Okay. Good morning, everyone. We are going to start right on time here, and kick off day one of the Cantor conference. My name is Eric Schmidt, and it is my distinguished pleasure to host our first presenting company of the day, Scholar Rock Pharmaceuticals. Delighted to have with us my good friend, David Hallal, who is the Chief Executive Officer. We may be joined by Vikas Sinha as well, the Chief Financial Officer. Let us dive right into what is going to be, I think, a very busy and memorable next 12 months for the company. David, just give us a quick lay of the land, maybe a two-minute overview of Scholar Rock today.
Thanks, Eric. It is great to be here with you and Cantor Fitzgerald. It is a really exciting time for the company. This is Scholar Rock's 15th year in existence. Vikas can join us up here whenever he would like. We have a series of regulatory, commercial, and clinical milestones in front of us in just the next 12 months. First and foremost, as Eric is noting, we are on file with the FDA with our Biologics License Application for apitegromab, which is a monoclonal antibody that we have developed for spinal muscular atrophy. We have taken that program through seven years of clinical development, a phase II TOPAZ study, a phase III SAPPHIRE study, and delivered the first-ever myostatin inhibitor that has ever demonstrated clinically meaningful and statistically significant improvement in motor function in a phase III trial.
Of course, that has led us to this moment in time where we are now on file with the FDA. We expect a decision in the next 21 days, with the action date of September 30th. Eric and I will get into that a bit further. We also expect to be refiling our MAA with the European Medicines Agency in the coming weeks and months. We will get into that, of course. Just like in the U.S., in Europe, we were delayed by an issue with our third-party fill finish manufacturing facility or drug product facility, Catalent Indiana. But we have successfully stood up an alternate fill finish facility in rapid time. We also noted just recently that we are anticipating also submitting our application for apitegromab in children and adults living with SMA in Japan.
So we will be submitting to PMDA by the end of this year and are super excited to enter that market of 120 million population country in a faster amount of time than we had otherwise thought. That is because we did gain agreement with the PMDA to be able to file without a local clinical trial for apitegromab. In addition to those regulatory milestones, we are super excited to commercialize apitegromab in the U.S., Europe, Japan, and up to 50 countries around the world. I am sure we will get into that this morning. Finally, we do have a series of important ongoing clinical trials that are happening at the company.
The first that I would note is the phase II OPAL study, which is a study with apitegromab in the youngest of patients suffering with SMA under two years of age that have received ZOLGENSMA, the gene therapy. That trial continues to progress and enroll nicely. We have also just recently announced for apitegromab and FSHD that we have started to dose our initial study participants in the phase II FORGE study. This is a 60-patient, double-blind, randomized, placebo-controlled trial for patients with the moderate phenotype of FSHD receiving apitegromab, and we look forward to robustly enrolling that study. Then finally, by the end of this year, we should have our initial data on SRK-439, which is a novel high potency, high affinity myostatin antibody. We are the world leaders in myostatin inhibition.
This is a standalone asset, and we will have a readout in healthy volunteers toward the end of this year, and certainly no later than JP Morgan, just into 2027. So busy time at the company, Eric. A lot of important milestones, all in the advancement of sort of extending our leadership position in myostatin biology as the world leaders that have been able to unlock the benefits of inhibiting myostatin safely and effectively. That really sets up for a whole host of things for us to do over these next 12 months, and more importantly, what we are going to discuss over these next 20, 25 minutes together.
Great. Terrific overview. Thank you, David. For those on the webcast, we have been joined by Vikas Sinha, the company's CFO. Good morning, Vikas.
Good morning.
Thanks for being here. Let's-
I would note that Vikas has enabled us to have the capital to do all of these things, as in our last earnings call, we indicated that we have a cash balance of nearly $500 million . Certainly, we are well supported by our balance sheet to drive all of our commercial, regulatory, manufacturing, and clinical development initiatives.
You just took Vikas' one question.
Oh, no. He's going to get into it in much more detail.
So understandably, David, a lot of interest in the PDUFA date, which you mentioned for apitegromab is September 30th, just 21 days away. You spoke to being optimistic for an approval decision at that time or before that time, at any time between now and then. Where is your optimism coming from?
