Hi, good day, everybody. My name is Ash Verma. Welcome to UBS Virtual Obesity Therapeutics Day. I'm a Biotech Analyst at UBS, and with us our next company for the Obesity Day is Scholar Rock. And so with us we have Jay Backstrom, who is the CEO, and Mo Qatanani, who is the Chief Scientific Officer. Hey, guys, can you hear me okay? Yes, good morning. Morning. Excellent. So thanks, thanks for taking the time. Really exciting to hear about the story and how the involvement has been on the obesity market. I saw that you announced the initiation of this phase II EMBRAZE trial yesterday. So I know a lot of people paying attention to this space and broadly, your pipeline overall. So maybe it might be helpful just to orient the audience a little bit, if you can give a little bit of a high-level overview of apitegromab, and sort of the rationale for how you're targeting obesity, and how, why it makes sense from a anti-myostatin therapies perspective. Yeah, sure, happy to do that. So I, I'm Jay Backstrom, for those that are listening in, the CEO of the company. I, I took over as the CEO back in October of 2022, and we've really made enormous progress over the course of the time that I've been here. To start, I think Scholar Rock was really founded on the understanding of how to selectively target the TGF-beta superfamily of growth factors. So selectivity for us is really important, 'cause it's very complicated biology, and, you know, the historic approaches, you would get off-target effects and unwanted toxicity, such as bleeding. So we've been very focused on selectivity. To that end, that's where apitegromab comes in. Apitegromab is highly selective, targets what's referred to as the latent or precursor form of the growth factor. It's important to understand that if... that, myostatin, which is what we're blocking, it has one primary function, and that's to regulate skeletal muscle. So if you block it, you release the intracellular mechanisms, you get more muscle. So it's a very clean target. You hit it, you get more muscle. So we selectively target that, and as a result, what we've seen in our early indication with apitegromab in spinal muscular atrophy. We've seen functional improvement in this, you know, motor neuron, neuromuscular disorder. So we've got really good proof of concept, and principle, and clinical data to say that we can enhance muscle and improve function. So that's kind of the framework to start. You know, if we look about the obesity field, which is, you know, you're following it, everybody, it's. You can't. It's everywhere all the time, right? It's just such a large market and such interest, and it's because, quite honestly, the current therapies, the GLP-1 receptor agonists and versions of that, are so highly effective in losing weight. They're highly effective. Yeah. But what has emerged is, within that weight loss, there's a loss of lean muscle mass. And, you know, the whole goal of managing weight loss or the treating of obesity is to improve outcomes. And so lean muscle plays such a critical role, that it's an obvious place to go if you have a drug that can target myostatin, that regulates muscle and can increase muscle mass, to then consider how that could be used to enhance, if you will, the profile of the current therapies, who are- we're seeing more and more the obvious loss of lean muscle mass. So that, that was the concept, right? We start with a selective target. We hit myostatin and only myostatin. And what our program has done is that we've taken apitegromab to the proof of concept study that you just described, the EMBRAZE trial. Apitegromab, to be clear, is our SMA program, so we are gonna push that forward. You know, we're gonna talk more, I believe, on the call about our next generation, if you will, SRK-439 anti-myostatin for obesity. But we took advantage of that apitegromab is in clinic to allow us to do a proof of concept study to demonstrate, and that's the trial's goal, that can we preserve lean muscle mass in the setting of standard care, so either tirzepatide or semaglutide, so that everybody gets that, plus apitegromab. Can we demonstrate that we can preserve lean muscle mass? That's the goal. Mm-hmm. You know, we do it very selectively, so we show that, then I think we have the answer that we would like. That we can run, we're running now. We'll have data, you know, assuming we... depends on the enrollment. It's. There's a lot of interest in the trial, so it's gonna probably roll quickly. But we've indicated that we'll have data about this time next year, and that's right around the time where Mo and his team will get the SRK-439 into the clinic through the IND. So it's very. It's kind of dual track. Yeah. We'll run the study, we'll get insight, but it's 439 that we'll really be doubling down on as we get that into clinic for the cardiometabolic obesity space. Great. That's, yeah, excellent start. So I think, yeah, maybe it might be helpful just, to try to understand, like, what is the, advantages that you have with 439, you know, compared to apitegromab. Like, and I guess, so you're doing this trial with apitegromab right now, and you can naturally