measures. It's been validated and was designed for SMA.
What's shown on the left, which are the nusinersen data, as you can see, upon initiation of nusinersen, over that gray shaded area, it's about a 12-month period, you see a nice increase, a four point gain, which is meaningful. This was the basis for nusinersen's approval. But what you see is once you get into 12-15 months, that increase stops, there's a plateau effect, and you see no further increase, which is really important to understand. But definitely see functional improvement with nusinersen. Similarly, the graph on the right is risdiplam, and it also shows an increase, although the order of magnitude is about 1.5-2 points. And similarly, over the course of time, no further increase, and if anything, a bit of decline on risdiplam. So you get initial functional gain, but a plateau phase for these therapies.
What does that look like against the Hammersmith scale? I said it's a 66-point scale, and you can see is what's shaded here is there's a lot of room to grow to help these children get to full function. So while meaningful and important, it's not enough. If we take a look and we listen to those living with SMA, what they describe is that they want to have more function. They want to preserve the function that they already have achieved, because this is inherently a progressive disease. So they don't want to lose their function, and they want to be able to do more things, as well as reduce fatigue. Fatigue is a fundamental issue considering the limited muscle mass. In fact, many patients have to plan their day accordingly because they don't have the energy to make it through all their activities.
So, a lot of room unmet need remaining. That sets the stage for a muscle-directed therapy. Scholar Rock was a pioneer in introducing myostatin, blocking myostatin in SMA. Again, myostatin is an excellent target. It regulates skeletal muscle. When you block it, it turns on the cellular machinery. Muscle hypertrophy follows, which results in increased function and strength. So this is like a perfect indication for an anti-myostatin program. We're positioned for success with our approach with apitegromab. As I said, this is the right target to add and enhance in this neuromuscular disorder, targeting the muscle. We have a proof of concept study with TOPAZ that informed our phase III trial for SAPPHIRE, and we have a safety profile that's unparalleled. We, and I'll talk more about that. We have over four years of experience now with a very, very safe program.
So what did we see in TOPAZ? Well, recall, I just shared the data on the Hammersmith scale and score with the four point increase that we saw with nusinersen. And on TOPAZ, all patients that came into the study were on the background of nusinersen, so they were receiving this. And this is an additional four point increase on top of what was achieved with nusinersen. And what's important to understand is that all those patients that came into the study, having been on the background of nusinersen, on average, were receiving it for two years, well into that plateau phase of the treatment. And so what we're seeing is this incremental additional benefit for those on top of nusinersen. That's the scale shown on the left. The scale on the right is another validated measure. It's the Revised Upper Limb Module. It measures upper extremity strength.
In the data that we're sharing here, these are for children that are either wheelchair-bound or can walk with some assistance, but not ambulate freely. So you can imagine the upper extremity strength would really be helpful for maintaining mobility and independence, and equally, you see a nice increase in the Revised Upper Limb Module. Very consistent observation in two validated scales. Importantly, we also included patient-reported outcome measures that caregivers described how much more activity their children could do. The scale on the top is an activity of daily living scale, and you can see that increases. The scale on the bottom is the level of fatigue reported, and that decreases. If we're targeting muscle, we're increasing it, we're increasing strength, you would expect more function, more activities, and less fatigue.
Again, all of the areas that those living with SMA are saying they would like and need for additional treatments. They're very much aligned with the unmet needs. And then safety. You know, my phrase, this is safety by design. We're hitting the right target, myostatin. That's if you block it, all you get is increased muscle, and we're hitting it at the right time. And as a result, we have over 90% of patients that were on the TOPAZ program still remaining on treatment. No treatment-related serious adverse events or hypersensitivity reactions, extraordinarily well-tolerated. So this is a reflection of the safety with such long-term follow-up, but also of the perceived benefit that individuals are getting staying on the program. We took that learning from TOPAZ. We took the best of what TOPAZ could show us, and we built that into a phase III trial.
In my experience with clinical development, that you're advantaged by having a proof of concept for phase III program, maintain high fidelity to the elements that you believe were successful in phase II. From that, we selected the population that had the greatest treatment effect. That was the non-ambulatory patients that I described earlier. We maintained a primary endpoint of the Hammersmith. We have good experience with that. It's a validated tool. We selected patients between two and 21, but focused on the two to 12. 12-month duration, we saw a nice increase over that 12 period of time, and we found that the 20 mg dose was the dose to take forward. And so with that, we have completed, and we're now nearing the end of this study. The SAPPHIRE trial design was a randomized, double-blind trial focused on patients on the background of nusinersen or risdiplam.
