Scholar Rock Holding Corporation ($SRRK)

[Audio Gap] We have David Hallal from Scholar Rock here with us. Thank you so much for joining us.

Maybe to start, if you could provide just an overview of your company for those who may not be familiar, including the updates that we'll see within the next year.

Great. Thanks, Tommy. It's great to be here once again at the fourth Goldman Sachs Healthcare Conference. David Hallal, Chairman and CEO of Scholar Rock, which is a Cambridge-based biotech company that has been focused on myostatin biology. And we're very proud that we are the world leaders in myostatin biology. This is obviously a target that was identified in 1997 the first anti-myostatin inhibitor went into the clinic in 2004, 2005. And really over the period of these last 20-some years, there have been multiple milestone inhibitors that have failed in clinical development. We stand alone with our unique technology platform and approach to myostatin biology as the first and only company that has successfully developed a myostatin inhibition program through mid- and late-stage development with a successful Phase III trial with our lead asset, which is apitegromab for children and adults living with SMA. As Tommy has asked, what does the next 12, 18 months look like for our company. We're super excited having hit a statistically significant and clinically meaningful benefit in motor function with the highest gold standard measure of the Hammersmith motor function scale in SMA for children and adults living with SMA to now be on file with both the FDA and the European Medicines Agency with action dates this year in 2026. So we're looking forward to launching opitagrimab into the spinal muscular atrophy space in 2026 in both the U.S. and in Europe. And then eventually, as many of us have done at prior organizations, we'll look to commercialize apitegromab in up to 50 countries around the world so that we can meet patients with SMA wherever they may be. Beyond apitagrimab in SMA, we're also very excited about some additional programs that we have ongoing we are going to be commencing just after the middle of this year, a trial with opitacrumab for patients with FSHD which we can talk about. It's a Phase II trial, randomized, double-blind, placebo-controlled. And we are also making sure that no patients with SMA elect behind. So we do have an ongoing Phase II trial, our OPL study. which is for those patients that are under the age of 2. So the youngest of patients living with SMA. And then to advance our technology platform forward, we can also catch up on the progress that we're making with a subcutaneous version of apitegromab as well as SRK-439, which is in and of itself, a different molecular entity. It's a high potency, high affinity, low frequency, low-volume subcutaneous injection. And that program is in healthy volunteers today and we'll be reading out that healthy volunteer study toward the end of 2026.

Okay. Great overview. And as we start with the SMA market, so multiple treatments, multiple modalities. As you think of your positioning as an add-on to improved muscle strength who are the early adopters in terms of phenotype and combination therapy? And who do you think it will take some more time to reach?

Yes. It's a great question. And maybe where I'll start, Tommy, is that really before 2016, SMA, which is a devastating disorder really was a very, very high need for innovation. And so over the last decade, what we've seen is the initial phase of innovation was ushered in for the treatment of patients with SMA, all focused on motor neuron health. And so these programs are SPINRAZA from Biogen, Evrysdi from Roche, Zolgensma from Novartis. And really, what we've seen over the last 10 years is that patients are living longer and having greater motor function from the focus on stimulating SMN protein, either SMN protein 1 or SMN protein 2. Obviously, SMN means survival motor neuron protein. And so these are necessary to protect the motor neuron from debt. And what we have seen from this last decade is that patients indeed are doing a little bit better. So patients are living longer, but they really are claiming almost all of them. that their #1 need is more motor function and more muscle strength. And so important to note that the motor unit, which is responsible for motor function is not just comprised of the motor neuron but it's comprised of the motor neuron and the muscle. The muscle is the principal organ that is clinically affected in SMA. And over these last 10 years where we've seen needed innovation around motor neuron health, there has not been anything to address the muscle component of this disease. And so we were super gratified with our Phase III SAPPHIRE study to show for the first time that patients that were on these SMN targeted therapies, if you will, were randomized to either receive placebo or apitegromab. And in our Phase III trial, what we were able to show is substantial improvement stat sig in motor function using the Hammersmith motor function scale and also nearly a 4x greater likelihood of patients having a 3-point improvement on this motor function scale when they received apitegromab as opposed to the SMN targeted therapies alone. So the way that we look at this is definitely not like an add-on therapy, but for the first time, we can start to treat the entire disease of SMA with these wonderful sort of SMN targeted therapies focusing on motor neuron survival in motor neuron health but then also addressing the muscle component of this disease. And so coming back to your question, when we look at the market, we really think every patient is going to be eligible for treatment because muscle is the principal organ clinically affected by this disease. And whether those patients are as we've seen with SMN targeted therapies alone, those patients tend to do better in the first 1 to 2 years, but they may plateau. And then we've actually seen in the long-term extension trials of those therapies or even in our Phase III trial, where the average patient was on those therapies for 5 or 6 years, there's usually a return to the progressing form of SMA, where those patients start to lose motor function again. And so what we were able to show in our Phase III trial as opposed to a loss of motor function, there was now a gain of motor function when those patients were randomized to receive apitegromab. So we feel like now with patients who have been on our therapy from our Phase II trials for upwards to 7 years that whether or not patients are improving on SMN targeted therapies, whether or not they have plateaued or whether or not they have returned to the progressing form of the disease, they are all candidates for treatment and we will be really discussing with the patient community and the physician community, the importance of not only wanting as much SMN protein as you possibly can get from those highly innovative SMN targeted therapies. But every patient with SMA should also want any myostatin, which is the body's natural negative regulator for muscle growth. So you would want to eliminate that in any patient with SMA. And we think it's quite a compelling case as to why there's a very, very broad group of patients that are going to be applicable and targets for apitegromab therapy.