transition to 439. Is there some additional steps that you might have to take to sort of justify that, that the profile carries from one molecule to the other? Sort of like, how, how you're thinking about that? Yeah, so two things. I'll let Mo describe... you know, give, you know, the differences between apitegromab and why we were looking forward to getting SRK-439 into clinic. You know, I, I would say that mechanistically, mechanistically, targeting myostatin very selectively, this pro form or latent form, that's the consistent theme between apitegromab and 439. So mechanistically, that's what we're really assessing, right? Yeah. We'll have to do the IND-enabling work to get 439 into clinic. But Mo, you want to just describe sort of what we're thinking about with 439 and- ... Yeah, I mean, as Jay mentioned, mechanistically, they're both selective. All our antibodies are selective, which is really critical. We do target the latent form or the precursor, so we lock it into inactive forms. It never really sees the receptor or initiates any signaling, both of them. Now, the difference with 439 is that with 439 from the get-go, it was designed for this specific patient population, the obese patient population. And where what you need there is, and what we thought is, a high-affinity antibody that will give you efficacy at lower doses to enable subcutaneous dosing from out of the gates from the get-go. So the profile for 439 is higher affinity, efficacy in the relevant models at lower doses, and we're seeing that at doses as low as 0.3 mg/kg to enable subcutaneous development of the molecule. So far, this is what we've seen with SRK-439. Yeah. So to be clear, apitegromab is an IV presentation. Yeah. It's monthly dosing. You know, currently, if you look at the Versanis Lilly program, it's an IV administration, right? And to be clear, I think it... You know, the Scholar Rock team has been thinking about cardiometabolic and using myostatin as a target, probably since 2019, so well before I joined. But that's the reason why we were able to move so quickly into 439 and getting it toward the IND. But it's designed to be able to be subcutaneous, low volume, that really would fit sort of a population we're trying to treat here. That's helpful. Great. So thanks, thanks for that. I guess, I mean, just, mechanistically, like the myostatin, you know, anti-myostatin, like, programs that are out there, I mean, I covered Biohaven as I was, talking to you about, like, how do you sort of think about, like, what is the competitive advantage that you have maybe versus some of the, you know, competitors in the field, either, either Biohaven or Versanis, like, in terms of the, the way that the molecule is binding, and, what, sort of mechanistic, differentiation you are bringing to the table? Yeah, I'm happy to. You know, it's really interesting- Sure ... right? If you-- we're gonna actually see if we can actually project a slide, Ash, if, if that... Do you think that'll come through or no? I believe so. Should work. Yeah, so we're gonna set one up, because I think a picture paints a thousand or, you know, whatever. If you take a look at the whole signaling pathway with myostatin, it signals through... Here we go. This is a really good presentation. We use this quite a bit. So if you take a look at what this schematic is showing is, at the very bottom of the slide is the ActRIIB receptor. It's represented as ActRIIB, but basically, that's the receptor, right? And if you kind of track up to the schematic on the left, where it says apitegromab-SRK-439, that is the pro latent form of myostatin, which then, if there's proteolytic cleavage, it's opened, you form the active growth factor, myostatin, and then it signals through the receptor. So that's the myostatin pathway. The pathway to the far right is the activin pathway. So similar, we're not targeting activin, but to show you that the ActRIIB receptor is the receptor for both activin as well as myostatin. But in addition, what's shown in the middle is GDF-11. It's another growth factor. These are very- this is a very complicated and complex set of biology. Activin is expressed in lots of tissues, and so if you perturb activin, you are at risk for having unwanted toxicities. Where myostatin, if you block it, you get increased muscle and less fat. That's it. There are clear animals that have the genetic defect. They are double-muscled animals, right? As an example, there's human mutations where there's just more evidence of muscle mass, but you don't have any unexpected or untoward effects because myostatin is that pure of what it does for the body. It regulates muscle growth. So, you know, I start off by saying Scholar Rock was founded on selectivity. That's because the lack of selectivity has plagued the field for decades, and it's the reason why not many TGF-beta targeted programs have made it to the commercial state, right? So it's been very difficult. If we go back up then to this slide. So this is a give you a walkthrough of kind of what's happening in the space. So the current Eli Lilly Versanis program, which is bimagrumab, is targeting the receptor at