Good morning. I'm Rushmie Nofsinger, Vice President of Corporate Affairs and Investor Relations at Scholar Rock. Welcome, and thank you for joining us today for our Q3 2023 business update call. This call is audio only. You can access the slides that we'll be referring to on the Events and Presentations section of the Investor Relations page on the Scholar Rock website. Moving to slide two. Before we begin, I want to note that we'll be making various statements about Scholar Rock's expectations, plans, and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date. Please refer to our SEC filings for the full disclosure of all the risks. Turning to slide three, I'd like to introduce the members of the Scholar Rock team who will be presenting during today's call and will be available for questions after the conclusion of the formal remarks. I am joined by Jay Backstrom, CEO of Scholar Rock, Ted Myles, Chief Operating Officer and Chief Financial Officer, and Mo Qatanani, Head of Research. I will now turn it over to Jay. Thank you, Rushmie. Good morning, and welcome to our Q3 business update call. We've made excellent progress so far this year and in particular in the third quarter, and I'm very excited about our future and believe we are well-positioned for success. Moving to slide four. Before I review the details of our progress, I want to start with Scholar Rock's pioneering approach to targeting TGF-beta superfamily of growth factors. The picture on the left of the slide depicts the latent complex that contains the inactive growth factor. The scientific insight that led to the understanding of the structure of this latent complex is part of the foundation of our industry-leading platform that targets TGF-beta superfamily of growth factors by selectively and specifically blocking their activation, by locking up the growth factor in the precursor or latent form. This highly specific approach limits the off-target effects that have been observed with less selective approaches that target the active forms of the growth factors or interfere with their receptors, such as the activin receptors. Apitegromab, our lead clinical program, targeting latent myostatin, prevents the formation of the active form of myostatin, a negative regulator of muscle growth, and leads to an increase in muscle mass and function in non-clinical models, and is the first anti-myostatin therapy to demonstrate clinical proof of concept. Moving to slide five. I was very excited to announce that we are leveraging our R&D platform and deep knowledge of myostatin biology to expand into a new therapeutic area of cardiometabolic disorders with our novel, highly potent, and selective anti-myostatin antibody, SRK-439, in combination with a GLP-1 receptor agonist. Scholar Rock has a long-standing interest in targeting myostatin for cardiometabolic disorders, given the role that muscle plays in glucose metabolism and insulin sensitivity. As you'll hear from Mo later in this morning's presentation, our approach to blocking myostatin is ideally suited for use in both SMA and in cardiometabolic disorders, since by blocking myostatin and only myostatin, we avoid off-target toxicities. Safety is critically important in treating SMA and in weight loss therapy, and we believe our selective approach, as we've seen with apitegromab in our SMA program to date, should lead to a favorable overall benefit-risk profile. Moving to slide six. Targeting the TGF-beta superfamily has broad therapeutic applications, given the central role this family of growth factors plays in wide range of cellular processes, including growth and differentiation. Our research teams have produced a robust pipeline of product candidates targeting latent myostatin and latent TGF-beta1. I'm very pleased with the significant progress we've made on our pipeline since the beginning of the year. Moving to slide seven. For this morning's call, I will start with an update on our clinical programs, highlighting the status of SRK-181, our selective anti-latent TGF-beta1 antibody in immuno-oncology, followed by an update on the progress we've made with our number one priority, apitegromab and SMA, and then turn to Mo to discuss our entry into cardiometabolic disorders with our novel anti-myostatin, SRK-439. Moving to slide eight. Slide eight provides an overview of the DRAGON trial. As a reminder, the main objectives of the DRAGON study, in addition to dose ranging and safety, included establishing proof of mechanism and proof of concept that by blocking TGF-beta one, a key driver for resistance to checkpoint inhibitors with SRK-181 in combination with pembrolizumab, that we could overcome the immune suppressive environment and restore responsiveness to the checkpoint inhibitor. To achieve these objectives, the Part B portion of the study included expansion cohorts in several tumor types and required all patients to have progressed on the most immediate prior anti-PD-1 or PD-L1 treatment. The study is rich in biomarkers, including paired biopsies, to assess if SRK-181 could overcome an immune exclusion phenotype and drive CD8-positive T cells into the tumor, as was demonstrated in our non-clinical models. The team made excellent progress with the DRAGON study since the start of the year, culminating in two poster presentations at the annual meeting of the Society for Immunotherapy of Cancer this past weekend. The first poster focused on biomarker data in support of proof of mechanism, and