It's great to be here with you.
Maybe just for those on the webcast that are maybe not as familiar with the story, just give us a quick two minute, and then we'll get right into some of the
Yeah. So quickly, we're in an exciting moment in time for the company. 15 years since we founded the organization and now really three weeks away from our PDUFA date with the FDA for our monoclonal antibody apitegromab, which is the first and only myostatin inhibitor that's ever been proven to deliver statistically significant and clinically meaningful benefits in a phase III trial, despite the fact that nearly all major pharma and biotech companies have tried to drug myostatin since it was discovered at Johns Hopkins in 1997 as the body's natural negative regulator for growing muscle. Obviously, if one could harness the potential of safely inhibiting myostatin and effectively inhibiting myostatin, you could restore and deliver muscle growth, muscle strength for a whole host of diseases. And we, of course, are focused on a set of muscular atrophies and muscular dystrophies.
The first, of course, is spinal muscular atrophy, where 35,000 patients globally are receiving at least one SMN targeted therapy. And in our seven-year development program, where we took no shortcuts, our phase III trial was 188 patients, and we delivered a statistically meaningful benefit in the highest bar, the Hammersmith Functional Motor Scale, for returning motor function improvement in those patients. So on file with the FDA and ready to launch, Geoff, we'll talk about that with our time together this morning. The action date for the FDA is September 30th. Looking to resubmit our MAA in Europe because we've recently withdrawn, all tied to the compliance issues at our third-party fill-finish manufacturing facility.
We were really excited to announce that we have an agreement with PMDA to file our JNDA by the end of this year, needing no additional clinical trials in a local Japanese population. This really advances our ambition to reach these 35,000 patients and upwards to 50 countries around the world, as Vikas and I and the team have done at other companies. We are super excited about that and look forward to digging in with Geoff this morning.
Yeah. Let's talk about the Catalent facility and kind of the background there. Now you are talking about proceeding the BLA right through the alternative facility. Maybe what gives you the confidence that there is no remaining kind of hurdles. Just give us kind of an update on the manufacturing.
Absolutely. Look, Geoff is appropriately so asking probably the question on everyone's mind, which is if we had a PDUFA date last year of September 22nd, 2025, all signs read positive for an approval. We were discussing the label essentially a day or two before our PDUFA date, and then we received a CRL for the sole approvability issue being a general site inspection at our third-party fill-finish facility, Catalent, Indiana, owned by Novo Nordisk. That same facility now has just had another poor inspection in April of 2026. That was a re-inspection that was supposed to clear the facility. Why are we confident that being back on file with the FDA with an action date in just 20 days, why are we confident that we are heading toward an approval? It really dates back to the following.
At the same time that we were working with Novo Nordisk and the FDA for them to remediate their facility and improve their GMP practices, we were also standing up an alternate fill-finish facility that was in good standing with both U.S. and European regulators. We actually announced on November 14th, which was our third quarter earnings call of 2025, that we were under a contract with an alternate fill-finish facility and that we had secured commercial manufacturing at that facility in the first half of 2026. So we did that very quickly. We rolled out tech transfer in breakneck speed. On early December, first week in December, we actually requested a Type C meeting with the FDA to talk about the progress at our alternate or second fill-finish facility.
That led to a March 3rd, Type C meeting where really what was on the table was the progress that we had made at this second fill-finish facility. And Geoff, it was during that Type C meeting with all the leaders of the FDA, OMQ and OPQ, who oversee facilities and product quality, that they said, "Look, this is an important drug for an important patient population. Our suggestion is that we actually have a horse race. Resubmit your BLA with both Catalent, Indiana, and your alternate fill-finish facility. Whichever one enables approval fastest stays in the BLA. Whichever one would not, you remove from the BLA with no timeline hit, no major amendment, and away we go." That was March 3rd of this year.
On March 31st of this year, we announced that we had resubmitted our BLA just the day before, and that we had resubmitted it in complete alignment with the FDA with both fill-finish facilities. Now, look when we heard inspectors showed up at Catalent, Indiana on April 13, just like a couple of weeks after we resubmitted our BLA, you might imagine with all the attention that Novo Nordisk was putting on remediating this plant, we thought that would have obviously been the fastest path to an approval. We would have dropped our alternate site, and then we would have resubmitted that alternate site as an sBLA after approval. We now all know that that inspection from April 13 to April 24 didn't go so well. The Form 483 had multiple observations that all read like the poor inspection in 2025.
