Hosting David Hallal, CEO, Scholar Rock. Dave, how are you doing?
Great. How are you, Mani?
I'm good. I was gonna say welcome to Miami, but this is essentially your home away from home as well.
Yeah. It's increasingly becoming a spot that we spend a little bit more time, and it's wonderful to see more of our biotech ecosystem coming down here. More great investor conferences. One of the best things that Leerink ever did was pivot from the New York site down here to Miami.
If you wanna say that louder so everyone knows it was my idea at one point, that would be great. I can't take credit for that, but I will try to. Rampant self-promotion aside, obviously a lot of the focus for you guys has been around the timing to approval for apitegromab. We've had the data in hand for some time.
Yeah.
I think most people who are listening to this, either remotely or here in person, are familiar with a little bit of some frustrations around the Catalent Novo facility. This hasn't been unique to you guys, but you've been probably the single most exposed company, which that's just sometimes the way the cards are dealt in life and drug development. Give us a quick update on where we are regarding conversations with the agency, whether or not a re-inspection has physically happened yet, and how to think about timing to a resubmission dependent upon Catalent. We'll talk about the second fill finish separately.
Great. Thanks, Mani. Yeah, as Mani was alluding to, back in Q4 2024, we were gratified to announce the positive results from our phase III SAPPHIRE trial, which was a very robust global 188-patient randomized double-blind placebo-controlled clinical trial for children and adults living with SMA. We had maybe the highest bar of all, which was the Hammersmith Motor Function Scale in SMA as our primary endpoint. We hit stat sig with a statistically significant and clinically meaningful benefit in motor function in patients that were receiving chronic ongoing SMN-targeted therapies like Spinraza and Evrysdi. We filed our application for approval in January of 2025.
We were granted priority review 'cause this is poised to be the world's first and only muscle targeted treatment for patients living with SMA, and we had an action date of September 22nd of 2025. As Mani noted, unfortunately on that day, while all signs read positive for an approval, we received a complete response letter, and the sole approvability issue was the state of compliance at our third-party fill finish manufacturing facility in Bloomington, Indiana, formerly owned by Catalent, now owned by Novo Nordisk.
Really since that time, there's been a heightened level of awareness for us and a few other companies that have been caught up in this process because the FDA has a regulation that any of the GMP facilities that you list in your BLA have to be in good standing with the FDA for that approval process to proceed to be a green light. While we were disappointed with that news on September 22nd, we took full advantage of the opportunity to schedule a Type A meeting with the FDA to discuss the matter at hand. We had that in-person Type A meeting on November 12th of 2025.
At that meeting, we were joined by Kenneth Hobby, the President of Cure SMA, the patient community that is eagerly awaiting the world's first and only muscle-targeted therapy, wanted to address the agency, as did Novo Nordisk, which to that point, had not had any feedback from the FDA on their remediation plan, which was a result of the poor inspection outcome that they had in July of 2025. At that in-person Type A meeting, we reported, that there was a shared sense of urgency between the FDA, Novo, and Scholar Rock to try to expedite the process to, remediate the facility, re-inspect the facility, and eventually for our BLA resubmission and approval.
We walked out of that meeting feeling like there was going to be a different cadence and level of communication now between FDA and Novo Nordisk as they remediated that plant. What we announced last week during our Q4 full year 2025 update is there has been a steady drumbeat of progress since that Type A meeting. The week after the Type A meeting, the FDA issued a warning letter to Novo Nordisk. That was actually a positive. We expected that to come. By not waiting four weeks, six weeks, eight weeks, it gave Novo the opportunity to expeditiously respond to that warning letter, which they did within 15 business days, and that was mid-December. Before Christmas, the FDA reached out to Novo Nordisk and actually scheduled a meeting in early Q1 to talk about this.