Yeah. Eric raises the most important point of all. Obviously, we were surprised and disappointed on September 22nd of 2025 that we did receive a complete response letter for our initial BLA for apitegromab. Notably, the FDA indicated in that complete response letter that the sole approvability issue at that time was the state of compliance, or lack thereof, at our drug product manufacturing facility, our fill-finish facility, which was Catalent Indiana in Bloomington. And of course, following the complete response letter, we worked very closely with Catalent Indiana, the owners, Novo Nordisk, to work aggressively to remediate the challenges in that facility. But at the same time, as Eric and I have discussed, while not a lot of folks were paying attention, we were very focused on standing up an alternate fill-finish facility in record time.
And so if you recall, Eric, we had our Type A meeting following the complete response letter on November 12th of 2025. That was a collaborative and constructive meeting with the FDA. We were joined at that Type A meeting by Novo Nordisk to discuss the progress at the facility. We were also joined by Cure SMA to discuss the high unmet need for patients living with SMA. So that was on November 12th. One thing that I am not sure a lot of folks paid a lot of attention to on November 14th, which was our issued press release for our Q3 earnings call, is that we indicated that we were now under contract with an alternate fill-finish facility, and we had secured commercial manufacturing in the first half of 2026.
The reason why we did that is we said as much progress as Novo and Catalent may make, we can't have the entire company and the future of the SMA community in the hands of a single re-inspection of that drug product manufacturing facility. So let us go ahead and find an alternate and stand it up in record time. And that is precisely what we did. We had a briefing book submitted to the FDA on December 3rd of 2025, again, when nobody was looking, and that is what really led to an important Type C meeting with the FDA on March 3rd of 2026. And this is where our optimism comes from. It was at that meeting that we discussed with the FDA the meaningful progress that we were making at our alternate drug product facility, in addition to the progress that was being made at Catalent Indiana.
It was during that meeting that it was really the FDA along with us that agreed that the best path to resubmitting our BLA was not just with Catalent Indiana, but with both fill-finish facilities. In the FDA's words during that meeting, Eric, "Let's have a horse race to see which drug product manufacturing facility can enable the approval of apitegromab fastest. Whichever one that is, you drop the other from the file with no timeline hit, and we work our way to your approval date." As we all know, the re-inspection from the FDA occurred between April 13th and April 24th of 2026. If that inspection at Catalent Indiana went well, one could have seen us dropping our alternate site from the initial BLA, because we did resubmit the BLA just a few weeks after that Type C meeting on March 30th.
That allowed the Class 2 resubmission date and the action date with the FDA of now September 30th. If that re-inspection of Catalent Indiana went well in April of 2026, one would have imagined that would have been the fastest path and we would have dropped our alternate. At the same time, we were filing a lot of apitegromab at our alternate facility. So much so that we now have more commercial apitegromab filed from our alternate site than we ever did from Catalent Indiana, and that product is at our third-party provider, awaiting labeling and packaging at approval. During the Type C meeting, we agreed with the FDA on the data that was necessary to validate and qualify and enable approval from that alternate facility, and we met those timelines. In fact, we beat those timelines and got that information to the FDA even earlier than they had expected.
I think what gives us the greatest level of confidence of all is while after that April re-inspection, we were obviously concerned, like others, that Catalent Indiana may remain in OAI and under warning letter. The FDA had indicated to us that we would not drop Catalent Indiana from our BLA until they reviewed the data from our alternate fill-finish facility. So when we let the world know that we had dropped Catalent Indiana from our BLA just a few weeks ago under the guidance of the FDA, I think it's important where our optimism comes from is that was only done under the guidance of the FDA after we know that they had reviewed our data from our alternate drug product manufacturing facility, and as we restated in that press release, our PDUFA date remains September 30th. Dialogue with the FDA has been strong.
It's been on both sides of the shop, both clinical and CMC, and we remain optimistic that we will receive approval in Q3 and start launching apitegromab for children and adults living with SMA in these coming weeks.
Okay. Really important point, maybe just to put a pin on that, David. When you pulled away from Catalent in early August, I think it was, at that point in time, the alternate facility was substantially reviewed and CMC, you think, is essentially cleared at that point.
That's right. Why do we know that? Because we don't want to be reading tea leaves. One, when we indicated to the FDA that we thought that now was the time to remove Catalent Indiana, they said, "Just wait a few days. Let us get through our review of your alternate drug product facility." We thought that that was an important element. We had also had a series of very perfunctory information requests from the FDA, all related to the second fill-finish facility. There had been an exchange of information with the FDA prior to then them handholding us on to how to drop Catalent Indiana from our BLA. It's important to note, all we've done is drop them as a commercial supplier of apitegromab in our BLA. The data, they remain our clinical trial supplier.
