Good morning, ladies and gentlemen, and welcome to Scholar Rock's third quarter 2026 conference call. At this time, all lines are in a listen-only mode. Following the presentation, we will conduct a question-and-answer session. To ask a question during this session, you will need to press star one one on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star one one again. This call is being recorded on Tuesday, November 10th, 2026. I would now like to turn the conference over to Scholar Rock. Please go ahead.
Good morning. I am Laura Ekas, Vice President, Investor Relations at Scholar Rock. With me today are David Hallal, Chairman and Chief Executive Officer, Keith Woods, Chief Operating Officer, Akshay Vaishnaw, President of R&D, and Vikas Sinha, Chief Financial Officer. During today's call, David will provide introductory remarks and a business overview. Keith will discuss the U.S. launch of ISEMBYLD and global commercial readiness. Akshay will review our regulatory and R&D progress, and Vikas will provide a financial update. We will then open the call for questions. Before we begin, I'd like to remind you that during this call, we will be making various statements about Scholar Rock's expectations, plans, and prospects that constitute forward-looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995.
Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date. I encourage you to go to the Investors and Media section of our website for our most up-to-date SEC statements and filings. With that, I'd like to turn the call over to David. David?
Thank you, Laura, and good morning. Thanks to everyone for joining our third quarter earnings call. Today, Scholar Rock is operating from a position of great strength, and we are executing with focus, discipline, and urgency. In mid-September, we received FDA approval well ahead of our PDUFA date for ISEMBYLD, the world's first and only muscle-targeted therapy for children and adults living with SMA. Following approval, we immediately commenced our U.S. launch. In early October, we resubmitted our apitegromab MAA in Europe for the treatment of children and adults with SMA. The application, which now includes our alternate fill-finish facility, has been validated, and we expect a CHMP opinion in the first half of 2027. In early November, we submitted our apitegromab JNDA in Japan, two months ahead of our guidance.
The application was accepted under priority review, and pending approval, we anticipate a launch in Japan near year-end 2027. In Q3, we also commenced dosing in our phase II FORGE study evaluating apitegromab in people living with FSHD. Finally, this morning, we announced we have entered into a definitive agreement to monetize our priority review voucher for $205 million, which will further strengthen our financial position to fund our ambitious global commercial and R&D growth initiatives. With this, let me turn to our U.S. approval and launch of ISEMBYLD. ISEMBYLD is a highly innovative myostatin inhibitor and the world's first and only muscle-targeted therapy approved for patients with SMA. Over the past decade, while SMN-targeted therapies have brought needed innovation to the SMA community by improving motor neuron health, significant unmet need remains. Muscle is the principal organ clinically affected by SMA and has been unaddressed.
To underscore this point, gaining muscle strength was the number one need amongst SMA patients in a 2026 Cure SMA survey. In addition, more than three-quarters of neurologists recognize that the future of treatment for patients with SMA is an approach that targets both the motor neuron and the muscle. Now, with ISEMBYLD, Scholar Rock is ushering in the next phase of needed innovation for the SMA community. Importantly, the FDA-approved label provides a substantial opportunity to serve patients. ISEMBYLD is indicated for all patients with SMA two years of age and older who are receiving an SMN2-targeted treatment. Our U.S. label is underpinned by the compelling clinical benefits ISEMBYLD can bring to children and adults with SMA.
For patients receiving an SMN2-targeted treatment in our global, randomized, double-blind, placebo-controlled phase III SAPPHIRE study, ISEMBYLD changed the progression of SMA from a loss of motor function to a gain of motor function. At the recommended dose, ISEMBYLD delivered a robust, clinically meaningful 2.2-point improvement in motor function compared with patients receiving an SMN2-targeted therapy alone, as measured by the gold standard Hammersmith Functional Motor Scale. With this strong foundation in place, our experienced Scholar Rock commercial team is now doing what we know well and what we do well. Launching a highly innovative first-in-class rare disease therapy with the potential to dramatically improve the lives of patients. Immediately following the approval of ISEMBYLD, our team swiftly and successfully executed initial launch activities, and we are very pleased with our progress in these earliest weeks.
Our launch metrics reinforce our expectations and confidence in our opportunity to serve the estimated 6,600 patients with SMA in the U.S. who are currently receiving an SMN2 targeted therapy. Shortly, Keith will discuss four strategic imperatives with regards to our early U.S. launch dynamics: awareness, education, demand, and access. I'd like to take a few moments now to touch upon demand and access. In terms of demand for ISEMBYLD through the end of October, we are seeing a strong number of patients enrolling in Scholar Rock Supports. In these early weeks since approval, we are very encouraged by the broad-based demand as reflected by both the consistent volume of patients enrolling into the program and by the wide range of prescribers and patients. In the first six weeks of launch, enrollments are balanced across all geographies nationwide.