We've discussed this protocol both with the FDA and the European Medicines Agency, and so upon success, this will be the basis for our registration. Randomized study, primary endpoint, Hammersmith, very good secondary endpoints of that Revised Upper Limb Module, and again, we'll look for safety and efficacy as we report out these data. And the goals are very clear because they're the goals that we know we need for regulatory approval, but importantly, they're the goals that the patient community were really asking for. Functional improvements, the PRO-related instruments of how they're doing, as well as safety and tolerability. So we've taken that program from initiating TOPAZ, following patients all the way now into four years. We're coming up on the hallmark of reading out in Q4 of this year for the SAPPHIRE trial, and we're continuing to follow patients long term in the ONYX protocol.
All the SAPPHIRE patients are rolling into that, and we'll continue to follow those patients to give us that long-term safety and efficacy. Very important, not only for our ability to manage the questions coming from health authorities, but also for payer interaction. And so where are we now? We're really, we're on the threshold. Our team is working to get the data locked and clean and report out in Q4. We're already preparing the BLA. We're planning for success, and upon success, we'll go forth with a regulatory application. But in addition, we're not done with SAPPHIRE. We're also gonna open up a study next year for those under the age of two. Very important, I believe, to get apitegromab as early in the treatment journey as we can, and that study is planned to initiate next year.
A lot of excitement on the R&D side, teams moving forward, and now we're poised. I started with our purpose, which we're trying. You know, you think about our business and why we're trying to do what we do, and I think the quote here from a young woman living with SMA is: "Muscle is everything. I want to live knowing I have the strength to take care of myself." That's what we're trying to bring to deliver this medicine, to really improve the lives and the quality of life for those living with SMA. This we believe is the absolute right indication for us to have our first commercial launch. There's clear unmet need. There's a concentrated and proactive care. There's centers of excellence. The patient community is absolutely engaged.
They're a pleasure to work with, just to watch their passion and how much they're committed to their community. And there's clear payer receptivity, given the fact that these children need additional care. So we feel very confident about how we are moving forward. Again, what we believe is the gold standard, validated measure, the Hammersmith, we built into our study. We've got long-term treatment experience already with those that were on the TOPAZ study, with safety and tolerability being demonstrated. And the way we run our trial, this should fit neatly into practice because it can be used on top of either nusinersen or risdiplam. And then finally, we have monthly dosing, as we think about convenience for those living with SMA. And as I mentioned earlier, this is a $4.5 billion market from the current existing therapies.
We believe we have the opportunity to generate over $1 billion in revenue with our program going forward in this area, where we believe we can make a significant difference. Three key elements for us on the commercial side: patient engagement; we've been doing that from the inception. We have absolutely great partnering with the SMA community. We're striving to have excellent patient experience. I'll talk a bit about that. Then our team is really focused on executing and delivering on our goals. With the patient engagement, we have had this ongoing, continued engagement, both with the U.S. and EU patient advocacy groups. In fact, we're working to amplify the patient voice. We just recently launched an unbranded campaign called Life Takes Muscle. It begins to showcase life of those living with SMA and the additional unmet need that's there. That's just initiated.
Seamless. Already discussing and getting ready to create the value that we need to optimize that treatment experience that would fit seamlessly into practice and then work to provide world-class customer support. As we go toward commercial, right now, we're building the foundation. 2025, we'll expand our commercial capabilities. We believe that our customer-facing footprint is efficient between 30 and 50 FTEs. We can do this extraordinarily well, and we're looking to expand geographically and launch in the US, thoughtfully in Europe, but we will look for either distributorships or partnerships outside of those regions. Our path to commercial success is the right market with the right medicine, and we believe we have the right plan to be successful. Chapter one on our anti-myostatin program on the road to becoming a commercial company.
Now moving into our program with SRK-439, focused on obesity and cardiometabolic disorders. I don't think I need to spend a lot of time on this slide. For those that are following this space, obesity is recognized as a top global public health issue. You know, the reach and the effect is over 1 billion adults and 250 million. So there's no question that this is an area that needs to be addressed, considering the healthcare costs associated with it. What we've seen, and again, we should celebrate the innovation in our industry, with the current therapies and the GLP-1 receptor agonists and various forms of that, we're seeing very, very significant weight loss. I think those that couldn't achieve it before are now finally getting to their goals.