It's kind of unprecedented that they would be on that kind of a timeline. Usually, you know, these processes take an enormous amount of time, and the FDA usually is not responding that quickly. We announced last week that early Q1 meeting between FDA and Novo Nordisk has since taken place. It was a positive meeting. The FDA had no additional requests to the remediation plan of Novo Nordisk. We expected this to continue to proceed. Shortly after that meeting that FDA and Novo Nordisk had, the FDA sent a field team out to the Bloomington, Indiana facility. It was not a formal re-inspection. It was a positive site visit. They spent a few days at the site.
They met with leadership, and at the conclusion of that site visit, they informed Novo that they would be coming back for a formal re-inspection, following the resumption of routine manufacturing activities which had resumed at the end of February. Now, Mani, to your specific question, you know, how do we see the cadence of events from here? We think now that there has been a resumption. This is a busy plant, lots of manufacturing. The FDA is aware of Novo's schedule. Somewhere in the not-too-distant future, we should see a field team show up for a formal re-inspection.
As we indicated last week, following you know an apparent positive re-inspection, and there should be some feel for how it goes, we would plan to resubmit our BLA to FDA, and then that would sort of start our clock once again for approval. Given the timely progress that has been made, this steady drumbeat of progress, we did reaffirm last week our prior guidance of a 2026 resubmission of our BLA and U.S. launch following approval, and we believe we're well within that range of all of this happening over the course of the coming months. As I look at my colleagues, my Chief Operating Officer, Keith Woods, and my CFO, Vikas Sinha, we are fully expecting to be launching our drug later this year.
Let's talk a little bit about the other piece of that. We talked about the timeline for Catalent, Novo, however you wanna call it, but however you wanna ascribe ownership of that facility. Obviously, the submission within this year has a belt and suspenders component 'cause you have a second fill finish facility. Talk to us about the timelines should that second fill finish facility be what the BLA is dependent upon for whatever reason, other delays.
Yep
... the Catalent gets hit by a comet.
Yep.
Whatever. Like talk about those timelines for the second facility, and what are the steps between now and a filing based upon fill finish at that location?
Great question. We believe the fastest path to resubmission and approval is the re-inspection of the facility. Whether it's a Class One or a Class Two resubmission, we believe the FDA will continue to work expeditiously to reclassify the facility and approve apitegromab for children and adults with SMA. What Mani is alluding to when he indicated this to me, you know, some time ago, the importance for us to solidify confidence to the SMA community and the investor community about our progress with a second fill finish manufacturing facility, we have taken this on as a massive initiative at the company. We said there is only so much within our control on the re-inspection of the Catalent Indiana facility now owned by Novo Nordisk.
Let's make sure with the belt and suspenders approach, we move as quickly as possible to qualify another fill-finish facility and our team has made, you know, massive progress there. As I announced last Tuesday, March 3rd on our Q4 call, engineering runs are now underway at our second fill-finish facility. We would expect all of the validation runs, the PPQ runs to follow all in an expeditious fashion. We believe that if a meteorite were to hit the Novo facility or for some reason they did not pass a re-inspection, we are still well within the guidance of a resubmission of our BLA and U.S. launch should we rely on that second fill-finish. That's a combination of very much like the progress we're making at the first facility.
It's a team effort between the, you know, the FDA exercising some level of flexibility for us in validating and submitting that second filler. It's the new second filler that's working to make a lot of capacity available to us in a timely fashion, and it's our internal Scholar Rock team that is, I think, potentially going to break a record here in terms of standing up, identifying, standing up engineering runs, validation runs, BLA submission, and approval for a new filling site. Obviously, we wanna leverage some of the data we've generated at Catalent Indiana on things like stability, but we feel very confident that's also well within the range of our guidance that we provided for 2026.
Let's talk about between now and when a filing happens. Where are you in terms of accumulated supply and inventory of drug, and what that means for patients currently and open label extension, expanded access, et cetera? Then we'll dive more into the EAP after that.
