Okay, awesome. Hey everyone, welcome to the Jefferies London Healthcare Conference. My name is Amy Lee. I'm a biotech analyst here. I have the pleasure of welcoming Scholar Rock, Akshay, and Keith right after their Type A meeting, actually. Very lucky timing for us. I will turn it over to them for opening remarks. Yeah.
Sure. I'm Akshay Vaishnaw, I'm President of R&D at Scholar Rock. As Amy said, we're just coming off a Type A meeting, which many of you who follow Scholar Rock will be familiar with. In 2024, we had a positive phase III study for apitegromab, our lead monoclonal antibody against myostatin, which was developed for spinal muscular atrophy. That positive phase III study led to a BLA submission in January with a priority review. We went through the review cycle, got all the way through, including advanced negotiations around the label and a draft label. At the PDUFA date of September 2022, we received a complete response letter. That complete response letter related to, well, first of all, I should say we were caught by surprise, actually, that we got the complete response letter.
It related to a single approvability issue, and that was due to compliance issues at our GMP manufacturing fill finish facility, Novo Nordisk in Bloomington, Indiana. That site received, subsequent to the 483 that they had a month or two before our Complete Response Letter, an Official Action Indicated notice a few weeks ago. All of that meant that apitegromab cannot be approved until the OAI is resolved at the manufacturing site at Novo Nordisk. Novo has been busy with that. We have been busy with that. Novo and ourselves went to meet with the FDA last week at the Type A meeting, and we made good progress in clarifying a path forward. We can get into that, but that's the backdrop of this meeting. Beyond that, I'd say this is my good colleague, Keith Woods. Keith is our Chief Operating Officer.
He can speak to you about our overall company shape and outlook, including the commercial aspects for apitegromab in spinal muscular atrophy. We believe myostatin antagonism has a great role to play in a vast array of neuromuscular disorders. We look forward to discussing that as well.
Excellent. Excellent. Let's start off with timelines and scenarios. There's a lot of moving parts. You have the Catalent site, and then kind of you guys gave very clear language on it would, you know, they would be ready for reinspection by the end of the year. You also have a potential backup filler. I would believe it's early 2026. How are you, one, thinking about timelines from here, and then kind of scenarios around Catalent and your backup filler?
Yeah, thanks, Amy. It might be helpful to go through the sort of main points from the Type A meeting.
Yeah.
As I said, we were delighted that actually we had an in-person meeting with the FDA, something I have not managed to do for seven years now. The FDA does not easily grant those. That was during the U.S. government shutdown. I think that is a suggestion of how important the meeting was to them and for us. We were also delighted that we were joined by not just Novo on our side and Cure SMA, the patient advocacy group, but also on the FDA side by all the key chiefs of the different divisions. You know, compliance, CMC, quality, the clinical division. All the right people were there to have a meaningful conversation. We guided on the unmet need and the urgency of the situation, which I think the FDA fully appreciated, and it was helpful to do that.
Novo, which this is the first time that they were engaging with the FDA in conjunction with us, and they gave an account of the submissions they'd made to date following the 483. They have a very robust remediation plan that has been submitted, and also subsequent submissions to show the progress they're making with the remediation plan. The FDA listened to all of that and said to them that it was helpful to understand the overall situation with Scholar Rock and the unmet need. It was also helpful to understand their progress. I'm paraphrasing here. It was good that they guided that they intend to write back to Novo in the coming days or weeks, they suggested, certainly before the end of the year.
That may have been in part because Novo said as part of their commentary that they feel that because of the very substantial progress they've made with their remediation, maybe up to 90% or so of the remediation complete, including all the critical items from the 483. The FDA commented, why don't they communicate now with Novo and outline their impression of the situation and the work to date? That communication will occur in the coming days and weeks before the end of the year. We don't know quite what form that communication will take. It could be, you know, an untitled letter. It can be a warning letter. We don't know. They didn't guide us on that. Whatever it is, the communication is to outline their impression of the work completed to date. If anything else is outstanding at this point in time.
The FDA did comment that, you know, subsequent to that exchange, they will expect a response back from Novo, the quicker the better, and that they would like to come out and reinspect the facility in the new year. We do not know exactly what that means when these communications will finish, but if they inspect in the new year, then once that inspection leads to redesignation of the OAI, that would lead to us resubmitting the BLA. We would hope that it would be a prompt review. Again, we discussed the path forwards in detail all the way to the review with the FDA. You know, the suggestion was that they want to act expeditiously. They do not tell us the exact classification and the timelines for that.
You know, the overall conversation led to a conclusion for us and for Novo that the current challenges can be overcome and that apitegromab could be approved next year.