We have hundreds of patients receiving drug from Catalent Indiana, and of course, data that we've generated over all these years from Catalent Indiana remains in our BLA. But technically, as you know, what has held us up over this 11, 12-month period of time is that if a manufacturing facility is going to be part of your supply chain, they need to be in good standing with the FDA. That has been the hiccup here for us, is the general state of compliance, or lack thereof, at Catalent Indiana in Bloomington.
Okay, so that's what happened in early August. Catalent stepped back, the alternate facility stepped forward, substantially reviewed. What's been happening with FDA dialogue since then, and what still needs to happen as we get closer to September 30th?
Yeah. You would imagine in the CRL, other than the state of compliance of our drug product manufacturing facility, which was the sole approvability issue, what the FDA was very clear with us on in that complete response letter is when we do resubmit, go back to the version of the USPI, the label, that we had exchanged with the FDA on September 18th of 2025. That was just a few days before the original PDUFA. That is why, by the way, we thought we were getting approved, because usually, deep labeling discussions are probably not happening if the CMC folks at the FDA are saying, "We are not going to be able to get there on your drug product manufacturing facility." When we resubmitted our BLA, we have resubmitted with that version of the label, the last label that the FDA had asked for.
It is important to note, Eric, that we received a version of the label, which we were substantially happy with the morning of September 18. The FDA wanted our comments by the morning of September 19. We delivered that ahead of time. It went back to the FDA the evening of the 18th of September. We had said even at that time, if the FDA did not take our comments, we would have been very happy with the version that we received on the 18th. But importantly, in the complete response letter, the FDA actually asked us for that version with our comments in it, and that is our starting point for these final labeling discussions, which we anticipate will now happen in a fairly rapid amount of time between now and September 30.
We are aware that the neuro division is super busy right now with a number of action dates. They just had an approval last week on September 3. But we know they are doing their work, and we are in constant communication with them. The only other thing they had asked in our complete response letter, and obviously one would do this if you are resubmitting a BLA, is just an update on our safety database from all of the patients that remain on apitegromab through our long-term extension study, the ONYX study. We now have patients that have been on drug for upwards to seven years. Then, of course, we had an EAP in the U.S. as well, and patients continue to get that drug.
While we have had good dialogue with both the clinical and manufacturing review team, we would imagine that the final step will ultimately be labeling and the patient brochure, and away we go.
Okay, perfect. Well, best of luck as you wrap up what's hopefully the end of a 12-month ordeal here and come to the finish line in the U.S. Let's turn our discussion to the EMA. I think earlier this fall or summer, I guess also last month in August, you pulled the MAA out of the EMA. Maybe just give us a little bit of backstory here. I think most of our listeners are probably familiar with the fact that the sole fill-finish provider in that MAA was also Novo.
Yeah. As I noted when we resubmitted our BLA, and I went out of my way to tell folks this, that while we were so pleased in the U.S. that we now had two independent paths to an approval, which was either Catalent Indiana or our alternate fill-finish facility, or both, I made everybody aware that we never had the equivalent of a complete response letter in Europe. So we were still betting on a reclassification of Catalent Indiana for our MAA and eventual approval in Europe. We did, of course, after we announced that we've resubmitted our BLA with two fill-finish facilities. By the way, that alternate facility is in very good standing with Europe. Europe has inspected that facility. That second facility that we've now added has a near-term and long-term positive inspection history with both U.S. and European regulators. So that's an important point.
When we raised to the rapporteur and co-rapporteur that we'd like to add, while we were in flight with our MAA, like to find a way to add the alternate site to our MAA, they indicated, they said, "You know what? The FDA knows we have a number of important drugs on file that are on hold because of Catalent Indiana. Let's just wait for the classification, and should that not go our way, then we'll decide next steps. But we really want to see this drug get approved." I think all along, EMA thought that the decision would come down following the April inspection, would at least come down by July, within the 90-day allotment guidance period that the FDA provides for classifying inspections.
As we all know, it went over 100 days now. When that did come down as maintaining the OAI from the April re-inspection, what that really meant was the rapporteur, co-rapporteur, Europe was in high holiday time in April. They probably would have had to review all the data from the alternate facility in August ahead of a September CHMP. If you do your math, we submitted our MAA in Q1 2025, so the European Medicines Agency had already offered us an enormous amount of flexibility with multiple clock stops. They do get a little worried about setting precedents with too many clock stops. We had several. At that point, they said, "Look, the best thing to do, because it's going to be hard for us to get up and down with this new data by a September CHMP meeting, why don't you withdraw?