There was definitely improvements at the plant, but not enough to get the FDA through it downgrading that facility. It kind of started to read for us like the most expeditious path was going to be this alternate facility. Importantly, we have now vialed more commercial apitegromab at this second facility than we ever did at Catalent Indiana, and vials from this second facility are now awaiting labeling and packaging in our third-party provider on the day of approval. We are in a very good position from a launch perspective. Now, specifically to Geoff's question, was it a poor inspection and we removed Catalent Indiana and we're kind of flying blind on the second facility? The answer to that question is no. In fact, what gives us great confidence is that we're in ongoing dialogue with the FDA.
Based upon the OAI classification of the April re-inspection, we actually said to the FDA, "We think it's time to remove Catalent Indiana." The FDA said, "Wait a minute. Let us just complete our review of your alternate facility, and then we'll actually walk you through the process to remove Catalent Indiana." And of course, in early August, we did announce, by press release, that we had removed Catalent Indiana from the BLA under FDA guidance, and that was following their review. I don't want to say that the FDA's ever completely done, but they definitely had a checkpoint in the way. So things are reading positive from both the CMC review and then the clinical review. There just isn't very much to do since the label was essentially finalized during the last cycle. And we remain very confident that we're going to be receiving an approval here in September.
Well, let me do one more and then, [Jeremiah], I am going to hand it over to you for a few. Just when you talk about the alternate facility, is the capacity similar? Talk about the ability to scale, and maybe the early stages of the launch.
It is an important point. This is not a boutique or opaque fill finish facility. It is a substantial facility with a track record globally. They have had European positive inspections as well as U.S. regulator positive inspections over the long run and recently. One of the things, Geoff, that we thought was important when we identified this facility was that they would have multiple lines that were actually ideal, where they had lines that were qualified for our vial configuration. Now, why was that important? That was important for speed, because if you change anything about your packaging, that would definitely not enable us to add a second vialer as quickly as we did. So we validated multiple lines with our engineering and PPQ runs.
We have scaled up manufacturing there, which of course, again, it is fill finish, so they are taking our drug substance and they are vialing it.
Their work has been extraordinary so far. As I noted, they are in good standing with U.S. and European regulators. They are on file with a number of Japanese applications as well. Over the long run, Vikas and I will always look for redundancy in our supply chain, but for now, we feel really good with this fill finish facility. One other important note I would like to make, when we disclosed that we had removed Catalent Indiana from our BLA, it was only as a commercial supplier of the drug. Their data remains in our BLA. We continue to use the drug. No one has ever claimed the apitegromab that has been vialed there is not a high-quality product. In fact, that is the product that we continue to dose our long-term clinical trial patients now for upwards to 7 + years.
Technically, some of the Catalent Indiana data is in our BLA. They are just removed as a commercial supplier of apitegromab for now.
Great. Yeah. Thank you so much for giving us an overview of some of what's been going on behind the scenes. You touched upon that the labeling was pretty much completed during the last cycle review back in 2025. Maybe help remind us, some of who are listening, about some of the discussions that had happened and maybe expectations for ambulatory versus non-ambulatory or maybe a broad label that could happen.
Yeah. These are excellent questions. I guess I would first start because we've worked, while we've been disappointed with the delay of a first and only muscle-directed, muscle-targeted treatment for SMA, we have been very grateful to the FDA for their collaboration during these past few months since the CRL. It would be maybe inappropriate for me to comment specifically on the label. But what I have said in the past is we were pleased with where the label was at the last exchange that we had with FDA, which was September 18, 2025. So that was just two business days before the PDUFA date. We had historically seen that the FDA, as it relates to SMA, has usually seen SMA as a single disease rather than a disease where they're chopping it up by age group, copy numbers, subtypes, or ambulatory status.
If you just look at the other drugs that they have approved, they've generally not done that. Obviously, the gene therapy was in a very young patient population. So our feeling is that obviously the under two-year-old population will not be on label because we just hadn't studied that in our clinical trials. It was really two and older. We do believe that very much in our label discussions, we were very much talking about SMA more broadly, and the benefits of SAPPHIRE that our phase III SAPPHIRE trial were able to demonstrate. So we were pleased. Just to give you guys a sense of the exchange, when you submit a BLA, you submit with your draft label.