Interesting. And you have had some announcements on the regulatory side around manufacturing, especially the Catalent Indiana facility. What are the next updates here and the impact to commercial supply as you look to a potential launch?

Yes. Tommy raises a very good point. We had a look at our Phase III study and presented it in Q4 2024, which was, again, for the first time after 20 or more years of efforts to effectively target and block myostatin apitagramab and Scholar Rock was the first and only effort to be successful. Based upon the strength of our Phase III study, the FDA granted us a priority review when we had submitted our application in 2025 with an action date of September 22, 2025. We, of course, had a very successful review with the FDA except for the net of our fill/finish facility, which was Catalent Indiana, owned and operated by Novo Nordisk. So the FDA had a general site inspection at Catalent, Indiana in the summer of 2025. During that inspection, they cited observations associated with GMP compliance. And as a result, as many of you know, a facility that is listed in anyone's biologic license application needs to be in good standing and good compliance with the FDA for that drug to be approved. This ended up being the sole approvability issue and why we received a CRL after hours on September 22, 2025. Nonetheless, we've worked very closely with Novo Nordisk. We've actually worked very closely with a second fill/finish facility. And we've been in ongoing dialogue with the FDA really since September of 2025 to get back on file with the F. So we have resubmitted our BLA. That BLA has been accepted and we have a new action date of September 30 of 2026. Importantly, what's an improvement over this BLA than our initial BLA is that we now include 2 fill/finish facilities in the BLA. So we have 2 independent paths to an approval. That is Catalent Indiana, should that be reclassified from its OAI classification, which means official action indicated and is unlikely that a drug would -- a new drug would get approved under that classification. So it would have to be downgraded to a VAI only through an inspection, which we'll get to in a second. Or the second independent path to an approval is our second fill/finish facility, which is already vialed all of teopitagromab that we need for launch in the U.S. and Europe. It's also all of the apitegromab that has generated the data for review of the FDA to approve our application with that second fill finish. And of course, there's a third potential outcome, which is we may get approved with both fill/finish facilities in the application. And frankly, the time lines are now overlapping with 1 another. So the FDA did have another general site reinspection of Catalent, Indiana in April of this year, so just about 6 weeks ago. They did cite more observations at that facility actually 8. And now the FDA has about a 90-day guidance period to make a determination as to whether or not Catalent in the inter remains an OAI or whether or not that gets downgraded to a VAI. And that 90-day guidance period takes us into late July. At the same time, the second fill/finish facility, as I noted, has now vialed all of the apitegromab that we need for launch that is going to be available also in July to support the launch. And so what we're expecting now is the FDA to be making a determination on both fill-finish facilities. And that's why we stand ready to receive an approval and launch this drug at any time between now and up to and through September 30, and we're really excited to finally get on with the launch and serve the SMA community that is desperately waiting for the first muscle-targeted therapy to be approved by the FDA.

