Scholar Rock Holding Corporation (SRRK) Earnings Call Transcript & Summary

Okay. Good morning, everyone. My name is Jason Russell with the Morgan Stanley investment banking team. Welcome to day 2 of the Morgan Stanley Healthcare Conference. Pleased to be here with the Scholar Rock team. Maybe before we jump in, a quick disclaimer. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/research disclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. So as mentioned here with the team from Scholar Rock, welcomed by Ted Myles, Chief Operating and Chief Financial Officer; and Mo Qatanani, CSO. And so I think a very topical conversation obviously for Scholar Rock, a big news year and a lot of focus on this company and on this space. So I think we'll jump right in. So maybe we'll start with apitegromab. You've got a big readout coming up before the end of the year. Maybe start with guidance on timing for SAPPHIRE. What are you -- what's your perspective on a successful outcome?

Yes. Great. Thanks, Jason, and thanks for the opportunity to be here. We're thrilled to be here in the exit Labor Day and get to the back-to-school mode and ready to run here. So yes, as you mentioned, we're very excited. We've got the SAPPHIRE data readout in Q4. It's been a long time coming. This is a pivotal study, studies put together and with feedback from FDA and EMA. So we believe it's a registrational study. If it hits the endpoints, it will be the basis for our filing. What we've talked about is that the study is designed for -- to detect a 2-point difference between the placebo group and the apitegromab group. So that's the win from a clinical trial standpoint. What we've observed with TOPAZ -- and the TOPAZ study is the Phase II study that's been ongoing for many, many years now with a long-term extension, which what we call ONYX. We've got patients where you just put out 4-year data. Over 90% of our patients are still on study past 4 years. And the data that we put out a month or so ago demonstrates sustained benefit of 5 -- 4 or 5 Hammersmith points, and then there's so much beyond that. We've gotten to see these patients and see them grow and thrive. And we hear from the community that, first of all, one point to patients really matters and can have a big impact, one point in the Hammersmith scale, which is the primary endpoint. But there's so much more beyond Hammersmith. And really, we hear about for the secondary endpoint is RULM, which is revised upper limb module mobility. This patient population that we're studying in SAPPHIRE is nonambulatory. So upper limbs are really, really critical. We're seeing really nice gains there in TOPAZ. And then we're hearing from patients that -- and their caregivers that they have more endurance. They have less fatigue. They can get through their day in a much more better way than they could previously. So of course, with SAPPHIRE, we're looking for clear that statistical significance. And then our expectations are beyond that we're going to look beyond Hammersmith and see how does it impact their lives. And we think that's going to be really beneficial as we ready ourselves to file and of course, commercialize the drug.

Great. Well, I think we're going to dive into that further. Maybe just going back on the timing for a minute. Q4 is the only guidance...

Q4 is the only guidance we're giving right? The study needs to close. The team needs to do their work and Q4 is the guidance.

Understood, at least admire me for trying.

Yes, yes, like a research analyst.

Maybe talk about the landscape a little bit. So there's another program out there. Biohaven has a program, also a second half '24 readout. Can you just maybe contextualize that program for us? How does your trial compared to -- I mean, SAPPHIRE compared to their trial? What are the key differentiating factors between the 2 really, obviously focused on yours?

Yes, I'll touch on the trial design and the merits of our study. I'll ask Mo to talk about the biological differences between the 2 molecules. And we really like our study. We're the only company that's done -- I mean completed a proof-of-concept study in SMA with our molecule. The great results that we saw in TOPAZ really informed our SAPPHIRE design. We focused -- our SAPPHIRE design is primary patient populations 2 to 12, non-ambulatory patients. We have an exploratory population for 13 to 21, so we have an opportunity, we believe, to have a broader label in terms of age. Ultimately, we're going to expand, but the SAPPHIRE population is really highly informed by what we learned in TOPAZ and being the only company that's had a successful proof-of-concept study in SMA, we think we're well positioned to design that study with the highest probability of success. I'll ask Mo to talk about the differences between our molecule and theirs.