More than 1/3 of the top 140 SMA treatment centers have enrolled initial patients, and a significant number of enrollments are coming from centers outside of the top 140. The mix of patients enrolling in Scholar Rock Supports is just as diverse. Importantly, ISEMBYLD treatment-naive patients outnumber those who are starting the transition from our clinical trials and EAP program. Children are the largest enrolled group of patients, but a substantial number of adults have also enrolled. Patients reflect the full range of disease trajectories, including improving, plateaued, and declining motor function. Consistent with SMN2 prescribing patterns, patients are balanced across Evrysdi, SPINRAZA, and High Dose SPINRAZA background therapy, including some who had previously received ZOLGENSMA.
Thus far, the pace of demand as measured by patients enrolling in Scholar Rock Supports has been very steady and consistent on a weekly basis, and we expect this trend to continue as we aim to serve an increasing number of new patients over time. As we expected, strong demand is outpacing reimbursement and access at this stage. While I am very encouraged by early patient-by-patient approvals across insurance types and sites of care, initial delays and denials are common for any first-in-class rare disease launch. Given the timing of when patient enrollments have been received, combined with the anticipated 60 to 90 days or longer from prescription to infusion in this very early stage of launch, we anticipate the majority of the patients who enrolled through October will begin infusions in 2027.
We expect steady progress on payer approvals over time and remain confident that it is a matter of when and not if eligible SMA patients will receive ISEMBYLD therapy. We are building an access engine that will ultimately support broad and reliable access to ISEMBYLD. Our initial performance across these early indicators reinforce our expectations and confidence in our opportunity to serve a steady and consistent number of new patients for quarters and years to come. Keith will share much more detail on our early U.S. launch progress in just a few moments. Turning now to our global regulatory and pipeline priorities. We are very pleased with the meaningful progress we've made in recent weeks towards serving children and adults living with SMA in both Europe and Japan. Akshay will discuss these important regulatory advancements and progress across our world-leading anti-myostatin pipeline later in the call.
Finally, turning to the financials. We reported $0.6 million in ISEMBYLD revenue in the third quarter, reflecting initial inventory shipped to our specialty network. We ended the quarter with $413.6 million in cash equivalents, and marketable securities. Now, with the sale of our priority review voucher that will bring in an additional $205 million, Scholar Rock has the financial strength and flexibility to support our key priorities without the need for an equity offering at this time. In closing, we have never been better positioned to deliver on the opportunity ahead as we work with urgency to improve the lives of patients living with SMA and other rare and severe neuromuscular diseases. With that, I'll turn the call over to Keith to discuss the U.S. launch of ISEMBYLD and our apitegromab commercial readiness globally. Keith?
Thanks, David, and good morning, everyone. ISEMBYLD's position to define a new standard of care for the estimated 6,600 patients living with SMA in the U.S. who are receiving an SMN2 targeted therapy. As I've shared previously, the vast majority of patients continue to experience persistent and progressive muscle atrophy that limits both function and independence despite receiving an SMN targeted treatment. Now, with the FDA approval of ISEMBYLD, we are ushering in the next phase of needed innovation with this first-ever muscle-targeted therapy. In the 13 business days between the approval of ISEMBYLD on Friday, September 11, and the end of the third quarter, we executed flawlessly on our key priorities. Immediately following approval, Scholar Rock Supports began working with physicians and families to conduct insurance verifications for initial patients.
Within one week of approval, ISEMBYLD vials were labeled, packaged, and shipped to our specialty network, and we filed the J-code application, which will give us an ISEMBYLD-specific J-code on April 1, which is the shortest timeline possible. We are very pleased with the progress in these earliest weeks. Our launch metrics reinforce our expectations and confidence in our opportunity to serve the broad SMA community. Let me now provide some important additional detail on our launch as it relates to awareness, education, demand, and access. Patient and caregiver awareness and engagement is meeting our high expectations. For example, in the days immediately following approval, we had nearly 1,000 patients and caregivers register for ISEMBYLD educational webinars hosted by Cure SMA and MDA.
Through our efforts with our Life Takes Muscle campaign, we had more than 10,000 opt-ins from patients, caregivers, and HCPs to receive notification of the ISEMBYLD approval. In terms of prescriber education, following the ISEMBYLD approval, our highly experienced U.S. team began engaging with the SMA treatment centers, their physicians, and care teams on the compelling clinical benefits of ISEMBYLD. Reach to the SMA treatment centers is already deep and wide. Through the end of October, so in just the first six weeks of our launch, our team has engaged with 95% of the top 140 SMA treatment centers. This is a tremendous achievement, given that in my experience, it would typically take at least four months to reach this proportion of your target audience. In terms of demand, as David said, we are seeing consistent volume and breadth of prescribers and patients.
Specifically, in just the first six weeks of launch, enrollments are balanced across all geographies nationwide.
