Fantastic. All right. Thank you. Good afternoon, everyone. Welcome to the next session here at the Jefferies Healthcare Conference. I'm Michael Yee, a senior biotechnology analyst, and really happy to have a couple members of the Scholar Rock management team with us. Importantly, that's somewhat of a new team that got introduced over the last month. I'd love, perhaps, although David, you were chairman, an opportunity for you also for the webcast to just briefly introduce yourself and also Akshay, and then we'll go into some hard-hitting questions. Great. Thanks, Mike. We're thrilled to be here. Given the announcement on April 28, Akshay, myself, Keith, and Vikas are really excited about the next phase of growth for Scholar Rock. A little bit about my background: I've spent about 35 years in the space at companies like Amgen, Alexion, Biogen. As it relates to Scholar Rock, as Mike noted, while I'm rounding out my first month as CEO, I'm starting my ninth year as board chairman. I have a lot of personal investment in where we are today as an organization and, more importantly, where we're going from this point forward. I've been working on Scholar Rock for quite some time with my partner, our President of R&D, Akshay Vaishnaw. Akshay? Thanks, David. Delighted to see everybody. Good morning, good afternoon, good evening, wherever you are online. Great to join you and the other attendees at this meeting. I've, as you know, been in biotech since 1998. We met first at Biogen in 2002. We had fun working together there. We kind of reunited back at Scholar Rock, which was great. I've had my journey since then through Alnylam for 19 years after that stint at Biogen. Thanks for dragging me out of retirement to have some fun at Scholar Rock. Yes. I mean, maybe that's a good sort of opening question because it is an important question since that announcement last month, which is, you know, for David, what would what or why would you move from Chairman to CEO and want to do this, you know, from an operating Chief Executive Officer role when you were Chairman and kind of, you know, overseeing it anyways? And for Akshay, coming out of retirement, obviously super successful R&D career at Alnylam, why would you come over to do this when you're in retirement? For both of you, what spurred that? It was a big announcement a month ago. Yeah. No, thank you. I think it caught you by surprise, Mike, a little bit. Definitely caught me by surprise. Look, you know, while we're on this theme of coming out of retirement, I'll say that I became board chairman at Scholar Rock. It was the first thing I did after 11 years at Alexion, building that into what we think, you know, became one of the special global rare disease powerhouse biotech companies. I saw a lot of similarities at Scholar Rock then as to what I saw at Alexion. Remember this, Mike, complement wasn't new, but Alexion could drug complement unlike any other company in the past that had failed trying to drug complement. What I saw at Scholar Rock in 2017 was the opportunity to drug Myostatin and do things differently than any other company had done in the past. As we all know, there had been many failures in targeting Myostatin. Over the course of this eight-year journey, we've had some ups and our share of downs. Any successful biotech company is going to have any number of near-death experiences. One of those, I think, really came after the 12-month TOPAZ data. Six-month TOPAZ data comes out. I am with my dear friend Akshay, who's on the board with me. We said to ourselves, this is going to be a major new therapy for patients with SMA. Stock runs from somewhere in the teens up to $30, $40, $50 a share. Twelve-month data comes out to us also convincing. Yet there was sort of a read-through on 12-month data that became, is it apitegromab? Is it Spinraza? There's no control group. Stock goes into a slide where for several years, in essence, Mike, we became the Rodney Dangerfield of biotech. `Oh my God, the stock went to like $4, $5. Yeah, exactly. Why come out of retirement? The theme of talking people out of retirement dates all the way back to Jay Backstrom, who is one of the best hires I ever made. He was the Executive Vice President of Acceleron when they were acquired by Merck for $11.5 billion. At Acceleron, they were largely drugging the same targets that we were at Scholar Rock. I thought he was the ideal CEO at the time in 2022 to demonstrate and take us from the TOPAZ era of a lot of doubt, but a lot of promise, into the SAPPHIRE era of demonstrating the confirmatory results that we saw in October. When I talked Jay out of retirement, it was clear. He was out of retirement too. Exactly. I'm noticing a thing. Right. It was clear to Jay and I that if he comes in for a couple of years and gets us to this stage, he just celebrated a very special birthday. We were only going to have Jay for so much time. As a result of that, we knew with the powerful data that we were sitting on, this was the ideal time for a transition to scale the company into a global biotech powerhouse. I was not going to do it alone. Jay and I discussed what we would need in the organization along with the board. Akshay was on the board. We thought about