Yes. Thanks, Ted. I mean with Scholar Rock platform, we are differentiated from others out there, most, if not all. What we do at Scholar Rock is target the latent form of myostatin or any growth factor, meaning that we actually bind to the growth factor before it gets activated and lock it in the inactive form. What that gives us is 2 main things. One is selectivity. So we only target myostatin. And myostatin does one thing, which is inhibit muscle growth. This way, you'll get muscle growth without the potential liabilities of hitting other factors like the other programs do. They had GDF11 or the Activin, and these bring potential liabilities with them that have -- we've seen in the clinic. The second potential advantage is when you bind to the latent and lock it in the inactive form, you actually inhibit that complex from signaling to begin with, instead of an antibody that goes after the mature form, competing with the receptor. So you have a competition now, you have to compete with a high-affinity receptor. In our case, you don't, just lock it in an inactive form. Again, that panned out with the only clinical data that shows efficacy in SMA that we put and recently put the 48-month data that looks really, really good and we're excited about it.

Yes. And obviously, company has been purpose-built here to focus on the area and so really have a deep history of knowledge and appreciate all the biology. Let's assume both work, yours and the Biohaven program. SMA, a lot of times people hear SMA, "Well, it's already a well-served market." There's a lot of drugs available. Maybe talk to us about that. How does your program fit into the commercial landscape? How do you think about the combinations and where you'll fit?

Yes, that's a great question. So the current landscape, as many know, there's 2 correctors, there's one gene therapy. This has been a renaissance. It's been a miraculous for patients. 8 years, 9 years ago, there was nothing for patients. We hear this from the community frequently. So absolutely miraculous what Spinraza, Evrysdi [indiscernible] have done for patients. But the job is not done. So this SMA is a neuromuscular disease. The marketed products take care of the neuro component. The muscle component has not been fixed yet. There's a lot of work to do there. That's where the next wave of therapy comes in. At the Cure SMA conference, you walk the halls, you hear in the hallway, muscle-directed therapies are coming. This is what we need, right? It's a progressive disease. Patients often get stabilization. So that's a big win for patients who get on the correctors and get that neuro component taken care of. They often get a bit of a bump in terms of function. And then over the long term, you see a plateau best case and then a decline. That's what we've seen. They just put out new long-term data that support that long-term plateauing and decline because it is a progressive disease. The community is waiting for a muscle-directed therapies. That's where we come in is for the reasons we mentioned before, we think we've got the best opportunity, and it will be great for patients. And we talked about the TOPAZ data and what that did. Beyond Hammersmith and RULM and those clinical measures, which is the endurance and the lack of fatigue and the activities of daily living, which we're really excited to see. From a commercial standpoint, look, it's a $4.5 billion market now. There's a lot of unmet need. There's room for multiple competitors to be successful. We like our program, the best in our study. And with good data, we think we'll be very well positioned to compete very favorably.

Yes, maybe just to pull on the -- pull the thread a bit. So most SMA patients already seeing combination therapy from an SMN regulator and [indiscernible]. So are we talking about a potential combination of 3? Or how should we think about that?

Yes. So let me -- I'll impact that a little bit. There's 2 components. So part of this is our plans and our ability to commercialize. We think this is almost an ideal opportunity for now small, hopefully, soon larger biotech company to launch its first drug, right? We know where the patients are. Significant portion upwards of 80% of the patients are on therapy right now. Example, the study we're running, patients are already on background therapy, right? So we know where they are. I know we're not going to comment specifically on pricing, but we've done a fair amount of work there. We've engaged payers. We've seen in the market, payers are willing to pay for multiple therapies, provided the data strong and patient value is there. So good understanding and knowledge of where the patients are. They're already in treatment, good pricing, fairly small concentrated market. We think this is really a nice setup for us to be successful commercially in the U.S. In Europe, if you think about the EU 5 and some other strategic regions, we haven't gone into a whole lot of detail there, but that's really our base plan. So in terms of multiple therapies, we are seeing patients or as an example, on Spinraza. I mentioned they get a nice benefit than a plateau and a decline. What we're hearing from the community is an attempt to slow that progression downward, they switch to Evrysdi or vice versa. It just demonstrates how motivated this patient group is and how if you have a muscle -- if you have muscle function and you have muscle function improvement, the last thing they want to lose -- they see as a deterioration of that. So we really think the door is open for muscle-directed therapy.

