SRRK - NASDAQ

Thank you, Sandra. Good morning and welcome to our Scholar Rock's Second Quarter 2024 Business Update. On behalf of our team, I'd like to thank you for joining our call. Turning to Slide 4, the focus of today's call is to highlight our exciting progress in 2024. After my introductory remarks, Jing Marantz, our Chief Medical Officer, will provide an update on our development programs, including a review of the 48-month data from TOPA

Thank you, Jay. If we can turn to Slide 12, Molly. We have three programs in the clinic. In June, as Jay mentioned, we have updated clinical data on our 181 program that was featured at an oral session at ASCO. On today's call, I'll focus on the progress of our SMA program, including an update on the 48-month data from TOPA

Thank you, Jing, and good morning, everyone. Next slide, please. I'm going to start with this slide emphasizes the points made by Jay and Jing earlier. We have a highly differentiated platform that is producing innovative and very selective candidates. Combined with our translational expertise, focus and passion, we have translated these innovations to success in the clinic across many therapeutic areas to benefit our patients. First, we developed a particular apitegromab, our selected anti-myostatin for SMA, proved its efficacy in translational mouse model, took it to the clinic and as you heard earlier, we have very promising data from our TOPA

Well, thank you, Moe. So, in closing, it is an exciting time for Scholar Rock. We have met or exceeded all of our goals to date, including conducting a prime pre-submission meeting with EMA in preparation for our European submission for apitegromab, initiating EMBRACE, continuing to advance SRK-439 to IND, and we're looking forward to the top-line readout for SAPHIRE as our next important milestone as we continue to initiate key activities in preparation for commercialization. Overall, a great time for Scholar Rock. That concludes our formal presentation. Sandra will now open the call up for questions.

Thank you. [Operator Instructions]. We will now take the first question from the line of Michael Yee from Jefferies. Please go ahead.

Hello, good morning. Thank you, guys, for the update. We had two questions. First, obviously, you are reading out in SMA, the pivotal study and some others are also reading out all around the same time. I guess I just wanted to understand your view on one of the competitors Roche because I think their antibody is similar. And so, I just wanted to understand if you have seen or believe there are any differences in that study design or readout, how to think about that as it relates to your readout also coming around the same time. And on the obesity side, I wanted to understand, first, are you stratifying with tirzepatide and sema? As I noticed you're offering both and those drugs do have different effects. And I want to know if you're stratifying and do you expect that your drug will completely eliminate the lean muscle loss and that is your base case for both of those drugs in your readout? Thank you.

All right. So, Michael, maybe I'll go ahead and tackle, this is Jay. I'll tackle the first question about the upcoming readouts. So clearly, we're excited to report out our top-line in Q4. What we've seen is we follow our others in the space, Roche in particular, they continue to suggest that they're going to report out from there, I think early phase of the study. So, they're really establishing dose and effect, as opposed to reporting out their top-line Phase 3 trial, which is ongoing. The most recent update that I'm aware of is that they're targeting somewhere in the 2026 or beyond phase. So, I think it will be interesting to see their results, but clearly in a different place and to remind them they are studying only with [Indiscernible] where we are agnostic to both nusinersen and risdiplam. And then with respect to EMBRACE, Jing can answer, but since I'm going to comment. No, we didn't stratify by semaglutide or tirzepatide in this proof of concept study. We're really interested in just seeing the effect on both. We think we should have an effect on both similar to our SMA program. We think we should be agnostic to treatment and we'll see. I think ultimately the amount of preservation for lean muscle will be interesting. I think what you saw from Mo is that the data presented at ADA were very impressive, because it did show that we did actually maintain and preserve. And then of course we saw continued increase in lean muscle mass upon cessation. I think those results likely will be reproduced in clinic. But again, we're running the proof of concept to see. So, looking forward to telling you the top line results, I'm glad we're going fast. The team is impressive, right. We've accelerated the enrollments and looking forward to reporting our top-line for both.

Thank you.

Thank you. We will now take the next question from the line of David Nierengarten from Wedbush Securities. Please go ahead.

