Great. Welcome back to the 46th annual TD Cowen Healthcare Conference. Thanks around for sticking around for Wednesday afternoon. We're saving the good ones for later in the conference to try to make everybody stay here in Boston. We're really happy to have with us for the next session, Scholar Rock and their CEO, David Hallal. We're gonna talk a fair amount about SMA, but maybe a little bit about some other diseases as well.
Yeah.
Maybe to start off with, David, do you wanna just kind of level set everybody with like maybe a high level kind of state of the company and what you think the key value creation milestones over the next 12, 24 months are?
Thanks Mark, it's great to be here with all of you. I recognize we're coming in on the back end of the conference, but we were in a quiet period until yesterday when we had our Q4 and full year 2025 earnings call, and then Mark hosted us last evening, which was really wonderful.
You know, on that call, what we articulated was a future for the vision that we have in building one of the next great global biotech companies, really anchored in the foundation that we believe that we can target the muscle with our highly innovative anti-myostatin pipeline more effectively than any company on the planet. We think that's one of our superpowers.
We've been able to effectively target myostatin, which is something that's been elusive in pharma and biotech for several decades, and we were able to successfully bring our first myostatin inhibitor, apitegromab, through the development process for SMA.
Now what that really leads up to for us is a year in 2026, which we see as a transformative year for the company, where we will receive our first two regulatory approvals in the U.S. and in Europe, and that will sort of catalyze what is our ambition to have a 50-country operating platform where we can commercial apitegromab for children and adults living with SMA.
Because this is what we know well and do well, we will be developing apitegromab and our second highly innovative myostatin inhibitor, SRK-439, for a series of additional, severe and rare neuromuscular disorders, where muscle tends to be, you know, one of the more prevalent organs that are impacted by the disease.
We see a future over the next 10, 15, 20 years, where we launch in the U.S. and Europe apitegromab for SMA. We commence, as we will this year, a series of development plans for apitegromab and other rare neuromuscular disorders, and we see ourselves in a period of sort of, you know, perennial launches in 50 countries around the world across the different sets of diseases.
SMA alone over the next 10 years, we will be launching in one country or another for quite some time. We think that that provides a real nice flywheel for growth as we serve an increasing number of patients with the diseases.
That really is what we see over these next 12 to 24 months as we execute on our clinical, regulatory, and commercial milestones, an opportunity to build a multi-billion dollar global franchise anchored in SMA alone, what will follow is a series of other opportunities.
Okay. Thanks for that overview. I think also one of the bigger updates yesterday was around really your partner, your manufacturing partner, Novo Catalent Indiana's facility and their work with the FDA to get that facility back and, you know, fully operational and producing product. Maybe you wanna kinda summarize that, and we can dive...
Yeah.
You know, the latest meetings that have happened there and why you have that confidence that you just expressed that you will be launching this drug in 2026.
Yeah. Thanks, Mark. As I think everybody knows, we had intended for 2025 to be our initial launch year for apitegromab in the U.S. In fact, we had this really sensational clinical data from our phase 3 SAPPHIRE trial where we enrolled 188 patients with SMA across sites in the U.S. and Europe.
We met the bar in our primary endpoint for the Hammersmith Functional Motor Scale in SMA, which is the highest bar in SMA, and we showed a statistically significant and clinically meaningful benefit and improvement in motor function for patients with SMA. We actually presented that data for the first time in Q4 of 2024.
We then filed our application with the FDA in January of 2025. On the basis of this being the first and only therapy that directly targets the muscle for patients with SMA, which of course is the principal organ impacted by the disease, the FDA granted us in our review process a priority review in the first half of 2025 with an action date of September 22nd, 2025. This transformative year of becoming a commercial stage company, we had anticipated that being in 2025. Just to recount kinda where we were, the review went extraordinarily well.
We did indicate in August of 25, which was just a month and a half before the action date, that we were notified that there was a general site inspection at our vialling facility, our fill-finish facility, which is Catalent Indiana in Bloomington. Through that general site inspection in the summer, there were deficiencies in the plant.