Right. Maybe last question here on SMA. These are kids. So your -- I think, inclusion criteria, children 2 years an order so how do we think about -- do you need to get to younger children? How do you think about that? And what other applications? And we'll get to obesity in a minute, but what other rare applications are you thinking about here for...

Yes. So we designed SAPPHIRE really highly informed by TOPAZ. And so it's 2 to 12 non-ambulatory and an exploratory population for 13 to 21. So that leaves out the older patients. It also leaves out the under 2 patients. We're very committed to the full SMA population. We feel that the data that we've seen suggests and I think more agree, the biology suggests that we could help patients across the SMA spectrum. We designed our study to increase our probability of success, so that would -- when we have success, we can then expand to the other patient populations. We talked at Analyst Day on May 22, and we disclosed our plans to go into the under 2 population next. And that study design is underway. And with success, we plan to open that study in others in short order, very committed to the full population.

Okay. Great. Well, -- thank you. Good luck.

Thank you.

Obviously, an event in the near term that people are watching closely. Maybe switching gears a bit. As I think about the history, maybe 2 or 3 years ago, you started -- maybe it's been less than that, you started to unveil another angle to the story. Obviously, obesity has been the talking point for the past 2 years, 3 years across our market. You started the EMBRAZE study. Can you give us an update on the specifics of that study? What are your goals? What are you hoping to learn and then we'll dive in a little deeper?

Yes. And we only disclosed our plans back in October. But you're right, we have been working on it for many, many years. We've got -- we're blessed. We have a gentleman by the name of Jeff Flier on our Board. He's a world-renowned expert in metabolism. So he's been talking for a long time based on the success we're seeing in neuromuscular with apitegromab in SMA. And he's been touting for a long time in the boardroom, the muscle -- lean muscle is the metabolic organ of the body, and we should do something here. The world sort of caught up. And I think it was really the watershed moment was Eli Lilly's acquisition Versanis. That really shined the light on the opportunity where the GLPs have an amazing impact on weight loss. Unfortunately, a big part of that weight loss is lean muscle mass that creates an unfortunate sort of spiral and metabolic health. So we raised a little bit of money and we launched -- we really unveiled our program, which is really a two-pronged program. First is the EMBRAZE study that you mentioned. So we're leveraged by -- we've got apitegromab. It's in the clinic, several hundred years of patient experience and safety. So we're crossing that. We're running a study with apitegromab in GLP, that's the EMBRAZE study and compare that to GLP alone. And so that's that -- we unveiled that we initiated that study again on May 22, Analyst Day. We were a couple of months ahead of schedule. We're really pleased with the momentum. It's a 100-patient study. It's a 6-month readout, and we are clicking along. I can't give much more detail than that at this moment, but it's enrolling very nicely. We're really, really pleased with the momentum there. And I think that speaks to the need that there is an understanding that GLP therapy is very impactful, but too much of the weight that's lost is lean muscle, and that's a problem for metabolic health. The other prong is Mo and his team are advancing our the asset that's ultimately going to be our cardiometabolic assay, is SRK-439, and that is really a remarkable molecule so Mo will talk about that molecule.