Hey, thanks for taking the question. It's on, epinephrine SMA. Just when you look at the longer-term data, is there any effect, that should be attributed to, the children aging or, are you confident in the differential still from the base case or from background therapy from the historical and clinical studies? Thanks.

Yeah. Well, maybe I'll start maybe if Jing wants to add about the historical data. It's really interesting, right. I think the beauty, David, as I see with the apetigramab program is that given the safety and tolerability that this can be chronic treatment for children with SMA. And if we think about the physiology for maintaining and enhancing growth and function, it actually would be optimal to see that continue through growth and development of these children as they get into young adults and hopefully maintain their activity of daily living and in fact, if not improve it further. So, I think that it's likely a combination. I think that the fact that we're continuing treatment is to the good. And again, what Jing said is very, very encouraging. I mean, we're very impressed as we continue to see the maintenance and sustained effect over time, particularly in light of the decline that you see with Nusinersen. I don't know, Jing, if you wanted to add to that.

Yes. So, I think that you covered most of it, Jay. So, there are a couple of things to add. One is that mechanistically, I think Jay pointed out this as well. Myostatin there has been a large body of literature that really speaks to the effect of the myostatin regulating muscle throughout life from early development all the way through adulthood. And so that has been well documented. And abrogation of myostatin has had no documented negative effects and that's true in animals and in human. So that's point number one. Point number 2 is that, the question I think Jay addressed this, there is probably a component of the development. However, what's really important is that the patient population that I showed you and Dr. [Indiscernible] and colleagues presented are very similar patients. If you look at our the TOPA

Thanks.

Thank you. We will now take the next question from the line of Etzer Darout from BMO Capital Markets. Please go ahead.

Great. Thanks for taking the question. Just a couple here. As we approach the top line SAPHIRE data, just wondered if you had any updated insights on sort of potential access or pair dynamics for the use of apitegromab to standard of care or will you need data in hand, I guess, for more productive conversations? And then as you advance sort of SRK-373 for fibrosis and you look sort of across your TGF beta portfolio as it grows, how are you sort of thinking about continue to kind of develop these assets relative to kind of the focus on anti-myostatin? Thanks.

Yes, very good. So, let me start with the top line and payer interaction. We've had preliminary payer interactions we've shared in previous calls and of course we continue to do that. I do think that there is the prior precedent set with the current therapy. So, I do think that gives us some insight into the value of functional gains in these children and the ability to add and enhance that. Of course, we will continue with more payer interactions as we have the top-line data. And as you point out, of course, that gives us a more rich and robust discussion. But I do feel from what I've seen so far, very pleased with the preliminary interactions and the recognition that these children need additional care. And I think that is further reinforced by the updated data that we've seen from Cherish and SHINE. It's really interesting. We've talked a bit about what to expect from the natural history. We've been looking for sources to give us information around it. We've said repeatedly that we expected it to plateau the nusinersen effect, but we did believe everything we've heard and talked to from the community and physicians, there is an inherent progressive nature to this disease and in fact the long-term data show that. So that's the kind of the evidence behind what we've been believing. And if you put that together with the data that we're sharing with TOPA

Great. Thank you.

Thank you. We will now take the next question from the line of Tessa Romero from JPMorgan. Please go ahead.

Good morning, Jay and team. Thanks so much for taking our question. So, the first question from us is on the longer-term data that you presented this morning. Can you tell us a little bit more about the distribution of the inputs on the Hammersmith? And what might be driving that need up from 36 months to 48 months, particularly in the 2 to 12 age group? Just curious, like, how wide has that range of observations been and has this increased or decreased with time? And then the second question we had was just if you could let us know what percent of patients have seen at least a 3 point of improvement for the age 2 to 21 group. I think it was about 39% as of 36 months. And then, if I can just ask on timing for SAPHIRE, is there any clarification you can give us on time between last patient out, which I think would be in September, and a possible top-line result. Can you give us any kind of like what needs to be done in that timeframe? Thanks so much.

