Good morning and welcome to Scholar Rock's presentation of top-line data from the phase 2 Embraze proof of concept trial. At this time, all lines are in listen-only mode. Following the presentation, we will conduct a question-and-answer session. To ask a question, you may press star, then one-one on your touch-tone phone. To withdraw your question, please press star, then one-one again. This call is being recorded on Wednesday, June 18th, 2025. I will now turn the conference over to Scholar Rock. Please go ahead. Good morning. I'm Rushmie Nofsinger, Vice President of Corporate Affairs and Investor Relations at Scholar Rock. With me today are David Hallal, Chief Executive Officer, Akshay Vaishnaw, President of R&D, and Jing Marantz, Chief Medical Officer, who is available for Q&A. For those of you participating via conference call, the accompanying slides can be accessed by going to the event section of the investors' page on our website. During today's call, as outlined on slide three, David will provide introductory remarks, Akshay will review the clinical results from the phase 2 Embraze trial, and then we will open the call for questions. Before we begin, I'd like to remind you that during this call, we will 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. I encourage you to go to the investors and media section of our website for our most up-to-date FCC statements and filings. With that, I'd like to turn the call over to David. David. Thanks, Rushmie, and good morning. Thanks to everyone for joining the call today. This morning, we are pleased to announce the top-line results from our randomized, double-blind, placebo-controlled phase 2 Embraze trial. At Scholar Rock, we are confident we are the leader in designing and developing potentially life-transforming therapies targeting myostatin in a very differentiated way. We design antibodies that bind to pro- and latent myostatin to achieve greater selectivity, allowing us to potently enable muscle growth with enhanced safety. As many of you know, in SMA, our approach was to selectively target myostatin with Apitegromab to safely and effectively improve motor function outcomes despite the use of SMN-targeted therapies. Indeed, we were gratified to demonstrate in the phase 3 SAPPHIRE registration trial that patients receiving Apitegromab had a statistically significant and clinically meaningful improvement in motor function as measured by the gold standard Hammersmith scale compared to placebo, despite the chronic use of SMN-targeted therapies such as Nusinersen and Risdiplam. Patients receiving Apitegromab had a gain of motor function, while those on placebo lost motor function. Importantly, Apitegromab was associated with a three times greater likelihood of achieving a three-point or greater gain on Hammersmith compared to SMN correctors alone. As result, we filed our BLA and MAA for A pitegromab for patients with SMA in the U.S. and E.U. Union, respectively. In the U.S., we remain on track for our September 22, 2025, PDUFA date, while also expecting approval in Europe in 2026. The robust medical evidence we have delivered with Apitegromab for patients with SMA through our TOPAZ, SAPPHIRE, and Onyx trials provides us with a strong foundation to evaluate our opportunity to meet the needs of patients living with other rare, severe, and debilitating neuromuscular diseases. We will be updating you on these plans later this year. I'd like to now turn to our phase two Embraze proof of concept study. Our effort with Embraze is to understand the role we may play in the treatment of patients with obesity. We are the world leaders in myostatin biology and know well that GLPs have brought needed innovation to patients with obesity and cardiometabolic disorders. While the benefits outweigh the risks, loss of lean mass is a well-recognized concern and something that the medical community is trying to address. The Embraze study is our initial effort in obesity, while our corporate focus is serving patients with rare, severe, and debilitating neuromuscular diseases. Due to lean mass loss and patients undergoing treatment with GLP-1 therapies, quality of weight loss is drawing more attention from the medical community. As shown here, a significant proportion of Tirzepatide-induced weight loss is due to reduction in lean mass, principally muscle. As we shared earlier this morning, we are pleased that the Embraze study met the primary endpoint. Specifically, Apitegromab dose stat, 10 mg/ kg with Tirzepatide, led to statistically significant preservation of lean mass, 54.9% relative to Tirzepatide alone, with a p-value equal to 0.001. Importantly, while Apitegromab increased lean mass preservation and our primary endpoint was met, patients on Apitegromab with Tirzepatide had a similar degree of fat mass loss and overall body weight loss as Tirzepatide alone, with an encouraging safety profile. With that, I'll turn the call over to Akshay to provide more details from the Embraze study. Akshay. Thanks, David, and good morning, everybody. As we all intuitively appreciate, preserving lean mass as a general health goal is extremely important and becomes especially so during weight loss therapy with GLP-1s. The preservation of lean mass during weight loss has the potential to enhance both cardiometabolic and musculoskeletal health. The goal of the Embraze study was to investigate the potential of our highly selective anti-myostatin