We were hopeful that they would have addressed those deficiencies with a response to those Form 483s. What we were disappointed to learn, you know, 6:00 P.M. on September 22nd, 'cause we thought everything was in line for an approval, including advanced discussions on the label, is that we received a complete response letter.
The sole approvability issue that was outlined in that complete response letter was the state of compliance of that facility now owned by Novo Nordisk, Catalent Indiana. As Mark is indicating, we provided an update on sort of what has transpired since our meeting with the FDA in November, where we were joined by Novo Nordisk, where we were joined by Cure SMA.
To really, one, just make sure that the sole approvability issue for sure was only the manufacturing facility in Indiana, and that there were no other review issues associated with our filing, and that was adequately discussed with the FDA. Really since that Type A meeting, we've seen a steady drumbeat of progress to remediating this facility.
For us to resubmit our BLA, we really are looking for this facility to be re-inspected by the FDA, have a successful re-inspection, and then we'll get on with resubmitting our BLA. What has happened since that November 12th Type A meeting is a series of positive events. The first thing is the week after that Type A meeting, the FDA did send a Warning Letter to Catalent Indiana, which highlighted some additional areas of remediation that needed to be addressed.
15 business days later, Novo Nordisk responded to that Warning Letter with a further remediation plan by mid-December. Just before the Christmas holiday, FDA reached out to Novo Nordisk and they scheduled a meeting for early Q1 to discuss the remediation plan.
What we indicated yesterday on the call that as Mark is referring to is that that meeting has since taken place, it was very constructive, and the FDA had no new requests of Novo Nordisk for their remediation plan. That was actually quite positive. Just a few weeks after that, meeting that FDA and Novo had, they sent a field team on-site, at Catalent Indiana.
That was a very constructive visit. Once again, the FDA did not have any additional requests of Novo, and they indicated that they would come back for a re-inspection of the facility once routine manufacturing activities had resumed, and they have since resumed at the end of February. Now it's just waiting for the inspectors to come back.
We think that Novo is prepared and certainly in a good spot for that inspection. We actually think the FDA is acting with a great degree of urgency that we think was really catalyzed by our in-person Type A meeting down in Bethesda, where we were joined by the SMA community.
We're certainly reaffirming our guidance that we would expect to be resubmitting our BLA and we would be commencing our U.S. launch following approval this year in 2026. We're gratified by the steady drumbeat of progress that's been taking place.
Yet I get asked this question as I was last night, Mark, and on our Q4 call yesterday, is, "Well, what happens if the inspection isn't successful?" We've been really pleased that we've also made meaningful progress with a second fill-finish facility where engineering runs have commenced. You know, frankly, within the guidance that we provided for a resubmission and U.S. launch following approval in 2026, that is also in frame, even if we were to rely alone on the second fill-finish facility.
We feel like we've really fortified our supply chain in these prior months, and we're well-positioned to, as I mentioned earlier with Mark, be on our way to launching in the U.S., eventually launching as well in Europe and 50 countries around the world as we see a multi-billion dollar opportunity for apitegromab and SMA alone.
I think we'll get to that secondary facility in a minute.
Sure.
maybe staying with the Novo Catalent Indiana facility, just can you explain kind of what the difference is between a field visit?
Yeah
An inspection? You know, is this kind of redoing it within the... Or are they looking at different things?
No, it's a great question. you know, first of all, I was asked on our call yesterday, "Is this, is this like normal? Is this something that they do before reinspect?" I said, "Nothing actually has been ordinary about this process." The reason why I say that is that I do think there's an appreciation at the agency, I think there's an appreciation at Novo, that there can be situations of non-compliance at a facility and a Warning Letter.
As you all know, sort of commercial drugs that are approved in these facilities continue to be filled and released from the facility uninterrupted. The only thing that becomes, you know, sort of hits a speed bump or in this case a stop sign for a while, are the drugs that are under review. That's kind of the leverage that the FDA has with a facility to bring them back into compliance, is that they cannot approve a drug that is under review.