Let's get that done and behind us. In the coming weeks, we'll decide on a resubmission date, and we recognize this is a one-issue resubmission." Hopefully, this can be expedited, but importantly, what I want everybody to hear me say is we cannot provide guidance on Europe until they come back from holiday, which is about now, until they give us guidance on when we can resubmit. I did note with Eric and a few others recently, we are ready to submit whenever they say. Should they say, "We will take your resubmission this month in September," we are ready. Why? Because we've already prepared everything for the FDA and are preparing everything for PMDA.
We're just waiting for their word, and then hopefully, in the not-too-distant future, we're both back on file, and hopefully our MAA can be reviewed in an expedited fashion, so we can get this drug to the children and adults living with SMA in Europe as well.
Okay, so from a disclosure standpoint in Europe, what would be the next announceable event? Then, once you are in position and the EMA agrees that you can resubmit the MAA, what might the timeline to approval regulatory review look like?
Yeah. Without having any guidance from the FDA right now, I think the next thing you will hear from us is that we have resubmitted, or at least we have gained an agreement to resubmit on this date. Whatever they can give us for color in terms of their review timing, we would like to provide for you. Again, we are hopeful. A lot of things can go our way here, believe it or not. The rapporteur and co-rapporteur can raise their hand, the ones that we have developed a great relationship with and say they want to stay on the program. That would read positive for us because obviously we have substantially reached agreement with them on everything. They wouldn't really need to review very much. Resources are tight, always, in Europe, so if we have a good relationship with the rapporteur, co-rapporteur, that could read very positive for us.
Whatever we know and when we know it, I think ideally the next disclosable event would be that we have submitted our MAA or that we have an agreement to submit by a certain date, and we will certainly provide that update, not only to the investment community, but importantly, the SMA community in Europe.
Okay. Thanks for those regulatory updates. Maybe let us transition to the good stuff, which is getting the drug to patients and starting to serve the commercial opportunity. From a high-level perspective, how do you think about SMA, either in the U.S. or globally?
I have to say that Vikas and I, Keith Woods, Akshay Vaishnaw, the team is we are so eager to serve patients more broadly with apitegromab. One of the things I will start with, Eric, if it is okay, is maybe just to provide the landscape for everybody. Before SPINRAZA, Biogen in 2016, 2017, SMA really had no innovation associated with it other than supportive care. Then, of course, we have now seen with the approval of nusinersen or SPINRAZA, followed by ZOLGENSMA and Evrysdi, a lot of needed innovation coming in over these last 10 years focused on the production of SMN protein and that providing better motor neuron health. But as many of you know, the principal organ clinically affected in SMA is the muscle, and there has never been anything to target the muscle. While the needed innovation has brought great benefits to the patient community, they want more.
They need more. Their treating physicians want them to have more. We developed apitegromab as the first ever muscle-targeted therapy in SMA that targets myostatin, which is all of our body's natural negative regulator for growing muscle. The last thing that you would want if you were a patient with SMA is to have any myostatin residing in your body, and that's why we developed apitegromab. There is a growing amount of understanding that if you can boost SMN protein with any number of these therapies that are now available, but you can also safely and effectively eliminate myostatin, that may provide the best clinical outcome for additional motor function for patients with SMA.
Of course, that was borne out in our clinical development program, our phase III SAPPHIRE study, 188 patients enrolled, double-blind, placebo-controlled, randomized clinical trial where we showed a clinically meaningful and statistically significant benefit in motor function as measured by the gold standard Hammersmith Motor Function Scale. That lays the groundwork. What's happened in these last 10 years is globally upwards to 35,000 patients are receiving at least one SMN-targeted therapy focused on boosting protein and preserving motor neuron health. That's our market today. Importantly, that market continues to grow. There is more than $5 billion in sales across those three products today, projected to grow to $7 billion or more in these next four or five years. That is obviously the marketplace that we are targeting is those patients that are receiving at least one SMN-targeted therapy.
As we designed our clinical trial, those patients were randomized to receive either placebo or apitegromab, and apitegromab showed this remarkable clinical benefit for patients. As it relates to the U.S., Europe, and beyond, obviously we would expect with U.S., Europe, and Japan, that would open up meaningful markets for us. I've indicated to Eric, when we've looked at some of the SMN-targeted therapies, about 1/3 of their revenues are in the U.S., about 1/3 of their revenues are in Europe, and about 1/3 of revenues are in Japan and rest of world. That may indeed follow because the rare disease playbook that we have seen and we've been a part of in the past at Alexion, but we will see. So 35,000 patients globally is our target patient population. 7,000- 10,000 of those patients perhaps are in the U.S.