the bottom. So that's where... So that's a monoclonal antibody, the receptor, so it blocks that. If you click up, myostatin and activin A, they're growth factors. There are monoclonal antibodies directed to myostatin and activin A, right? So you can target the growth factor themselves, but these are the mature forms, but you can target that. And then if you click up one more slide or on the left, that's where we're coming. We don't even let myostatin get formed. It doesn't even get activated, so we completely block it at the beginning. So that's- those are kind of the main strategies. So ligand traps would be similar to the bottom. You know, I call out bimagrumab because, you know, it's been really the lead, and there's been a lot of talk around it. But that, that's its target. It's that receptor. And if you look at some other forms, for example, the adnectin, which is T alfa. T alpha is not a monoclonal antibody, so it's not blocking the antibody specifically. It's, it's an adnectin. I think the best way I could characterize it, it's a bit like a sponge, so that when myostatin is activated, it can then bind to it, so it will catch it. You know, whether it does or doesn't signal through the activin receptor, I can't say, but it definitely has overlap between GDF-11, which is another growth factor, and there are some unwanted toxicities associated with all of these approaches. I think what's really important to keep in mind is if we think about the use in the setting of treatment of obesity, it's an extraordinary large exposure. There's so many, you know, we think over half of Americans will meet that definition by 2030. So you've got a very large population, and this really, as we heard from, you know, our one of our experts yesterday, Dr. Ania Jastreboff, on our... We hosted an investor call. You know, as an expert in the field, she sees this as lifelong care. This is chronic care. You're gonna need to treat for a long time to get to the patient outcomes that you want. So I say all that because if you're starting to perturb the biology that's associated with these signaling pathways, you may not see it in a single healthy volunteer study, you may not even see it in a six-month approach, but over time, these things will begin to manifest. And so what we're seeing, if you take a look at the profile that we've generated from apitegromab, which is our SMA, spinal muscular atrophy, we've got over four years of care for patients on that trial. We've seen none of these events on the right, none of these events, right? It's because myostatin is such a pure target, and our strategy is so selective, that my phrase, it's almost by design, not almost by, it's by design, that we're not seeing these things because of the selection of the target and the... how we, how we hit it. So those are the so as our view of, of how to- where the field is going and what the need is, benefit-risk has to be top of mind. Yeah. It's all about benefit-risk, and so there's a lot of discussion around the right strategies, and that's because we're generating data. You know, right now there's a lot of proof of concept studies going, a lot of data being generated, and, you know, data will help inform us going down the road, right? But from a starting point, from the data that we've generated with spinal muscular atrophy, where we see we're the first, we're the first company to demonstrate functional improvement in any clinical study by trying to target myostatin. That was the TOPAZ data. First to do that. So we feel very good about the efficacy side of the equation, but frankly, the safety side is almost irrefutable, to be honest. I mean, this is biology that happens when you perturb it. So we feel... That's why we're really, we're excited we're starting the EMBRAZE trial. We're really looking forward to generating those data. But importantly, really looking forward for Mo and his team to help get SRK-439 into clinic. It's starting to emerge, frankly, from our perspective, as almost the best-in-class profile, but of course, we'll need to generate data to support that. But the non-clinical data look really, really good. Yeah, that's great. All right. So I guess, I mean, one thing that I wanted to ask, like for 439, I mean, so you've seen some animal data, I believe, that it can show and preserve lean muscle mass. I guess, what would be like a dose translation in humans, and sort of what are your thoughts on that? Anything that you can comment on, specifically on what type of dose would be... I know you mentioned that you have like it's efficacy at lower doses because of the high affinity, but I'm just curious what your model suggests in terms of, like, translating from animal to humans. Yeah, I mean, we're building these models as we speak now. We're really encouraged by the efficacy we see in mice. As I mentioned, it's an efficacy with doses as low as 0.3 mg per kg. We've done some cyno studies as well that actually lines up with some of the findings that we see in the mice. And based on our experience with apitegromab, I mean, we've done that years ago, and we built these models, the profile that we're driving towards is