We think the importance of this drugThe special nature of the SMA community, it's a rare disease that affects both children and adults, has created a lot of urgency around this, and that's what I think in the backdrop, Mark, is what creates sort of this unusual situation of after a long period of time, probably before the FDA even really was connecting the dots on our file being tied to Catalent Indiana.
You had an inspection that completed in July of 2025, and then no communication with Novo until our Type A meeting when we invited Novo on November 12th. Since that, and since there was this shared understanding of the unmet need and shared urgency, you know, between us and the agency, there's been this drumbeat of communication between FDA and Novo. The warning letter came out the next week.
I think that easily could have taken a lot longer to come out. There was the Novo response, then there was the scheduling. Look, how many meetings post-Warning Letter get scheduled within, you know, two weeks of submitting one's response? That's probably pretty rare. That meeting took place in early Q1. The way that we sort of think about this site visit is it sort of underscores it has the FDA's attention.
They were able to take field personnel, which are always overstretched on inspections and site visits, and they were able to prioritize them just weeks after the early Q1 meeting, and that just kinda sets the table for what we believe the next step will be, which will be the eventual formal re-inspection of the facility.
We see this as a good thing in continuing the drumbeat of progress. By no means would we point anybody's attention to this is a normal, you know, sort of checkpoint along the way. We think it's unusual, but we think our situation is positively unusual and that there's a lot of attention on our application at the FDA.
Okay. Once this re-inspection happens, I guess, you know, there's kind of dual track. One, you will find out some information about the inspection at the day that that inspection ends and they leave the facility. There is a formal process, maybe it won't follow the formal process, to get the OAI finding removed. Is that what you'll be waiting for to resubmit or? It's would you be more aggressive than that in terms of how your timing of your resubmission?
It's a great question. Right now our plan is to re-resubmit our BLA upon some pretty strong evidence that there was a successful re-inspection. That seems to make sense for us. I don't think that we would necessarily have to wait. I don't think the FDA would expect us to wait for the formal reclassification of the facility, downgrading it from OAI or upgrading it. I don't know which way you wanna go.
Right.
Sounds like it should be probably an upgrade.
Yeah.
From OAI down to like VAI. Our anticipation would be that we'd have a pretty good feel for how the inspection goes. There's usually a closeout meeting where the site is presented with the findings of the inspection, and that should give us a general sense that we're on the right track.
I have indicated that other things that could impact our timing of resubmission is just as the FDA continues to have all of these touch points with Novo, if they ever give us an indication to just get back on file, like it makes a lot of sense, we see all this progress that they're making, we've had meetings with them, we've had site visits with them.
We 'd be open to that as well. I think we do wanna do it, and when you do hear that we're doing it will certainly be done in accordance and in alignment with what we're hearing from FDA as an appropriate time to resubmit.
Okay.
Maybe I'll address this. I've been asked this a lot, Mark, why don't I front run it? Okay. They have the re-inspection. Seems like it went well. How long does it take to reclassify the facility and review your application? Again, we just don't know. I think reflexively many of these resubmissions automatically get a Class 2, you know, sort of resubmission, which basically gives the FDA from the date of resubmission six months.
We have pointed to examples at that same facility with other companies where they too were rejected, received a Class 2 resubmission, yet were approved within 30-60 days. In other words, the FDA didn't wait, you know, the full six months. We'll know it when we see it. We're trying to understand it.
I hope that the same sort of urgency the FDA has shown since November twelfth, they'll continue to show, not just through re-inspection, but all the way through reclassification and eventual approval of our BLA.
Do you think that reclassification has to happen or do they have, you know, granted, it can run in parallel to a review, but does it have to happen before a label is actually issued to you or?
Because this is an, you know, a unique situation. You know, we're expecting that that reclassification would happen. We have heard that, let's just say you get a Class 2 review, it can happen within, you know. A reclassification can happen somewhere between 30 and 90 days. It could be well within that range of when a resubmission were to happen.
Okay.
resubmission timeline.