approach to reduce the loss of lean mass in individuals with obesity. Participants were randomized to one of two arms of Apitegromab at 10 mg/ kg with Tirzepatide or Tirzepatide plus placebo. The primary endpoint change from baseline at week 24 in lean mass was assessed by DEXA scan, with a subsequent eight-week follow-up period where both Apitegromab and Tirzepatide were discontinued. The top-line data being reported today is from the 24-week treatment period. Full data, including for the additional eight-week follow-up, will be presented at a medical congress in the future. Let me start with the baseline features of Embraze. A majority, that's 82% of patients, were female, consistent with those of GLPs today. The age range was also consistent with GLP studies, with a mean age of 44.2 in the Apitegromab group and 42.6 years in the placebo arm. A majority of the trial participants were obese, meaning a BMI grade 2 equal to 30. We're delighted that the study confirmed our hypothesis. First, consistent with prior findings, that highly induced weight loss was due to loss of lean mass. Now, looking at the graph on the left, the combination of Tirzepatide with Apitegromab shows that 10 mg/kg significantly improved lean mass preservation relative to Tirzepatide and placebo. Specifically, at week 24, individuals receiving Apitegromab showed a 54.9% preservation of lean mass, which equates to 4.2 pounds of lean mass preservation versus Tirzepatide alone. The primary endpoint of the Embraze study was therefore met with statistical significance, a p-value equal to 0.001. Importantly, with respect to our secondary endpoints, the reduction of body fat mass and overall weight loss that resulted with Apitegromab and Tirzepatide were consistent with Tirzepatide alone. The graph in the middle shows that patients receiving Apitegromab with Tirzepatide over 24 weeks lost 18.8 lbs of fat mass, whereas those on Tirzepatide alone lost 17.7 lbs. Looking at weight loss once again, Apitegromab with Tirzepatide is consistent with what we see with Tirzepatide alone. These are indeed exciting results. The Embraze study met the primary endpoint, showing that significant and much-needed lean mass preservation occurs with Apitegromab and Tirzepatide versus Tirzepatide alone. Next, turning to safety, I note that Apitegromab already has over 600 patient years of data showing that it was well tolerated. The Embraze trial further demonstrated that treatment with Apitegromab in combination with Tirzepatide was well tolerated, with the safety profile of the combination being encouraging and consistent with the known profile of Tirzepatide. Adverse events, serious adverse events, and discontinuations due to adverse events were balanced between treatment groups. There were no serious adverse events or discontinuations due to adverse events related to Apitegromab. The data from Embraze confirms that our approach of selective myostatin inhibition has the ability to preserve lean mass and, in doing so, with an encouraging safety profile. In summary, despite the small sample size and a short treatment period of only 24 weeks, Embraze achieved what we had hoped it would. The key takeaways are, first, the Embraze results are another proof point of our innovative platform. Selectivity does matter. Second, with efficacy, Embraze demonstrated that combining Tirzepatide with our anti-myostatin Apitegromab, we were able to preserve lean mass by 54.9%, which equates to 4.2 lbs of lean mass preservation versus Tirzepatide alone. We observed high quality of weight loss when adding Apitegromab at 10 mg/kg to the Tirzepatide treatment arm. Third, data for the secondary endpoints were largely consistent between arms. Last, safety continues to be a distinguishing feature of our approach to inhibit myostatin. Embraze showed that Apitegromab was well tolerated and consistent with the known encouraging safety profile. All the data discussed today, including the full secondary and exploratory outcomes, will be shared at a future medical congress. Now, as we wrap up, let me address the path forward from here. Despite the excitement of the Embraze data, we're committed to our focus on SMA and additional rare, severe neuromuscular diseases. We look forward to the Apitegromab PDUFA data in SMA and, following its potential approval, studying it in the range of high unmet need neuromuscular settings. We'll share more regarding the last topic later in the year. However, today's Embraze results with 10 mg/ kg Apitegromab demonstrate what we believe to be a clinically relevant and muscle-related outcome in an adult population with obesity only further underscores what this dose has already shown in a pediatric population with SMA. Further to our commitment to neuromuscular disease, I want to introduce you to our next selective anti-myostatin candidate, SRK-439, which builds on the validated approach that delivered Apitegromab. SRK-439 is a novel, highly selective myostatin inhibitor. In preclinical studies, it exhibits an approximately 10-fold greater potency against myostatin without any changes in safety in GLP toxicology studies. The non-human primate subcutaneous administration of SRK-439 produced a remarkable gain in lean mass of up to 15%, beginning at doses as low as 0.3 mg/kg. We're looking forward to initiating clinical studies with SRK-439, with the IND targeted for later this year. There's great potential for SRK-439 to be an