I'm on record as saying we were never, even in the first red line from the FDA, we were never in a different stratosphere from the FDA on what the label should look like. We were always seeing things very similarly. It was very collaborative in the last cycle. They sent us the latest red line on, it was like 10:00 A.M. on Thursday, September 18, and why we thought we were going to get approved in that cycle. Remember, this is before Catalent, Indiana was classified as OAI and before they got a warning letter. So here we are in deep label discussions. They send us the label the morning of September 18. They wanted it the morning of September 19, which was Friday. The PDUFA was Monday the 22nd. We sent back comments to that. We had sandpaper out.
We definitely didn't have major tools, chainsaws, axes out at all. We were sandpapering some of their comments. We sent it back in the evening of September 18. What they asked for in this cycle, in this re-review of the application, is for us to go back to the label we sent to them on the evening of the 18th. That was the starting point for this cycle. That's why we were. I'm also on record as saying, even if they took none of our comments that we sent back on the 18th, we were in a win scenario for the SMA community. We were in a spot where we would have been able to serve a meaningful proportion of the SMA community that could benefit from apitegromab therapy. Hopefully, we'll be able to share in a lot of detail the label in just a few weeks.
Awesome. That's great to hear. Maybe let's then shift to what could happen after apitegromab launches, and we're all very interested in hearing what the branded name will be. Maybe just as the initial patients start to flow through, maybe tell us about your expectations for age, two years above, or what adult status, ambulatory status, background SMA targeted therapy, maybe prior treatment history. Just trying to get a sense of where you're thinking of the flow of patients coming in and what they may look like.
It's an excellent question. Where do we think the demand comes from? Is it the younger patients who perhaps doctor's ambition is to provide as much normal musculature before atrophy sets in? Is it adult patients who maybe have missed some of the benefits of the SMN-targeted therapies because they had a lot of motor neuron deterioration, even in 2016 when Spinraza was first approved, when the first drug was approved? It's a little bit of all. It really depends on the patient, the family, and the doctors, and maybe I can walk you through that. As a reminder, we took patients that on average had been on either Spinraza or Evrysdi for about five years in our phase III trial. Those patients were randomized to either receive nothing at all, placebo, or apitegromab.
What we demonstrated in that trial is that those patients that were on Evrysdi and Spinraza over the 12-month treatment period actually were losing motor function. That's actually pretty consistent with some of the long-term data that even those companies have shared of their registration trials, that patients do better initially when they get more SMN protein. They gain motor function, they plateau, and then they can start actually losing motor function again. What we demonstrated in the SAPPHIRE trial is patients went from a loss of motor function to a gain of motor function. In fact, what we believe will be the recommended dose, the 10 mg per kilogram dose, there was a 2.2-point difference in the Hammersmith Functional Motor Scale, which is the gold standard and highest bar to hit.
Even Evrysdi did not hit that prospectively in their phase III trial, and we had a statistically significant benefit there. We had a 3.8 x greater likelihood of a three-point improvement or more when patients on Spinraza and Evrysdi were randomized to apitegromab versus not. This is, again, a pretty broad patient population. The TOPAZ study, we did have children as early as two years old in that study. They have done exceptionally well. What we are hearing is the following: 90%-95% of patients claim today with SMA that their number one need is muscle strength and more motor function. Nearly the entire community is saying, "We need more muscle." 75% of neurologists are now saying that we believe the best way to treat SMA patients is by treating both the motor neuron with SMN protein and the muscle by eliminating myostatin.
Because it is those two things that actually make up the motor unit, which actually is what provides patients motor function. Why would anyone want to have the body's natural negative regulator for muscle growth floating around their body if they had SMA? We think the dynamics are really solid for demand for the drug at approval. We will get into, I am sure, reimbursement and access here as well. I think the way I would answer your question is I think it depends on the patient, their patient demand for the drug, and the physician as to whether or not there will be more children or more adults. I think it will be a pretty balanced mix across the board, dependent upon the physician, the patient, and the family.
But we just know there is very strong support to access apitegromab once it is approved because each and every patient feels like they can benefit from more motor function driven by muscle strength and muscle growth.
Just to follow up on that, what are the strategies, I guess, to maybe maximize awareness? How would you characterize among the experts and the SMN community the awareness for apitegromab today? Do you need to get in guidelines? Do you need to have pre-discussions on reimbursement with payers? What types of things can you do prior to formal approval to kind of help manage that?