But we're also seeing attendant with that is a 25%-40% loss of lean muscle mass, which for healthy weight loss over time, doesn't seem sustainable. And I'll talk about the reasons for that, because when you take a look at the role that muscle plays, it is a significant metabolic organ. It contributes not just to our ability to function, move, and strength, but it, it's related to our basal metabolic rate, glucose uptake, insulin sensitivity. It plays a significant role in metabolism. And given the crosstalk between muscle and adipose, it also helps reduce visceral fat. So our fundamental belief is this is essential to preserve and not have this loss over time for healthy weight loss management. Our strategy around targeting this is back to the strategy and the foundation of the company. Benefit risk matters in any of the therapeutic areas that we're in.
You can tolerate more risk in areas like oncology. In the area of weight loss management, benefit-risk lower. We believe from our way we've created this, what we understand about myostatin, we have the best opportunity to have the best benefit-risk profile because we hit myostatin and only myostatin. And what's depicted here on the slide is that Apitegromab and SRK-439 focus on that precursor form. So we block that only. We don't have any activation, we don't engage with the receptor, and as a result, we don't have the unintended consequences. There's a variety of strategies. There's a lot of different approaches to try to maintain and preserve lean muscle mass, starting with the receptor at the bottom, which is the program bimagrumab, targeting the mature growth factors, which would be activin or myostatin.
There are a variety of ways to approach it, but the other approaches, because they're not exquisitely specific and exquisitely selective against myostatin, begin to introduce the biology associated with the other ligands, with the other growth factors. And what's shared here are what's been reported to date from the existing programs. Much of this is related to hitting activin. Activin plays a role in reproductive biology. There's embryo-fetal tox associated with it, but we're also seeing if you target activin specifically in the mature form, there's other unintended consequences, including bleeding and skin infections, et cetera. So activin is expressed on a variety of tissues. You start to block that, you're interfering with the biology of activin. These are gonna be on-target effects as activin plays a role in so many cellular processes, unlike hitting myostatin, which only regulates skeletal muscle. We believe that's a differentiated profile on safety.
SRK-439 is its own unique product. It has its own IP. It came out of our portfolio of programs for myostatin, exquisite selectivity, and the goal is for healthier weight loss management, and I'll show you at very low and effective doses. The figure on the left shows how we target it. Again, this is blocking the precursor form, so we don't allow it to activate. And what's depicted here is a graph showing affinity, and the green curve shows how we have a concentrated effect on hitting myostatin. But the other things that are shown here are GDF-11 and activin, which are overlapping, as I showed you on this previous slide. We have no effect whatsoever, so absolutely specific to myostatin. We don't interfere with any of the other growth factors.
What we've been able to demonstrate through our non-clinical models, these are diet-induced obesity models, well-established, been used across the industry. And what I'm gonna walk you through on the graph on the left is this is a percentage change of lean mass. So this is looking at muscle mass in these animals. And, you know, if you kind of just walk through the graphs, far left is control, you see no effect on lean mass. The green one that goes up, we're showing that we increase muscle mass by blocking it in this model, by giving SRK-439. So we have that, that effect. That's expected, consistent with all of our non-clinical data. The purple bar is semaglutide, semaglutide, and what you see is what's expected, a reduction in lean mass.
And then the other green bars are showing that we have a dose-dependent effect of reversing that. So clear evidence in our non-clinical models that we can reverse that lean muscle loss, and in addition, there's loss of fat, given the cross talk between muscle and fat. Further, as we've done additional experiments, recall I said that muscle plays a role in insulin sensitivity and glucose metabolism. What's displayed here, if you look under the treatment, is that we've had an additional lowering of glucose on top of semaglutide in this model. So we are further able to reduce glucose. So keep that in mind as we think about potential clinical benefit that's associated with this combination approach. And then finally, the question that we've received quite frequently is that I've pointed out that we have the, probably the cleanest profile because we're hitting the right target exquisitely, specifically.
But do you need to hit activin in order to have efficacy, or are you leaving efficacy, quote, unquote, "on the table?" And the reality is, we've taken a look at our non-clinical model again. We've done a head-to-head comparison study with an anti-ActRIIB antibody. It's a murine equivalent of the bimagrumab. And in this model, what you can see again is the expected reduction in semaglutide on the purple. But as you can see, at doses of 0.313, we have this reversal of that lean loss. We compare it to the same doses for the bimagrumab version, you see no effect, and the only effect that you see in this program is at the 20 mg/kg dose. That's the dose that's been published. What we're seeing is no difference in efficacy, but we're getting the efficacy at far lower doses.