Okay. And understanding that you probably can't get into that much detail here, but to the extent that you can say what you're aiming for in the language for the label, maybe in terms of SMA type age, ambulation, combination therapy, et cetera.

Yes, it's a great question. And in fact, the nice thing, if there is such a thing about receiving a CRL is, first and foremost, you know exactly what the approvability issue is. And as we noted on September 23, after receiving our CRL is the FDA made it very clear that the only approvability issue was the status of compliance at our fill/finish facility. What that meant, obviously, and we had a very successful review up until we received the CRL was that the FDA was very comfortable with the clinical package, both safety and efficacy. And in fact, they indicated that when we do resubmit, just go back to the same label that we had sent them at the tail end of the review period, and that actually was like within 24 to 48 hours of our PDUFA, we had a good sense as to which way the label was going to turn out. And we were -- as we noted, we were pleased with where we were. But there was never -- during the review, there was never a significant gap between where the review division was at the FDA and where we were in terms of what we thought would be appropriate use of the drug in patients with SMA. To get to your point specifically, we -- the FDA has tended with the other approved treatments to be more -- see SMA as a single disease as opposed to 1 where they're looking at ambulatory status or copy numbers or age they're generally taking a broader view. And so while I won't comment on the specifics of the label, we feel like we're well aligned with the FDA when we do have an approval where we will be able to address a wide range of patients living with the disease where there is biologic plausibility that by inhibiting and fully eliminating most patients have the best chance for an improvement in motor function. So don't see any major restrictions. Obviously, we did not study now we are, but we did not study apitagurmab in SMA patients under the age of 2. So we wouldn't expect to be able to at launch, treat infants and toddlers, but we do believe at the age of 2 and above, those are going to be a population of patients that we're able to serve given the strength of our clinical data. And I'm looking at my Chief Operating Officer here, Keith Woods, we think that in the U.S., there is going to be a wide range of patients to serve with apitegromab. So we're sort of pleased where we were in September of last year, and we expect that as the starting point to finalize the discussions.

With the ongoing BLA. And you also have an infant study, when could that expansion happen?

That's exactly right. So the OVAL study is really our obligation, more than maybe a commercial opportunity. It's really our obligation of the SMA community to make sure that we understand the youngest patients living with SMA, what the role of apitagrumab is. And so that study is ongoing. We would expect after approval and when we generate data, the PK/PD data, the safety data is all going to be very important for the FDA to consider maybe broadening the label to those patients who are under the age of 2.

Okay. And then maybe if you could speak to what you see as critical really to execute on the launch. And as you think of aspects such as in clinic versus at home infusion, access reimbursement, noting that this is a Medicaid representative population. Maybe if you could just speak to kind of those metrics or points that you're really looking to execute on?