infrequent subcutaneous anti-myostatin antibody, and we look forward to exploring its potential as another Scholar Rock highly innovative therapy for patients suffering with severe neuromuscular disease. With that, I'd like to turn the call back over to David. David. Thanks, Akshay. In closing, while we are pleased that the highly selective anti-myostatin approach from our innovative platform continues to deliver, we are acutely focused on the key priorities that will enable us to build and scale Scholar Rock into the next great global biotech powerhouse. Over the next couple of months and beyond, we are focused on, first, the upcoming September 22nd PDUFA date and the anticipated U.S. launch of Apitegromab for patients with SMA. Next, the potential E.U. approval in mid-2026 in a series of country launches in Europe, starting in Germany. Our ambition is to reach patients with SMA in up to 50 countries around the world by extending in all regions, including Asia-Pacific and Latin America. Fourth, develop Apitegromab and SRK-439 for additional rare, severe, and debilitating neuromuscular diseases. Finally, today's Embraze results validate our goal to explore the potential of our anti-myostatin approach in combination with GLP therapies to enhance the quantity and quality of weight loss and obesity. While we remain focused on advancing Apitegromab and SRK-439 in clinical development for rare neuromuscular disorders, Embraze raises the exciting possibility to partner our potent and selective approach to targeting myostatin. In that regard, we have a number of earlier stage research assets, both anti-myostatin antibodies and the fusion of those with GLP therapies, which we think have the potential to be meaningful therapeutic candidates in the future. With that, we'll now open the line for questions. Operator. Thank you. As a reminder, if you'd like to ask a question, please press star one,one. If your question hasn't been answered and you'd like to remove yourself from the queue, please press star one,one again. Our first question comes from Michael Yee with Jefferies. Your line is open. Hey, guys. Thank you and congrats on the data today. Maybe just two questions. One is, I think what I hear is your enthusiasm for the data, but also perhaps maybe an opportunity that this could also be used in other rare diseases or other muscle diseases such as DMD, and perhaps that's a life cycle extension or other opportunity to think about on top of the lean Apitegromab and SMA. I just wanted to understand whether perhaps there's more value in that rather than just partnering out, and how you think about 439. My second question relates to, obviously, your strong comments around regulatory review, and I just wanted to understand, with a couple of months left here in the review, do you plan to hire a salesforce, or have you hired a salesforce, or just remind us how you think about "preparing for launch"? Thank you. Yeah, thanks, Mike. It was wonderful to be with you recently in New York, where we did share our view on the value of our platform and the products coming out of the platform of Apitegromab and SRK-439 and sort of how Akshay and I and the company are looking at rare, severe, debilitating neuromuscular disorders and how we can really extend our leadership position there. I'll ask Akshay to comment a little bit on what you say on the value that we see in SMA approval, how we think, and how we're going to shed more light for the community on our approach to DMD and other rare, severe, debilitating neuromuscular disorders. I'll come back to your second question in a moment. Akshay? Yeah, thanks, Mike. I think we can't be more excited about today's results. As you say, the opportunities abound for us. With respect to Apitegromab and SRK-439, our focus on severe neuromuscular diseases is truly there, and we continue to think about, obviously, not just SMA, but the plethora of additional neuromuscular disease opportunities. Now, you highlighted Duchenne muscular dystrophy. I agree with you. I think that's a very important area of unmet need and one in which we have very good preclinical data, which we shared at MDA earlier in the year, and a clinical setting we're thinking about very carefully. We want to share much more with everybody later in the year about our first entry into an additional neuromuscular indication beyond SMA. We believe there are many more beyond that. Upcoming, we'll share some preclinical data with FSHD and on and on. We look forward to that, but couldn't be more excited with the proof point today in Embraze. Thank you. Mike, as I think Akshay and I have shared, we do think about 439 as a high-value new therapeutic candidate with our ambitions in that space. You are absolutely right when we think about, well, what is the value for all stakeholders, including our investors, and us partnering 439 in this space or holding it for the research and clinical development of a wide range of rare neuromuscular disorders. We get pretty excited about that potential. Secondly, regarding the regulatory review, Akshay will comment in a moment. As Keith Woods has shared, we have had the medical affairs and market access teams in place, all of the work to establish our U.S. commercial team. Obviously, we announced the arrival of Rebecca recently, who will be our Chief Brand Officer and U.S. General Manager. She joins us from Argenx, and she is leading the charge along with