Great question, Geoff. It's in fact one of the benefits of the delay we've had over this past year, is we did build a U.S. commercial organization and U.S. medical organization that was ready to launch last September. Fairly small, didn't really burn us from an expense perspective. In fact, Geoff, to your point on awareness, it's actually been quite helpful to map out the patient journey at all the SMN. There's 140 SMA treatment centers in the U.S. It actually helped us to educate the community that the innovation around motor neuron health has been incredible from Spinraza, Evrysdi, Zolgensma. Incredible. But that the principal organ clinically affected for patients with SMA is the muscle that's actually in the disease.
And so that education, that motor function is a sum of motor unit strength, not just motor neuron, not just muscle, but the combination of those two has really been helpful. And so we've seen surveys done in 2025 versus 2026 that show last year at this time, about a quarter of KOLs said they would call all of their patients and offer them apitegromab at approval. That number a year later, that percentage has jumped to like 42%, 43%. So just with the awareness factor, and I think patients thought apitegromab was coming last September. I think that delay has created even more interest in accessing the therapy, and that's why we think the landscape is pretty strong from the outset on demand.
Obviously as a once-monthly infusion, we'll have to be thoughtful about pricing reimbursement and access to treatment, which always can be a little bit of a bumpy road when you're introducing a new drug. And certainly we can speak about that as well. But I think the demand dynamics and the awareness of this therapy, and I think the patient advocacy groups like Cure SMA have been wonderful about getting the message out that this is a first and only muscle-targeted therapy to likely be approved by regulators and available for patients here in 2026.
Maybe it'd be helpful just to talk through maybe your market research on the different modalities in SMA, and initially obviously started off with just Spinraza, and then you've layered on multiple therapies. So how has the sort of from mono to doublets, is that-
Yeah
Is that still reasonable going forward? You probably won't have a triplet type of approach. I don't know, maybe that's not a crazy scenario down the road.
We're sort of breaking down the treatment of SMA in three eras. There's the pre-2016 era, which was really one of disease of high mortality, early mortality. When you would go to a patient meeting, you would hear all the ventilators in the background. There was just nothing to address motor neuron or muscle health, and one of the only therapies patients had was physical therapy, and then supportive care like vent support. Then the needed innovation was ushered in by Spinraza first, and then of course followed by Zolgensma and Evrysdi, and again, all focused on SMN protein production to try to preserve whatever motor neuron function one could have. At the same time, as patients have been living longer, they now want to live better. They really want to be able to do more.
They want more self-care, and they view that as being driven by, again, muscle strength and motor function, which is why more than 90% are saying that is their number one need, and that's consistently coming out of Cure SMA surveys. I think what we've done well, Geoff, is to differentiate that we are a completely different modality that is not in competition with the SMN-targeted therapies, but we are truly addressing the other half of the motor unit, which is the muscle. Again, the way we designed our clinical trial showed that if you did nothing at all, this is what your outcome will be from a motor function perspective. Then if you take your background SMN-targeted therapy and apitegromab is also administered to patients, you have again an improvement in motor function.
By the way, in our long-term data from our phase II trial, we see patients plateau but never really are giving up their gains that they had, and we think that is just such an important element of the outcome. I think it's also why, by the way, we're at 95% compliance, 250 patients in our phase II, phase III clinical trials. Those patients remain on therapy upwards to seven years later. Back to your point, Geoff, I think where we come from is no matter what the physician and patient want for SMN protein production, is fine for us. That's actually great for us. We just think they're only going to have one choice to address the muscle component of the disease, and that is going to be apitegromab, and so we get super excited about that.
One other element I just want to underscore to Geoff's point about how much more the patients want. Even though there is no well-controlled clinical trials using more than one of these SMN-targeted therapies at the same time, about a third of patients in the U.S. are either sequentially or concurrently getting two or more of these treatments. They might be getting Zolgensma as a one-time gene therapy, and then followed up with Evrysdi or Spinraza. Some are getting two or more of these therapies, all because physicians and patients do want more motor function, and we think that bodes well for us. As to whether or not there will be triplet therapy for some of these folks on two therapies or not, I don't know, but I do know that is certainly underscoring the need for more innovation. What we see, first era was no innovation.
Last 10 years have been the era of SMN-targeted therapies ushered in a massive era of innovation for patients with SMA. Now 2026 and beyond ushers in the muscle-targeted era of innovation for the SMA community, and we're excited to be really at the forefront of bringing that forward.
Great. Maybe now let's pivot over to the payer side of things. I know you kind of touched on some of the challenges that, or maybe some of the bumps in the road that can be part of launching a rare disease without a J-code implemented immediately. Maybe talk a little bit about expectations for the initial launch, maybe some of the authorization criteria that patients and physicians may have to go through, and maybe what your expectations are for some of the greater friction points the first six months to the year.