Great. Mani raises a very important point. We have, and we've expressed this to the FDA. We have tens of thousands of vials to support the SMA community now. That drug was vialed before the OAI designation of the Catalent Indiana facility, which means official action indicated, which means, you know, do better or else. That is the drug that we are using to maintain hundreds of patients of extension trial and early access patients, you know, on therapy. We've done a robust product impact assessment of that drug that's been vialed. We do not believe the observations that we're seeing that the Catalent Indiana facility owned by Novo impacted our drug apitegromab in any way. That is ready to go for approval. It would be labeled, packaged, and sent out into the community.
It is important to note, because I'm living it every day, that not everybody here understands. While an OAI classification and a warning letter may prevent a new drug application from being approved at this facility, this facility continues to manufacture, uninterrupted, all of the commercially approved drugs in that facility, and that continues to be released into the marketplace on an ongoing basis. This is the drug that we're maintaining hundreds of patients on in the U.S. and Europe. At approval, that drug would then be released into the marketplace, like I said, labeled and packaged with all of our approval packaging. Should, you know, when I mentioned, "What about the second facility?" The second facility will be releasing drug in 2026 as well.
That's great news for us in terms of the guidance that we have provided. All of this is in line with our ambition anyway to have redundancy in our supply chain so that we can fulfill our commitment to the SMA community to provide our highly innovative apitegromab for children and adults living with SMA. We do not need, and I think this is what you're getting at, Mani. At approval, we have no needs to having to manufacture more product to supply the marketplace. The launch product is vialed and ready to go from Catalent, Indiana, and it will be vialed and ready to go and releasable from the second fill-finish facility several months from now, which also is very supportive, again, of our ambitions for a 2026 launch.
Having laid out that timing to launch, let's talk about commercial readiness. Obviously a little bit of icing the shooter risk here.
Yeah.
-from a launch that was expected having been delayed. What is your commercial team doing now in terms of preparing the market for this launch, and what is your strategy to accelerate uptake and address what may or may not be a challenging reimbursement environment, given this is relatively novel territory where you're labeled for add-on therapy?
Yeah.
SMA? We haven't actually had something labeled for that purpose before.
It's a good question. As I think many of you know, on April 28th of 2025, I made the transition from independent board chairman for eight years at Scholar Rock into the board chair and CEO role. On the very same day, I was, you know, really proud and gratified to announce three executives joining me on the same day, who I have a long history with, a long track record with. Akshay Vaishnaw, who is our President of R&D, and before that for 19 years had been serving in that role at Alnylam. Akshay and I worked together back in 2002 at Biogen. We've had a long-standing relationship. Keith Woods joined us as our Chief Operating Officer.
Keith and I, this is our third chance to work together, and we worked together at Amgen in the 1990s, again at Alexion from 2010 to 2017. And then of course, he did his best work yet, when he went to argenx and launched VYVGART as the Chief Operating Officer. And then of course, Vikas Sinha, we've been working uninterrupted since 2006 together, Vikas. Why I had that preamble to answer Mani's question is there had been some planning done, for the commercial launch when we came in. It was April 28. The PDUFA date was September 22.
Keith is expert at this and I think assessed a lot of things that had been done, and I think with a little bit more time, you know, would have changed some things, and I think with this time has changed some things. He's been trying to strengthen our efforts to be ready for this launch. So since then, we've hired, trained, and deployed the team in the field. That's number one. Number two, we've anchored them with a disease awareness campaign because you obviously cannot promote when you are not yet approved. Back to your point, Mani, about the uniqueness of the label, motor function in SMA is not driven only by motor neuron health. It's the sum of motor neuron health and muscle health. The motor unit is actually the sum of motor neuron health and muscle responsiveness and muscle health.
While the motor neuron is the origin of the disease, the muscle is the principal organ impacted, clinically affected in SMA, and patients have never had a drug to address the muscle. The commercial team has really been spending time with 140 SMA treatment centers, with thousands of neurologists that treat these patients and neuromuscular specialists, and really making sure we do lay the groundwork, staying way short of promotion, lay the groundwork on disease education that does this make sense that our data ultimately is supported by being able to target the muscle. That's actually been important. The team has been building relationships in the field. They've been supporting patient events that Cure SMA has around the country on many weekends.
