Welcome, everyone to the 42nd annual JP Morgan Healthcare Conference. My name is Tess Romero, and I'm one of the Senior Biotechnology analysts here at JP Morgan. Our next presenting company is Scholar Rock, and speaking on behalf of the company, we have CEO Jay Backstrom. Jay, over to you.
All right. Well, thank you, Tess. Good afternoon, everybody. It's a pleasure to be here representing Scholar Rock at this year's JP Morgan Healthcare Conference. I'm really pleased to have the opportunity to highlight the progress we've made since I joined the company a little over a year ago, and to outline the exciting year that we have ahead. I will be making forward-looking statements, so I'd suggest you refer to this slide for my disclaimers. You may also refer to the section entitled Risk Factors in our quarterly and annual reports. For those new to Scholar Rock, we are a global leader in harnessing the life-changing potential of TGF-β biology, and as a team, we're working tirelessly to fulfill our mission to create new possibilities for children like Christopher and Emily, who are living with SMA.
We're very fortunate to know Christopher and his family through their participation in the TOPAZ phase II clinical trial, and to witness their incredible commitment to making their children's lives better every day, a commitment that serves as both inspiration and motivation for all of us at Scholar Rock. We are building a fully integrated therapeutics company on the foundation of three pillars: a revolutionary scientific platform that has produced a robust pipeline of innovative products, a focus on transformative therapeutics, starting with our industry-leading anti-myostatin programs, and with an experienced and disciplined team dedicated to delivering on the promise of our pipeline. Over the past year, we have strengthened our team and have been laser-focused on execution. Scholar Rock has been a pioneer in bringing a differentiated approach to harnessing the therapeutic potential of TGF-β superfamily of growth factors.
Utilizing our structural insights and industry-leading antibody design, our research teams have designed a pipeline of fully human monoclonal antibodies that selectively hit the right target, the latent or precursor forms of the growth factors, as shown in the center of this slide, and at the right time, prior to the activation of the mature active growth factor. Blocking and preventing the activation of the mature growth factor has the potential to improve efficacy, and by selectively targeting the pro and latent forms, avoids off-target associated effects that have been present with targets such as hitting the receptor or the mature growth factor. We've made significant progress over the past year in advancing our growing pipeline and starting with our industry-leading latent myostatin programs.
In addition to our lead program of apitegromab in phase III for spinal muscular atrophy, we are expanding our anti-myostatin clinical portfolio into cardiometabolic disorders, starting with the phase II proof of concept study in obesity with apitegromab and advancing a novel anti-myostatin antibody, SRK-439, to IND. In addition, our latent TGF-β1 pipeline, we have completed enrollment in our phase Ib program for SRK-181 in immuno-oncology, where we demonstrated proof of mechanism and clinical proof of concept in combination with pembrolizumab in heavily treated patients who progressed on a prior checkpoint inhibitor, and we continue to move our latent TGF-β1 program in fibrosis closer to IND. Finally, our novel selective anti-RGMC antibody is also moving toward IND for iron-restricted anemia, a program for which we shared data at the most recent ASH.
So with that as introduction, I will focus the remaining portion of today's presentation on our anti-myostatin programs, starting with apitegromab and spinal muscular atrophy, which are also referred to as SMA. As a reminder, SMA is an inherited disease of the motor neuron caused by a mutation that leads to a deficiency in the SMN protein, a protein that is essential for the health and survival of the motor neuron. This protein deficiency leads to progressive motor neuron loss, which begins before birth, and which in turn leads to muscle atrophy and progressive muscle weakness. There are currently three approved therapies for SMA. All are directed at increasing the amount of SMN protein and work to slow further degeneration of the motor neurons, but none target the muscle directly and do not reverse the existing muscle atrophy.
So there's a potential to further improve function by directly addressing the muscle and a compelling scientific rationale for the role of apitegromab in this neuromuscular disorder. There's a broad spectrum of muscle weakness and functional impairment in SMA, where muscle weakness can lead to deterioration in mobility, swallowing, and breathing difficulty, and can cause debilitating fatigue. However, even in those who can walk without assistance, such as the young boy pictured here, challenges remain. Given the lack of strength and endurance, individuals often must choose between activities and find that even small tasks can be difficult to perform. SMA is a global disease that affects over 20,000 in the U.S. and Europe, and the market is expected to grow over the next 10 years, with more patients being screened and treated.