it, Akshay, and we thought about how special could it be to take four like-minded individuals that have built companies like Alexion, Argenx, and Alnylam, put us together on day one, and help us scale as an organization, and do some really special things from an innovation and platform perspective in developing new therapeutics, as well as bringing apitegromab to patients with SMA to every region around the world, which Keith just recently. Let me add to that because while two of you are up here, two others actually I think are important to drive a potential to have this drug around the world commercially, not an easy task for a small biotech. You have two others you might want to call out their names in terms of what they came from and why you think that their experience should be able to help launch this drug successfully around the world. Keith Woods and I first came to know one another at Amgen, then worked again together at Alexion. His best work to date has been what he did as Chief Operating Officer at Argenx and really driving home a very successful launch of VYVGART, not only in the U.S., but in 30 countries around the world. He joins us as Scholar Rock's Chief Operating Officer. Once again, just like Akshay, talk Keith out of retirement. It was not just me. It was the opportunity at Scholar Rock and the opportunity of the four of us to work together. Mike, I'm now commencing my third consecutive decade of working with Vikas Sinha, who for 12 years oversaw the build-out and scale at Alexion globally, where he was the CFO there and really helped us to build an extremely efficient company on both the top line and the bottom line and build our strategy that really was built to last. We think the combination when we all sat together for dinner, it wasn't just any one of us. It was the combination of four of us coming together with our collective experiences, but our desire to do good for patients, which really make at this moment in time what we're doing to prepare for the launch of apitegromab really special. Perfect. Okay. The four of you definitely have a long tenured track record of having done it very successful at some of the most successful orphan rare disease companies. Hopefully that is setting the stage for what you should do for Scholar Rock here on the precipice of an FDA approval for another rare disease drug. Okay. Let's take some of that because there's certainly no shortage of important developments coming. All of this sort of happened like a month or two before some important phase II obesity data in Myostatin. Actually, just days ago, another company, Regeneron, put up some obesity Myostatin data. Lilly's got their data in a couple of weeks. Tell me about your phase II Myostatin obesity readout. What should we expect given that it feels like Regeneron has put a bar out there of 50%? Do you think that's a reasonable bar? Are you going to be better, lower? You know, what should we expect? Thanks, Mike. I'll make a few comments. When's this data coming, I guess? Yeah. That's June. We are in the month in which we will provide you all detail once we see it on our EMBRAZE study, our exploratory phase II study, which compared patients newly starting on tirzepatide with or without apitegromab. The readout is a 24-week endpoint looking at preservation of lean mass. We are excited to have a look at that data and share it all with you later this month. We do think that Regeneron in many ways sort of underscored a lot of our thinking at Scholar Rock. As the world leaders in Myostatin biology, we felt like it was our obligation to understand how we might be able to address one of the blemishes with GLP-1s, that being the loss of muscle. That is why we embarked on our journey. A couple of things from the COURAGE trial, and then I'll bring Akshay in. I think it confirmed what everybody knows is about a third of overall weight loss comes from lean mass, not an ideal outcome from GLP-1s. Number two, I think it demonstrated that Myostatin alone can provide important preservation of lean mass. I think it also underscored, as we said, safety is at a premium in this patient population. Should one inhibit more than Myostatin, there could be some unintended consequences that would really limit a product profile in this setting. I think we saw some of that for sure with the triplet regimen. One other thing I would just note is that, you know, we've continued to see an exquisite sort of safety profile with our therapy apitegromab with the unique approach at Scholar Rock. We look forward to having a look at our data for the first time and sharing it with all of you. Akshay has been thinking a lot about what we saw earlier this week from Regeneron and what to expect with EMBRAZE. I would just hand it over to him to comment. Yeah, you covered a lot of it well, David. I mean, I think the COURAGE data from Regeneron validate all the work that had gone on in mice from ourselves, from others investigating anti-Myostatin in combination with GLP-1 in diet-induced obesity and other models. Clearly, the Regeneron data are encouraging in terms of the preservation of lean mass, which I think is highly desirable. If we think about this being maybe the first chapter of the