Yeah, The secondary fill-finish facility, maybe can you walk through kind of the steps that need to happen now? You said start engineering runs, but to meet that window of a filing and even a launch within 26.
Yeah. Mark was on it, by the way, when we had our CRL in September, I think he wrote some really important notes about the importance of, you know, a second vialer no matter what for us and how we could accelerate that in certain timelines. Just take a step back.
When Novo bought this facility from Catalent in December of 2024, it was with the intention of not being a CDMO, but with the intention of internalizing those operations for their own portfolio, for their own products. We ourselves knew that we needed another vialing facility, as everybody else will. We were sort of under some agreement, but we were under the impression we had probably till 2027, 2028 to add another vialer.
These things, the bottleneck, and by the way, in switching vialers or adding vialers is, first of all, finding commercial capacity isn't always easy that's equipped to match a line. Stability can be a bottleneck. Comparability testing can be a little bit of a bottleneck. And then release testing. A lot of times the vialer also does the release testing.
They do all the assays, and that is technically one of the more complicated things to do. In our situation, the way we were able to expedite this tremendously, even before any FDA flexibility, which I feel like the FDA is open to, you know, thinking flexibly about this for us, given the situation that we're in, was we found a great vialer, U.S.-based, nearly about three dozen products that are commercially being filled there.
A really strong historic inspection history and a recent positive inspection history. A line that we were able to jump and contract and reserve space for in this first half of the year that was configured to our vial. No changes to our packaging, 'cause that would be important. An ability to leverage stability data from our all the experience that we have at Catalent, Indiana.
I think importantly, Mark, our release testing is not done at the vialer. It's actually done at an independent site. We don't even have to move that, which is super helpful too. All of that has led to, as I noted, we've commenced engineering runs. They're in flight. All of our validation runs, PPQ runs, everything else is scheduled to be happening and humming here in this next period of time.
As I noted, our go-forward plan is we would submit a supplemental BLA 'cause we'll expect to be approved at Catalent Indiana, and that this could be quite expeditious. We've also always looked at this as if all else failed, and for some reason the inspection didn't happen or the outcome of the inspection wasn't positive, how did we feel about our guidance of a 2026 resubmission and launch?
We feel like with the conversations that we've had with the FDA about our second vialer, we're well within the framework of being able to resubmit, gain approval, and launch the drug all in 2026, even it's not as fast as a re-inspection that we believe is coming up in the, you know, near period, you know, coming period of time. We think it is absolutely within the frame of the remainder of 2026.
Okay. Maybe you've also a couple-
Your agreement with the FDA would be, okay, what is really needed to submit? Could it be a rolling resubmission? What is needed to... These would be all the conversations that we would have. That's where I think we've found some common ground, which I think is patient-centric common ground right now with the FDA.
Okay. In some of your earliest comments, you're talking about the ex-U.S. launches as well. I mean, what's the status of the MAA review? Is approval in Europe also dependent on, I guess, either resolution at the Catalent Indiana facility or a positive resolution or this second facility coming online?
Yeah, it is. In a word, it is. We've been very upfront with European regulators. They're well aware of what's going on. There is a mutual recognition agreement and clause between FDA and EMA. Having this plant in Indiana remediated, having it inspected, having them talk to All of those things would be important for us.
We are still forecasting an EMA decision near mid-year. Then the EMA has also been very good about saying, "Look, if for whatever reason we're off by a little bit, you know, we're certainly wanna work with you guys on this as opposed to like a decline where you go back and restart the clock all over again." I think we're in a good spot with European regulators.
We're also, most importantly, in a good spot with the FDA doing their work to remediate the facility. I think EMA and us have a reasonably good agreement to be pretty, you know, flexible here in kind of understanding this timing.
Okay. How should you know, given where you were headed, where you seem believe you were headed from a label perspective, just how should investors think about pricing for apitegromab? Are existing kind of chronic SMA therapies a good comp 'cause it's the same disease? Is that not the right way to think about it?
