SRRK - NASDAQ

Good morning and welcome to Scholar Rock's Fourth Quarter Financial Results and Business Update Call. All participants will be in listen-only mode. After the company’s prepared remarks all participants will have an opportunity to ask questions. [Operator Instructions] Please note this event is being recorded. Before we begin, I’d like to point out that 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 on 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 sections of our website to find our most up to date SEC statements and filings. A recording of today's event will also be available on our website should you want to rewatch at a later date. I would now like to turn the conference over to Jay Backstrom, President and CEO of Scholar Rock. Jay, please go ahead.

Thank you, Operator. Good morning, and welcome, everyone and thank you for joining our fourth quarter 2024 business update. We had an outstanding year in 2024 and we’re off to a great start for 2025. For today’s call, I’ll start by providing review of the SAPPHIRE results and our progress towards our regulatory milestones. Tracey Sacco, our Chief Commercial Officer, will share the terrific progress we're making with our commercial preparation and are planning for a 2025 launch as we're working with a sense of urgency to serve those living with SMA globally, starting with the U.S. and then I'll follow with a review of our innovative Myostatin platform and our ambition to transform the current GLP-1 treatment paradigm for weight management. Following our prepared remarks, Tracey and I will be joined by Ted Miles, Chief Operating Officer and Chief Financial Officer, and Mo Qatanani, our Chief Scientific Officer for the Q&A portion of today's call. Moving to slide four with our success in 2024, the stage is set for what will be a transformative year for Scholar Rock. And as I said, we are working with a sense of urgency to bring apitegromab to those living with SMA and we continue to hit our milestones on time or ahead of schedule. Starting with the regulatory applications for apitegromab and SMA, we submitted the BLA in the U.S. in January and we remain on track to submit the MAA in the EU in March. We look forward to sharing the SAPPHIRE data at the Muscular Dystrophy Association's annual meeting in Dallas on March 19th where this data will be featured as an oral presentation. We will also be sharing our work with the murine version of apitegromab in a non-clinical model of DMD, setting the stage for us to expand the development of apitegromab into other neuromuscular indications. We also continue to make progress on our goal to expand treatment to even the youngest of those with SMA, and we're on track to open the OPAL study for those under 2 years of age in the third quarter. For our cardiometabolic program we remain on track to share the top line data from EMBRA

Thank you, Jay. Moving to slide seven. Despite successes in treating the motor neuron over the past eight years, progressive muscle weakness continues to be a critical unmet need in SMA and there's currently no approved muscle targeted therapy to treat this muscle neuromuscular disease. Patients and caregivers have described to us the debilitating impacts of progressive muscle weakness and how it significantly detracts from their independence and their ability to perform basic daily activities like eating, dressing, getting in and out of bed or their car, brushing teeth, climbing stairs and using the bathroom. This is why 97% of patients surveyed by Cure SMA identified improving muscle strength as an important need that they want to see from a new SMA treatment. From our own market research, we know that more than 80% of treating neurologists agree that preserving muscle should start as early as possible in SMA. The SMA community is collectively calling for more to treat this relentless progression of muscle weakness and improved motor function in SMA. Next slide. Today, roughly two-thirds of the 10,000 people living with SMA in the U.S. and 35,000 individuals living globally have already received an SMA and targeted therapy. Yet we see from the data that Jay just presented that despite these effective therapies, progressive muscle weakness still robs these individuals of their ability to function over time. This is why 74% of neurologists recognize that in the future, a combination of modalities to target the motor neuron and the muscle will be necessary to treat SMA. The future of SMA will be to directly treat both the muscle and the motor neuron to provide the best outcomes for patients. Apitegromab is the potential first approved muscle targeted therapy in SMA is leading the transformation of SMA care. Next Slide Scholar Rock has been at the forefront of preparing the market for this potential new treatment paradigm in SMA. Last year we introduced Life Takes Muscle, the first muscle focused SMA disease education campaign that amplifies what we've been hearing from patients and caregivers for years about the devastating impacts of progressive muscle weakness. Life Takes Muscle has resonated with both the patient and HCP communities and led to continued strong engagement with Scholar Rock. Additionally, our MSL team has also been meeting with leading CureSMA centers and engaging with top treating neurologists and care teams to educate on our Phase three SAPPHIRE Top Line data. And Scholar Rock continues to partner and learn from our patient advocacy partners who have been so effective already in helping to bring new treatments to the SMA community. Next Slide. We're doing all this with a team of experienced professionals with deep rare disease and launch experience including prior SMA launches and we're continuing to be a magnet to attract top commercial talent as we build out our team. Next slide 2025 is an important year for Scholar Rock and we are positioned for a successful launch. We'll continue to build on our stakeholder engagement and education and this quarter have initiated outreach to top U.S. commercial and federal payers ahead of our potential Q4 launch. We will also be scaling our customer facing team of roughly 50 sales, reimbursement and patient support personnel in late Q2 and early Q3 to be hired and onboarded ahead of our potential launch. And finally, Scholar Rock is building out our patient services offering and preparing to offer home infusion as an option at launch to provide excellent support and optionality to patients and treaters alike. We have been laying the groundwork for years and now we're putting the broader team and infrastructure in place for a successful U.S. launch to meet a critical need in the fight to continue to improve the lives of those living with SMA. I'll now turn the call back to Jay.