obesity story, there are many chapters to go. If patients are going to be on these therapies for a long time, which they probably will be, or cycling on and off to lose 33% each time of the masses, muscle is just not the right thing to do. It's not right metabolically. It's not right from a functional perspective. David, you've said aesthetically as well. I mean, it can change your appearance and not always for the better depending on muscle atrophy. I think the Regeneron data do signal that this class of treatment will continue to be studied in the future. However, the other thing for us from a Scholar Rock perspective is that as with many other anti-Myostatin antibodies, you know, there was that safety signal that many people have noted, particularly in the high-dose arm with the anti-Myostatin antibody. I think the treatment emergent severe AEs were roughly 50% greater, and the serious adverse events were about twice the rate. You know, that's notable, I think. I think we all want to understand those issues better. Myostatin has been a very difficult target to drug. I think our safety experience with it and the way we've approached the way the antibody was built in the first place stands us in good stead. We are very encouraged about the safety profile we have. We look forward to the EMBRAZE data. It is only a very short period away now. I think the preservation of lean mass is something we look forward to. Hard to speculate on the quantity. Also pretty confident that from a safety perspective, we will continue to look good. Okay. They kind of set a level and a number that I think honestly a lot of people thought is not shocking either way at 50%. Previously, the management team had said 20%-40% is kind of good. Is that, or at least powered for that, I guess. Right. How do you kind of thread 20%-40% versus 50%? You know, how are you thinking about that? Appreciating safety is important. Yeah, I'll start. I mean, we're within, you know, the month in which we'll disclose it. I guess we'll know it when we see it. Again, I think for the first time, like you all, we saw the Regeneron data, and that kind of sets a bar on what one can expect with the inhibition of Myostatin alone. One of the things, Mike, that we're still asking ourselves is, okay, you know, six months can only tell you so much. It seems to make sense that preserving lean mass over a longer period of time may garner more insights clinically from a metabolic functioning and even aesthetic perspective. I don't know whether it's, you know, 20%, 40%, 50%, or something different in there, what it all means yet. I think everybody's still trying to understand what's the clinical regulatory approach in an evolving marketplace for the GLPs in and of themselves. I know that Akshay and I, along with Keith and Vikas, we think about how important it is for us to stick to our knitting in rare, severe, debilitating neuromuscular disorders with an opportunity to serve patients globally with SMA. Under the leadership of, you know, one of the best R&D executives in the industry, thinking about the pipeline and a product as we think about additional rare, severe, and debilitating neuromuscular disorders. Do we want to just be careful not to necessarily step into a trap by following something that still has plenty of questions associated with it, but nonetheless some important data that does indicate that there can be a role for Myostatin inhibition in this patient population? I think I heard that loud and clear, but it's certainly also the analyst view. I would say Wall Street view that the primary focus, which is a perfect transition into the SMA opportunity and then other indications like DMD, that should be your bread and butter and where you are spending tremendous amounts of time and focus. Whereas obesity is interesting. You said trap, but you know, the idea is that we need to figure that out a bit and see where the landscape goes. That's, you know, and it's always been said as something that's possibly partnerable. Let's see how that goes. Let's transition then into the idea that you are on file for apitegromab and have a PDUFA around September 22. Right. If I got that right. Therefore, how have FDA interactions been in the CDER group of the neuro division or which division? That's right. Okay. So you filed. How are the interactions? How are things going? We're into June. The PDUFA is only four months away. Marty McCary will be here in about 10 minutes. Maybe we'll bring him in the room, but no, in all seriousness, tell us about your ongoing interactions with FDA and what you feel about how things are going. Akshay? Yeah. I mean, thanks, Mike. It's obviously been a few months now, so we're well underway. This is neither the right time or place to get into the details of the day by day with the FDA. One thing I can reassure everybody is that notwithstanding the noise we've heard about what's going on in D.C., from our perspective, the BLA review has gone well. We're happy with the progress. Everything seems to be functioning as on time. That's why we've continued to guide about September 22 as the PDUFA date. We really don't have anything to report there other than good steady progress per the clock. There's