efficacy with low doses to enable low volumes and low frequency. So, you know, the target would be, you know, once monthly or so. And so far, things have been lining up. Again, we're still building the model, but so far, from the data that we've seen, it looks like SRK-439 will be hitting, will be hitting that target profile. Why don't you show that study? Yeah, so as an example, so the bimagrumab. Yeah. Yeah. We just shared yesterday for the first time, so we've obviously, this is now in the public domain. Mm-hmm. Once again, some of the Mo's team is just doing some really incredible kind of series of studies to further give us insight on what we're hoping to see with 439 to guide us into clinic. And again, one of the questions that really is out there, which is, you know, are we gonna get enough efficacy if we don't engage sort of the activin pathway? Is myostatin sufficient? And, you know, I just showed you why we believe that avoiding hitting other ligands in this growth factor family is good because of the safety issues. But what Mo did within our non-clinical models is, I'll let you walk through this data. Yeah, I mean, we used the diet-induced obesity model, which is a standard in the field, that everybody uses, including GLPs in their approval. And we did a head-to-head study with SRK-439 or the murine equivalent of bimagrumab, in this case, in gray. And as we've seen every time, is when you treat these animals with semaglutide, you do see a significant reduction in lean mass. So this graph actually is a quantitative MR, looking at percent change in lean mass from start to finish of the study. And as you can see in purple, a pretty significant reduction in lean mass when you treat them with semaglutide, as expected, that has been seen in humans as well. Now, if you add SRK-439 on top of semaglutide, you see this reversal or preservation of lean mass with doses, again, starting at 0.3 mg per kg, and then maxing at between 1 and 3, which is what we've seen in other studies as well. Now, if you compare that to the anti-activin receptor antibody, that's the murine bimagrumab. We chose the dose of 20 mg per kg for that antibody, because it's the only dose that was published in a diet-induced obesity. And you can see that you only see preservation at this highest dose, 20 mg per kg. But really nothing below that dose compared to our SRK-439, where almost the 1 mg per kg is the equivalent of the 20 mg per kg in bimagrumab. So really, you know, selectivity is gonna get us safety, and we're not losing efficacy by being selective in this case, as compared to the, to the receptor or antibody against the, the receptor. So this, it's more and more data to tell us that the profile of SRK-439 is the best fit for this patient population. Again, this is a chronic disease. Yeah. These patients have, a lot of times, a lot of different comorbidity. So safety is gonna be key, of course, while having efficacy. Got it. Okay, that's great. I mean, I guess, in terms of... We've seen, like, some data from Biohaven in healthy volunteers, like, for SRK-439. Like, like what's your sort of expectation on fat loss and lean mass changes? Like, what would, like, an ideal good data look like, that can position you competitively? I mean, from a healthy volunteer's perspective? I mean, what we can comment on is, let's look at the challenge. What is the challenge? The challenge is not losing weight. There is... I don't know if you heard Dr. Jastreboff yesterday, and she's the lead, you know, she actually ran GLP-1 studies, tirzepatide. The challenge is not about how much weight we can drive to lose, right? That has been solved. We're losing now 24%-25% of body weight, and sometimes it's too much. The challenge is the quality of that weight. When you're losing that much, you know, 30%-40% of that weight loss is lean mass. That's the challenge- Yeah ... and it's gonna be a challenge long term. So how do we fix that challenge? And this is where a safe, therapy, like an anti-myostatin, comes in to preserve that lean mass, so that over the long term you have a better metabolic profile. And we've seen that, at least in animal models, where when we preserve, that's in the Keystone, poster we published, when you preserve, lean mass with SRK-439 on top of semaglutide, you actually have additional reduction in blood glucose. So we're thinking about the, the healthy weight management over, over a long period of time, long term, with this therapy. Yeah, and maybe to go back to your question, right? 