Yeah. Thank you for raising it because we do think this is a sophisticated community with great levels of persistence in everything in their life. They've obviously all already had experience with payers to obtain their SMN-targeted therapy, and yet we do expect with any new rare disease therapy, there will be some speed bumps along the way. While we think demand will be high, and while we have actually developed up a patient assistance program known as Scholar Rock Supports, every patient and family will be assigned a Scholar Rock sort of care coordinator to help usher them through the reimbursement process. There are a number of things that we think could delay access to treatment. I don't think it will be a stop sign, but I think it may delay in the form of a speed bump. One, as you noted, is a miscellaneous J-code.
This is a once monthly or every four-week infusion, and we will have a miscellaneous J-code. Let us assume we get approved in September. It would at least be Q4 and Q1 that we have a miscellaneous J-code, and then starting next April, we would have a drug-specific J-code. That really does help with reimbursement and timely reimbursement. You mentioned medical policies. Let us assume from your earlier question that our label is more broad than our phase III clinical trial enrollment criteria. We do know, and you all know this from all the companies that you cover, oftentimes an initial medical policy may be more narrow than even the FDA label. That could prevent initially some patients gaining access to treatment, but again, we think that is a matter of when and not if, because it is a very difficult thing for payers to stand by.
We do think with 140 SMA treatment centers of excellence, some of those centers are going to have formulary status issues that they will need to walk themselves through. And they will also have to think about the logistics of integrating a once 28-day infusion into their practice. Do the patients get it at the hospital? Do they get it at the physician office? Do they get the medicine at an infusion center? And frankly, as we have also mentioned, we have got a 10,000-nurse home infusion network, and we would like patients to be able to get it at home if that is at all possible.
I do think we will see a high conversion rate in a short amount of conversion time, probably a year after approval, but we will definitely have to be playing a little bit of Whac-A-Mole in the first year, along with the SMA community, to make sure that every patient who can benefit from apitegromab will have access to apitegromab.
Just have a few minutes left, but I wanted to ask about the global opportunity. Maybe give us a status update on European, Japanese, or OUS filings.
In August, we announced three things related to our global regulatory update. The first is that under FDA guidance, as I've already mentioned, we removed Catalent, Indiana from our BLA, and the PDUFA date remained September 30th, because there was some concern that removing that might have created a delay in a PDUFA action date. That was not the case. That's number one. Number two, based on the fact. We never had the equivalent of a CRL in Europe, so as a result, we had received the benefit from European regulators of multiple clock stops waiting for the inspection outcome of Catalent, Indiana, which was the only fill-finish facility in our MAA. Then when it came down in April of this year, I'm sorry, of August of this year, just last month, everyone was on vacation in Europe.
There was really nothing they could do about adding the second vialer. It was their advice to us to withdraw the MAA. That would be the way to remove Catalent, Indiana, and add the second vialer and resubmit the MAA. We are ready to resubmit whenever they tell us to. As you guys know, in Europe, there's a specific day each month to resubmit. We're just waiting to get a go-ahead on, is that this month, is that next month? Hopefully, that will be an expeditious review, but I really have no guidance on timeline yet. Once they get back from vacation and give us that guidance, we'll be letting the world know, probably in the form of we've now resubmitted our MAA. There's a little bit of a pushback in Europe. We have built the team in Germany. They are ready to go.
What we announced also last month, Geoff, with a little bit of a pushback in Europe, is we think it more than makes up for a little bit of a delay in Europe, is the acceleration in Japan. Because if PMDA said we had to do a Japanese clinical trial, that would have been multiple years in the making. But they looked at the merits of our global clinical trial program, the importance of apitegromab for the SMA community, and they agreed that we could file our JNDA by the end of this year. Again, we'll be able to advise when we submit, when it's accepted, and what we think the review timeline will be.
But as you know, as a 120 million population country, that more than makes up for a little bit of delay in Europe, where we would have only initially launched in Germany, an 80 million population country. So we're super gratified for that. As I think all of you know, there are no other muscle-targeted therapies, even in clinical development in SMA. So our ambition to reach patients in 50 countries around the world, Europe, U.S., and Japan gets us to close to 30. We think we're well on our way to doing that without any meaningful competition over the next 5 - 10 years. We think this is really our market to develop and grow and protect with a significant moat for many years to come.
Well, with that, David [inaudible] , thank you very much.
Great to be here with you, Geoff. Thank you.