Collectively, these early patterns, including the steady and consistent pace of demand, reinforce the breadth of the ISEMBYLD opportunity and our confidence in the potential for sustained long-term growth. Turning now to access. As we expected, strong demand is outpacing reimbursement and access at this stage. Specifically, in these early days of launch, the time from prescription to infusion can be more than 60 to 90 days on average due to a number of factors, including the need to use an unspecified J-code for ISEMBYLD until April 1st, payer policies that have not yet been established, the time required for prior authorizations and appealing denials, and finally, the requirement for hospital formulary approvals, which takes time. Since approval, our team has been engaging with payers to discuss the value proposition of ISEMBYLD.
Through the end of October, we have reached payers responsible for more than 90% of covered lives in the U.S. We are encouraged by the productive payer discussions to date, and we are very pleased by the early published policies that align with the ISEMBYLD label, including two of the top payers in the U.S., Anthem and Centene, that together represent 47 million covered lives. Importantly, we are seeing ISEMBYLD payer approvals on a patient-by-patient basis from commercial and government plans that have yet to issue policies. These approvals so far are independent of patient age, time on SMN-targeted therapy, geographic location, and infusion site of care, whether hospital, independent infusion center, or at the patient's home.
We are also grateful that Cure SMA sent a community-wide ISEMBYLD access letter to U.S. payers, Medicaid officials in all 50 states, and all state governors urging timely, broad access to the first and only muscle-targeted therapy for children and adults with SMA. As we continue to work through reimbursement and access, we are pleased that as of the end of October, 98% of patients with ISEMBYLD prescriptions are coming through Scholar Rock Supports, our world-class patient support program. This enables us to assist the patient in navigating a clear path from prescription to payer approval and initial infusion, and to provide ongoing treatment support.
Given the timing of when patient enrollments have been received, combined with the anticipated 60 to 90 days or longer from prescription to infusion, in this very early stage of launch, we anticipate the majority of patients who are enrolled through October will begin infusions in 2027. We expect steady progress on payer approvals and remain confident that while initial delays and denials are common for any first-in-class rare disease launch, it is a matter of when, and not if, eligible SMA patients will receive ISEMBYLD therapy. Our initial performance across these early indicators reinforce our expectations and confidence in our opportunity to serve a steady and consistent number of new patients for quarters and years to come. I would now like to turn to our launch readiness in Europe and Japan. Starting with Europe, we continue to advance our launch preparations with an initial focus on Germany.
We're executing our U.S. playbook, deepening relationships with key treatment centers, prescribers, and advocates, and we're preparing to rapidly advance reimbursement submissions upon approval. We look forward to a CHMP opinion in the first half of 2027 and a launch in Germany later in 2027, followed by other key countries over time. In Japan, in line with our JNDA submission to PMDA, we are now building out our Scholar Rock team, establishing in-country operations, and advancing our commercial readiness activities as we prepare for a potential launch near the end of 2027. In closing, we are now beginning to deliver ISEMBYLD to SMA patients across the United States, and we look forward to expanding our 50-country operating platform so that we can serve the estimated 35,000 people living with SMA globally who are currently receiving an SMN-targeted therapy.
We are working with urgency, one patient, one caregiver, and one family at a time to deliver on our ambition that every patient who can benefit from ISEMBYLD should have access to ISEMBYLD. With that, I'll turn the call over to Akshay for a closer look at our R&D initiatives. Akshay?
Thank you, Keith, and good morning, everybody. With ISEMBYLD now approved in the U.S., our R&D team is focused on three priorities. First, securing regulatory approvals to enable apitegromab treatment to be available for children and adults with SMA in up to 50 countries globally. Second, executing a lifecycle program for apitegromab, which includes clinical, excuse me, which includes clinical development of the subcutaneous formulation, access for the youngest of SMA patients, and developing it in new neuromuscular indications. Finally, our third priority is progressing SRK-439, the next program from our world-leading anti-myostatin platform. Let me turn first to global regulatory progress. In Europe, in alignment with the EMA, we're very pleased to have resubmitted the apitegromab MAA in early October, just weeks following the withdrawal of our original application.
Importantly, the expeditious resubmission of the MAA includes the alternate fill-finish facility that supported the approval of ISEMBYLD in the U.S., in place of Catalent Indiana. The MAA has now been validated, and the review is ongoing. We continue to engage with the EMA and anticipate a CHMP opinion in the first half of 2027, with an initial launch in Germany following European approval. We're also pleased to announce today that we submitted the apitegromab JNDA for the treatment of children and adults with SMA in Japan. Based on constructive discussions with the PMDA, they agreed that the existing apitegromab data package, including the phase III SAPPHIRE study, are sufficient to support our filing in Japan. We received orphan drug designation for apitegromab in SMA, and notably, our application was accepted under priority review, for which the PMDA has typically targeted an approximately nine-month review cycle.