Well, thank you Tracey. And now turning to our cardiometabolic programs and moving to slide 13. It's impressive to see the impact of the innovation from our industry and how the approved GLP-1 receptor agonists have transformed the management of weight loss. Obesity is a top global public health issue and the potential public health impact of these highly effective weight loss therapies have been incredible across a number of chronic conditions including diabetes, sleep apnea and cardiovascular disease. With an estimated 40 million projected to receive treatment GLP-1 receptor agonists, the current market is anticipated to generate over 100 billion in sales. Moving to slide 14. With the extraordinary amount of weight loss seen with the current GLP-1 receptor therapies, there's also a substantial amount of lean muscle that is also lost, ranging from 12% to 40%. With the widespread use of these therapies, there's an increased awareness of the associated weakness and reduced strength that accompanies this loss of lean muscle mass and of the significant weight regain that occurs when stopping therapy with disproportionately more fat being regained than lean mass, leading to a worse body composition and leading to unhealthy weight gain. Beyond strength and mobility, muscle is the main metabolic organ and plays a significant role in energy metabolism, increasing basal metabolic rate, glucose uptake and improving insulin sensitivity. Given the critical role that muscle plays in overall health, we believe our highly selective approach to blocking myostatin when added to the GLP-1 receptor agons can enhance their profile by reducing the loss of lean muscle mass without introducing additional toxicities leading to healthy and sustainable weight management. Moving to slide 15 to illustrate what can be expected from Tirzepatide, this figure is from the Tirzepatide SURMOUNT-1 study and illustrates the percent change in body weight over time. The area shaded in green represents the first 20 weeks of the study, the time period corresponding to the efficacy assessment in EMBRA

[Operator Instructions] Our first question comes from Allison Bratzel with Piper Sandler. Your line is open.

Hi, good morning guys and thanks for taking the questions. Maybe one on SMA. Just with SAPPHIRE data being presented next month at MDA, can you just discuss your sense of what additional data points are going to be most meaningful to patients and docs when you present that full data? Just maybe help frame that update for us? And then one on obesity, just maybe help us understand what you need to see on the primary endpoint to be confident in taking 439 forward. I think in the prepared remarks you discussed a 20% to 40% improvement in lean mass as being clinically meaningful. Just. Did I hear that right? And then what are you hoping to see on additional endpoints like A1C and body composition? Just curious to get your thoughts there. Thank you.