Okay. Excellent. Just a little, because you said a lot of, you know, interesting things, right? I think 90% is around already what's been remediated. Can you give us color on what the remaining 10% is? We've looked at, you know, some of these precedents for OAIs. We've noticed the ones that generally take longer to resolve are, you know, you have mold everywhere. You have, you know, it's, you know, XUS sites that, you know, these people are just not trained on fill finish. You know, the observations that was, you know, in the Form 483, it's a lot of it was process related. There was some contamination. Just give us a sense of how difficult, you know, kind of the remaining items are to remediate.
You know, as I said just a little while ago, Novo's impression and our impression is that they've remediated all the critical items. There were no mold issues. There were no structural issues at the site. This is a U.S. facility. You know, one way to think about the major items is to do with the quality management systems at Catalent. You know, Novo came into Catalent. They purchased the site in December of 2024. They had started upgrading all the systems and processes at the site from January. That work takes time. When the FDA came unannounced in July for an inspection, the work was ongoing but not complete. Of course, with the remediation plan, they have put, you know, urgent measures to complete it all as rapidly as possible. They reported out that all critical findings, you know, have been attended to.
That typical cycle of, you know, any site like Catalent or any manufacturing site is run under strict discipline with many standard operating procedures. Things can go wrong from time to time. They have to be identified, the root cause, you know, drilled into, a corrective action plan created, and then all the documentation to see that that has been remedied. Those are the kinds of, you know, items that they needed more discipline on. We are pleased that Novo, which is obviously a high-quality global company, has made a firm commitment throughout 2025 to upgrading all those systems. They obviously have vast experience given the scale they play at. They are committed to changing the culture and philosophy and have made substantial progress, as I said.
Excellent. When it comes to reinspection, right, I think you specifically used the word reinspection ready. Can you give us a sense on what that necessarily means? Do you need to remediate everything? Who determines, you know, is it Novo that is determining if they're reinspection ready? Kind of the timelines from when the inspection could actually occur and then when, you know, the OAI could be resolved.
Yeah. The inspection ready comment came from Novo. They're obviously experts in how the plant is run and the quality systems. You know, as you might expect, anyone that's running a GMP manufacturing facility or anyone doing regulated work of any kind has mock audits. You know, they want to assess the kind of progress they've made. They don't say that lightly, we believe. And all those kinds of measures have been taken. Exactly the timings and what precipitates that, that's in the back and forth between the FDA and Novo. So we can't speak to that. Certainly, I would reiterate that the FDA did commit to getting a communication out to them in the coming days or weeks. They wanted Novo to respond effectively and efficiently to that. They commented on an inspection in the new year.
When that would be is hard to say because the FDA does not announce unannounced, well, they are unannounced inspections, right? They are general site inspections. They just walk in on a plant. That is what they did in July. They will do that and schedule that at their behest. We cannot comment on that.
Okay. That's super helpful. You've mentioned shared urgency and constructive several times. I just want to clarify because, you know, there's the division of neurology who has every incentive, you know, to get a rare disease out. And then there's also the, you know, office of inspections or compliance that is reviewing this. When you say shared urgency, are you talking about it from both divisions? And how should we kind of think about that in terms of timing?
I mean, again, I don't know that I can tell you of timeframes other than what I've said already. I think it was good to have a face-to-face meeting like this, get around the table with all the right people in person. I mean, the clinical division has approved several drugs for SMA, as we know already. They are very familiar with the unmet need and the potential of our drug. They gave it priority review status. They clearly appreciate the impact this drug can make. You know, we, for example, shared data showing that delayed treatment will lead to poorer outcomes for patients with our drug, apitegromab. That kind of data we believe is impactful. The people from compliance and CMC and quality, they're not reviewing, you know, all that stuff every day, understandably.
I think it was important to highlight to them so they could assign our work with the apitegromab and that site the appropriate priority. I think that was one of the positive things that came out of the meeting. That is why it was constructive and collaborative. Because one of the things that obviously we work with a lot of consultants in this kind of situation, Novo does, they were at pains to reassure us that everyone at the FDA in these situations wants to do the right thing, but we need to help them. You know, the reviewing division reviews the safety and efficacy packages, but, you know, the quality guys are not doing that. It was helpful to actually share those data and share what Cure SMA, the patient advocacy group, was saying about why patients need this drug.
Awesome. Yeah. Will you share an update when the reinspection occurs or when the reinspection is set?
Yeah, you know, without knowing the timings of all these events exactly, other than the sort of general timeframes that are reviewed, I think our next anticipated update would be, you know, early in the new year, JPMorgan, something like that. Other than that, we'll be guided by what's going on back and forth and what's appropriate to share if it's material or not. There are no other plans other than that right now.
Awesome. On your backup site, this was actually kind of surprising to us because we were under the impression it was going to take a little longer to get your backup site up and running. So just want to confirm, when you say that it's commercial ready, are you talking about, you know, the stability batch testing has been done on the site and you can use it as a primary manufacturer if need be? Or are you talking about, you know, it's just, you know, the physical slot availability?