Keith and I, this is our third company together and one of the things we like to do is fall back on our blueprint that's helped us in the past, you know, around therapies like Soliris and Ultomiris and Vyvgart. One of the things we always think about are, you know, three key factors associated with determining price.
One is the rarity of the disease. By the way, there's, let's just say 5,000-8,000 patients in the U.S. that have received an SMN targeted therapy with SMA, and 35,000 globally inclusive of the U.S. As a result, like this is a pretty rare disease, in which case we think the overall, you know, sort of patient population is very acceptable.
Meaning modest budget impact, you know, overall from a payer perspective or a single payer government perspective. Number two, we think about the severity of the disease. That is that what is the natural history of this disease, despite using all best supportive care, all best standard of care?
What we've now seen from companies that have these SMN targeted therapies in our own phase 3 trial is despite the needed innovation that the SMN targeted therapies have brought to the SMA community, there is generally a plateauing and a return to the progressive form of the disease where motor function is lost. We have demonstrated in our clinical trials, we go from a loss of motor function to bringing patients to a gain of motor function.
We'll think about, you know, sort of the natural history of the disease, and then we'll think about the impact of our drug. As I noted, the move from loss of motor function to gain of motor function. All those things I think will factor into the pricing decision.
Recognizing Mark, in this case, probably pretty important to also have an awareness of where those current therapies are that address the motor neuron component of the disease. Our drug is the first to address the muscle component of the disease, but that's probably an important factor for us to think about as well.
Okay. Well, hopefully approved later this year, how should we think about that initial launch trajectory? Who are the kind of lowest hanging fruit to join the trial? You know, how should we think about patients maybe coming in from an EAP or a long-term extension, being just transitioned to commercial product?
Yeah. We, very gratified to tell you guys that over 90% of the patients that we've enrolled in our phase 2, phase 3 trials, remain on our long-term extension trial known as ONYX. We enrolled 58 patients in our phase 2 trial known as TOPAZ, and 188 patients in our phase 3 trial known as SAPPHIRE. If you do that math, that's a reasonable number of patients.
Mind you though, not, you know, there's a split where the majority of those patients are actually in Europe, not in the U.S. These were global, these were multinational trials. We think about that. We did have an EAP open in the U.S. until the day before our PDUFA, 'cause we were that certain we were gonna get approved.
We do have a number of EAP patients, you know, on therapy, in the U.S. as well. They, by the way, they continue to get apitegromab on an every four-week basis from the drug that we have filed at the Catalent Indiana facility. Remember, the clinical supply is uninterrupted too. It's just holding up new approvals.
The way like Keith and I think about the launch uptake is the following: We think there was robust demand, you know, for the therapy before our September 22nd PDUFA. I think the delay has probably enhanced that a little bit because there's this understanding that there is, for the first time, a drug that can target the muscle.
Now that patients are living longer with the SMN target therapies, they really wanna have, you know, better motor function, and they do start to lose motor function again. We think from the patient and caregiver community, robust demand, 95% of patients report that motor function and muscle strength is the number one need that they have. 75% of neurologists indicate that they believe you cannot just address the motor neuron, but you also must address the muscle for optimal motor function.
Dual modality is important, and that supports the demand scenario, Mark. I think the thing where we on launch uptake, the thing that we're a little cautious about is it is an every four-week infusion. There will be a miscellaneous J code. SMA therapies tend to all be prior authorization. New therapies, in many cases, get rejected reflexively initially.
Medical policies at payers may start out being more narrow, maybe more tied to the phase three criteria versus the label. It just could take time. We are in a mode of, you know, that's the thing that we think flattens out the launch curve a little bit. We think we'll have robustness in start forms and enrollment forms.
We think those patients will eventually end up on reimbursement, and have access, but we think it might just take a little bit of time. Our overall long-term ambitions from a revenue perspective are we see this as a multi-billion dollar opportunity and a massive opportunity in the U.S. alone. We are being extremely thoughtful in just making sure that we understand that initially it may take some time to get to a steady state of converting those enrollment forms into reimbursed patients.