the second provided a clinical and biomarker update from the renal cell carcinoma cohort from the Part B expansion, the cohort with the most patient data, including follow-up. I will start with a review of the biomarker poster. Moving to slide nine. This poster focused on biomarker data in support of proof of mechanism, and based on paired biopsy data, demonstrated that SRK-181, in combination with an anti-PD-1 therapy, increased the infiltration of CD8-positive T cells across several tumor types, including melanoma, shown here. This was seen in the compartmental analysis that measures the percentage of CD8-positive T cells in the tumor, tumor margin and stroma from two melanoma patients. As shown on the graphs on the left, there was an increase in CD8-positive T cells observed after treatment, overcoming an exclusion or desert phenotype, which was present at baseline. Similarly, as shown in the histopath image on the right, there's an increase in intensity of brown staining, representing CD8-positive T cells in the post-treatment biopsy, also demonstrating the influx of CD8-positive T cells into the tumor. We were excited to see these data, which essentially reproduced the non-clinical findings that formed the scientific rationale for SRK-181. Turning to slide 10. The second poster presented at SITC provided an update on the renal cell carcinoma cohort from Part B. Overall, 28 patients were evaluable for response. It's important to note that the patients enrolled represented a heavily pretreated population, who received a median of three prior lines of treatment, including a checkpoint inhibitor and tyrosine kinase inhibitor. All had disease progression on their prior anti-PD-1, PD-L1 treatment. The slide includes three graphical displays from the poster and highlight the treatment duration, as shown in the swimmers plot, anti-tumor activity, as shown in the waterfall plot, and the spider plot that illustrates both duration and tumor response. As can be seen, there is clear evidence of tumor reduction, with a 21% overall response rate that is durable beyond six months, and a disease control rate of 57%. The overall response rate is significantly above what we would expect from a checkpoint inhibitor alone in the setting of prior anti-PD-1, PD-L1 progression, which is expected to be less than 5%. With respect to safety, the combination was generally well-tolerated, with the most common treatment-emergent adverse events, predominantly skin toxicities of rash and pruritus. Moving to slide 11. In summary, the DRAGON trial delivered on its objectives of showing proof of mechanism and proof of concept, with promising overall response rates in a heavily pretreated, relapsed, refractory patients with clear cell renal cell carcinoma, all who progressed on prior treatment with a PD-1 or PD-L1 therapy. Now that DRAGON has met its objectives, we plan to close enrollment in December, begin closeout activities, while we continue to treat those patients who continue to benefit from therapy and remain on study. We also plan to present ongoing data from DRAGON at future medical meetings. We would like to take this opportunity to thank the investigators, the study staff, and in particular, the patients and their families who participated in or are currently participating in DRAGON. Regarding the SRK-181 program overall, we believe the data from DRAGON support advancing the program, and we plan to conduct an end-of-Phase I meeting with FDA in the first half of 2024 to determine the next steps. Turning to slide 12. I'll now focus on our lead clinical program with apitegromab in spinal muscular atrophy, or SMA. As a reminder, SMA is an inherited neuromuscular disorder caused by a deficiency in a protein, the SMN protein, that is essential for the survival of the motor neuron, which in turn is responsible for controlling muscle movement. When the SMN protein is deficient, the motor neuron degenerates, resulting in muscle weakness and atrophy, leading to significant impairments, including the inability to sit, stand, and walk, depending on the extent of involvement. Currently, there are three approved therapies for SMA. All work to increase the amount of SMN protein, but none target the muscle directly. Apitegromab, by targeting latent myostatin, prevents the formation of the active form of myostatin, a negative regulator of muscle growth, and is the first anti-myostatin to result in improvements in motor function, as shown in our Phase II proof-of-concept study, TOPAZ. Moving to slide 13. As we shared at the Cure SMA event in June, we were excited to present the 36-month data from the pooled non-ambulatory patients from TOPAZ, the same patient population included in our Phase III registration study, SAPPHIRE. As shown, there was robust, consistent, and sustained improvement in the motor function scales, the Expanded Hammersmith and Revised Upper Limb Module, which are also the primary and secondary endpoints in SAPPHIRE, as well as improvements in the patient-reported outcome measures, as reflected in an increase in activities of daily living and reduction in fatigue, all measures that are consistent with improvement in muscle strength. Turning to slide 14. I'm very pleased with the progress we've made this year toward executing on the promise of apitegromab in SMA. We have met or are on track to meet all of the 2023 goals for the program that we outlined at the beginning of the year. In addition to reporting