We have actually built a home infusion network of about 10,000 nurses nationwide, so there would be nurses close by for any patient that may at approval access this therapy through home infusion. We've continued ongoing dialogue with national and regional payers so that they also understand. You know, the direction of the clinical program, and they would be, you know, more apt to then react ultimately to the approval. You know, we're certainly expecting that to be soon. Then two other things we've launched with our extra time. Keith noted that Scholar Rock Supports is going to be our patient assistance program that we've been spending a lot of time. Every single patient who enrolls in that program will be escorted with white glove service through the reimbursement and access process.
Then we've launched a second version, Keith, 2.0, on Life Takes Muscle, which is again a community-centric disease awareness initiative to really talk about the importance of muscle and SMA. All of that has been fantastic. To your point, Mani, Keith and I worry that, you know, as well that we, you know, we hired a very seasoned team that is used to being in the field of battle, but now they've been out there for a few months without an approval. How do we keep them sharp? We keep them sharp with ongoing training programs, kind of our own war games and boot camps internally, and then metrics in the field from a pre-approval awareness type of program, which has been great. This is what we expect at launch.
We expect there'll be a lot of demand from patients and families and physicians. We do expect payers because it's kind of what they do. You know, there will be some headwinds in terms of simple, reliable, and trusted reimbursement and access at launch. We believe we will settle into a really nice conversion rate. This community is well seasoned on accessing therapies that may be initially difficult to obtain through payers, and we believe it will be great teamwork between us, the physicians, and the SMA community to access the drug post-approval.
Let's talk a little bit about the demand dynamic. We'll start with a quick question, which is, in the EAP, what is the split of age of patients in the EAP as sort of a soft indicator of how to think about the split of demand?
Yeah. Keith mentioned this at this morning's breakfast, which Mani had hosted, that we had about a 50/50 split in the U.S. EAP between adults and children. As I've noted for quite some time, the FDA tends to lump and not split SMA. They see it as one disease. They don't get into splitting things by ambulatory status, copy numbers, age. I don't wanna comment specifically, but we left the label in a constructive place. We're always very aligned with the review team at the FDA on that label.
What we also are well aware of is sometimes a new drug at approval, even if the label were to be broader than your phase III enrollment criteria, there could be some initial speed bumps on the way of access, and that's something that we'll have to work through. We certainly have an enormous amount of conviction in the near and long-term opportunity we have to serve patients in the U.S. and around the world. You know, recall, and I think Mani maybe will get to this, but there are very robust numbers in the U.S. and around the world of patients that have received an ongoing SMN targeted therapy, and that really becomes our opportunity at launch.
When we think about the global opportunity, obviously, like a lot of rare diseases, or genetically inherited diseases, excuse me, the U.S. opportunity often is quite large as a proportion of global, which is not always the case in primary care, et cetera. Talk to me about how to think about the opportunity set in Japan, in Europe, in Gulf Cooperation Council countries.
Yeah.
Although things are somewhat iffy there right now. Just how to think about these markets globally and what are the puts and takes versus the U.S., 'cause obviously these systems are different, reimbursements different, access is a different question?
All of our experience has been like at Alexion, about a third of our business was in the U.S., a third was Europe, and about a third was rest of world. Maybe on the margins, Europe was slightly larger than rest of world. We were successful with a narrow price band, so we didn't have like a massive discount, you know, outside of the U.S. As you're noting, some of these countries, these single payer, bureaucratic systems don't love to pay for certain things like cancer drugs like we do in the U.S. For rare genetic diseases that affect children and adults, they generally have a they wanna support their citizens, and so that's what sets up for a large global opportunity.