Yes, Tessa. This is Jay. Maybe I'll tackle those. You have really good questions about the granularity around the updated 48-month data. And as Jing mentioned on the call, we have plans to really advance that and get that at a medical meeting where we can go with much more granularity about the detail, the distribution, the percent that it achieved 3-point change. Just recall, when we were asked about 48-month data at the beginning of the year, we were planning. We know this is important data set, we were planning to do it, just not now. We were able to do it now frankly because the team has just been so incredibly driving toward getting us in good shape for SAPHIRE. I didn't want to distract them from the SAPHIRE data. That's critical to us. The 48-month data is really important, but on a priority list, SAPHIRE to a priority, They're delivering beautifully tests. So that allowed us to update the 48-month data. So as Jing said, this is a bit of a snapshot, so more to come. We'll give you more detail as we get this in front of a medical meeting. And then that goes to your second part of the question, not distracting this team from where they're going and how to get there. The classic is we have got to clean and lock the database and be sure that the data meets all the quality checks that we have to for registration. So, there's some established timeframes in there. So, I'm not going to give any more granularity on the timing in Q4, just to say this team is driving to get us there as quickly as possible with high-quality to be able to allow us to really stand behind the integrity of the data. They've done a fabulous job to date. And I hope you get the energy from me on this call, right. These teams are really driving. We are driving, we are focused, we are delivering, so we'll get it as soon as we can, Tess, coming soon as I said in my remarks.

Okay. Thanks so much for taking our questions.

Thank you. We will now take the next question from the line of Gary Nachman from Raymond James. Please go ahead.

Thanks. Good morning. So, the SAPHIRE Phase 3 study is only at the 12 months. But if positive, do you think the label could potentially include some of this longer-term data from TOPA

Yeah. Good question. So, let me start Gary with the first one about the long-term data from TOPA

Alright, great. Thank you.

Thank you. We will now take the next question from the line of Srikripa Devarakonda from Trust Securities. Please go ahead.

Hey, guys. Thank you so much for taking my question. I know you've just started enrolling for the obesity study with apitegromab. It looks like you're seeing better enrollment than expected. I was wondering if you can provide a little bit more color, if possible, on what sort of patients, seem to be the target for this? And also, you're targeting the certain ratio between overweight and obese patients, does it matter? And given the just following up on an earlier question, the tirzepatide and semaglutide, they have slightly different profiles. So, is there anything you took into account in terms of trial powering assumptions about the distribution between tirzepatide and semaglutide? Thank you.

Yeah. Good question. So Kripa, this is Jay. And maybe I'll start with the trial design and then I'll have Jing add on to it and talk about sort of the patient population that's being included in the study. Again, this is a proof of concept study, so we really wanted to be able to kind of see an effect on that preservation of lean muscle mass. I think to your point, tirzepatide and semaglutide both have the effect. I think the speed with which you see that decline differs between the two. And so there may be some difference in terms of when you can detect our ability to preserve that. But I think seeing the effect on either of those groups would be helpful. So, we considered it, but we didn't really as the earlier question came from on the call, we didn't stratify by that for the study, but we believe that we'll be able to demonstrate the effect that we expect to see. And then Jing about the population that we've included in the EMBRACE study?

Yeah. So, Kripa, we did not strive for a particular ratio for the overweight versus the obese population. Just importantly, the objective for the study is really to have a quick proof of concept, as I mentioned, really just to kind of assess the ability to preserve lean muscle in the context of GLP Agnist. And as to your second question about the ratio between the difference between semaglutide and tirazepam, our view is -- we do not think there's a fundamental difference between those two. If you look at the degree of weight reduction, I think tirazepatide probably has a greater degree of weight reduction, but the overall safety profile are quite similar between the two and the proportion of the lean muscle loss in the context of GLP-1 are very similar between the 2, their ability to kind of reduce cardiovascular risk in both study have showed that. So, in our view, it's basically it's more thinking about the pathway of those GLP agonism to lose weight, but then lose muscle along that and how do we counter that, so we can preserve lean muscle. That's really the primary objective and the trial is set up to do that. And so therefore, that's our focus.

Okay, great. And then just one more follow-up question on that. So, this is a proof of concept study, your primary endpoint is changed from baseline in lean mass by DEXA scan. By the time you're ready to do a pivotal trial, do you expect any update or change in FDA guidance in terms of how to develop muscle preservation drugs or do you think you have all you need at this point of time?