the 36-month TOPAZ data in June at Cure SMA, we also opened the ONYX long-term extension study, which will serve as a platform for patients from both TOPAZ and SAPPHIRE. to continue to receive apitegromab. Importantly, ONYX provides an opportunity to further strengthen the body of evidence on long-term safety and efficacy. As we announced in September, we completed enrollment of our Phase III registration study, SAPPHIRE, a major milestone for the study, and look forward to reporting our top-line results in Q4 2024. Assuming success and regulatory approval, we expect to be a commercial company in 2025. From a commercial perspective, the launch of apitegromab will be leveraged by the established SMA market. Finally, our team is in the planning stages for additional follow-on SMA studies, including in children under the age of two and in ambulatory patients, allowing us to extend the potential benefit of apitegromab to the broadest patient population possible. Now, moving to slide 15, I'd like to turn this portion of the program over to Mo, who will provide an overview of the cardiometabolic program. Mo is the Head of Research and brings a wealth of experience in both neuromuscular and cardiometabolic diseases. As I mentioned in my opening remarks, Mo's team has been working on targeting anti-myostatin for cardiometabolic diseases for quite some time, and Mo will walk you through this research. Mo? Thank you, Jay, and good morning, everyone. Now on slide 16. Our approach of targeting the pro and latent forms of myostatin allows us to have exquisite selectivity to inhibit myostatin signaling and nothing else. A non-selective approach that targets pathways outside of myostatin or muscle has the potential to have deleterious effects. For example, inhibition of the closely related GDF-11 growth factor signaling may have negative impacts on bone, and inhibition of Activin has demonstrated effects on reproductive biology, likely limiting the use of products which target this pathway in women of childbearing age. By inhibiting myostatin and only myostatin, our antibodies provide a profile that drives efficacy without the potential liabilities that come with non-selective approaches, which is critical, especially in this patient population. We are now on slide 17. Obesity is recognized as a top global public health challenge, with an estimated 1 billion adults worldwide, including half of the population in the U.S., projected to be obese by 2030. This is associated with several serious comorbidities like heart disease and type two diabetes, and staggering costs to the healthcare system. Weight loss, by any means, leads to loss of not only fat but also lean mass, and this is evident in the GLP-1 receptor agonist-mediated weight loss that are experiencing rapid uptake, and where lean mass losses may be 25%-40% of the total body weight loss. Loss of lean mass is a key predictor of adverse outcomes in older patients, and maintaining lean mass through exercise during weight loss has demonstrated longer-term benefits versus weight loss alone. Therefore, it is important that it is possible that maintaining lean mass in the context of weight loss may promote additional fat loss as well as greater long-term metabolic benefits. Moving to slide 18, where we'll be discussing SRK-439. SRK-439 is a novel preclinical anti-myostatin antibody that is in development. As mentioned earlier, we leveraged our extensive expertise in myostatin structure and biology to develop this molecule to specifically address the patient population with cardiometabolic disorders. SRK-439 has attractive properties and potential to address the muscle loss associated with weight loss. It has high in vitro affinity for pro and latent myostatin to potentially lead to efficacy at lower doses. It maintains myostatin specificity with no GDF11 or activin A binding to limit any potential undesirable off-target effects, especially in this patient population. It also maintains a good developability profile and is amenable to subcutaneous formulation and dosing. Now on slide 19, where we show our efficacy data with SRK-439 in combination with GLP-1 receptor agonist in diet-induced obesity mouse model, a standard model used in the field. As expected, the decrease in body weight induced by the GLP-1 receptor agonist, liraglutide in this case, led to a decrease in not only fat mass, but also lean mass, as you see with the tan bar. Combining SRK-439 with a GLP-1 receptor agonist confirmed our theoretic hypothesis and led to dose-dependent reversal of lean mass loss, in addition to enhancement of fat mass loss. Now on slide 20. Slide 20 highlights the efficacy of SRK-439 in diet-induced obesity mouse model in combination with semaglutide, a more effective GLP-1 receptor agonist. Semaglutide did lead to significant loss of lean mass in addition to fat mass loss, as seen in the tan bar. However, when combined with SRK-439, the loss in lean mass induced by semaglutide alone was dose-dependently reversed, leading to maintenance of lean mass while enhancing fat mass loss. It is worth noting that we see lean mass preservation with doses as low as 0.3 mg/kg of SRK-439, which highlights the favorable profile of SRK-439 for development in this indication. Turning to slide 21. To summarize, our approach is explicitly selective in targeting myostatin and myostatin only and avoids potential liabilities of off-target inhibition. The selective inhibition of myostatin in combination with GLP-1 receptor agonist-driven weight loss may lead to healthier, more durable weight management, and we look forward to testing this in the clinic. Now on slide 22. In summary, our preclinical data supports advancing SRK-439, a novel investigational myostatin inhibitor for the treatment of cardiometabolic disorders, with an initial focus on obesity.... We are moving SRK-439 towards IND submission in 2025. To inform the development of SRK-439, we plan to initiate a Phase II proof-of-concept trial of apitegromab in combination with GLP-1 receptor agonist in obesity in 2024. The data readout of that trial is expected in mid-2025. Now I will turn it over to Ted for summary. Thanks, Mo. Moving to slide 24. 