Keith in hiring our team ahead of an expected or anticipated approval around our PDUFA date. Akshay, any comments on just the kinetics of the regulatory discussions? Yeah, no, as we discussed in New York, Mike, we're very happy with the progress so far, and we continue to feel we're very much on track and look forward to working with the agency towards that PDUFA date of September 22. Thanks, Mike. Thank you. Thank you. Our next question comes from Alison Bratzel with Piper Sandler. Your line is open. Hey, thanks. Good morning, and thanks for taking the question. David, I think you addressed this at the end of your prepared remarks and in response to the last couple of questions, but I do want to drill down and make sure I understand this. It sounds like 439 is going forward in neuromuscular indications only. Can you just help us understand why that makes sense strategically, why it makes sense to advance earlier stage assets in obesity rather than 439? Just looking at this approach in obesity more broadly, could you help us frame just what you're looking for in the Myrcamab updated ADA just to inform on how the latent myostatin targeting approach compares to targeting the active and type 2 receptor? Same question, comparing Embraze data to that data shown in the COURAGE trial for Trevogrumab and Garetosmab. We'll just be really interested in any thoughts there. Thank you. Yeah, Ali, I'll start on the rare neuromuscular franchise and cardiometabolic. They can weigh in on what we expect at ADA and beyond. Ali, I benefit from history. And as you know, I spent a lot of time building what I think is one of the most durable franchises in rare disease at Alexion, where over a 10-year period of time, we established Eculizumab into a multi-billion dollar therapy that was serving patients with multiple devastating rare diseases. We learned full well what the value in our experience there was to have additional therapeutic options for patients over time to play both offense and defense with this very valuable franchise. That, of course, became the move from Soliris to Ultomiris, and both of those continue to be important products. When I think about the opportunity we have here at Scholar Rock to be the leader and extend our leadership position in rare, severe, debilitating neuromuscular disease therapies, as I've noted, we see Apitegromab and SMA alone globally as an opportunity to drive tremendous growth through the end of this decade and into the next. When we also think about additional opportunities to meet the needs of patients, we've talked a little bit about DMD, and there will be others that we shed light on in the future. I not only think about the opportunity with Apitegromab, but how valuable would it be for us to maintain ball control on SRK-439 as a subcutaneous, very potent, very selective, independent therapeutic candidate to Apitegromab? We think that can have tremendous value for our stakeholders as opposed to, let's just say, continue on these efforts, which I think are very extraordinary efforts. We love the results that we see today, but we think that this is an undertaking that may be better placed with those companies a little bit more focused on the cardiometabolic and obesity space. Maybe for a closer look at ADA, but Myrcamab and other things, Akshay can weigh in. Yeah. David, Ali, I think ADA obviously is going to be an interesting meeting for everybody. We've had the Trevogrumab data, was it last week or the week before, now our data, the Myrcamab next week. I think first and foremost, what we all want is to achieve high-quality weight loss for patients with safety. High quality means not just quantity of weight loss, but also preserving lean mass. We think that will have profound clinical benefits for patients in the long run. If we want to do that safely, I think today's data distinguish our highly selective anti-myostatin approach against pro and latent myostatin. The safety that we were encouraged by in our SMA studies is now further demonstrated here in the context of an adult obesity population. In a prevalent setting like obesity, let's be clear, these drugs need to be very, very safe, given that I think with respect to Trevogrumab, the efficacy data, everyone has digested. I think everyone also noted some of the safety signals there, which Regeneron highlighted. We do not see any of those kinds of issues with our approach today. I think some of the discussion here for me goes back to the science of what's happening. If we look at our selective approach targeting pro and latent myostatin, it keeps us away from the rest of the pathway members like GDF11 and Activin A or acting at the receptor level at ActRIIA and B. I think that's just a more complex situation. While it does have potential benefits, it can also have potential safety ramifications. I think the focus for us next week at ADA and the Myrcamab data, and of course, really should speak to the data, it's not for us to do that, but safety will be very important to go over carefully. Let's see what they can add in terms of efficacy beyond what the GLPs can achieve alone. I'll leave it there. Thank you. Thank you. Thank you. Our next question comes from Tess Romero with JPMorgan. Your line is open. Hi, David and team. Good morning, and thanks so much for taking our questions here. At this point, what are the gating items that you're working through with respect to filing the IND for SRK-439? The