Currently, it's a $4 billion market, with each of the three approved therapies generating annual revenues in excess of $1 billion. We believe that the established market dynamics, a well-defined patient population, established treatment centers, and the outstanding patient advocacy organizations who have been champions for bringing new therapies to those living with SMA, all support our ability to enter this market as our first commercial opportunity. So as we enter 2024, we are on the threshold of a new treatment frontier for SMA, muscle-targeted therapies, an area where Scholar Rock has led the way. Despite the availability of the SMA therapies, substantial unmet need remains. The figure on the left displays the extended Hammersmith functional scores, which range from zero to 66, and the 3.9-point increase shown in dark blue that was achieved with nusinersen.
As can be seen, there is clear room for further improvement and a need for additional treatment options. Both patients and caregivers want the new therapies to be able to increase muscle strength, to be able to improve their activities of daily living, to maintain and preserve the existing functions that they've already gained, and to be able to go through the day with less fatigue. All should be achievable with a selective muscle-targeted therapy that can safely lead to gains in strength. Apitegromab, a highly selective, fully human monoclonal antibody targeting latent myostatin, offers significant potential to address these unmet needs. Myostatin, a negative regulator of muscle growth, is an ideal target for a muscle-directed therapy since blocking myostatin leads to an increase in muscle mass. Apitegromab specifically inhibits myostatin and has the potential to build muscle and strength to improve patient outcomes.
Again, Scholar Rock, who is at the forefront of evaluating the potential benefit of selectively blocking myostatin in SMA with our phase II TOPAZ study, evaluating apitegromab in patients on a background of nusinersen therapy. As demonstrated in TOPAZ, treatment with apitegromab demonstrated sustained functional improvement beyond that which was achieved with nusinersen alone and is the first and only muscle-targeted therapy to demonstrate clinical proof of concept in SMA. Displayed are the results at 36 months for the non-ambulatory patient groups aged two to 21 from TOPAZ, the same patient population that was included in the SAPPHIRE phase III study. As we reported at Cure SMA in June, treatment with apitegromab led to functional gains in both valid functional scales: the Hammersmith, reflected in the upper left, the Revised Upper Limb Module, or RULM, shown on the top right of the graph.
Importantly, these gains that were achieved at 12 months were sustained over, and/or improved over the three years of treatment. In addition, improvements were also noted in activities of daily living, and a reduction in fatigue is shown in two patient-reported outcomes. These improvements, seen at 36 months, align with the areas of importance for patients and caregivers from improving muscle function, all by blocking myostatin selectively. With respect to safety, overall, apitegromab has been well-tolerated, as reflected in over 90% of patients still on treatment now as we enter into four years of therapy. The safety profile is consistent with our approach of blocking myostatin, hitting the right target at the right time, since it avoids off-target effects that can occur with other approaches. To date, the most frequent reported adverse events were consistent with the underlying population.
It is noteworthy that there are no reports of treatment-related serious adverse events, no reports of hypersensitivity or infusion reactions, and no reports of positive anti-drug antibodies. So building on the success of TOPAZ, SAPPHIRE, our phase III randomized placebo-controlled registration study, was designed to incorporate the key learnings from TOPAZ, including the selection of the patient population, the non-ambulatory Type 2 and Type 3 groups, the age, where we range from two to 21, the endpoints, and the dose, all in order to optimize the probability for success. As we previously announced, we successfully completed enrollment of SAPPHIRE that included patients on either nusinersen or risdiplam. And in addition to the primary endpoint, which is the mean Hammersmith change from baseline at 12 months, the additional endpoints include the Revised Upper Limb Module, as well as WHO milestones and patient-reported outcome measures.
So as we enter 2024, we have an important and exciting opportunity ahead, as we are on the threshold of bringing a new class of treatment, muscle-targeted therapy, that has transformative potential to change the standard of care and to meaningfully impact people living with SMA. We look forward to reporting the top-line results for SAPPHIRE, expected Q4 this year, and to continue to gain long-term safety and efficacy from ONYX, the open-label long-term extension study. Moving forward, we are planning to expand to reach more patients living with SMA by scaling for our commercial launch in 2025, conducting additional clinical studies in those under the age of two, including those on gene therapy, and in the ambulatory population, as well as developing a subcutaneous formulation. So we'll be very busy, but also a very exciting time for Scholar Rock as we go forward into 2024.