2023 has been a year of significant execution across our portfolio, and we're well positioned going into 2024. We're seeing great productivity coming out of our scientific platform, as our unique approach of targeting the latent form of growth factors to achieve exquisite selectivity appears to be improving patient outcomes in SMA and in oncology. We are excited to be applying this selectivity toward cardiometabolic disease areas, where we believe safety is so important and our approach is highly differentiated. Our upsized public offering that we completed last month puts us in a strong financial position with our cash runway that extends into the second half of 2025. We're focused on advancing the myostatin programs, SMA, and cardiometabolic. Additionally, we believe we're well positioned to bring in non-dilutive funding as we continue to evaluate potential partnership opportunities for other programs within our portfolio. We view strategic business development as an important way to advance promising programs by leveraging the infrastructure, capital, and expertise of other companies. We ended the third quarter with $219 million of cash and cash equivalents, and our October capital raise netted approximately $93 million. Our capital allocation strategy includes a substantial reduction in our spend on SRK-181 as we complete enrollment of DRAGON and continue to support remaining patients on study. Our primary focus as we conclude 2023 and look to 2024 includes investments to advance apitegromab in SMA and our newly announced cardiometabolic program. With the capital in hand, promising programs underway, and our strategic imperatives aligned with our core competency, unparalleled selectivity of myostatin inhibition, we are excited about the future and our ability to serve patients with our important novel therapies. This concludes our formal remarks. I'll now turn it over to the operator, so we can start the Q&A. Operator? Thank you. The floor is now open for your questions. To ask a question this time, please press star then the number one on your telephone keypad. We'll just pause for just a moment to compile the Q&A roster. Your first question comes from the line of Michael Yee with Jefferies. Your line is now open. Hey, guys. Thanks for the question, and congrats on all the progress. We had two questions, one on SMA and one on cardiometabolic. SMA, in your Phase III, I believe the primary analysis is based on two to 12, and I was wondering if you have any thoughts around the proportion of the study that is probably more of two to five versus, say, older? And whether there is any prespecified analysis that has an analysis to look at the younger patients versus the older patients in that study, after observing what happened with DMD gene therapy and how that played out, if there's a prespecified analysis for younger patients. And then on cardiometabolic, an interesting hypothetical question, appreciating that this is an obesity drug that you're trying to develop. Do you anticipate that the regulatory path is traditional obesity, just weight loss, whether there's an endpoint also that would be accepted by the FDA for muscle gain? And I was wondering how you think about that. Thank you. Yeah, that's good. So Michael, thank you. This is Jay. Thanks for the question. Let me start with the SMA. So yes, our primary analysis is the two to 12. We haven't disclosed the proportion of that group who are between the ages of two and five. And at this juncture, our primary analysis and prespecified analysis certainly include the older cohort. But as you know, upon top-line data, we have the opportunity to look across the age groups. So we will certainly look at that in the top-line results. So I think that took care of the question on the SMA patient population. With respect to cardiometabolic, yeah, very interesting question. I think with respect to the current approval for weight loss, it is the amount of weight loss that occurs that is the primary endpoint. As you know, this is an evolving field, and I think recognizing that, you know, the need to preserve lean muscle mass is really critical. And the efforts now that we're in and others are in, I think will help inform future regulatory endpoints. But, you know, we will need to demonstrate at some point across the program improvements in either function or patient-reported outcomes. So I think that will need to be a standard part, but I think it's a stay tuned, as I think as we move forward. For our proof of concept study, we're certainly going to be focused on demonstrating that we can preserve and maintain lean muscle mass. I think for a proof of concept, that's mechanistically sound, and that's our approach going forward. Thank