Yes. Good, Allie, hey, good morning. So this is Jay. So first, starting with SAPPHIRE. We're really excited to have the opportunity for those data to be presented at a Congress and particularly the MDA conference where there's a lot of interest and a lot of investigators will have a chance to see the data beyond what we could share on the top line results. And as we shared previously, I think what's really important is the overall consistency and impact of the -- totality of the data. We've shared, we've got effect across age groups and we're going to share additional endpoints and you'll see again, I think there'll be interest in seeing the consistency and the impact we have across those additional endpoints. So I think that'll be a really nice opportunity to really underscore that we really are on the threshold of bringing, I think a really nice new effective therapy to change standard-of-care and SMA. And then with respect to EMBRA

Excellent. Thank you.

One moment for our next question. Our next question comes from Michael Yee with Jefferies. Your line is open.

Hey guys, thanks for the question. Good morning. Just following up on thoughts around the obesity readout in the second quarter. I appreciate that the expectation is that you should preserve lean muscle. I was just wondering about how you guys are thinking about the biology or the effects of what would happen on the actual weight loss. There shouldn't be any material change, but I'm just wondering if there could actually be maybe more weight loss because of the metabolic effects of myostatin and building muscle, or there could actually be headline a little bit less weight loss just because you're actually preserving the muscle. So just thinking about the biology area there certainly in the first 24 weeks and how to put that in the context of preserving muscle. Thank you.

Yes, Mike, thanks for the question. I try to frame that a bit in the prepared remarks. So for week 24, given the magnitude of weight loss that's already occurring with Tirzepatide, really don't expect at that time point to see we think the weight loss will be comparable between the two arms. Recognizing that there's a potential with increasing muscle to potentially affect weight. But the magnitude of the weight loss, which is appetite, is probably going to make that a wash. And so we think it'll be comparable week 24. But to add to your point now that's at week 24. If we look at effects over time and the potential effect on basal metabolic rate and maintaining, there absolutely is the potential to see some additional incremental weight loss over a period of time on treatment. But I want to set the expectations for week 24. We're expecting to be confident.

Got it. Thank you very much.

One moment for our next question. Our next question comes from Tessa Romero with JPMorgan. Your line is open.

Hi, good morning, Jay and team, thanks so much for taking our questions. I look forward to seeing you guys at MDA. So what is the right way to think about the exploration of additional neuromuscular indications where apitegromab could have potential here? What framework can you give us with respect to those decisions? In other words, how you will best allocate capital while also ensuring proper investment in the launches for SMA and also the cadence and timelines with which you could or would start these clinical studies. Thanks so much.

Yes, Tess, thank you for the question. Very, very important question. We're going through that work right now. As I indicated at the JPMorgan conference, with the success of apitegromab and SMA, I mean, I almost feel obligated for us to take a look at the adjacent neuromuscular indications to see if in fact we can have an opportunity to impact and improve lives for those that have other diseases like DMD, FSHD, Becker’s and even ALS. So what we're showing at MDA is a bit of the work and thinking behind our approach to this. I'm very keen on translational models to the extent that they can give us insight and I feel very fortunate with Mo and his team to be able to do these models. And so we're going to start showcasing how we're beginning to think about, for example, DMD a little bit with that non-clinical data. We're actively engaging experts across these indications to really begin to think about how we can take a look at both not only the opportunity in terms of the unmet need, but the probability of technical success and can we understand and enrich a patient, subset of patients that we can really show meaningful benefit. We're doing all of that work. And as we put all that together, that'll set the framework as we think about further investment in those indications, which as you can imagine is going to be, function of technical success, unmet need, potential opportunity, etcetera. So we're doing all that work now over the course of, frankly we started that work even last year. So that work continues and as we get closer to that, we'll certainly share how we think. With respect to our ability to, to do this, in addition to doing our launch, we have a clinical team that really has demonstrated their ability to execute clinical trials. SAPPHIRE is finished, we have the ongoing study and the long-term follow up, but we're positioned to be able to take on an additional clinical study, if not two, but certainly one as we think about going forward. And again, what I tried to share at JPMorgan was if you think about what we're trying to build here and the value we're trying to create at Scholar Rock. It starts with SMA, and, as we said, we think that there's a potential $2 billion plus opportunity for us in SMA alone, considering what we believe will be a paradigm shift in treatments. And then if you start to build around at these additional neuromuscular indications, we're on the threshold, assuming execution and success, to build a multibillion dollar neuromuscular franchise. And I think at the end of the day, if we do that properly, will definitely increase shareholder value, but importantly, extend our reach to those in need.