Now, I'm pleased to provide an update on our cardiometabolic program. Probably need no reminder to indicate the significant public health impact that obesity has. It's now recognized as the top global health issue, representing a large market with growing numbers, and by the year 2030, it's estimated that obesity will affect over one billion adults and over 250 million children and adolescents. This is a costly chronic disease associated with more than $170 billion in excess costs annually in the United States alone, given the serious comorbidities that are associated with obesity, primarily heart disease and Type 2 diabetes.
The GLP-1 receptor agonists have been highly effective in reducing overall weight, but the weight loss strategy is associated and challenged by tolerability issues and lack of durability, but also importantly associated with a significant amount of lean muscle mass loss, ranging anywhere from 25%-40%. The goal of weight loss should ultimately to be sustainable loss, and we believe that maintaining lean muscle mass is essential for healthy and sustainable weight management. To illustrate that, the preservation of lean muscle has many benefits for overall health beyond maintaining strength, especially in the setting of associated comorbidities. Specifically, muscle is a metabolic organ and increases basal metabolic rate, it enhances glucose uptake, it enhances insulin sensitivity, and, given the crosstalk between adipose tissue and muscle, reduces visceral body fat, all important for healthy weight management.
Scholar Rock has had a long interest in the role that myostatin plays in cardiometabolic disorders. The figure illustrates our differentiated approach to selectively inhibiting the activation of myostatin and is worthy of taking a bit of time to review it, considering the number of different strategies that are now approaching targeting myostatin. As shown in the upper left, apitegromab and SRK-439 block the latent form of myostatin and prevent the activation of the mature growth factor. So by blocking, myostatin doesn't go to the active form, nor does it engage in the receptor, so there's no signaling. By selectively targeting the pro form of myostatin, we avoid inhibiting other growth factors, including GDF11 or Activin A, since both potentially have detrimental effects.
If you look at the effects that can be present or possibly present with GDF11, it can lead to skeletal and kidney formation defects and potential negative impacts on bone. Activin A clearly has an impact on reproductive biology. Strategies that target the receptor, the ACVR2B receptor, for example, blocking that, will affect the signaling pathways, not only for myostatin, but for GDF11, and Activin A as well, and by impeding those signaling pathways, are at risk for bringing additional potential toxicities that may not be necessary for the effect on myostatin alone. Again, by selectively blocking myostatin and only myostatin, which is the Scholar Rock strategy, we avoid interfering with the GDF11 and Activin A signaling, and this should lead to improved safety.
We believe that safety is paramount, especially in the setting of weight loss therapy, considering the history of drugs and weight loss that have been highly effective, but have been restricted because of toxicities and a negative, unfavorable benefit -risk. Approaches that target the receptors or the mature growth factors, including monoclonal antibody strategies or ligand traps, cannot achieve the same level of specificity as can be achieved by selectively targeting the pro and latent form of myostatin. We leveraged our extensive expertise in myostatin structure and biology to develop SRK-439, a molecule designed specifically for the patient population with cardiometabolic disorders. SRK-439 is a preclinical candidate in development with the potential to address the muscle loss associated with weight loss.
It selectively binds to the pro or latent form of myostatin and has other attractive properties, including high in vitro affinity for pro- and latent myostatin, and is optimized for subcutaneous formulation with the potential for a low dosing volume. All features which we believe are favorable going into a population of obesity and cardiometabolic disorders. We have been conducting preclinical studies in the cardiometabolic area for years and have utilized well-established diet-induced obesity mouse models, including with SRK-439. Shown in the graph on the left is the percent change in lean mass from baseline, and on the right, the % change in fat mass. Adding SRK-439 to semaglutide, which is shown in the mustard-colored graph on the left, has demonstrated dose-dependent increase and reversal of lean muscle mass associated with improvement in fat mass loss as well when we add SRK-439 to GLP-1 receptor agonist alone.