Yeah. So, you know, it was incumbent upon us to build redundancy into the system. And so we had already been working on that. I think the CRL and everything that's happened since then just introduced additional urgency. And so we've managed to accelerate the backup site. The good news is it's a U.S. manufacturing facility. It's been inspected many times before. They've passed and have good standing with the FDA. So we're very encouraged by that. The tech transfer to them has begun. We've got slots ready for the new year. So the typical cycle is, you know, engineering slots, then so-called PPQ runs, and then analytics and stability testing. And so that work has all been planned and we'll start executing in the new year with urgency.
You know, one of the other things is we commented on the earnings call on Friday that we anticipate a supplemental BLA for this second site within 2026. Again, we can't commit to a timeframe because we have to do all this work. Obviously, we've done some planning and it allows us to say something like that. We're also helped by the fact that we're trying to keep as much constant in terms of the fill finish process between Catalent and this new site. That's very helpful because that helps the FDA validate the new site. There are fewer boxes to check. There's more carryover of data and more flexibility from the FDA in those situations. We've also had preliminary discussions with the FDA about that at the Type A meeting.
You know, we feel that's why there could be an SBLA for the second site by the end of 2026.
Interesting. Yeah. In terms of capacity, I guess two-part question, capacity for this second site, could it supply, you know, the U.S. and Europe? Then from a second, you know, from logistics of including the second site into your, you know, resubmission, would that be class one, class two? How does that differ versus if you use Catalent?
You know, in terms of capacity, do you want to take that on?
Sure. In terms of capacity, I can tell you that either facility would be able to produce enough supply for us to launch in the U.S. and Europe. In fact, we have enough supply already waiting for us at the Catalent facility that's already vialed and ready to go as soon as we have FDA approval. Based on the new facility, we would have, by the time the SBLA is submitted, enough supply built there that if it was our sole site and it became the BLA instead of the SBLA, it could still provide supply for U.S. launch and European launch.
Awesome.
You know, in terms of the timelines for the second site, I really can't comment on that.
Right, right, right. No timeline, but class one, class two resubmission.
We can't commit.
Okay. Worth a try.
Yeah. You know, I think the thing we all have to bear in mind is that for the FDA, all of this kind of work has to be scheduled and, you know, they can't commit a priori without seeing what body of work is involved and so forth. We have to just wait for a little more time.
Okay. Awesome. Switching gears to the actual expectations for launch, I know you've made some, you know, questions, comments about the label and the approvability and, you know, how the site was the only thing that's potentially holding up approval. Obviously, you can't tell us what the label looks like, but if, do you, I guess the way to ask it is, do you expect the addressable patients that you previously put out at launch to be the same after your discussion with the FDA?
You know, speaking to the label, I think in the preamble, I said that the BLA review was essentially complete on September 22. What that means is that there had been negotiations about a draft label. I think we reached a good place. We do not know what the final label will be. That, of course, comes when the full approval will be in hand, hopefully in 2026, as we were discussing. You know, some useful guideposts about the label. The label often reflects what was done in the pivotal studies. In phase three with apitegromab in SMA, we studied children two years and old. In fact, the age range studied was two to 21, so children and adults. No children under the age of two were studied. No children on Zolgensma, you know, infants on Zolgensma were studied.
I think that that threshold at two is important and could be important to guide the FDA in terms of how they think about it. The other piece that's important to bear in mind is that the FDA has, you know, generally, if we look at the other three drugs that have been approved, they've often looked at the therapeutic hypothesis, the data in hand, which may have been in this population. And then they've just sort of expanded, you know, to a broader population because of the impact of the drug and the therapeutic hypothesis and the consistency of the therapeutic hypothesis across the disease spectrum. We don't know what the final label will be, but we were encouraged by the negotiations and we hope that, you know, our final label will follow that kind of pattern.
We certainly feel that the case is made for myostatin antagonism in children and adults across a range of disease severities and disease subtypes.
Okay, got it. So if I were to interpret it correctly, it sounds like, you know, older than two years old, potentially broad non-ambulatory, ambulatory classes one.
I, you know, you said that. I didn't.
Okay, okay. No need, no need to comment. Awesome. If we, just in terms of kind of market segmentation at launch, do you think kind of the low-hang, the initial launch patients will be kind of an add-on therapy? Could you get any naive patients? You know, can you kind of remind us on what you think the addressable patients are in the U.S. and ex-U.S.?
Yeah, so I mean, first of all, we know that, you know, there's more than 11,000 patients with SMA in the U.S. and we know about two-thirds of them are currently on SMN targeted therapies. You know, how we studied the product is alongside with nusinersen and risdiplam. And so we expect the initial patients that will go on therapy to currently be on an SMN targeted therapy, which makes this nice for a rare disease launch because we're not out looking for the patients. We already know exactly where they are. As far as how it segments amongst those that are currently being treated, you know, in data that's been shared with both nusinersen and risdiplam, you see a great response to these SMN targeted therapies and it's outstanding because it's been life-changing for these patients.