'Cause it, you know, we're trying to do kind of cross-program comparisons, where it's not always clear exactly how things were done to generate the data. But I would say, kind of taking a step back, blocking myostatin should result in an increase in lean muscle mass. So, you know, it's the question of, are we getting more efficacy by one strategy versus the other? But in general, there's a range that you can expect to achieve. And so that is fundamentally the principle around adding it to a GLP-1 receptor agonist, try to preserve that lean muscle. What Mo said is that, what really is intriguing to us here, and the reason why we were interested in this since 2019, is, you know, Jeff Flier sits on our board, he's a renowned expert in this space. Muscle plays such a critical role in metabolism. It just does. Mm. Basal metabolic rate, glucose uptake, insulin sensitivity. So what Mo's team is generating is data that further support that when we enhance that muscle mass, we're getting the metabolic expectation, which means that improvement in glucose. There's crosstalk between muscle and fat, so to your question, we would expect to see some additive effects and further fat reduction because of that interplay between muscle and fat. But we'll need to see the data, and this is what I think the next year will generate. We'll see some of that data from our apitegromab proof of concept study, 'cause we've got DEXA scans as the primary endpoint, so we'll be able to take a look at that. We've also built in exploratory. We didn't select patients where we would absolutely see this effect, but we built in exploratory endpoints to look at hemoglobin A1C, for example, because we do believe... If you think about a regulatory approval, hemoglobin A1C is an accepted regulatory endpoint. So if you can show that you can hit that and improve that- Yeah ... that would really be a good thing. So, so that's, that's our thinking. I think we'll, we'll see it. The metabolic profile should be enhanced. Preserving lean muscle should help reduce falls and fractures. There are certain subsets of patients that are gonna be vulnerable to that. And frankly, we heard yesterday, which is really, really interesting, you know, of all the programs done to date, with the fabulous weight reduction that's been seen across the programs, there's not systematic collection of DEXA scans in these studies. There are sub-studies- Yeah ... there are subsets. We're not seeing the magnitude of effect, nor is there a determined effort to understand, are you really seeing signs and symptoms of muscle weakness? And what we heard from Dr. Jastreboff yesterday is, you know, she's dealing with middle-aged men who lose weight, who now complain of losing strength. So this is gonna find its way more and more in the space. You know, we believe we have a very elegant solution to this. Obviously, there's a lot of interest in trying to target it, but I think at the end of the day, our theme yesterday was muscle matters. It really does. Yeah. It really does, and I think it's just for lots of reasons. So yeah, I think I definitely agree with you there. I guess, like, in terms of lean muscle mass and the level of benefit that we are seeing with some of the competitors, and given that, so where you are right now in terms of clinical development, right, like the expectations or, like, what good outcome looks like may change over the, let's say, next five years, right? So it's kind of like a moving target that you're trying to solve for, from how I understand it. I mean, by the time that you get to the market, like, what's sort of your expectation on, like, lean muscle gain? Like, what type of- ... you know, what type of benefit or level of efficacy on that would be good? I mean, I think like Versanis showed, like, 3.6%, if I, if I remember that phase II data correctly. Do you think that the- Yeah. As the competitive landscape is evolving, can that bar shift up, and where ultimately, like, what level would you think you might have to get to? Yeah, that's a really, really good question, right? I mean, I think... So if we, if we fast-forward five years, I'll give you my view. This is forward-looking statement for everybody in the audience. It's just my, my view. We're gonna see that there will be strategies to really offset the loss in lean muscle mass, whether that is a combination approach, or whether that is someone who's trying to combine a targeted for myostatin and/or an activin receptor, plus a GLP-1, that development, I think, is gonna go... The field is going in that direction, so that's where the field is going. I think... And And I think if you take a look at that, I like our position, 'cause I don't think that means we're behind. I think we're gonna just be right in that wave of demonstrating how important it is. We spent a lot of time yesterday, and again, this is, you know, you can't, you can't influence the way FDA thinks about primary endpoints. The field can, the data can, and I think that more and more is coming forward. What we heard yesterday from Dr. Jastreboff is that, you know, 5% weight loss is like, you know, it's a 2007 idea around weight loss. We're talking about improving health outcomes. And so there's other measures and parameters that we might be able to see that demonstrate benefit. But in the here and now, we're gonna generate data, and Mo is showing it repeatedly, where I think we can show that we can enhance the metabolic profile, and that's an approvable endpoint, and we can do that in combination. So my phrase, we can enhance the profile of the existing therapies. The other thing that was very, very interesting yesterday is, you know, it's fun to put these events on because we start to think more broadly than our day-to-day, right? Yeah. You