So, SRK-439, we've been working on myostatin since the inception of the company. So we know the space really well. And SRK-439 was designed for the obesity population. As Ted mentioned, particularly when it was clinical, it will allow us to get the answer really quick in the clinic of our hypothesis, and that's why we initiated the EMBRAZE. But the molecule that's going to go all the way in obesity, that's SRK-439. And it was designed for obesity on multiple levels. One is like with all our approaches in -- at Scholar Rock, we target the latent myostatin. So we blocked myostatin and lock it just like with everything around. Secondly, it has a higher affinity for the myostatin. And from our preclinical data that we've shared throughout the year, we're seeing efficacy at very low doses of 0.3 mg per kg, and that enables a subcutaneous profile to the best-in-class profile for the obesity population. And just to talk a little bit about SRK-439, in the past year, we have shared at different conferences, the differentiated profile of SRK-439, starting with the Keystone where we showed that it is able to preserve the lean muscle loss that you see with GLP-1 therapies in a diet-induced obesity that the translational model that people use across the industry. In addition, beyond preserving lean muscle mass, we see an additional reduction of glucose levels in these animals on top of the GLP-induced reduction. So in the long term, you can see this beneficial metabolic profile that maintaining lean mass and preserving lean mass safely. That's really key here because we selectively target myostatin and only myostatin. We've seen with [indiscernible] we have more than 200 patient years of safety profile, and it looks really good so -- versus other approaches that can target other factors that bring in the liabilities. And most recently, with the American Diabetes Association, we presented also an oral presentation on the effect of having SRK-439 on board when you withdraw GLP-1 therapy. So GLP-1 therapies have 2 main challenges. One is the reduction in lean mass as you lose weight. And we've shown with SRK-439, that you preserve that. The second one is, once you take the GLP-1 from the patient, you have this withdrawal that you rebound your weight gain. And a lot of times, the weight regain is more on the fat side. What we showed in the American Diabetes Association is that when you have SRK-439 on top of GLPs, you withdraw the GLP, you attenuate this fat regain. And that's going to be beneficial in long term with your body composition. And keep in mind that recent data have shown that with GLPs, both [indiscernible] and Lilly's after 2 years, the majority of patients are off the medication for a lot of reasons. So what you want to do is having SRK-439 to maintain that lean mass, to maintain that body composition and reduce the fat regain that you get when you withdraw. So we published that in June in the American Diabetes Association and there'll be more data that we'll share as well as the differentiators of SRK-439.

So a lot of different permutations of what could happen here in the landscape, whether it be combo, combo then a transition over to only a muscle-directed therapy. Okay. Great. And maybe question on dosing. So 439, just as we all think about the transition, are we going to go from only injectables to orals, like what's the dosing regimen for 439 anticipated to be?

The anticipation on the profile -- and that has been panning out in our preclinical model, it's going to be a subcutaneous -- low-volume subcutaneous injection with a low frequency. And we've seen with [indiscernible] once monthly. So we're targeting that sort of frequency. So it will be subcutaneous low volume, low frequency, maybe around once monthly.

I would encourage those who are interested to look at in our archives and transcript, the May 22 Analyst Day is when Mo really showcased a lot of the new work his team had done. And actually, they created a model of bima, the Versanis, Lilly molecule and did a head-to-head study and showed 20 -- it was the same efficacy at 120 of the dose.

Correct. Our 1 mg per kg was as efficacious as the 20 mg per kg for the bima.

We really think about like selectivity that Mo talked about really results in safety with selectivity, you get fewer off-target effects. What we've seen is very few or no off-target effects. And because we're so focused on that latent myostatin just shutting off the faucet before the messes on the floor, just shut it off, go upstream and shut off myostatin and only myostatin. We think we've created a really elegant solution to dial out all the safety issues. And that's going to be so important. The hundreds of millions of patients on GLPs and hopefully, on a muscle preservation strategy in the long term and safety -- in chronic therapy, so safety is going to be paramount in this patient population, and we think that's where we're going to be very well advantaged.

I mean maybe a little humor at 7 in the morning, Lilly is going right after you. We have a fireside chat. So bima, let's talk about that for a moment. What is bima? Help orient us -- that's obviously a very different approach. So let's set the stage there and then go from there.