you, guys. Our next question comes from the line of Allison Bratzel from Piper Sandler. Please go ahead. Hi. Good morning, team. Thanks for the update today, and thanks for taking my questions. So first on SRK-439, maybe a question for Mo. Could you just provide some more color on the different properties of 439 compared to apitegromab? And just really distill for us why 439 is better suited to go forward in obesity. It seems the subQ format is a major differentiator there? You know, just curious if subQ administration of apitegromab is something you've explored. Any color there would be helpful. And then just on a related note, could you help us understand what is gating to IND filing for apitegromab and obesity? Also, same question, you know, what's gating to IND filing for 439, and what gives you confidence that IND filing will be ready to go in mid-2025? Thanks. Hey, Allie, this is Jay. Maybe I'll take one part of that three-part question, and then I'll turn it over to Mo. There's the question around the IND, what's required to get the IND filed for apitegromab. Why I'm, you know, really delighted that we have the opportunity to proof of concept with apitegromab is because it's already a clinical stage asset. So it's a matter of really putting together the scientific rationale and submit the IND for a new indication to agree, and we get to cross-reference a lot of the existing documents in the current apitegromab IND and SMA. So it's really a matter of kind of completing the regulatory dossier to do that and then engage FDA. So that work, frankly, we had started even prior to announcing our going into this area. And then maybe I'll let Mo talk about the IND-enabling work that's required for SRK-439, and then more details. Yeah. Thanks, Jay. I mean, I'll start with talking about SRK-439. SRK-439 is a novel, molecule that we developed based on our extensive understanding of myostatin and the structure and the epitope space. It is highly selective. As we mentioned, it only binds, myostatin, utilizing our platform. It has attractive property, and from the get-go, we developed it to target this patient population. So it has very high in vitro affinity, leading to, potentially lower doses when you're looking at efficacy with these. And we've seen that in the mouse models that we've done, and we continue to do in other models as well as we develop the molecule. It also, amenable to high concentrations. Again, this is to support, subQ profile, especially for this patient population. So the overall profile of SRK-439 was designed, by design, for this patient population to have higher affinity, efficacy with lower doses and concentration to enable subcutaneous dosing. From an IND-enabling studies, we, you know, we're going forward with the typical IND-enabling studies. We're initiating all of the IND-enabling studies as we move forward into next year, as you see the talks, the PK studies and all of these things, as well as cell line developments, et cetera. Got it. Thank you. Our next question comes from the line of Tessa Romero with J.P. Morgan. Please go ahead. Good morning. Thanks for taking our questions. Two questions from us this morning, if we could. First one is, have you disclosed the statistical test you are using and what the powering assumptions are for the SAPPHIRE trial around the primary endpoint of the mean Hammersmith change from baseline at 12 months? If not, what can you tell us at this time as to how we should be thinking about this? And secondly, a related question: Will you consider disclosing the baseline characteristics before the top-line results next year? Thanks, guys. Yeah. So this is Jay. Maybe I'll take the questions. You know, from the statistical powering assumptions, you know, we've really not fully disclosed it, but just to kind of put color to that, for the Hammersmith, you know, we expect to certainly be able to demonstrate a three-point change. By the way, we powered the trial, and we have adequate power to demonstrate that. And again, we're doing hierarchical testing on that and then the following secondary endpoints. So I think we're well positioned to, to replicate in SAPPHIRE what we saw in the TOPAZ study. And then with regard to baseline characteristics, you know, Allie, we're looking at that very critically as sort of our publication planning and data disclosure plans. You know, really, we try to do that time to important congresses as we think, and conferences we think about over the year. More to come as we disclose that, but not likely to occur anytime in the near term, given the cadence of, you know, the medical conferences. Okay, great. Thanks for taking our questions. Our next question comes from the line of Srikripa Devarakonda from Truist Securities. Your line is now open. Hey, guys. Thank you so much for taking my question. As you develop apitegromab and SRK-439 in obesity, I actually had a couple of, you know, maybe basic questions on myostatin and obesity. Some studies have shown that myostatin is upregulated in obesity. Just wondering how well this dynamic has been characterized in patients. Is there a lot of variability? And how do you think that could potentially impact how effective the drug could be in these patients, especially, you know, if you consider the background of obesity versus SMA, where you've shown activity? And given that the studies show myostatin is also reduced as patients lose weight, do you think there's an optimal window where