Yes. Maybe I'll start first with sort of demand generation and then we'll get to access and reimbursement. So as I noted earlier, the wide range of patients that we studied in our 188 patient randomized, double-blind, placebo-controlled Phase III trial, the SAPPHIRE study. We actually see a wide range of patients that are going to be appropriate for therapy. As I noted, as long as the patients are on an SMN targeted therapy, no matter whether or not they are having an improvement in motor function, their plateaued on motor function or they have a decline in motor function, we believe that the opportunity to completely inhibit myostatin again, the body's natural negative regulator for muscle growth can improve the outcome for those patients. And so I also noted some Cure SMA, which is a phenomenal patient advocacy group has done plenty of surveys of the SMA community and 95% of patients continue to report that their #1 need today is muscle strength and improvements in motor function. And so we do anticipate that there is going to be significant interest from the patient community and the family community. At the same time, we've also seen that approximately 3/4 of all neurologists and neuromuscular specialists. Also we're acknowledging that while there's been great innovation with motor neuron health with the SMN targeted therapies, that this is a disease that requires treatment of both the motor neuron and the muscle. So you got 95% of the patient community saying, we really want something to address the muscle. About 3/4 of the physician community saying, yes, it seems like the best way to treat patients is by addressing both the motor neuron and the muscle. And we think that, that setup is quite nice for us in terms of demand generation of the community wanting to access opitagrumab at approval. So let's pivot now to access and reimbursement. Maybe just to level set everybody here. Opitagrimab is an IV therapy. It is approximately a 1- to 2-hour infusion and it's delivered monthly. Technically every 28 days. And so on average, patients would have to dedicate probably 1 to 2 hours a month to receive the infusion. And we recognize that it's important to provide patients and families with options on how they're going to receive those infusions. So as Keith has acknowledged on some of our prior earnings calls, we've established a 10,000 infusion nurse network around the country. So wherever patients are, we can deliver this medicine to them potentially in their home. We also recognize a lot of KOLs are going to want to commence treatment at their sites and then maybe look for something a little bit closer to home, but we want to provide that optionality to patients. I think what's important also to note is we've now had patients on apitegromab for upwards to 7 years. The combination of our Phase II and Phase III clinical trials has resulted in more than 90% of patients that remain on open-label apitegromab in our open-label extension study, otherwise known as the On-X study. And so we do believe that were set up for -- given the strong value proposition of apitegromab for a program that will, we think, deliver very, very high compliance for patients. Now let's actually take the payer side of this. You mentioned that it's a Medicaid dominant population. We do see that the market in the U.S. is probably 50% commercial, 50% government that will be either Medicaid or Medicare. We do know as an infusion product, we will initially have a miscellaneous J code. So not a drug-specific J code at least for 6 to 9 months that can usually result in like automatic denials or deferrals and delay reimbursement. We also recognize a lot of the SMA expert treatment centers, maybe hospitals where there might be formulary status that's needed. And then we also recognize like a lot of payers, especially Tommy, to your earlier question, if the label might be broader than the Phase III clinical trial population, payers are going to have to also take a little bit of time to establish their medical policies for apitegromab. So all of that results in, we think, not a matter of if, but when reimbursement happens and as we've typically seen with many new infusion drugs at launch, there can be delays, there can be denials, there can be appeals. And our own experience and Keith has had maybe more than anybody else, that it can be upwards to 60 days from an intended enrollment form, start former prescription to funded supply that can happen at launch. And then eventually, over the first 9, 12, 15 months, we'll get to a steady state of a more rapid prescription to reimbursement coverage and fusion. So we, as a company, have established a white glove service known as Scholar Rock support, so we'll be able to enroll every individual patient and family in our reimbursement and access program. We also have an in-field reimbursement team and infield sort of coordinator of care with every patient and every family. And so we want to make sure that we can work very, very closely with physicians and the patient community and helping them through this process. So over time, we are super optimistic about the opportunity to serve patients, but we do know upfront, and this is just to manage everyone's expectation, given the amount of time that it might take from prescription to funded access and infusion, it may be a steady launch, not necessarily like a pent-up hockey stick at launch. We think the demand will be there, but it will take a little bit of time for access. Overall, though, we see this as a massive opportunity to serve patients and a massive opportunity for growth through the end of this decade and well through the next in the U.S. and Europe and up to 50 countries around the world.

Okay. That's very helpful. And is there anything else that you would want investors to understand about this asset before we pivot to the rest of the pipeline?

The only thing I would want investors to understand, and I've said this a lot, we've talked a lot about getting through the final steps in the regulatory process, again, largely through our third-party manufacturer who is doing fill finish. We've talked about things like as you said, access and reimbursement. We've talked a lot about launch curves. But the only thing I would want everybody to understand is there's somewhere around 7,000 patients in the U.S. that are likely going to be appropriate candidates for treatment and then another 28,000 outside of the U.S. that are going to be appropriate candidates for treatment. So approximately 35,000 patients globally across all of the SMN targeted therapies, this is a $5 billion market today, and it continues to grow. More innovation is coming around the motoneuron health sort of therapeutic options, but we are the only ones to address the muscle component. And that's why we are quite confident that this is a very, very large opportunity to serve patients in a very, very large opportunity to grow our business for many, many years to come. So what I'd like everybody to think about over time is I know we're thinking about the first 6 to 12 months of launch. The more important thing is massive opportunity for strong steady growth through the end of this decade and well into the next. And every single year, we'll be bringing new countries on board. There'll be new launches, new patients on board, and that's why we think we are 1 of the strongest global growth stories on the horizon and biotech right now, and we're super excited about it.

Okay. Great. in FSHD, we've seen a lot of recent activity from the DUX4 targeting agents. You have a different approach. As you look to starting your Phase II study, what are the key endpoints here? And what does success look like? And overall, could you maybe frame your positioning in this market?