Yes. So bima is an antibody against the receptor -- the Activin receptor. So by nature, it's not selective. So you inhibit the receptor, you're pretty much inhibiting all the growth factors that bind to the receptor, including myostatin, GDF11, Activins. And when you inhibit these other factors, Actvins, for example, play a role in a myriad of biological functions. When you inhibit those, it comes with potential liabilities. And that has been shown in the clinic with bima and other antibodies that target the Activins, where you have GI issues, reduction in reproductive hormones, nosebleeds with the Activins and as well as acne and some immunological negative effects. And that's part of the biology of these other factors. What we do is be very selective to myostatin. Myostatin does one thing, inhibit muscle growth. You inhibit it, you actually increase the muscle growth and that has been shown. There's even human mutations in myostatin that you see increase in muscle growth and nothing else, right? So like Ted said, especially in this patient population, in obese patient population, safety is going to be paramount. And you want to have that safe efficacy to be able to dose in this population chronically.

Great. I won't ask you to predict when or where, but that's obviously a very important study. The bima study, Phase IIb that they're running. Just for the space -- and I think we were expecting some data earlier this year, and we didn't get it, and they get the opportunity to do that. What are we expecting there? And how should we position or characterize that readout based on what we have?

We should ask that in 20 minutes. I think the Street was expecting a readout this past summer. They backed away from that guidance, and that's why we've been focused on doing what we do and why we were so excited to unveil the head-to-head study that Mo and his team did and we're moving forward. So SRK-439, we're guiding that it's going to be in the clinic or file the IND in mid-2025. The EMBRAZE study is clicking along. We initially guided to midyear 2025. We recently pulled that into Q2 2025. So we are running our play. We're very excited about our molecule and the differentiation. Yes, we'll see what we decide to do.

That's a very fair.

But what that highlights is the need in this space. The differentiation is the approach. Our approach is that you need to be selective to myostatin to preserve that muscle mass safely. Other people have taken other approaches. And as Ted mentioned back in May 22, we published from a preclinical perspective, a head-to-head study with bima and SRK-439. And SRK-439 was more in a translational mouse model. So why do you need to inhibit all these other factors and blend the liabilities when you can get the efficacy just by hitting the myostatin.

And that work that you did Mo, was it specifically bima? I mean I assume you built that in-house? I mean, how similar will the...

Yes, it was in-house. It's a preclinical equivalent of bimagrumab. So the CDRs or the business end of the antibody is the same. But you put it on a mouse backbone because that enables you to dose frequently without immunogenicity with the human. The same is -- so Versanis and Lilly did the same thing when they did their mouse studies. I think you have to put it on a mouse backbone to enable repeated dosing.

Okay. We won't dive into -- you've already covered at a high level that data, but encourage folks to go dig that up, that's great. What else has to happen between now and the IND filing, as you mentioned, any hurdles that we're concerned about?

There's no hurdles. I mean, as we mentioned in the past year or so, we've been publishing data -- pharmacology data on the differentiated SRK-439. The things that are left now that we're in the middle of is the IND-enabling studies, so GLP tox and the CMC works to enable IND filing in mid next year.

Okay. And just to tie it back together with the proof-of-concept study with apitegromab, you have not given guidance on when we will see those results.

Q2, Q2 of next year, yes. Initially, the guidance was midyear 2025, but as we've hold -- gotten an understanding of how well this is enrolling the momentum, we pulled it in a little bit.

Okay. So get the opportunity to have those results and then immediately pivot to the purpose-built molecule, while you're presumably filing a BLA at the same time on SMA? Yes, you've got a lot going on.

Hopefully, the BLA will be filed before that, but yes. With the data in Q4, as we talked about, everything that can be filled in, in the BLA is already being filled in, and they're just waiting for that final data to be dropped in. We put a little daylight as possible between that data readout and the BLA file.

Great. Maybe wrapping up on 439 and we kind of already had the conversation on SMA, let's talk about obesity. I mean, combinations, pricing, payers. Frankly, it's hard to digest at some point what's going to happen here -- what are you expecting? How is this market going to evolve?