Thank you.

One moment for our next question. Our next question comes from Marc Frahm with TD Cowen. Your line is open.

Hi, this is Alex. I'm from Marc. Thanks so much for taking my question. So the FDA recently issued a draft guidance on obesity clinical trials, which appear to reinforce the agency's focus on BMI and over overall weight loss rather than shifting the focus to body composition changes and preservation of lean muscle mass. What do you view as the potential implications here for your cardiometabolic program, namely 439? Thanks.

Yes, it's a good question. We're obviously following this with great intent and seeing and looking carefully at FDA's updated guidance. From my perspective, kind of watching FDA over the years, they tend to move slowly, they tend not to go as fast as the field is trying to get them to go in terms of endpoints. So we were not surprised that they retained BMI. The things that we took of interest, though, from that guidance, which I think further reinforces why I think we're actually on the right track here. It is now, very clearly in that guidance, they're asking all sponsors to include within their clinical development very least a subset of their patients to understand the amount of lean mass loss on their treatment. So it's recognizing that the loss of lean mass has the potential to not be a good thing. So let's assess that at baseline and understand it across programs. So I think that further reinforces the question around lean mass. They clearly indicated in that guidance of if there's an interest in body composition, come talk to us. So that, to me is a bit foreshadowing where they may be tilting, but clearly that's not within the guidance. Now the body composition matters and the field is declaring that as a really important event or endpoint. So I think that's something that we'll continue to follow with great attention, but also which I believe we will affect positively if in fact we preserve lean mass. So we'll have a nice impact on that. But then they also said what is very clear is that if you're doing a combination program, then you need to demonstrate some additional benefit from our drug, for example, SRK-439. And what I was trying to showcase in today's discussion to bring further clarity to that, but what I said pretty consistently across our entry into this is that those endpoints that could be regulatory approval endpoints are metabolic parameters such as further reduction in hemoglobin A1C. Clearly there's a potential for that given the role of muscle. And there's clearly an opportunity to find a way to demonstrate that losing this amount of lean mass really results in functional loss that's significant. And we have the potential within a subgroup of patients to show those functional measures and improvement, which ultimately I think will be sustainable. And then there's other ways that we can look at how we can manage through mitigating weight regain, maintenance approaches, etcetera, with a lot of ideas of how to move this forward when we get into clinic. But I think the guidance to come back to it are consistent. But I think also we're pointing the way and I feel very good about the fact that we're in this space.

Great. Thank you.

One moment for our next question. Our next question comes from Gary Nachman with Raymond James. Your line is open.

Thanks and good morning. So back on EMBRA

Yes, Gary, thanks for the question. I'll start with the 439 question and then I'll turn to Tracey to address the question on our interaction so far with payers. It's interesting. It's like having two children and you're going to say which one is better, right? I mean, I think what I would say to you, Gary, on 439. I really like the profile that we're developing, I really do. I think the work that Mo and his team are showing is this is performing beautifully. It has greater affinity for the target and that could potentially help us certainly at least with the very much with the dosing, such that we can then go in with the low dose sub Q formulation. So that is a clear, clear advantage and we're looking forward to that. Now with respect to how much different and how much better, that's a really interesting question, Gary, because what I was trying to say is that apitegromab is like signal seeking, yes, we can show this 439 is the program, and we will need to further explore with 439 how we optimize the dose of 439 and how we begin to get some better insight into how it's impacted across these functional measures. So that's part of our thinking on the IND opening studies. So more to come with 439. At the very least it's going to have similar effect. I do think though it's designed to be low dose kind of sub Q presentation which in this highly competitive space I think is something that we need to do. And so more to come but we're really moving rapidly on that toward IND and then Tracey, you want to make a comment on the payer interactions today?