second question from us is just how do you think about the need or the desire for a subcutaneous option for SMA targeting myostatin? Is this a calculation that you are thinking through as you try and optimize or maximize this opportunity for the company? Thank you. Yeah, thanks, Tess. As Akshay and I both noted, we're anticipating an IND later this year for 439. We've indicated really over the last couple of months that we've always viewed SRK-439 as a high-value asset, independent of which therapeutic area it was aligned to. And really, I think when we think about 439 within the rare, severe, debilitating neuromuscular disease area, we're just underscoring what we think is a tremendous opportunity for ourselves with Apitegromab, which, of course, as we noted today, is an IV infusion, about a once-monthly, one-hour IV infusion. But we do think about optionality. I think Keith has noted in prior calls and prior investor meetings, competing with ourselves makes a lot of sense for us to have maximum optionality for the patients and families we aim to serve with SMA and additional severe neuromuscular disorders. And then also thinking about the medical community. We become very excited about the opportunity that's in front of us and how we can build and grow that opportunity for many, many years to come. Thank you. Thank you. As a reminder, to ask a question, please press star one one. Our next question comes from David Nierengarten with Wedbush Securities. Your line is open. Hey, thanks for taking the question. I had just one on the safety side, just to double-check. I mean, were there discontinuations? Were there any safety signals? I guess I had two questions. Maybe as a follow-up, were there any indications of improved muscle quality and strength along with the preservation of lean mass? Thanks. Thanks, David. Akshay? Yeah. From a safety perspective, I think no news is good news. We're very happy with the very balanced safety outcomes between the treatment and after. Essentially, the safety profile looks very much like whatever AEs we're seeing, and the balance between the arms are associated with the Tirzepatide effects on the GI tract, which are well-known for GLP-1. Overall, the study safety, both the Tirzepatide and the combination arm, look very encouraging to us. We'll share more at a medical congress in the future. That safety builds on now in an adult setting what we had already seen in a largely pediatric population in SMA. I think that's all to the good. Beyond that, for the secondary and exploratory outcomes on various metabolic parameters and also exploratory motor outcomes, we'll share again at a future medical congress. I think the top line is that this is a very short study of 24 weeks, and the sample size is pretty modest at 100. Principal outcome of the preserved lean mass, longer, larger studies in future will hopefully demonstrate the translation of that to clinical benefits. As of now, in the 24-week context, they look largely balanced across the two arms. More to come at a meeting. Thank you. Our next question comes from Evan Seigarman with BMO Capital Markets. Your line is open. Hi, Malcolm Hoffman on for Evan. Thanks for taking our question. I wanted to ask, when you think about Apitegromab results and what you can pull from these results for potential follow-up molecules, are there any specific trial enrollment criteria you think would be most useful to consider in the future if you or others are hoping to show additional weight loss over incretins alone? Or is this really all about kind of the molecule specifically? Appreciate your comments here. Thanks. Thanks. As we noted today, we think that our highly innovative and differentiated platform and then products coming out of the platform position us actually quite well to develop highly innovative therapeutics for the obesity space. We think we're the best in the world at drugging myostatin. We think the drug in and of itself and the way that we design these drugs is very, very important. I would only note that for Akshay and I to share with perhaps smaller groups of folks, we have a lot of insights on the way to design these trials and really deliver some wonderful results that can be quite insightful, not only about preserving lean muscle mass, Akshay, but of course, delivering the functional outcomes that will make a difference for patients over time. Yeah, I think you covered it there. Thanks. Thank you. Our next question comes from Gary Nachman with Raymond James. Your line is open. Hi, guys. And congrats on the Embraze data. With 439, aside from better administration as a subQ, do you expect the anti-myostatin effects to be roughly similar to what you saw with Apitegromab in obesity just based on the preclinical data? Could you potentially push the dose even higher and maybe get even better effects in terms of the weight loss and preservation of lean muscle mass? And then just to confirm, I know you mentioned it a couple of different ways, David, but will you only look for a partner to help fund an obesity program, or will you consider maybe at least doing it alone, at least in the early stages, to try and get more value out of that whole program? Thanks. Why don't we start first with Akshay and 439 and what it holds from a promise perspective? Is it about just administration, or is it about drugging myostatin even more potently? Akshay? Yeah. Thanks, Gary. SRK-439, as you saw from