you treat patients with anti-myostatins? Thank you. Yeah. So maybe I'll start just talking about what we would expect to see in clinic with apitegromab, and then follow with SRK-439 in obesity. I think what we can say, which is, I think, very clear now, and we've shown that, I believe, in the TOPAZ study, is that targeting myostatin does result in preservation, if not increase, in lean muscle mass. I think we've shown that functionally in TOPAZ. I think there's consistent observation across. So myostatin is a very good target, and it certainly should be able to do that in the setting of obesity, where you have normal muscle. So I think that's the case. The fact that, you know, there was up, you know, that their signaling is high in myostatin, I think is interesting, but I do believe that we'll have an opportunity to demonstrate that in this setting, just as we will demonstrate it in the SMA setting. Great, thank you. Our next question comes from the line of Etzer Darout from BMO Capital Markets. Your line is now open. Great, thanks for taking the questions, and congrats on the progress. How are you thinking about the development of SRK-439? I mean, given the size of the obesity indication, and I guess is the proof of concept data with apitegromab the catalyst for an update, if you will, on development plans? And then maybe on SRK-181, just, you know, maybe next steps for the program, and maybe a little bit more color on what you described earlier during opening remarks and maybe the opportunity for future programs to be in sort of earlier lines of RCC, for example. Thank you. Yeah. So let me start with 439 and proof of concept and sort of overall path forward. You know, again, I think we're designed. We've shown to date at Scholar Rock that we can run randomized Phase III studies, we can run proof of concept trials. And so as I think about the cardiometabolic space, certainly to get apitegromab proof of concept, which will really, in my opinion, validate our approach. And as we report that out, we'll then, at the time, open up with 439, getting right into clinic, really positions us to drive 439 rapidly forward also to that proof of concept. And so that's our near-term horizon. You know, anything beyond that, I think really we're still open for discussions around how we get to bigger, broader trials. But I think for what we can do on our end, I think we can certainly drive value, if you will, for the company by driving to the clinical data in that proof of concept setting. So that's really our thinking around, and what Mo laid out very beautifully about how we're looking at both apitegromab and 439. For 181, you know, you know, the data that I shared, you know, and the way I try to put the color on it, this is really a tough group to treat. And to see this level of response rate in this heavily pretreated, failed on checkpoint inhibitor, I think really shows that proof of concept, which is why we reached those conclusions. But I think like in any therapy, and particularly in immunotherapy, earlier lines of therapy are really the place to take any such treatment if you really want to have major impact, because patients have been so beat up and progressed so much through these therapies that getting earlier makes sense. And so, frankly, that's the, that's the whole concept behind an end-of-Phase I meeting, is really to engage FDA and review our data and then begin to work with them to, to kind of lay out what would be the next logical steps in, in any further development of SRK-181. And as Ted said, right now, for us today, really pleased with the way DRAGON performed. I think it's met its objective, it's done its job, if you will. We'll wind that down, reset, take a look at what's happening with the FDA interaction. in the meantime, in 2024, it's really all on our focuses on our anti-myostatin programs. Great, thank you. Our next question comes from the line of Andres Maldonado with H.C. Wainwright. Your line is now open. Hi, thank you for taking my questions, and I'll reiterate my congratulations on all the progress. So one quick question from us on 439. So I guess in the context that the goal of next-generation obesity programs aims to really hone in and solve the issue of variability of patient response, you know, could you maybe talk about how much in this variance do you ascribe muscle loss, you know, driving that variation of patient response? And then a follow-up question to that would be, you know, given the safety and tolerability of apitegromab, which has been positive, are some of the treatment-emergent events more worrisome in the context of the combination? Thank you very much. So okay, maybe we'll do a tag team with Mo. I think your question is sort of the variability in weight loss that occurs with the current GLP-1 receptor agonist, and you see kind of a range across. Some patients do well, there gets to be a plateau for some. I think it probably, in my, as I review the literature and look at the data, some of it may very well be starting points for the patient's ability to get to adequate doses. I think there's a lot of things that affect the overall weight loss. From the muscle mass loss that we've seen, there is a range, but it's a fairly, you know, it's what? Between 20% and, say, 40%, that is definitely related to that. And so those are kind of related events, but our focus really is on that preservation of lean muscle mass, which we believe we should have a consistent