Okay. In one of your earlier comments, you also brought up the subcutaneous form of apitegromab that's now in the clinic, as well as there's the next generation by inhibitor, which is also subcu formulation. Can you explain kinda how those fit together with each other and then also obviously with the current IV formulation?
It's a great question. One of the things, again, you know, maybe robbing from our past and our blueprint, we've always recognized that, if you're, you know, the best in the world at something, whether or not you have a highly innovative first asset in being the best in the world at something like inhibiting myostatin and succeeding where all else failed, make sure you continue internally to compete against yourself because we do believe every individual patient that we serve, there's probably a 10-15-year relationship with the patient and the family that we're gonna have. Let's make sure that in every four-week infusion isn't where we stop.
Let's really think about all the different options that we can provide to patients and families, one of the things we do think about is a subcutaneous formulation of the drug. It's not trivial, given the disease, for patients to. We will have home infusion set up. Keith highlighted that we've established a network of 10,000 nurses in the U.S. alone for home infusion.
Let's make sure that we're providing optionality. In January, we presented our phase 1 data from subcu apitegromab at 800 milligrams compared to IV apitegromab at 800 milligrams. These were overlapping pharmacodynamic profiles. We think we have a formulation that is gonna be very suitable for this.
We're gonna wait for the approval of IV apitegromab to then engage with regulators on the clinical regulatory strategy for subcu apitegromab, but it is well in sight of something that is, you know, very much out there for us. I just wanna comment on SRK-439. This is a drug that has showed effectiveness, completely different drug, came out of our labs.
It's about 10 times more potent than apitegromab and has shown activity with as low as 0.3 milligrams per kilogram. We are dosing healthy volunteers now. We see it as a high affinity, high potency, low frequency, low volume, potential subcutaneous formulation. At one point, Mark, as you recall, some folks thought, "Okay, maybe that's gonna be our cardiometabolic drug," you know, because we have studied our technology along with tirzepatide, as an example.
We think we're building such a valuable multi-billion dollar rare neuromuscular business, wouldn't it be great to make sure that we're bringing that also to these patients as another option? We'll see what we see in our phase 1 healthy volunteer data.
We'll present that later this year, we'll make some determinations on, you know, which patient populations, which indications that we develop that drug in. You know, we think that it is certainly very promising as well. We think they can all really fit together in the world of bringing a lot of innovation to patients and families and a lot of optionality over time.
I know we're running over, but maybe we can squeeze in one just on FSHD.
Yeah
because you're starting that. Just, maybe just can you run through the timeline of, when, you know, you can start to generate that data that shows that this really is more than just an SMA story?
We have some really, there's two things, one clinically, one pre-clinically, that have given us great confidence that FSHD is the right next disease for us. Clinically, there have been some very rigorous exercise programs and/or studies with anabolic agents that have shown that because FSHD tends to be a patchy disease with dysfunctional muscle and functional muscle.
The functional muscle is really important for us that if we can deliver apitegromab, we can really see a clinical benefit, of motor function and motor strength by addressing the functional muscle. We've seen that these rigorous exercise programs which people could not possibly do every day, gives us the proof of concept that clinically there's something here. By the way, 30,000 patients diagnosed in the U.S. and Europe, and no approved therapies for FSHD.
We're pretty excited about that. We have a really good FLExDUX4 mouse model that we used our murine version of apitegromab in, and we actually showed that we were able to develop great muscle mass, muscle strength, and exercise endurance in those pre-clinical models. Now we've launched the phase 2 FORGE study, 60 patients, robust, randomized, double-blind, placebo-controlled, and we're gonna start dosing patients a little bit later on this year.
How long do you think it'll take to get to data, roughly?
I think Akshay just wants to see one on kind of the hockey stick on enrollment. We will probably have some form of interim analysis on our way to a 12-month endpoint and we aren't expecting data until, you know, maybe in the out years here.
Okay.
Okay?
All right. Thank you.
Thanks, Mark.
With that, we'll sign off. Thanks a lot.
Appreciate it. Thanks, everybody.