We're clearly more potent, and that's by design. We designed 439 to be low volume, subcutaneous administration. We have greater potency than bimagrumab in this murine model. And with that, we're moving forward with what we believe as we continue to generate data from 439, is we have the potential best-in-class with our approach to targeting myostatin. So where has that taken us in our clinical program? Well, we've got a dual approach. What's reflected here on the graph is where we are with our apitegromab and SMA, and we're looking forward to the Q4 readout and then upon success, commercial launch. Because apitegromab is in clinic, we also took the opportunity to do a proof of concept study with apitegromab in the setting of use of tirzepatide or semaglutide to assess our ability to preserve lean muscle mass. We've opened that study.
I'll give you more detail on that. At the same time, we're driving SRK-439 to clinic. So the EMBRAZE was our proof of concept to demonstrate that our selective mechanism can preserve lean muscle mass. We're doing with apitegromab, not with the expectation of moving apitegromab forward in obesity, but to do it because we can then inform our program further with 439, but to also answer that question, can we do this and preserve lean muscle and to demonstrate safety? We shared the protocol and our design a few weeks ago at our investor event. We were planning to open this study in June. This time, we've exceeded that. We opened it up sooner. We're very delighted that that program is going.
In brief, it's a randomized study, hundred patient trial, randomized 50/50 to receive either apitegromab on the background of tirzepatide or semaglutide. It can be either. We're going to be agnostic to this, and that's compared to placebo on top of tirzepatide or semaglutide. It's a 24-week study. The primary endpoint is DEXA scan, which is the standard approach to assess lean mass, and we believe that this trial will demonstrate our ability to preserve lean muscle mass in the setting of standard of care therapy. We also have, at the end of the 24-week period, a withdrawal period where we're going to then do a reassessment to assess whether or not we can potentially attenuate the rebound effect that occurs when you withdraw these agents. So very excited about the trial. The program is underway quickly.
We also have some very nice exploratory endpoints that will be helping us inform the direction of our 439, such as looking at effect on hemoglobin A1c and some other functional measures. A lot of questions around the regulatory path. Combination therapy is a standard approach, well accepted by the FDA. The expectation is we need to be able to demonstrate additional benefit from the use of an anti-myostatin like SRK-439. The ideas around here, which we're going to generate further data on, is this potential effect on hemoglobin A1c, which is a well-established FDA endpoint, and or additional functional include in select patients to demonstrate that the benefit that they're achieving from maintaining lean mass. So in the end, we believe, again, we have the right target. Starts with the target, starts with how we hit the target.
Myostatin is expressed in muscle, so when we block that, we get the attendant effect of increased muscle mass. Our safety, from what we've seen in our SMA program, is unparalleled, and we anticipate the same with SRK-439. This will be opening up as we're planning right now out of the gate with a subQ formulation. Where does that take us as a company? Well, we've got a number of anticipated events coming up over the next several months. We recently showcased our immuno-oncology program at ASCO, where we demonstrated that we overcome resistance to a checkpoint inhibitor. We have another oral presentation coming up June 23rd at the American Diabetes Association meeting, where we'll showcase 439 in a non-clinical asset being featured at an oral presentation at ADA. The EMBRAZE study, I said we've opened up.
We're running that as quickly as we can, and that we anticipate will read out maybe around this time next year, earlier, depending on the accrual. And SAPPHIRE, which is our key milestone, is going to come up in Q4 this year. Upon success, we will be a commercial company in 2025. And then finally, as I mentioned, we're not done with apitegromab and SMA. We have plans to expand it further. We were very pleased that we've been endorsed by the EMA Pediatric Committee, through our under two study, and we have plans to do that in 2025. And so where are we?
Well, from what I believe is a world-class scientific platform, we have clearly the leading differentiated approach to targeting TGF-β biology within our platform, and we're on the, really on the cusp, if you will, or the threshold of becoming a world-class pharma company. Unparalleled selectivity. We have broad opportunities in our space. We're in high-value therapeutic areas, and we have a team that's seasoned, locked, and focused, really driving hard to execute. The phrase, "Patients are waiting," you know, we have such engagement with the community in the SMA, you can't help but be involved with that community and not want to work harder and move faster. We're on the threshold of doing that, and upon success, I can assure you that our commercial team is going to run with the passion that's appropriate for this, this community.
So with that, as we advance on our journey, I'll leave you with three things. Selectivity really matters in TGF-β biology. The history suggests if you're not selective, you're going to be left with toxicity. We manage that. We're in areas of high value. We're driving to achieve that. We're well-positioned for success, and we really are a very, very exciting time for the company. The next 12-24 months will be transformative. So with that, listen, thank you for your attention. It's been a pleasure to be here and share these thoughts with you this morning.