These results provide the scientific rationale and support the hypothesis that inhibition of myostatin in combination with a GLP-1 receptor agonist-driven weight loss may lead to the retention of lean muscle. So to summarize, considering our long-standing interest and expertise in the role that blocking myostatin can play in cardiometabolic disorders, we see an opportunity for safe, durable weight loss by adding a highly selective anti-myostatin to a GLP-1 receptor agonist to preserve lean muscle. Our preclinical studies provide strong rationale for the combination, and that we believe that our approach of hitting the right target, the pro and latent forms of myostatin, and hitting only myostatin, will avoid off-target effects, contribute to a favorable benefit risk profile, so critical in the setting of obesity and cardiometabolic disorders.
We are aggressively moving forward toward a rapid proof of concept in obesity with apitegromab in combination with a GLP-1 receptor agonist, while at the same time advancing our SRK-439 toward IND. Together with our lead program in SMA, we have several important milestones over the next 12 months, including data being presented for SRK-439 at the Keystone Conference in February, the start of our proof-of-concept study in obesity targeted for mid-year, and the readout of SAPPHIRE, expected in Q4. So in closing, it's an exciting time for Scholar Rock. We are at excellent progress and momentum in 2023 by completing the enrollment in SAPPHIRE. We expanded into the cardiometabolic disorders with our anti-myostatin programs, and we had a successful $98 million public offering, which extends our projected runway into the H2 of 2025.
Building on this success, as we go into 2024, we are focused on advancing our anti-myostatin cardiometabolic programs, as I just described. We are looking forward to delivering the top-line results for SAPPHIRE in Q4 and initiating key activities to build our commercial organization in preparation for potential 2025 apitegromab launch. So we have great momentum going into 2024, excellent catalysts and milestones coming forward in 2024, and overall, a potential transformational year for the company. Great time to be at Scholar Rock. Very exciting time for all of us. So thank you.
Thank you, Jay, for the presentation. So we are going to kick off a little Q&A session. Please just wave your hand if you do have a question and you'd like to ask it live. So, Jay, you talked a little bit about some, some of the key learnings from the phase II TOPAZ trial. How specifically in the patients with Type 2/3 non-ambulatory SMA, how does that inform what we might see in the pivotal SAPPHIRE study expected to read out in the Q4 here?
Yeah, good question, Tess. I mean, I think what I feel good about as we were designing SAPPHIRE is that we did have TOPAZ that could inform sort of how we designed it, as I mentioned, the patient population we look for. When we looked at the non-ambulatory group, what we saw overall was a, you know, a four-point increase and some range within that, which really gave us great confidence as we went into phase III, that we'd be able to design a study that we could show an effect that I think if we look at clinical meaningful impact, it's a three-point change, and so we thought we had a really nice opportunity to demonstrate that.
I think to add to that, though, is what I try to illustrate, and it's really clear as we talk more and more to the patient community, you know, the measures on these validated scales are really important, but even small gains in function matter so much to the community to really have significant impact on their lives. So I think anything in that range of one to three is really important. But the non-ambulatory group really showed us the greatest treatment effect size that we thought could really maximize our potential in a phase III study.
Okay. And as you think about the spectrum of endpoints that you're collecting in SAPPHIRE, we know the Hammersmith is your primary endpoint. How, w hat are you, or how well-powered are you to show that three-point endpoint? Or do you- would you agree that you are well-powered?
Yeah, as a phase III study, right, I think we want to be sufficiently powered to be able to demonstrate the effect, and I think we certainly feel very good about the powering assumptions under that three-point change.
Yeah
W ithout question. You know, what I also illustrated, and I think if you look at the TOPAZ data, and I really like the one slide that shows the scales, the Hammersmith, the Revised Upper Limb Module, and the PRO instruments. Really shows the consistency and robustness of results, again, giving us confidence that as we go forward into the SAPPHIRE study, we'll see similar effects.
Okay. And what endpoints are the most important when you speak with physicians?
Yeah, it's interesting, right? I think the Hammersmith has been clearly sort of the established, I would almost suggest the gold standard measure, considering its history. It was the registration endpoint for nusinersen. I think that really kind of matters. It has a range of activities that it measures. But the Revised Upper Limb Module, the more I looked at this, really is an interesting measure, particularly as we think about non-ambulatory patients, because it really is a measure of upper limb function. And if you think about the activities that one needs to do, potentially, if you're wheelchair-bound, it really is: Can I raise my cup? Can I comb my hair?