With the 60 to 90-day process to secure pricing and reimbursement following approval, we anticipate a potential launch in Japan near year-end 2027. Turning now to our pipeline. We're pleased to now be serving initial patients with ISEMBYLD in the U.S. However, our commitment to continued innovation for the SMA community has never been stronger. To this end, we're advancing our high-concentration subcutaneous apitegromab program. This program is designed to provide optionality for the SMA community as a small-volume self or caregiver-administered anti-myostatin antibody. Following the September FDA approval of ISEMBYLD, we're now initiating engagements with regulators, and we plan to provide an update on the development path forward following alignment with FDA and EMA. In terms of reaching the youngest of SMA patients, we continue to have robust enrollment in our phase II OPAL study.
This study is evaluating apitegromab in infants and toddlers with SMA under the age of two who've been treated with an SMN1 targeted gene therapy or who are receiving ongoing treatment with an SMN2 targeted therapy. This study is important because it is anticipated to expand the impact of apitegromab to the full spectrum of patients. Notably, the rate at which this study is enrolling underscores the significant unmet need and the potential for apitegromab in the youngest of SMA patients. Turning now to our next indication for apitegromab, facioscapulohumeral muscular dystrophy, or FSHD. FSHD is one of the most prevalent inherited muscular dystrophies, with approximately 20% of patients becoming wheelchair-dependent. There are no approved therapies for FSHD. In September, we were delighted to announce that apitegromab was granted fast track and orphan drug designations in FSHD by the FDA.
In September, we also announced the commencement of participant dosing in our phase II FORGE study, a randomized double-blind placebo-controlled trial, which is expected to enroll 60 patients. Enrollment is progressing well, and dosing is ongoing. Lastly, we continue to progress the next generation of our anti-myostatin platform with SRK-439, our high-potency, high-affinity subcutaneously administered myostatin inhibitor. We're excited about this program, and dosing in our phase I healthy volunteer study is progressing very well. We expect to have top-line data by year-end and intend to share those with you in early 2027. In closing, we've accomplished what the industry pursued for nearly 30 years, bringing the first approved myostatin inhibitor to patients. Now, we're working with urgency as we leverage our world-leading platform.
Our ambition is to extend apitegromab access to all patients with SMA across our planned 50-country operating platform, whilst also extending this breakthrough to patients with additional rare and devastating neuromuscular diseases. With that, I'll now turn the call over to Vikas to provide an update on our financials. Vikas?
Thank you, Akshay. We are very pleased with the U.S. launch of ISEMBYLD following its FDA approval in September. We remain in a very strong financial position as we continue to invest with discipline. For the third quarter, total revenue was $0.6 million, reflecting initial ISEMBYLD inventory shipments to our specialty network. As we shared previously, we expect to keep inventory at our specialty network to a minimum. Looking forward, as Keith mentioned, in these early days of launch, the time from prescription to infusion can be more than 60 to 90 days on average, leading to steady and consistent growth in revenues over time. As it relates to cost of goods for the third quarter, the cost of inventory manufactured was expensed prior to FDA approval. Total operating expenses for the third quarter were $106.6 million, which included $17.9 million in non-cash stock-based compensation.
Excluding stock-based compensation, operating expenses were $88.7 million. We are pleased that with continued investments associated with our anticipated global launches, we remained disciplined in managing our overall spend. Turning to our balance sheet, we ended the third quarter with cash equivalent, and marketable securities of $413.6 million. In November, we entered into a definitive agreement to sell our priority review voucher for $205 million, which will add significant non-dilutive capital to our balance sheet. The cash is expected to be received upon the closing of the transaction. With the approval of ISEMBYLD, we also now have access to an additional $150 million under our existing debt facility. The strength of our balance sheet reflects the disciplined execution of our plan and provides the financial flexibility to fund our strategic priorities without the need to access the capital markets at this time.
We continue to operate with financial discipline, and our prioritized investments remain focused on four areas. First, supporting the successful launch of ISEMBYLD in the U.S. Second, advancing launch readiness in Europe and Japan as we build the foundation for our planned global 50-country operating platform. Third, strengthening our supply chain to support our expanding pipeline and our anticipated growing global commercial demand for ISEMBYLD over time. Fourth, advancing our highly innovative clinical programs. With that, I'll turn the call back to David. David?
Thanks, Vikas. Scholar Rock is operating from a position of strength, executing with focus, discipline, and urgency as we transition to a commercial-stage company and continue building our foundation to become a global biotech powerhouse. Our U.S. launch of ISEMBYLD is off to a very encouraging start, and as we look at the growing global SMA market, we are working to deliver on our ambition that every patient who can benefit from ISEMBYLD should have access to ISEMBYLD. I continue to be very grateful to our patients and families, the investigators and treating physicians who have partnered with us, Cure SMA, and the advocacy community, and my colleagues at Scholar Rock for what we've accomplished to date. Together, we brought the first muscle-targeted therapy to the SMA community, and now, in the earliest stages of the global launch, beginning in the U.S., we are just getting started.
With that, we will now open the line for questions. Operator?
As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. In the interest of time, please limit yourselves to one question. Please stand by while we compile our Q&A roster. Our first question will come from the line of Eric Schmidt of Cantor. Your line is open, Eric.