Right? So we all know -- I mean, I think 2 years ago, no one would have expected this market to be what it is right now, and it's been huge. And I think everyone is trying to get their arms around it. So we feel very strongly that there's an unmet need. Obviously, the GLPs are here to say they're doing great things for patients. There's a need to preserve lean muscle mass within that therapy -- within that therapeutic index. We also feel very strongly that our molecule -- our approach is a very -- should have a very prominency on the table. We have a very credible approach to this issue. How the whole landscape evolves, we'll see. I mean there was article in Barron's a year or so ago, the GLPs could break the whole health care, is right? People smarter than me are going to have to figure that out. 439 is purpose built for this space. It's going to be designed -- and it's been designed as a subcu. We think it's going to fit really nicely into that treatment regimen. As this industry, this part of the industry evolves, we think 439 will have a prominent place there. People ask about the regulatory pathway, right? So right now, a weight loss drug gets approved with 5% weight loss and the GLPs are producing 20% to 30% weight loss. So there's a lot of room for that story to evolve, and we can continue to help patients retain lean muscle mass and improve their overall metabolic health.

Great. Okay. So a couple more minutes here. Maybe just take it back to the DNA of Scholar Rock and what you guys have built as a company, help orient us on what is likely to stay in your own control and in your own hands? What's available? How do you think about collaborations and partnerships, access to GLP-1s, for example? And also, you have an oncology program that we haven't touched on, but maybe just touch on how you're thinking about prioritizing those assets.

Yes, in a really, really interesting fibrosis program and a really interesting anemia program. So we're a little bit blessed with the biotech curse of having more opportunities to help patients than capital and bandwidth. So it becomes paramount to prioritize. So first and foremost is apitegromab in SMA. And as we talked about with a successful SAPPHIRE readout, we're going to expand and try to help all the SMA patients that we can help. There's more breadth in there. There are other neuromuscular indications where we think apitegromab might be able to play a role. And so we see apitegromab as being really a franchise. We can build a franchise around this molecule. Talked about commercializing in the U.S. and select regions in Europe. That really is priorities 1, 2 and 3 within the company. The obesity study is really very exciting. And you can see we've talked about this where you can see a scenario in the middle of 2025 as EMBRAZE reads out and if it's positive and it sort of proves the hypothesis, at the same time, we have a clinic-ready molecule that's demonstrated significant superiority across the competitive landscape. That could be a really interesting time to partner with a company that has the global clinical and commercial infrastructure that's probably required to ultimately commercialize a drug in the obesity space. As we talked about, it's big, right? It's a big one. So we'd probably be advantaged to have a partner ultimately in that area. In terms of oncology, very excited about that data. The DRAGON study we completed enrollment. We really -- the spend on that program dropped significantly from 2023 to 2024, but we continue to take care of patients who are on study, and patients are staying on study and that continues to produce data and demonstrate that there's an active drug there, and there's a need there. It remains to be seen, we're going to get some clarity on what the next step would be in one or more of the cohorts, and that could be an opportunity to pull in some help to advance that program as well. And then, of course, the fibrosis program that doesn't get a lot of airtime, but there's a wide array of disease areas within fibrosis that we could go after there, and that in itself could be a franchise of orphan drugs.

Yes. Maybe just one clarification on your EU strategy in SMA or the filing time line similar and do you have what you need coming out of SAPPHIRE to be able to file presumably?

Yes. So the SAPPHIRE study was put together with feedback from FDA and EMA. SAPPHIRE is a global study. It's about equally weighted between U.S. and Europe in terms of sites. I'm going to comment on patients, but it's about equally weighted. So we should be ready to go. And U.S. first in pretty quick succession will be Europe.

Great. All right. Well, you guys have an exciting next 6 months to a year, and we're looking forward to see it all unfold. Any closing comments?

No. Again, I appreciate the opportunity to get back from summer and be here with everybody and be at the Morgan Stanley conference. And we have a great day of investor meetings and we are back to work and ready to go. Patients are waiting for our therapies.

Great. Thank you. Thank you for joining us.

Thank you.

Thank you.