In fact, in the pictures that I showed of the patients kind of trying to explain sort of what it means to have the disease, the young woman that was illustrated in that graph, we actually had a video that we shared at the investor event that we held in the summer, and she was commenting on having to be able to raise her cup, right? So if you can strengthen that activity, that's a powerful scale as well. So I think, to me, when you look at it, it's the totality of the data. I think the Hammersmith, clear. I think the Revised Upper Limb Module is complementary, gives us different sense of activities that patients really think they need to be able to do to meaningfully live independent lives.
You know, I think a question that we've gotten for many a year is just how to think about the control arm. What are the key data sets that helped underpin how you're thinking about how the control arm will perform on the Hammersmith to achieve that treatment effect size that you're hoping to see?
Yeah, I think, you know, as you try to look at sort of how you assess the control arm. You know, you're left with basically what the published literature shares. There are some existing datasets you can look for. And I think as you know, what we've done, if we took a look, we've had the nusinersen data that we've shared, we've shown in our CHERISH and SHINE studies. You get a nice lift on these therapies, and then you get a plateau effect. And so we looked at that over time. It's really a function of how long patients are on treatment. But when you get to about 15 months of nusinersen, you're pretty much what gains you've achieved, you're probably unlikely to get more. And so we looked at that data to really kind of help inform.
Okay.
Right? So I think that's, you know, f rom talking with our experts, looking at the data, I think those are reasonable assumptions that you're gonna see flat, although it's an inherent progressive disease, and there is the potential for the control arm to actually lose points.
Okay. What has been the physician feedback around the safety profile of the drug?
Well, it's such a good question. So we held an event in June, and we were highlighting the features that we thought are really important for apitegromab. And Tom Crawford at the end chimed in and said, "You know, this is the cleanest safety profile I've ever seen," quote, unquote. Right? So that's a Tom Crawford quote. It's extraordinarily clean. And again, that's, I would argue, by design. I mean, the points I've been emphasizing on selectively targeting myostatin really should translate into the safety profile that we're seeing because if you knock out myostatin, you get increased muscle and less fat, and you don't get any other untoward safety effects. And so that's what we've done nicely. And so really, what we're seeing in the safety profile, as I mentioned, are things you would expect from children with viral infections or.
Yeah
S coliosis that follows the disease, but it really looks extraordinarily clean, and that, that resonates with the physicians working with the study.
Okay.
I think the retention rate we've seen in TOPAZ is a really good proof point for safety.
Mm-hmm.
and possibly efficacy as well. It's well over 90% into four years. These are patients that are not easy to move around and get to a center, and families are continuing to bring them in for treatment on a regular basis. That high retention rate speaks volumes for us.
You know, undoubtedly, there are risks associated with any clinical study. What do you see as the key risk or risks to SAPPHIRE? And, like, how do you mitigate those, and where have you been particularly focused as you think about your program and learning from programs that have preceded you?
Well, if one looks at sort of the top reasons for clinical studies to fail, which would be the risk that you're discussing, they kind of rank order: patient population with heterogeneity, such that you have an effect, but you dampen that effect because of different response rates, so heterogeneity can affect it. As I described TOPAZ, we selected a pretty homogeneous population because we were selecting that non-ambulatory group. So I think we controlled for that heterogeneity in our trial design. Not getting the dose right, and, you know, FDA is very big on sponsors getting doses right.
I think also has a risk. But we did a dose ranging. You know, we had 2 milligram, 20 milligram, saw a nice dose effect, so I think we controlled for the dose risk. Sometimes we do an endpoint in a proof-of-concept study, say, response rates, for example, in oncology, and then you go to survival or time to event endpoints.
Mm-hmm.
That effect doesn't change because you changed the endpoint. We didn't change the endpoint. We studied Hammersmith. We maintained Hammersmith in the phase III, so I think we controlled for that endpoint piece. So we controlled for another, a number of events. And then the other thing that you need to control for is if there are differences in potential subgroups you want to protect through stratification, and we stratified by nusinersen versus risdiplam. And what we saw in the TOPAZ, time to getting, the SMN therapy matters, and so we also stratified for, did the children get it before the age of five or after the age of five? So we really factored a number of those, things into control risk. And we had a phase II to inform the design. So those, to me, are the key mitigating risks.