Yeah, Srikripa, this is Jay. I think the answer is going to be it's going to be an evolving field and I think FDA will begin to take into consideration the strategies to really have healthy weight loss management. Although, as you know, I think regulatory change tends to be delayed. So, whether we get greater insight as we go forward remains to be seen. Having said that, I feel very good about the information we've received to date from the FDA. I think we need to demonstrate clinical benefit in addition. And I think as you see from Mo and what really gets me excited is we're walking through what Mo and his team are doing on the non-clinical data. I'll just ask you to take a look at that. It's starting to foreshadow where we could take this medicine, right? We have an effect on glucose metabolism. That's a clear measure of clinical benefit. The data at the ADA showed that we preserve the lean muscle. In fact, we maintain the lean muscle and in fact increase the lean muscle mass upon withdrawal of semaglutide and we mitigate the weight rebound, the fat rebound. So, you're seeing opportunities where what we've been saying is sustainable. And I think we can find strategies there on the maintenance side or in combination to really position I think those trying to lose weight -- to not lose it at the expense of muscle, which plays such a critical role in metabolism.

Great. Thank you so much.

Thank you. We will now take the last question from the line of Mark [Indiscernible] from TD Cowen. Please go ahead.

Thanks for taking my questions. A lot have already been answered. But maybe to follow-up on Mike's question right at the beginning, just on these kind of differences between the molecules and the trial designs in SMA, do you guys view that those differences are so significant that they're very likely to lead to completely different outcomes for trials in terms of just outright failing to reach statistical significance or succeeding in other cases? Or do you think that these are likely to be just more subtle kind of aspects of the overall kind of profile that you're able to market to, that each company might be able to market to in terms of, how big that efficacy signal really is and obviously the safety profile? And then I'll have a follow-up question after that.

Yeah. Okay. Sorry, Mark. This is Jay. Yeah. So, talking about the differences in the profiles of the programs, because I got a side distraction as you were answering the question, I want to make sure I got it correctly, in terms of what's expected to be seen from each of the different profiles?

Yeah. Is it significant enough that it's going to be very important to success failure or do you view it as subtler as to just how impressive the data is going to be?

Yeah, it's really interesting. I mean, let's start first and foremost. Again, I made a comment about we're treating children and young adults and we have plans to move even into earlier ages under 2, right. So, if you think about that, as everything we said about our strategy, safety really trumps. You've got to be able to have a safe therapy, you've got to be able to administer it. It's got to be able to be administered without regard for growth and development, and we've been able to demonstrate that across. So, safety is really paramount. I think that there is differences in terms of each of the strategies, but I like our strategy on the safety side. So, let's start there. I think with respect to kind of what to see from the efficacy side, again, I think we've selected the Hammersmith scale for a reason. It was what's used for Nusinersen. There are other motor scales, but quite honestly from the field, I believe this is the gold standard and we're really looking forward to reporting out our data against that gold standard measures. So, I think that's important. I think the tolerability, which is linked back to safety, but the tolerability will be critical as I think about it from a payer interaction and our ability to commercialize. We have seen very little, if any drop from our TOPA

Okay. That's helpful. And then just obviously, we're hoping that the trial will be positive. Can you just remind us what else you may need to gather to be ready to file that BLA? Is it really just the data and writing it up or, are there other things on the CMC side that still need to kind of come in house?

Yeah. As you know, with most applications, this is a work in progress. The beauty of it is, is that we've been preparing the BLA over the last 12 months to 18 months, to be honest, right. There are sections that you can complete and do. The non-clinical sections that work is done. Those reports are written. They are being included. The CMC team is doing their CMC work and PPQ runs and getting all that stuff, so that's running beautifully. And then the clinical team is really working to populate the modules. There are some things that we will incorporate the TOPA

Okay. All right. Thank you.

Thank you. There are no further questions at this time.

Okay. Well, listen. Thank you all. We're going to close the call. Thanks for your interest, and I appreciate you joining us today.