no sign or messaging of any adcom. Is that safe to say? You know, I mean, I think everyone would agree that if there was going to be an adcom and we'd heard that, we're obliged to share it. Just the very fact that I haven't said that today should signal that today we haven't heard about the need for an adcom. The obesity data that is coming with the drug, that is standard practice to have to submit that data and just send that in because the patients have been treated on that, even though I hope that would not trigger a major amendment, but that is just additional safety data. Yeah, no, you know, we'll do a day 120 safety update as per expectation. That's all just, you know, SOP. You just do that. We have no surprises. So it's all good. Okay. Therefore, things are progressing on track. How are you thinking about a label? Philosophically, obviously, like the fact that you ran it in non-ambulatory, but then obviously ambulatory is a key part of the market. Obviously, age groups, your primary analysis was based on 2- 12, but you know, SMA certainly spans beyond that. You ran this study because you want to focus on a group to ensure success, right? We do not want a huge homogeneous population. Actually, you look at Biohaven's design, they had a whole bunch of things going on. Roche also is planning to do ambulatory, non-ambulatory, and a whole bunch of things. That could be risky, but it also means that they could have a broader label. Do you expect a broad label or what is the view about that to set expectations? Yeah, maybe I'll start and bring Akshay in. First of all, we are very proud of our development program for apitegromab and took no shortcuts with the robust nature of the TOPAZ phase II study, which was hypothesis generating and really helped us to design the SAPPHIRE trial. We now have more than 95% of those patients from both of those trials. More than 230 patients remain on our long-term Onyx study. As you might imagine, some of those patients have now been on therapy beyond, you know, five years. We've most recently released the four-year data from TOPAZ. We think that body of evidence and the way the FDA has looked at SMA as a single disease bodes well for us in terms of our ambitions to be able to reach as many patients with SMA as possible. Akshay, I will hand it over to you. We often talk about how the biologic plausibility and the way that this therapy works really bodes well for how many patients we can serve independent of ambulatory status and/or age. Akshay? Yeah. I mean, I think it's fair to say most people agree that the role of Myostatin in health and disease throughout life is well established now. We've certainly validated that in SMA. As we've done our SMA work, and David was alluding to, we see efficacy across the entire age range from 2 to 21, which we've formally evaluated. We've seen that across two studies. I don't for a minute think, given that Myostatin is a physiological player in muscle throughout life, that if a child is one and a half years old, that suddenly it's not working there. We know Myostatin is there in SMA children, you know, from birth. We know it's there to be inhibited to help them progress better than they do on SMN correctors alone. Our anticipation would be both biologically and based on the data that we've seen that it should work in younger patients and it should work in older patients beyond 21. You said the primary efficacy population was 2-1 2, which is correct. Of course, as the program's gone on, TOPAZ and SAPPHIRE, children who are 2- 12 have gotten older and many are beyond 12. In TOPAZ, we've shared up to four years of data. Many of those children are well beyond 12. They continue to have great efficacy. In the phase three, you had a whole cohort above 12. Right. They have progressed beyond 21. I think there's a wealth of data. You don't think age is even relevant in terms of what the... I mean, I'm giving you the scientific argument from our data. Now, ultimately, the agency has to be the arbiter, right? I think the concept of a single disease and the rationale for Myostatin as a target now, data make a great package for them to adjudicate on. That's what we're hoping. Ambulatory, non-ambulatory, I mean, that's almost 50/50, but you know, it's a proportion of the disease. And we're talking about the difference about whether someone needs walking assistance or a walker or whatever versus someone who doesn't. Yeah. You know, whether or not that would be relevant. Yeah. I mean, we certainly studied ambulatory patients in cohort one of the TOPAZ. And we saw some positive data there as well. Again, this is a single disease attenuated by the SMN2 copy number. And really, biologically, it makes every sense to treat it as a single disease in which, you know, our hypothesis is antagonizing Myostatin is going to help create benefit for these folks. It would definitely be clear there would not be a type 1 part of the label. There's a type 2, 3. Is that fair too? You know, we've already said that we'll be studying zero to two years of age range formally. You know, that should say to everyone that we want to unequivocally demonstrate what we already believe based on the science will occur. We will be doing