You know, it's a risky business, right? I think, you know, drug development's for, not for the faint of heart. But I would argue that knowing that it's a validated target, that we know that if you hit myostatin, you should get the function. We saw functional improvement. All of those things, I think, give us, you know, high confidence that we have a, a reasonable chance of getting a positive study.
Assuming you do have a positive study in hand, what are the next steps for Scholar Rock, getting apitegromab available to patients?
Yeah. So you know, I kind of signaled on this slide right now, very thoughtfully, we are preparing for a positive outcome and beginning to think about the steps that we would need to take to commercialize. I spent a little bit of time indicating that we believe that we really, this area of SMA, we're well-positioned to enter that on a commercial front. I don't know, Ted, you want to make some comments?
Well, yeah. I mean, it, it has all the hallmarks, right? It, it's a concentrated treatment regimen. You know, we know where the patients are.
Mm-hmm.
90%+ of the patients we'd be targeting are already on therapy, many covered by the 55 sites that were in our SAPPHIRE study.
Mm-hmm.
So we are preparing for commercial launch, certainly in the U.S., and then quickly to follow into Europe. The study is a global study, so with U.S. approval, we will hopefully also get European approval. And we're doing that in a very measured way, right? So as we sit here today before data, there's a bit more risk in the company. So we're deploying the capital very carefully. As soon as that data card is turned over and positive, we see that as a de-risking event, and we'll start to really ramp up for commercial.
You know, I think, Jay, you outlined how you see apitegromab's mechanism relative to some other programs in the space. You know, I think a question I'm getting a lot recently is how to think about the program update that we're gonna get from the Versanis asset mid- it seems like potentially mid-year now with Lilly. How do you see about the relevant read-throughs from that update, if any, to your program? Like, how might you interpret those data when they come out?
Well, you know, the strategy of maintaining lean muscle mass, I mean, it'll be interesting to see to what extent that happens in the combination with the GLP-1 receptor agonist, 'cause that's the, that's the premise, that there's targets and ways to target that, and it'll be interesting to see to what extent that's achievable, with a couple caveats. It's combination.
There's a lot of different ways to look at those dose combinations that are in the program. I'll be interested to see the tolerability in the combination sets because I think that will be informative. But I think if there's a demonstrated effect on preserving lean muscle mass, I think that will be a very positive outcome for those considering targeting myostatin, for example.
Yeah.
But I do think, you know, long term, and things that we really highlighted, 'cause there's a lot of questions around this. You know, we believe that we will be able to have the effect that we need to have in preserving lean muscle just by hitting myostatin alone. We don't believe that we need to have any of the other ligands, like Activin A, to achieve that. We believe we'll get that. So we'll have the efficacy. I think we're gonna show when we-- You know, I think about our proof of concept, so you're-- the read-through from Versanis to us. The proof of concept for apitegromab, in my mind, should answer two questions, principally.
Yeah.
Proof of concept. 'Cause we already have a dose, we already have a good understanding. But it should say: Does our selective strategy preserve lean muscle mass in the setting of GLP-1 receptor agonist weight loss? And we can answer that in a proof -of -concept study. And then, we will have an opportunity to see whether our safety profile adds any additional toxicities to the GLP-1 receptor agonist profile. 'Cause I think both of those will kind of reinforce the position that we believe is we won't have additional toxicities, and we'll be able to preserve lean muscle. But the Versanis data will be very interesting to see if, in fact, they had demonstrated that.
Is there any other color or granularity you'd provide us on the cardiometabolic side around key differences between apitegromab and SRK-439 that could make 439 better purposed for cardiometabolic disorders? And, you know, as you see it today, what do you think are the most important preclinical data that you have in support of that?
Yeah, so a couple things. So, you know, apitegromab and SRK-439 share the same selectivity around the anti-myostatin. We moved the apitegromab into clinic with an IV presentation, right? We have, as I mentioned, intention to move a sub-Q formulation forward so that we have that as an option, you know, kind of once we get further down the road with the program. You know, the SMA population, weight-based dosing, size, they're different, right? If you consider in weight, weight loss. And so, frankly, Mo and his team and our research side, our research team, took a deep look and really were trying to take a look at: How can we enhance a profile that would really lend itself to targeting, you know, BMI, patients with weights that are really in excess of what we're seeing in the SMA space?