know, deliver, you know, execute. We're starting to get a chance to really look a little broad- more broadly. But you know, regardless of the form of weight loss, you lose lean muscle mass. You lose it, whether it's diet, you lose it clearly with bariatric surgery. That's the longest longitudinal data, and of course, we're losing with therapy. So we need to think about this in general, if this is maintained chronic treatment. So my point 5 years from now, I'm believing you're gonna see this as an element to... in the treatment landscape. Whether there'll be enhanced, better way to preserve the lean muscle mass remains to be seen. I think from our strategy, but we need to have data to show it. Just intuitively, if we're blocking the growth factor before it even has a chance to circulate, that suggests that you should have a potential efficacy advantage than is now circulating, and you're trying to catch it. You know, it's like shutting the water off before it drips. You would seem like that would be a more elegant and potentially more effective solution. And with Mo's team and their engineering, you saw how, you know, the lowest dose we're getting effect will be very interesting for us. So I think we're, we're kind of right there. We're, we're entering the field, I think, at a good time. But it will evolve over time, but I'm glad we're in it. I, I think we have a nice solution. Yeah, that's great. So I guess, just start talking about, like, the tolerability overall, I mean, the sort of the approach overall, where it's going. I mean, so there's, like, decent amount of, like, side effect profile with some of the GLP-1s. I mean, do you believe the combination of myostatin inhibitor with GLP-1 could exacerbate? I mean, I know you have, like, a more specific molecule. Right. So just, That's fine ... are you getting the, any kind of, like, an incremental tasks in the long run that might, No. No, that's, that's the thing. That's where I was kind of pointing out, I think from... You know, I always think about safety and tolerability and toxicity. You know, frankly, it starts initially with what you're trying to block, right? How... What, what is the implication to blocking any given target, right? Any receptor, any ligand. If you block it, what does that mean? What's the biology, you know, the body's response to that blocking? And we're starting with a very, very pure regulator of muscle. That's it. Block it, you get more muscle. So that's really important. And if you take a look, as you're, as you were describing, you know, I think the GLP-1 receptor agonists have their own profile. Yeah. Our data that we've generated from spinal muscular atrophy, we've got four years of data, we've seen no serious events are related to the drug. There's nothing that would suggest any of these effects that are more likely related to perturbing the other signaling pathways, because myostatin doesn't do that. And so we've... It's really clean. It is really very clean, right? Now, you're gonna see- you know, we- we're gonna show side-by-side comparative data when we report out our phase III trial. You know, we have reports, these are children that we studied in our, in our TOPAZ trial without a comparator. But, you know, it's viral illnesses, things you would expect children to get living through seasonal allergy or seasons, but nothing like this at all. We've had no bleeding. That's plagued the field. Telangiectasias, as you know, it's been reported with one of the approved therapies, which targeting using a ligand trap. So I think from your question, and this is what really, you know, I thought about, if we had such a GLP-1 receptor agonist that we wanted to use as broadly as possible, I wouldn't want to combine it with an agent that would add to its toxic profile. I I would not want to do that. And that's where I think when you look at this, the trade-off, I don't think we're trading off. We are coming in very clean on the safety side. We should have no additional liability, if you will, or toxicities added. And in fact, that's one of the things that I'm looking forward to with the EMBRAZE trial, right? I said, so we started that study-... For those that didn't see it, it's a randomized study between either semaglutide or tirzepatide. We're agnostic to it. We think we can work on either, and then it will be a 24-week endpoint, where we'll randomize to receiving apitegromab or placebo. So it's very clean study. 