that work. My point was type 2, 3 versus type 1. Yeah. I don't think anyone would think you would be inclusive of a type one in the label. Yeah. I, you know, this... Large part of the market. Yeah. Generally speaking, type one will present very early. This whole distinction between type one, two, and three and four, you know, is becoming less and less relevant, I think, to physicians and families. It is the question of what's the degree of severity of your disease? What's the best treatment for you? I believe, and this is market work, is that type one patients are obviously start and present early on in infancy. Yeah. Because of the underlying correctors and drugs that people are getting now, they are living now towards ages where they are part of the market and potential customers. The idea of type one versus two, three is based on copy numbers. If they are three, four, five, six, seven years old, just because they have a type one copy number, why would they not be able to get the drug? Technically, you did not study them. Yeah. I guess if you looked at it, you'd be like, well, the guy's non-ambulatory. He's six years old. What's the problem? Yeah. Yeah. No, I mean, I... You don't think type one, two, three may also may not be so relevant. I don't know. No, no. I fully anticipate that, you know, for the patients that we've studied, we've established a case for antagonizing Myostatin in the entire population, including type ones. And now, you know, the agency will have to do their thing, but there's no reason why the drug should suddenly not work in a five-year-old who was classified as type one. All right. Last couple of questions and last couple of minutes. One of the things is that if this drug is approved later this year, there are existing drugs out there. In one sense, it could be a strong launch because everybody knows where the patients are. They're at these centers. You've been at the centers. Do you think that this should be a strong launch? How should we think about that? People are already on existing drugs. Those are expensive drugs. Generally, the reimbursement arena has been pretty favorable for these kids. How are you thinking about a strong launch? It's a great question, Mike. You know, first of all, from a reimbursement landscape perspective, you're absolutely right. In fact, without any well-designed controlled trials, there's a reasonable proportion of patients that even have been receiving and being reimbursed for more than one SMN targeted therapy. Yeah. So they get gene therapy literally a year or two or three later, they can get on Spinraza. That is being, you know... It's out there. The patient community, the medical community, and the payer community is supporting that. As I think about sort of the kinetics of the launch, I think certainly a tailwind is that, you know, unlike our experience at Alexion, where we had to really invest in, you know, deep disease awareness and diagnostic initiatives, here the patients are known. There are some headwinds, though. I think the headwinds would be, you know, sort of you're launching without a J- code. You've got to go through individual payer processes with a reasonable proportion of patients being state by state Medicaid. You've got a lot of large centers that, again, logistically want to get set up and sort of maybe stage their patients in terms of who gets therapy and when. There might be their own internal processes to set themselves up for that. You know, we are extremely optimistic over the long run for our opportunity to serve patients. I think we also want to be thoughtful. We would expect a consistent and steady addition of new patients each and every quarter, but I do not necessarily see it as a massive bolus like we saw, you know, maybe with Spinraza when that ushered in the first new era of treatment in SMA back in 2017. I think the feedback, and we'll certainly do more work as we get closer to June, that there will be patients that are identified in advance, that those patients at those centers would be good candidates. Those are, you know, early patients that could come onto the drug. So... Yeah. One other point I'd make, Mike, that I know you know quite well as we presented at our MDA presentation in March in Dallas, you saw the SAPPHIRE patients who were a little later. You saw the TOPAZ patients who were a little earlier. I think each center and each investigator will make those decisions on which patients they want to try first because early has provided some incredible results. Late has reversed disease progression back into motor function gain. We think there's a wide range of patients that are going to benefit from therapy. Now, given that you have a whole team now that has been a track record of executing on these drugs around the world, you did file in Europe, correct? So that was around the same time. So that's an approval date, early part of 2026? It might be closer to mid-year. Yeah, that's right. Mid 2026. Okay. That is also on tap too. We'll pay attention to that as we get into 2026. Yeah, right. Good. Thank you guys very much. I know we have a ton of meetings and then also more tonight. Yes. Thank you guys very much for being here with us. Thanks, Mike. Thanks, Mike.