the slide during the former remarks, is a very promising agent, and it looks to be more potent. Now, how that translates in the clinic will be a matter of let's do the phase one and go from there. We know, however, that Apitegromab is also an outstanding anti-myostatin agent. We believe we maximize saturation of the target at 10 mg/ kg. The very important data we saw in SMA is the result of that. Now we're seeing a really pretty profound result on muscle mass preservation in the context of the adult obesity population. I think we know how to saturate this target, and at least preliminarily, all our data would suggest we do it with safety. Further comments on SRK-439, let's get that phase one done and come back after that. Back to your point, we think we've demonstrated that we can do a lot from a capability perspective on our own design, best-in-class therapeutics, design clinical trials that can be highly informative and, again, delivering results at a high level of statistical significance, in this case with Embraze, the preservation of lean mass. I think the question that we've asked ourselves is, given the amount of patients and the amount of time, and is this the best use for our capital and our time as a company to continue down the large pivotal registration trials, or is this something that is better left for those companies that are investing an enormous amount of capital and time into that space? When we think about the opportunity to create tremendous value for all stakeholders, first and foremost, patients and families, importantly, our investors, we really want to stay disciplined here. We do believe we are best positioned to develop, as I noted in my prepared remarks, with an anti-myostatin approach and/or fusion therapeutics with our anti-myostatin approach and GLP pathway therapeutics. We think we're well-positioned to design what could be very meaningful medicines in the future. Okay. Thank you. Thank you. Our next question comes from Kripa Devarakonda with Truist Securities. Your line is open. Hey, guys. Thank you so much for taking my questions and congratulations on the data. For Apitegromab and SRK-439, I was wondering if you're thinking about this more as a lifecycle management. David, you talked about Tirzepatide and Altamix, and that's a great example. Is that the best analogy? Or knowing how different the drugs are right now, is there a way you can prioritize different indications between the two as you think about developing them? Maybe a more academic question, but I was wondering if what you're seeing is true preservation of muscle with the anti-myostatin, or if there is actually a change in the composition of the muscle that you see at the end of the study versus beginning study? Thanks. Thanks, Kripa. Yeah, it's a very good question. It's not just purely lifecycle management. I think we see a wide range of opportunities for us in addition to SMA. We think we have really demonstrated some remarkable opportunities here through the incredible work over the last six-plus years in SMA and how we learned from that, and then looking at the other innovations in the world and moving forward treatment options for patients with other neuromuscular disorders. We think that we have an opportunity to do something very special here across these diseases. We also think we've demonstrated, as Akshay and I noted earlier, something pretty special in the obesity space as well. Today, right, when we think about Apitegromab and its long runway of value creation in SMA and then other additional severe and devastating neuromuscular disorders, we just think there's so much to do. Why not have ball control with our current two assets, but then also be very thoughtful on how we might be able to impact, as I noted, even through partnership, how we could impact the obesity space over time? Akshay? Yeah. Just to go to the kind of scientific and translational aspects of what might be going on here, Kripa. We do not know exactly fiber composition and change in the human context, but we do know a lot from the preclinical context. We know that our anti-myostatin agents lead to profound changes in type 2 fibers and power-related outcomes for muscle. The other thing to note, and the large body of human data here, is that the ratio of lean mass to fat mass obviously changes insulin sensitivity, metabolic rate, and other metabolic parameters. In that regard, you note that the ratio goes from 30/70 for lean mass to fat mass for Tirzepatide alone to 15/85 for Apitegromab and Tirzepatide. I think that can only be good for individuals with obesity. Again, this is a very short-term study. We've got to imagine this playing out over many years and how that will change over time, hopefully beneficially for patients. We also know from prior human studies that every kilo of lean mass lost can, there's a study by Dirk Verbiesen, which some of you may be familiar with, result in changes in leg strength and exercise capacity and insulin sensitivity. These are very early days. I think the most important principle we've established is that we can safely be associated with preservation of lean mass in the obesity setting with patients undergoing Tirzepatide treatment. Longer, larger future studies will uncover what that does to better metabolic health and also better physical functioning. Thank you. Our next question comes from Marc Frahm with TD Cowen. Your line is open. Hey, thanks for