Yes, sure. Payers have been very receptive to hearing from us even as a new company and are very interested in learning more about our innovation as the first muscle targeted therapy in SMA. They are familiar with SMA and recognize that there's still a continued need to treat this relentless disease. And we know today that a third of lives covered of U.S. commercial payers already have policies covering what I would call combination treatment of an SMN-targeted therapy post gene therapy. So that's a reflection of the openness to address this recognition of unmet need. Ultimately, we expect U.S. and European payers alike to enable access reflective of the value apitegromab brings in SMA. And our data and overall profile are really strong. We have a clear added benefit across all cohorts and a highly favorable safety profile. So it sets us up for really strong discussions.

Okay. And just pricing. Any latest thoughts there? Just typical, like in line with the other SMA treatments.

Yes, I mean at this point, we're not in a position to share pricing but ultimately we expect that access to be covered reflective of the value we bring. And we do have a sense of what the pricing is in the, in the SMA market today.

Okay, great. Thank you.

One moment for our next question. Our next question comes from Kripa Devarakonda with Truist Securities. Your line is open.

Hi, this is Alex on for Kripa. Thanks for taking our question. To talk about the future development path for the muscle preservation drug. To be a little specific, we know that overall we definitely see the benefits of more muscle is better. But when it comes to the regulatory review and the specifics on the endpoint, you mentioned a couple different avenues that you could explore with the HPA-1C and to mitigate weight regain. But when it comes to the strength endpoints we know we've seen grip or stair climb. Are these endpoints that are on the discussion table or are there other strength related functional outcomes that come to mind as potential options going forward for the program? Thanks.

Yes, really good question. As you can imagine, we've given this a lot of thought as we think about how to then really meaningfully move 439 forward beyond just identifying the right dose. And you know what, I kind of add color to your point. I think about once we establish the dose, can envision that we would then have subgroups of patients in our proof-of-concept efforts to demonstrate the impact we could have on for example hemoglobin A1C. And in that context we would definitely enrich for a subset of patients where we think we can meaningfully show that difference. So that's a very clear regulatory path forward. That's the metabolic value, the additional benefit of preserving that lean muscle. So that's one example. And the other example that you touched on, which comes immediately to mind, we've demonstrated functional improvement in SMA. So clearly functional measures and functional improvement are interesting. We're not wed to grip strength and stair climb. We're giving a lot of thought around this. I think there's a lot of insight that we're gaining from our work and our review and discussions. And we'll have a really good opportunity when we open up the IND with 439. It's begin to meaningfully engage FDA in our thinking around the development program, thinking around meaningful functional measures and endpoints and at the same time get some sense of how we impact those functional measures as we build the program from SAD, MAD into those early POCs so that we'd be in a really strong position to know exactly how to run in a registration program. So that's our thinking and I feel really good about it. It's like we're. It's like stair stepping, right? I love the fact that we've got EMBRA

Yes, that's great. Thank you for the color, and I'm.

Not showing any further questions at this time. I'd like to turn the call back over to Jay for any further remarks.

All right, well, just to close. Thank you for your interest. I mean, it really is an exciting time. I try to put energy into my voice when I do those prepared remarks. I feel like I have more energy when we get into the Q&A period, but honestly, this team is hustling. Thank you for your interest, and we look forward to sharing the updates and progress over the course of the year, and then we'll close the call.