We've seen when we've looked at some of the SMN targeted therapies, this pattern sort of, you know, very similar to a third. By the way, within that third, Japan within a third outside of U.S. and Europe, Japan tends to be a very dominant player, as well. We're thinking that it could follow a similar pattern. I will say that there's still a lot we don't know about MFN, though we think we're well-positioned for that with very minimal impact should it affect us, the way they're looking at sort of what percentage of Part B and Part D would it impact. We think we're really unabated with our ambition for our global launch.
Keith, we sometimes say to ourselves, given the nature of how things are looking in the U.S., you know, it could be upwards to 40% U.S., 60% rest of world, but we'll take it one country at a time. The cadence is something like this. U.S. launch, game on. European launch, the first country we launch in the second half of this year will be in Germany. Then we'll go country by country with each individual reimbursement process. We're looking at Latin America and Asia-Pacific, and you even noted the Gulf Cooperation Council states, which of course, it's a difficult time right now. There are a number of markets that even with U.S. approval, there are unique ways to potentially provide access to funded access to the drug as well. Our ambition is a 50-country operating platform.
I think what I would want the audience to know is there's 35,000 patients globally that have received at least one SMN targeted therapy. To receive an SMN targeted therapy, you need to have funding, reimbursement, and access. That kinda gives you the idea of the tremendous opportunity we have in SMA alone with Apitegromab, and why we believe that opportunity alone provides a robust growth engine for Scholar Rock through the end of this decade and well into the next. Then, of course, we have some ambitions to think about other neuromuscular conditions as well, with our platform and with Apitegromab.
We just have a few minutes left, but I don't wanna let that part drop.
Okay.
Talk to me about the plans platform-wise in terms of other indications and expansion opportunities for apitegromab.
Yeah
or current formulations. Paint your strategy going forward beyond this launch.
One of the strong beliefs I've had through experience is that when we begin serving patients and families, one patient, one family at a time, that's we're beginning a ten-year or more relationship with them. One of the things my team hears me say all the time is, we owe it to them to compete with ourselves and provide every level of innovation to patients and families. What we've been embarking on is we obviously have Apitegromab, which is delivered every four weeks via IV. We presented important phase I data from subcu apitegromab at JP Morgan, and we will look to have regulatory discussions post-approval on what the clinical regulatory strategy will be for subcu apitegromab. We think that will be important.
We are also now dosing healthy volunteers with SRK-439, which is a high-affinity, high-potency, myostatin inhibitor with its own set of intellectual property, that has shown effectiveness at about one-tenth the dose of apitegromab. That could be a very low volume, low frequency subcu injection, and we'll have a look at that data later this year. Our idea is that the rare, severe, debilitating neuromuscular disease space with SMA, FSHD, and a set of other diseases is quite robust. Between IV apitegromab, subcu apitegromab, and SRK-439, we think that's an embarrassment of riches to continue to develop and invest in that pipeline and in those programs to bring more and more innovation, not only to the SMA patient population, but all of the patient populations in the future that we aim to serve.
We think that positions us well for many years to come.
Great. We just have a quick minute left. Talk to me about where we are in terms of, I know this is maybe more of a cost question, but.
Yeah
in terms of balance sheet, how you've addressed the capital stack and your ability to draw down more capital without tapping capital, well, equity markets to potentially fund a launch.
Yeah. I wanna thank Vikas 'cause we announced you know a new loan last week of $550 million up to $550 million staged. Within that, we paid off our prior loan of $100 million . By the end of this month, we will be pulling down another $100 million . We closed the year at about $368 million on the balance sheet. We continue to really without diluting the company, we continue to provide ourselves with the capital needed to prepare for the commercial launch, continue to have you know to fund the robustness of our pipeline, and continue to build redundancy in our supply chain and manufacturing. We feel like we're very well-positioned.
As you know, Mani, the things that we're also excited about is we will qualify for a PRV at approval. We will qualify to pull down more of the loan at approval should we need that, and really try to thoughtfully manage dilution at this time. I think that has really enabled us to really be aligned with our investors during this time of delay to approval and launch. We're well-positioned from a capital perspective.
Great. I have now run us over, so I'll wind us down.