A big chunk are in Europe, and obviously there's a number of these patients in upwards to 50 countries around the world, which we will aim to deliver apitegromab directly as a company to those patients. Eric, just recently, we've opened our European operations out of Switzerland, and we built our team in Germany. That'll be the first country we launch in Europe. Now with the expedited path to filing with PMDA, we'll be opening our initial office in Tokyo under a strong general manager who will start with the company in October. So a lot on the plate for the company. We think there's going to be a lot to share with you as it relates to the U.S. launch of apitegromab in this next 12 months, so we're super excited to share that with you.
But really over the next 10- 15 years, we feel like we're going to be launching in new countries each and every year, delivering apitegromab, which is a chronic treatment for patients with this disease who are largely receiving chronic, ongoing SMN-targeted therapies.
Terrific. Thanks for that. I think, David, you've commented to me before that at least at the outset, you think patient demand for the drug is going to far outpace what you're able to sell and provide, given the logistical factors that we all need to deal with, reimbursement, infusion access, et cetera. How do we think about breaking down those barriers and how long it might take to get to a more open environment?
Importantly, where our optimism comes from on the demand side is that the number one need that the patient and family community ask for, and this is data from Cure SMA, 95% of patients, when they do their state of SMA, 95% of patients are demanding more muscle strength and more motor function. Universally, they're looking at this therapy as the next big thing. Secondly, 75% of neurologists are now indicating that the ideal way to treat a patient with SMA is with an approach of treating both the motor neuron and the muscle, which is comprised of the motor unit. The motor unit is what drives motor function. Then, of course, the delay, Eric.
I think the delay of upwards to a year has led to more and more awareness in the community that apitegromab can be a game changer, a potentially life-transforming therapy for patients with SMA. So there's our optimism for demand. Now, on the access side, this is a monthly infusion. We'll have a miscellaneous J-code at launch. SMA treatment centers probably have formulary-related issues they will need to deal with. They'll have to think about how to incorporate a monthly infusion into their practices. We also know that payers will have to develop a medical policy. Does the medical policy follow the label, which we anticipate would be a bit broader than our phase III clinical criteria, or will they want to tighten an initial medical policy that's more narrow than our FDA label?
All of this, we believe, is resolvable over time, but we do believe there is likely to be some delays with initial denials and reimbursement. That is why we have guided folks to that we have an enormous amount of optimism on the long-term potential of apitegromab and SMA as a multiple billion-dollar annual business over time. Just give us these first three, four, five quarters to work out some of the reimbursement, we call them speed bumps, not stop signs. We will get through this with a community that is well experienced at overcoming reimbursement barriers. But the strength of our clinical trials, the strength of our label, and the strength of our data really sets up very well for at some point in time, we will have simple, reliable, and trusted, and broad access to apitegromab for the SMA community.
But with many higher priced rare disease therapies, there can be some speed bumps along the way. That is what we are just cautioning the market to keep in mind in these first three, four, five quarters.
Okay. We have only got a minute and a half left, David, but given that apitegromab is really the only drug that has been successful in late-stage trials, it builds muscle, and that you have all these other potential opportunities, Duchenne , Becker, spinal and bulbar muscular atrophy, FSHD, how do we think about the franchise extension?
I mentioned when Akshay joined me in running the company off the board, Akshay Vaishnaw, who for 19 years was the President of R&D at Alnylam, I said keep in mind he did not come here just to see apitegromab get approved in SMA, that he shared my optimism and our optimism that we had a pipeline and a product. So when you think about Scholar Rock, think about on one axis, apitegromab, high concentration subcutaneous apitegromab, and then SRK-439, three therapies that we think very uniquely inhibit myostatin. As Eric noted, the only myostatin inhibitor that has ever been successful in advanced clinical trials. Then on the other axis, think about, as Eric noted, SMA, FSHD, and a series of rare and devastating neuromuscular disorders. We believe this is a true pipeline and a product with a lot of optionality.
I know we are up on time, but I would just like to say FSHD is the next indication, not the only indication, and we will have time, Eric, to update you on the progress with the phase II FORGE study. Also, we will be looking at other preclinical models for other rare neuromuscular diseases and provide you an update in early 2027 into the additional indications that we will be looking for as well. Thank you for your time. Great to be here at Cantor with you, Eric.
Thank you, David, Vikas. Appreciate your being here all day with us. Take care.
Thank you, guys.
Thanks, guys. Thanks, everyone.