Well, thanks, and appreciate you taking my question. It sounds like the patient demand is very substantial, but you are obviously working through some of the payer hurdles that you expected to encounter. Just maybe quickly on the demand side, has the bone fracture warning been any issue at all for you? On the payer side, you mentioned the wins at Anthem and Centene. Congrats on those. Anything specific about the coverage that you could provide on those wins? Thank you.
Thanks, Eric. I will start. Regarding fractures, no. There has been no impact on demand or prescribing patterns, and we see this really as in line with some of the work that you and others in the community have done in holding some sessions with KOLs or treating physicians. So it has had no impact. As it relates to the payers, Keith and I are certainly gratified that Anthem, Centene, this is tremendous progress to have published policies in line with our label this early in launch. It is an extraordinary accomplishment. For more color on that across the wider range of payers, I will turn it over to Keith.
Yeah, thanks for the question, Eric. I just gave two examples of published policies. There are actually more that are out there that are aligned with our label already. I called these out because Anthem is the number two payer in the entire U.S., and Centene is also one of the largest payers in the U.S. As I stated in the prepared remarks, our team has been already able to meet with the payers that cover 90% of covered lives. Trust me, we are out there and are very encouraged by the discussions that we're having. I can tell you that we anticipate additional policies to be aligned with our broad label to be published over the next six months. You ask, can we give you some color around those policies? They're truly aligned with the label. There's not an age restriction to them.
There's not a type restriction to them. There's nothing about ambulatory status in there. It really allows for a policy that can allow access to a broad range of SMA patients.
I would just close by saying all of that is underpinned by the strength of the data that the phase III SAPPHIRE data study had reflected, which is a great basis for these relationships and collaborations with payers.
Our next question comes from the line of Kripa Devarakonda of Truist Securities. Your line is open, Kripa.
Hi. Thanks for taking our questions. This is Alex on for Krita. Congrats on all the progress. This is great. We are all excited about the launch. For us, the 60 to 90 days from script to infusion, do you expect that that will continue up until you get the J-code in April, or could that be trimmed down as more payers establish policies? Thanks.
Yeah. First of all, I think I would just like to make a comment before handing it over to Keith. I think the one thing, we are super excited with the sort of early observations related to the launch. I think the one thing we are heartened by is not only our team's experience in reimbursement and access, but as you might imagine, the 6,600 patients in the U.S. currently on an SMN2 targeted therapy, they and their physicians have already been down this road before. That is why they are on an SMN2 targeted therapy. They understand that certainly initially at approval, these are very sort of common steps to take. But why Keith and I wanted to reiterate on today's call, it is a matter of when and not if these patients on label are able to access ISEMBYLD therapy, the first and only muscle-targeted therapy that has been approved by the FDA.
As it relates to sort of the movement from 60 to 90 or longer to a more shorter steady state, I will hand it over to Keith for his comments. Keith?
Yeah. Alex, thanks for the question. I guess first of all, we are really pleased with the effort of the team to get the application in for the J-code for ISEMBYLD so that we have really the shortest possible wait time until we have the official J-code on April 1st of 2027. You ask, is it going to take until then before some of these timelines start to condense? The answer is there are several factors that lead into that, sometimes greater than 60 or 90 days. The J-code is just one of the contributing factors. As we get more payer policies established, that will help us to decrease the level of denials that we have. It is not going to take away the prior auths, so there is still going to be that step. It is a timely process, okay?
They will have to go through prior auths, just like they do with SMN-targeted therapies. Also, I would call out to you that formulary status in a lot of these 140 treatment centers, it doesn't happen overnight. I'll give you an example. We have some hospitals in the top 140 that have already had P&T committee meetings and included ISEMBYLD onto their formulary, and they are now waiting to have it officially entered into their treatment ordering system so that the product can be ordered. We have other hospitals that they didn't put ISEMBYLD on their P&T committee until after the first of the year. So there's several elements that lead to this.
To give you the long answer, the long answer, a little shorter, is yes, this time will condense over a period of time, and we will get this down to a more manageable. But the 60 to 90 days, not only is this not outside of industry norm, it's accustomed to what I've seen in previous launches.
Great. Thanks so much.
Our next question will come from the line of Cory Kasimov of Evercore. Your line is open.
Hi. Good morning. This is Adi on for Cory. Could you maybe share what share of your enrolling patients are coming from outside of the EAP and ONYX extension population, and how should we think of these different populations going on the commercial drugs? Thank you.
Yeah. I mean, I'll just quickly comment on that. I think Keith and I addressed it. We do have more treatment-naive patients to ISEMBYLD enrolling in Scholar Rock Supports than the patients that are beginning the transition from both our EAP and ONYX in aggregate. And we think that that's reflective of the very broad interest from both prescribers who are going to be new to ISEMBYLD and also patients that are going to be new to ISEMBYLD. Then, with those enrollment forms coming in, the patients are of a diverse background by age, by SMN2 targeted therapy, by disease trajectory, and we're just gratified that our ambition is to make sure across the U.S., the 6,600 patients with SMA that are currently on an SMN2 targeted therapy, that we reach a very high proportion of those patients over time.