For many patients, they plateau off over a period of time and then they begin to regress. Fortunately, with apitegromab, we've actually studied in all of these segments across the treatment paradigm. In our Topaz study, it was patients that had only been on SMN targeted therapy for a limited period of time and they were still improving. When adding apitegromab, their improvement became greater. We have a number of them that started while they were in that plateau period and they continued to improve once we added apitegromab. Even those that were regressing were able to reverse that muscle loss and have muscle gain by adding apitegromab.
In speaking to physicians, I can tell you when you say low-hanging fruit, I think it's going to be a physician by physician and patient by patient choice because I'm hearing everything from I'm going to go to my patients that are progressing first to others that are saying the data supports earlier treatment is better and I want to get apitegromab on board with these patients that are currently on an SMN targeted therapy.
Excellent. When it comes to kind of infusion capacity that you are seeing across these centers, number one, are these patients, the geographic footprint, are these mostly around the centers of excellence or are there some in the community site? Then kind of the infusion capacity for these centers?
I mean, first of all, I think you're going to see a change in the overall treatment paradigm and how that plays out, including that of the location. Because when apitegromab is launched, it's going to be the first monthly IV infusion, right, compared to the other SMN targeted therapies. What we hear from the KOLs is they will start apitegromab in their facility in these SMA treatment centers. Then based on convenience, based on the patient's insurance and their family's desire, we are agnostic as to where the patient gets their infusion. We're going to have home health available for those whose insurance will pay for it. We also have a full team of nurse case managers that will work directly with the facility and the patient and their family to find an infusion site that's most convenient for them near their home.
Whether that would be an outpatient infusion center of a community hospital, a freestanding infusion center, it's really going to be based on the patient's choice with their treatment team's approval.
Excellent. Maybe one on U.S. versus ex-U.S. pricing. I mean, we've seen from multiple companies that ex-U.S., it's been harder to negotiate price ex-U.S. and there's a good subset, you know, of SMA patients in Europe. How are you kind of thinking about pricing and kind of the market opportunity in Europe?
Yeah, I mean, first of all, I'd like to say that the market opportunity in SMA, just based on the SMN-targeted therapies alone, is almost 70% of the business that we currently see in SMN-targeted therapies. And that's dollarized also. I'm not talking about patient numbers. Considering that you see lower prices outside of the U.S. with most SMN-targeted therapies, that means that on a patient number, it's greater than 70%. So not being able to do business outside of the United States is not going to be an option for us. We'll be pricing first in the U.S., but then we have worked on how we will sequence around the globe. We plan to go to Europe, Japan, South America by ourselves. In some cases, we'll work with distributors. And so we're building our plan around this.
I think the new thing that comes into play is exactly how will most favored nations play out. So we've got some ideas, but we're not exactly, you know, it's not, it's not, the ink's not dry on this one yet. So we're going to leave ourselves that flexibility.
Awesome. And then just one real quick on pipeline. I know we're coming to time, but your NextGen 439, I guess the question that I have is, given, you know, it's generally similar, can you run expedited, you know, trials and get to registrational studies quicker?
I mean, I'll just begin with your comment, generally similar. It's similar in the sense that it is potent and specific against myostatin. And I think Scholar Rock's distinguished itself in that regard. It seems to be significantly more potent. So we think that that's very exciting, but we'll get the phase I data next year in healthy volunteers. And our goal is to do exactly what you said, but you have to watch this space. We're working on that right now.
Awesome. Finally, cash runway expectations. I think you've actually said you were looking at royalty deals on the third quarter call. What kind of programs are you looking at? Are you seeing kind of appetite in the myostatin space, whether it's obesity or even in rare diseases for partnerships? Yeah, general comments on runway.
Yeah, I mean, I'll just say from a business development perspective, there's great interest in Scholar Rock's anti-myostatin portfolio from companies that work in the obesity space. We've said that we're going to focus on rare and neuromuscular disease, but there are a lot of ongoing conversations with all the players you might imagine to discuss collaborations in that space. On Runway, Keith, you want to?
Yeah, we closed quarter three with $369.6 million. Also during quarter three, we fortified our balance sheet raising about $91.7 million with an ATM, along with another $50 million that we pulled down in loan. In quarter four, we expect $60 million more to come in from pre-funded warrants that will be exercised during this quarter. It takes our cash runway into 2027, and that's also being conservative. That is assuming zero apitegromab revenue. And it's also not considering any of the monetization of the potential PRV provided we have FDA approval before the end of September.
Amazing. With that, thank you so much. Really appreciate it, Scholar Rock. Thank you, everyone.