effect across. Hence, we'll look at our proof of concept studies to move forward. But I think that's, that's the thinking there. And again, I think it, it's really interesting to your point about safety, and we've emphasized this because I, it really matters. It really matters. I think about weight loss therapies over time. They've been effective, but they've all been troubled by toxicities and safety issues that have prevented their continued use. I think what we're seeing with the GLP-1 receptor agonist is to date, and there's been wide patient exposure, you know, we're seeing some effects, but nothing like what we've seen in the past that would really warrant stopping these therapies. So that's a good thing. But any additional therapy that comes into this space, that's an add-on therapy, that's used to kind of offset some of the negative effects, like loss in the muscle, in my mind, really needs to bring no additional risk of toxicities, if possible. And that is where I believe, if you look at all of the conversations going on in other areas, other companies coming into lean muscle mass, I do think our approach, by hitting myostatin and only myostatin, will avoid off-target effects. And I think Mo walked through that. If you look at what happens when you hit activin receptors A and B, you start to get into some things that you may not want to see, right? That over time could potentially be troublesome, and that's also true with GDF11. So I like our approach. It shouldn't bring any additional risk to that risk-benefit profile. We'll obviously see that when we report out our Phase III data, but so far... We're seeing that in TOPAZ. We have patients coming on four years with really a very, very clean safety profile. I think in the cardiometabolic space, we separately want to continue with that, and I think we're positioned to show that. Our next question comes from the line of Ernesto Rodriguez-Dumont with Cowen. Please go ahead. Hi, thank you for taking my questions, and congratulations on the progress. Just to follow up on the myostatin on the obesity program functional endpoints for regulatory purposes. So, other myostatin programs that show muscle gains in other settings, are there any hints of functional changes from those programs that could lead the way to identifying a functional endpoint for the obesity program? And then also, do you expect the therapy to be a chronic therapy in conjunction with the GLP-1, or do you expect that there to be some kind of biomarker and limit to the therapy? Thank you. Yeah, so I think there's a couple of things. Again, back to the regulatory endpoints and, you know, we're going to begin the engagement with FDA and other agencies as we advance through IND and get more interaction with our clinical programs. But as an example, you know, the functional measures. Well, you know, as you know, we've included functional measures in the SMA program. You know, those were tailored specifically for the underlying disease. There's other ways to measure the grip strength and certain other measures that we could assess that would show that you're preserving and maintaining motor function. So that's something to consider. There's also measures that we can include that would look at quality-of-life measures. As you know, there are some significant associated GI effects with the current therapies. It's possible for our approach, and what Mo showed, which I think is very intriguing, is that we do have the potential to have some additive effect on weight loss, and by that activity, potentially getting the same effect on weight loss at lower doses. So, so there's really... I mean, we've got a lot of ideas around this. We're really at the beginning of this effort, beginning of the effort of kind of mapping out the full clinical program to registration, but not at the beginning efforts of our deep thinking around myostatin and targeting this space, right? So we've got a lot of good ideas, more to come, but I think we can, we can, do that. And then in terms of chronic therapy, that's a very, very interesting question. As you know, I think there's a challenge with maintaining therapy on the current GLP-1 receptor agonists. There is the potential for rapid rebound. If we take a look at muscle as a metabolic organ, which it is, the chances of restoring and preserving that could have some very interesting effects on maintaining the weight loss, even at lower reduced GLP-1 therapy. And what we're showing, at least from our perspective, is that we certainly can give apitegromab chronically. TOPAZ data is really underscoring that. As I mentioned earlier, we have patients on four years. So again, a lot of questions to address in the clinical program, which is exciting for me. But I'm really excited by the fact that Mo and Mo's team have SRK-439, that they've moved since I joined the company, to now talking about moving toward IND. Really good progress from our research team. Okay. Thank you. Very helpful. There are no further questions at this time. Mr. Jay Backstrom, I'm going to turn the call back over to you. Yeah. So listen, thank you. Thank you for your interest. Again, just to reinforce, I'm really delighted with the work our team has done, very pleased with our progress, and I really look forward to kind of driving through the rest of this year and really running into 2024, where we have some really major milestones. So with that, we'll close the call, and once again, thank you.