I think our early observations are certainly suggestive that we are on that track.
Yeah. I mean, what I would add is I am very encouraged by the fact that the treatment-naive patients outnumber those of EAP. I can tell you that as a commercial leader, I'd be disappointed if I was sitting here reporting to you that the main patients that we're getting in are that we're transitioning clinical trial patients and EAP patients. So I'm pleased with that result. With that being said, we are in the process of transitioning over the EAP patients, but just as they enroll, they go through the same process as every other patient that we've just walked through. You still have those hurdles to overcome with J-codes, and they're part of insurance companies that have not yet established policies. They could be being treated somewhere with the hospital, where the hospital formulary comes into play.
They are going to still experience that same type of delay. For our ONYX patients, they are completing closeout visits with their physicians to conclude that study, and then they will begin enrolling into our program. I would expect you are going to see enrollments from EAP and ONYX patients over the next couple quarters to come. What I do want to call out is I want you to look at the retention rate that we have had with approximately 98% of our TOPAZ and SAPPHIRE patients rolling over into that open-label study, some of them for up to seven years. Now here we are seven years later, and 93% of them remain on therapy. I feel quite confident that we will have strong rollover and retention over the next couple of quarters.
Okay. Thank you.
Our next question will be coming from the line of Tess Romero of JPMorgan. Your line is open.
Hi, David and team. Thanks so much for taking our questions, and we appreciate all the early color here. As you move ahead with the ISEMBYLD launch, what is your latest thinking on the specific metrics that you will be providing consistently here to us beyond revenues? Relatedly, can you share a view of what you might be able to provide on this topic at our conference in January? Thanks, guys.
Thanks, Tess. As Keith and I outlined today, we think it is important to share the progress that we are making across the top 140 SMA treatment centers in the country. As we noted today, we are gratified in just the first six weeks of launch that more than 1/3 of those are already enrolling initial patients. I think it is important to note they are just initial patients as they get started themselves with the process. We think there is a tremendous amount of growth, both in getting deeper in those first more than 1/3 of the 140 top SMA centers. There are more patients to serve there over time. Then, of course, we have a wide range of the other centers that we believe it is just a matter of time. I think that that penetration into those centers is very, very important.
As Keith noted today, it is very important to highlight the covered lives from the payer perspective, and we were certainly gratified to see what we saw from both Centene and Anthem. Of course, you will have much more color on revenues. As we noted, patient infusions only began in October, following the near mid-September launch, and that will be an important metric, I think, for many to focus on as we believe we serve a steady and increasing number of patients for quarters and years to come.
Great. Thank you.
Our next question will be coming from the line of Tazeen Ahmad of Bank of America. Your line is open.
Hey, good morning. A couple questions. Based on the type of patients that you've been starting to enroll, I know it's early in the launch, as we try to think about what the average cost per patient is going to be given the weight-based dosing, you're getting mostly children, you said, but you also have adults coming online. Can you give us some color on how to think about that. Then, based on your language on your prepared remarks about these patients mostly being able to get on drug from October through the rest of the year in 2027, is it logical to think that you might have more of a bolus of sales in the first two quarters of 2027? Thanks.
Yeah, I'll start maybe on the second part of that question, and then I'll hand it over to Keith. We actually think that the reflective demand, the very steady pace of new patient enrollments into the system across a broad range of centers, prescribing physicians, and patients, we actually see this as sort of a steady as she goes, consistently adding new patients quarter- on- quarter, year- on- year, and just a very healthy growth story. I would say that those comments, I think what we just wanted to reflect, is that Scholar Rock Supports has been very busy. As Keith noted, they started on insurance verification shortly after the approval.
But, yeah, we just wanted to manage that if one does the math with the 60 to 90 days, and we think the enrollments that are in-house at Scholar Rock Supports, those patients are going to receive the ISEMBYLD that they want and they deserve. But that you have these sort of typical speed bumps, no stop signs, but speed bumps along the way that can result in initial infusions for more patients being in 2027 than with six, eight weeks to go. I'm not even counting the holidays from November 10th through the end of the year. We just expect more of those patients to get initial infusion in 2027 versus 2026. Regarding the dynamics of weights and what we're seeing patients that are both younger in age, but also the adult patient population, I'll have Keith comment on that. Keith?
Yeah, I guess just to go back on one thing, Tazeen. The question of bolus, I'd actually be more concerned if there was a bolus and then the level of enrollments let up. But as David stated, it's been consistent and steady on a week-over-week basis. We track these things not just on a weekly basis, but on a daily basis here. I actually find it much more encouraging, the fact that we continue this nice pace of enrollments. As far as the type of patients that we've enrolled, we did share that there's more peds than there are adults. That is also the case in the Cure SMA database, which is the largest database in the U.S. for SMA patients, and that is the database that we used to set the price of what a typical patient would cost when we did the launch call.