Yes. Great question, Tommy. So we believe, as I presented it at the JPM conference in January that there is a host of genetic and acquired myopathies and neuropathies that may be a particular interest for us with our platform with apitagrimab and eventually with sub-cuepitogram mab and 439. In other words, we believe we sort of have a platform and pipeline that we can develop for this product alone. And while we are really excited about more and more correctors being developed, as you mentioned, those that are targeting DUCs 4 and FSHD. We believe that the muscle component remains a high unmet need in many diseases beyond SMA. And so we've been exploring. We've done some preclinical work in DMD. We've now done preclinical work in FSHD, and there's more to come. So we see a series of potential rare and neuromuscular diseases that we can apply our expertise to. What we've announced is as of earlier this year, is that FSHD would be the first disease outside of SMA that we would target. By clinical data looked very robust. So we Flex DUCs 4 mouse model. We applied our antibody to those mice. And what we saw is an improvement in muscle mass, muscle force and exercise endurance. And actually, it provides a strong preclinical rationale, very much like what we saw in SMA. So that was important. What we also saw when we looked at FSHD is that there's actually some clinical work by looking at rigorous exercise programs and/or the use of anabolic agents like HTH and testosterone that show that by targeting the muscle alone, there was improvements in lean muscle volume as well as functional measures. And so we said, we actually think that as a monotherapy, we can actually throw off a proof-of-concept and yet all of that should also apply should there be great success in the corrector therapies addressing DUCs 4, it could be used potentially monotherapy or in combination with those corrector therapies. FSHD, 30,000 patients diagnosed in the U.S. and Europe. Usual onset of disease is sort of adolescents to early adulthood. It's a devastating disease in which about 1/5 of patients end up in a wheelchair or needing an assisted device. And again, the other thing that we're pretty attracted by an FSHD is it tends to be a disease with where you have -- because of DUCs 4, you have patchy dysfunctional muscle, but you have patchy normal musculature, which also may be the reason why targeting the muscle alone can show a benefit. So coming to the forge Phase II study, 60 patients double-blind, randomized, placebo-controlled, the primary endpoint will be lean muscle volume at 12 months, but we will look at some functional measures as well. I think the regulatory endpoint that some are using today is a combination of lower and upper extremity of functional outcomes like quantitative muscle testing. We'll be looking at that as well in our study. And we look forward to start enrolling patients. We're looking at more of the moderate form of the disease. So there is enough normal musculature whereas a monotherapy, we can show a benefit. And we're looking forward to enrolling the study and sharing some results sometime in '27 or early '28.

Okay. Great. And maybe just as a last question and overall strategy question. As you look on the forward future for the company, maybe rare versus prevalent diseases and wholly owned versus partnerships? How are you thinking about those aspects?

Yes. Tommy raises a very good point. Our very compelling Phase II EMBRACE study was just published yesterday in nature and has received a lot of press. And this was a study that we did in over 100 patients that were randomized to receive either tirzepatide or pita with tirzepatide. And what we showed was a lean mass preservation that was quite striking with a p-value of 0.001. And so the question has been like in the world of cardiometabolic, obesity, longevity, how as world leaders in myostatin biology and muscle health, how do you see yourselves applying your platform moving forward. I think what we've said is that we think what we know well and do well is rare neuromuscular these serious diseases that impact both children and adults, and we want to apply our resources there. But we've also said that 1 thing we could see ourselves doing because we have some fusion protein technology in-house is that we could see some kind of a uni molecular approach to our myostatin inhibition platform and GLP, GLP-1 RAs and we just had an abstracted ADA this past week, kind of unveiling that. We think there could be a partnership in the future where leaders in the cardiometabolic space, combined with us leaders in the myostatin space, maybe could work on something together, but we think the appropriate approach might be of fusion protein as opposed to a stand-alone asset. So for now, we want to take what we know well and do well and apply it to a broad range of rare neuromuscular disorders that can then fit into this 50-country operating platform that we will build to initially serve patients with SMA, hopefully then serve patients with other rare neuromuscular disorders like FSHD, DMD or beyond. We'll provide you updates on that progress and then continue to build out sort of our rare disease platform for many years to come.

Okay. Great. Well, thank you very much for joining us, and we look forward to watching the progress.

Thank you. Thanks, Tom. Thanks, everybody, for tuning in.