Which leads to higher affinity and really a formulation that would lend itself right out of the gate to go into sub-Q. So those were a lot of features that were behind it. It has its own unique set of conditions, so it has its own unique IP, and there's some other features that we have yet to disclose. But it certainly lends itself to going straight into sub-Q, which I think is gonna be important in this setting, at volumes that really will make sub-Q very, very conducive.
In the meantime, with apitegromab, before we have SRK-439 in the clinic, can you walk us through, in a little bit more detail, what a proof of concept study looks like for that program? How soon do you think you can be in the clinic, and, yeah, what are the key goals for you for that study, and what would that enable you to do with SRK-439?
Well, first of all, we're actively advancing to get this study open. What I've signaled here is that we're targeting mid-year this year.
Yeah.
You know, accelerated drug development. If we can go faster, that's great, but we're really targeting mid-year. So that's the first thing. I think we're, you know, in the process, y ou know, talking about the clinical trial design, so, Tess, I'm gonna say to you, I, my preference is to really go over that in great detail when we're really at the threshold of posting on ClinicalTrials.gov. Then we can go into all the detail and the nuance around the trial. However,
Yeah
B ecause you asked me the question, and I think I've shared it in different settings. You know, it's a proof of concept study to show that we can preserve lean muscle mass, so it's gonna be a combination study on a background of GLP-1 receptor agonist. And if it's lean muscle, then the endpoint is gonna be measured lean muscle, which is a DEXA scan. So we can do that. We can do it in a manner, I don't think we need a year to show that, so we can do it at a shorter timeframe. And if you look at it, what we've said, if we start mid-year, we're gonna have results mid-year the following year. That suggests that we're able to do this pretty quickly. So those would be the color. But again, going back to what we want to show with apitegromab.
I've fielded a lot of questions since we've entered into the space about the different strategies for hitting myostatin and lean muscle, and the need for Activin A to do it or not do it. Is that important, or is it not important? And again, I think to demonstrate that we can preserve lean muscle with our very selective strategy will certainly play forward beautifully with that SRK-439, 'cause that's the premise. And I think the safety will be extraordinarily clean, which again, is the premise. So showing those two things as we get 439 to clinical will really be important. In addition, it's like any clinical program, once we've started, we're running, we're operationalizing the study, just like we did with TOPAZ. We ran TOPAZ, we ran right into SAPPHIRE.
We'll be able to operationally get SRK-439 advantaged, and we'll have more insight as to what's happening as we go forward in our ongoing studies with SRK-439, 'cause we'll be engaging with FDA discussions. So, I mean, really a lot of excitement, a lot of forward-looking comments. But first things first, we just—we'll get the study open, and as soon as we have that trial out there, we're gonna be happy to walk through the design in more detail.
Okay. Any preview of the maybe models or types of analyses we may see at the Keystone Symposia in February around SRK-439? I think you press-released that you might have a presence there.
Yeah. So we will have a presence. We have been notified that we'll have, you know, an acceptance for a presentation. But to respect that this is yet out there in the public domain, the details of what we'll share, we'll get as we get closer to the conference, we'll share. But I will say to you that we certainly have, as I mentioned, intention to really bring forward a lot more over the course of the year of what we've done with SRK-439, because our research team have really done a lot of very interesting work. And so we'll have a cadence of data disclosure that are in our non-clinical programs that'll start to signal what is very, I think, intriguing opportunities of what muscle can do and our approach to that as we go over the course of the year.
Last question from me on obesity, just, and then we'll wrap it up. It came through from an investor. The question was really around, like, how you think about the right time to potentially have a strategic partner for this program or these initiatives that you have at Scholar Rock. What's the latest thinking there that you might, you know, comment on today?
Well, the initial thinking, of course, is after we generate data and prove out the concept. This market is pretty robust and fast-moving, so.
Yeah
There might be a scenario where something happens sooner than that. But that's about as far as we can comment on, on BD discussions. Suffice it to say, ultimately, the 439 molecule in obesity, that is the molecule for obesity and cardiometabolic disorders, that's gonna go into clinic and into commercial with a partner.
Okay. Well, I think that might be a great place to leave it. Thank you so much, Jay, Ted, for being here. We really appreciate it. And thank you for all the listeners for joining. Hope you have a great rest of the conference.
Thank you.
Thanks, Tess.