So, we are closely monitoring where our weight distributions come out as these patients enroll. Obviously, that's something that is involved on the enrollment form. But right now, just as you have in the Cure SMA database, much more peds than there are adults in the database, and as we've said, same here.
Our next question will be coming from the line of Michael Yee of UBS. Your line is open, Michael.
Hey, guys. Thanks. Congrats on all your progress. Maybe just two questions. One on early demand. Maybe David, you guys have said very strong demand, but not necessarily quantified it. Would you say that you have hundreds of patients that have gotten into the access program or hundreds of patients that have filled out start forms? Maybe you could just sort of quantify the early demand for us. That would be super helpful as we build out our early models. And then second question is on subcu. I don't think there was a question asked on that. Do you think you could just do a PK bridging study, or would you need some sort of at least sort of an open-label efficacy study, somewhat similar to how Leqembi had to do that? Thank you.
Yeah. Thanks very much, Michael, and looking forward to being with you shortly at your conference. As it relates to enrollment forms, as we noted, we're not quantifying that, but we did try to provide some perspectives for you all. And we thought one important thing was we had more enrollments in Scholar Rock Supports from treatment-naive patients. So, those patients that have not yet had the opportunity to benefit from the first and only muscle-targeted therapy approved for patients with SMA, as opposed to those patients that are now beginning the transition from both EAP and clinical trial or ONYX patients. And so, that's the extent of sort of providing you guys some perspective, but I think that may be very, very helpful for you. As it relates to the journey for the subcu high concentration program, I'll hand it over to Akshay.
Yeah. Thanks, David. You are absolutely right, Mike. Subcu bridging via PK/PD is a legitimate route to seek approval of a new route like the IV to subcu transition. We obviously are going to make the case robustly with the FDA and other regulators with that as the centerpiece. We have to complete the dialogue now before we report back on the final path ahead. But certainly, that should be a key piece of it. Yeah.
Thank you.
Our next question will be coming from the line of Ritu Baral of TD Cowen. Your line is open.
Good morning, guys. Thanks for taking the question. I wanted to ask just a little bit more about current trends in, I guess, the vanguard of patients interested in ISEMBYLD. How is average weight stacking up against your expectations, and also sort of predominant function? You mentioned they were mostly children, but right now, are you seeing patients on the upswing or more stable patients? Then just a quick follow-up on those non-center of excellence sites beyond 140 that are already prescribing. How would you characterize those sites, and would they, either the patients or the sites, need any special support from the hub to onboard those patients? Thanks.
That's great. Great question, Ritu. I think as Keith was noting, we're pleased that while the larger group of enrollments are coming from pediatric patients, there's a substantial proportion coming from adults. I think it's early to call on sort of weights and dose, but we stand firm with the work that Keith did with Cure SMA, by far the largest database in the U.S. on sort of what the typical patient will ultimately be. Then, we did try to provide a little bit of color on the diversity of patients coming into Scholar Rock Supports by a number of different characteristics, and I'll hand it over to Keith to make those comments.
Yeah. I think that we're very pleased by the diversity of patients that are enrolling into the program, and there really can't paint a patient with a single brush, because I can tell you that the age range is quite a variety from the peds to, we've had enrollments from 60+ year-olds out of community neurologists in rural areas. So, there's quite a diversity of the types of patients that we're getting, and they're really, whether they are still improving on their SMN-targeted therapy or whether they've plateaued or whether they're declining, we've seen each different type enroll into the program. So, really encouraged about that. As far as additional work from the hub, one patient is just an individualized patient because they can even be at the same treatment center, but they have different insurance, which might make them eligible for a different location on where they can be infused.
They might live very close to the key center, but they also might live two hours away, so they want to look for an alternative infusion center. So, this is truly a patient-by-patient basis. That's why we offer Scholar Rock Supports, because we offer that white glove service, not just to help you get enrolled, but to help you all the way through the treatment journey.
Thank you.
Our next question will come from the line of Allison Bratzel of Piper Sandler. Your line is open, Allison.
Hey. Good morning, team, and thanks for taking the question. Thinking about ex-U.S. launches coming up in 2027, could you just talk to launch preparations and expected trends there, and just how you would expect the geographic patient mix to evolve, just given there are more patients on SMN-targeted therapies ex-U.S.? Thank you.
Keith, do you want to talk about launch prep in Europe and Japan? Actually, maybe I'll just start on the mix. As I think you all know, when you look at, by almost any metric, patients on SMN-targeted therapies and/or reported revenues from the three companies that are commercializing those therapies, there's probably a bit more than 1/3 of revenues in the U.S., and nearly 2/3 of revenues outside of the U.S. Given some of the pricing dynamics and the difference in pricing, there tends to be even a higher proportion than the nearly two-thirds of revenues outside of the U.S. of those patients on treatment. That's why this journey that we are taking to reach patients in upwards to 50 countries around the world is so important. We take our mission very seriously.