24 weeks, DEXA scan, answers the question, do we preserve lean muscle? Yes, no, very clear, right? But also, we'll be able to show side-by-side safety of the tirzepatide plus apitegromab, or semaglutide plus apitegromab. And from our SMA data, it suggests to me that we won't see any additional toxicities that you don't expect other than what you see for the GLP-1s. It's not clear to me what we'll see with these other strategies, except to say that I think there's more potential issues by hitting these other pathways than just hitting myostatin alone. Yeah. So while we were just talking, I think that that would helpful. Just, I got another question from investor. Basically, I guess, yeah, this is sort of like getting to what you can comment on the competitor data, so I'll give it a try. So like, do you believe that this is there any safety issues seen in the DIO mice with the bimagrumab? Or is this like just not seen preclinically? I guess, like, it sort of has a read-across to your program, but just curious if you can share any thoughts on that. Well, from... Go ahead. Yeah, I mean, the DIO models, these are geared towards efficacy. So, and we haven't looked with the bimagrumab. With the bimagrumab, and this is published data, you do see the dramatic reduction in FSH and reproductive hormones preclinically, as well as in the clinic. That has. This is a clear effect of hitting activins. I mean, activins were discovered based on their ability to enhance the FSH secretion, and when you inhibit the activins, like when you're targeting the receptor, you actually reduce FSH. So you have an impact on reproductive hormones, and that's why there's a lot of restrictions in the clinical trials. With bimagrumab, also in the clinic, I mean, we don't have to talk about mouse studies. If you look at the list of AEs, which comes from the non-selective targeting of the receptor, they do see high rate of GI problems, like diarrhea. If you're thinking about incretins and GLP-1s, and their GI issues, so adding that on top, I think is not gonna be a advantageous. Yeah. All right. Okay. All right, that's great. I mean, just, you know, a couple of questions to just, like, close out here. So, yeah, like I think I was mentioning to you, like, for Biohaven, and they have the sort of like the same, you know, mechanism. And the way that I think Biohaven has sort of framed it is that, it's a big endeavor to take on, like, the obesity market, for a small biotech company, like, especially I think, the amount of, like, capital that this, this may require over, you know, the next several years. So the way that Biohaven has sort of talked about it is that, you know, they, they are potentially looking for, partners, with big pharma, to advance the program, before, like, committing any significant amount of, capital into it. So just curious from your perspective, like, how do you think, that... Yeah, I know the focus of, like, Scholar Rock has been primarily on SMA. What got you excited, and you think that this, the intensive capital requirement that you have, for getting involved in obesity, do you think that you, you are sort of go, go alone strategy is, the right approach for you? Or, or do you, or do you think that, a potential partnership at some point of time might, be necessary? Yes. We've been pretty clear right from the beginning. I mean, I think given the size and scale of this market, this is definitely an area that we would benefit from a partner, no question about it. I think it's really interesting, right? So we had a very successful financing last fall on the basis of us entering into this space and the data that Mo had generated, because this really looks like an elegant solution to what will be, I think, even a greater emerging problem, the more we understand it and study it. But yesterday, we hosted an investor event, and I made it very clear about how we think about value creation as a company, right? So let's look, we have apitegromab and SMA, and we have SRK-439 and cardiometabolic or obesity, right? The spinal muscular atrophy market, this is like the right entry for us to be our first commercial product. It's an established market, right? We've got identified patients. We have centers of excellence. We've engaged beautifully with the Cure SMA community. The patient advocacy group wants more therapy. It's something that's within the scale and reach of us to be our first commercial product. By contrast, SRK-439, it's a beautiful product. We can drive it to IND. You know, we could generate proof of concept studies as a company our size. But along that journey, to really maximize the potential for patients and the value created for the company, I agree, a strategic partnership would be optimal for this program, and we're continuing to generate data that shines the light on why we believe this would be a partnered asset that a company would want. But yes, absolutely. But in the meantime, team's executing, right? I think, you know, we're delivering on what we said. We'll get that proof of concept done. We'll drive to IND. Those are value inflection points for the company, right? We can create that value, and along the way, as we generate interesting data, you know, it's a beautiful ecosystem that we're in, right? You start to shine a light on a program, and you can tend- Yeah ... tend to generate more and more interest. So we believe we have the program to generate interest in, and we'll continue to do that. Great. Excellent. Those are all the questions that I had. Thank you. Thank you so much for taking the time. Thanks for participating in our obesity day. Good luck, good luck with the program, and you know, looking forward to speaking with you soon again. All right. Thank you. It was a pleasure to join you this morning, so thank you very much. Thank you very much. Yeah. Yay, Mo, take care. Have a good one. Bye.