taking my questions. Congrats on the signal that was shown today. Just maybe back on SMA, just the review. Can you maybe comment to kind of where the discussions are there? One, confirm that there's still no plans for an, but then also just the discussions towards an indication and whether there may be some interest of the FDA in kind of thinking about SAPPHIRE as a unique population versus the wider SMA patient population. Yeah. Thanks, Mark. As we've noted, conversations with the agency continue to be very constructive. We believe there's a wide and long body of evidence that we've created from our phase two TOPAZ to our phase three SAPPHIRE, and now our long-term extension of more than 230 patients remain on therapy. We'll continue to work with years on the body of evidence that we've generated over these many years. Akshay, anything else to add? Yeah. I mean, I think on the specifics of the AdCom, I think, as we've said in public forums before, to date, we've heard nothing about that. Obviously, we don't go into the day-to-day of our regulatory dialogue. If we were to be informed of an advisory committee, obviously, it's material and we'd have to let everybody know. We are very encouraged by the tempo of progress that we've seen to date. Again, that's why we re-guide the September 22 date for later in the year. Thank you. Our next question comes from Dennis Kennedy with LifeSci Capital. Your line is open. Hey, thanks for taking the question. Congrats on the data this morning. Do you see any particular segment within the overweight or obese population that stands to benefit most from a lean mass preserving agent based on the data shared today? I know it's a small n, but any identifiable subgroup of patients that responded particularly well in terms of lean mass preservation? Yeah. So Dennis, I mean, this is obviously an important question. I think what you're alluding to is that we're in the very early stages of the study of these various agents in obesity. Unmet need is being redefined. Market segmentation is going to occur. I think physicians will adopt a much more sophisticated approach as they look at the different age ranges and the different needs as we age. In that regard, I do think that I'm most interested with respect to today's results and the impact we can have in settings like sarcopenic obesity. This is a term many of you will have heard of. As we get older, we all lose core strength. We all lose lean mass. Applying GLP-1 in individuals who are obese as they're aging is obviously a prime setting where you want to preserve lean mass. We know that core strength and maintaining core strength in age leads to prevention of falls and other adverse physical outcomes. I am very interested in what agents like our anti-myostatin portfolio can. Thank you. Our next question comes from William Wood with B.Riley Securities. Your line is open. Hi. Thank you for taking my questions today. Congratulations on the data. Just two from us, actually. I was curious on the lean mass, fat mass assessments. Could you remind me how often DEXA was performed and if you could speak to the kinetics of the fat lean mass loss over time? Essentially, was there greater lean mass retention at the beginning and then it slowly lost efficacy over time? How did the kinetics of those both change over time? And then. Thank you. Yeah. Yeah, William. We can say that the profile of overall weight loss, the kinetic over time, was very similar to what's previously been observed in Tirzepatide studies. I say that with respect to both arms in our study. We'll obviously share more at a medical meeting in the future. With respect to the specifics of lean mass evaluation and the time points, DEXA scans were conducted at two time points, baseline zero and at 24 weeks. We do not have specific lean mass data between those two time points, but the overall weight loss profile looks very similar. I think inferentially, I imagine that the lean mass effects are commensurate with that. That is a speculation on my part. We do know that at week 24, however, we see 54.9% preservation, which is a terrific result. Right. Gotcha. I appreciate that. Also, just based on September enrollment completion for Embraze, it looks like just sort of being near the end of 2Q, you might be nearing the completion of the 32-week exploratory section where patients have come off drug. Could you provide any qualitative, even pooled commentary on what you're seeing in terms of weight regain or functional changes, understanding it's only about an eight-week time point, but what you may be seeing and how you think that may sort of dictate for a maintenance portion or off drug on the ability of muscle to keep fat loss off or fat off? Yeah. I mean, the follow-up period obviously is an interesting point. We've tried to focus our energies on getting the primary endpoint out, the week 24 data. We're still analyzing the follow-up data, and we'll get those out in the future, presumably at a medical meeting. That is all I can say for now. I know that safety overall was well maintained throughout the study out to week 32, but as far as the parameters, we'll have to finish our analysis and comment on that. Got it. Appreciate you taking our questions and congrats again. Thank you. Thank you. Thank you. I'm showing no further questions. This concludes the question-and-answer session. You may now disconnect. Thank you for your participation. Good day.