This is the first and only muscle-targeted therapy for patients with SMA, and we want to reach those patients no matter where they are. As it relates to the launch of preparations in Europe and Japan, I'll hand it over to Keith for his thoughts.
Yeah. Allison, thanks for the question, Allie. First of all, as we've stated, after the EMA approval, after our rapid resubmission, the first country that we can proactively launch in is Germany. I can tell you that that team is already built out, that we have several members of the team that are actually over here with us in Cambridge this week, along with we have a visiting KOL from Germany here this week. We are already working on disease education awareness. We are establishing relationships with those key centers. In Germany, we are permitted to and do have an EAP over there that is currently enrolling patients. So, we're really operating on the U.S. playbook when it comes to Germany.
We've already been building out reimbursement dossiers for other countries in Europe that we will begin to pursue immediately after approval, because we cannot actively promote in those countries until we successfully get reimbursement. With that being said, it also means we're being responsible in how we source these countries, and that would revolve mostly around medical affairs in the countries as opposed to any type of promotional effort until we can be very confident and very close to securing reimbursement. Additionally, before I go to Japan, I'd just like to note that there are other countries over in Eastern Europe, outside of the United States, that we are able to work with based on a U.S. approval and a U.S. label and a U.S. pack. We have a team that is working on the international partner markets.
We are turning over every stone so that we can get to the 35,000 people that are living with SMA and on an SMN-targeted therapy. Lastly, Japan. The team is in the process of being built out. We've got about five employees there right now. Our general manager is hired, and the great work from Akshay's team with regulatory, has us on pace to where we'll be launching in 2027. As you know, Japan is really a key market for SMA. I say that because, number one, after you get your approval from PMDA, you set price within 60 to 90 days, and then everybody is insured. We won't have to go through these policies. Everybody's insured. It's also because this is a rare disease and it falls into the intrinsic category, it's a very low out-of-pocket expense.
We look forward to continuing our work with the KOLs in Japan and preparing for a launch in late 2027.
I will just comment. The way I look at it, U.S. will obviously be a major cylinder firing for a long time. With the mid-September approval, 330 million population country, reimbursement is essentially open season. In Europe, the first market, let us just say second half of year, becomes Germany, 80 million population country. Then, toward the very end of 2027, if all goes well with the review, under priority review in Japan, we pull in another 120 million population country. So, very, very important to have this sequence laid out for us, for both the U.S. and ex-U.S. growth that we expect to be delivering for many quarters and years to come.
Our next question will be coming from the line of Gary Nachman of Canaccord Genuity. Your line is open.
Great. Thanks, and congrats on all the progress. So, anything different you are seeing in the SMN portion of the market with increasing use of High Dose SPINRAZA or potential safety concerns with ZOLGENSMA that might impact you in any way down the road on how ISEMBYLD is used, whether good or bad? There was such a buildup for ISEMBYLD's approval. Is there still a lot more to be done in education and awareness of the importance of muscle function for these patients in the U.S.? Or is it really more just blocking and tackling on the initiation and access that you have been talking about? So, I am curious how you would characterize just the level of awareness at this point for the importance of using something like ISEMBYLD. Thanks.
Yeah, Gary, I will just comment. 93% of patients in that 2026 Cure SMA survey said muscle strength is a need. It was by far the number one need across the population of SMA patients, combined with three-quarters of neurologists saying the ideal way to treat SMA now is by focusing on both the motor neuron and the muscle. Keith, I think, provided a lot of awareness of metrics that suggest there is a tailwind there for us, then it becomes blocking and tackling, which we think is largely all manageable, both with our experience and the experience of the SMA community. So, we are pretty excited about that. Then just quickly on the dynamics, as Keith and I said, the balance across SMN2 targeted therapies is quite nice with consistent with the prescribing patterns.
We see HD SPINRAZA as a net-net positive for us, because anything that can bring needed innovation to motor neuron health is just helpful for us in terms of being able to address the principal organ clinically affected in the disease, which is the muscle. Then finally, I think it's early to tell on ZOLGENSMA. We tend to be extremely neutral with whatever physician and patient's preference is on motor neuron health. Then, of course, ISEMBYLD represents the first and only option for addressing the muscle component of the disease. So we'll keep you apprised, but we're very gratified by these early observations.
Great. Thank you.
Our next question will come from Phoebe Tan of Jefferies. Your line is open.
Hi. Thank you for taking my question. I just had a couple on the patient population. So, are your patients currently leaning towards sort of a more similar enrollment to what we saw in phase III, so non-ambulatory SMA patients in 2 - 12-year-olds? Additionally, how many additional patients do you expect to unlock with the subcu formulation and the phase II OPAL study for the two-year-olds and younger? Thank you.
Thanks, Phoebe. We will be seeing you soon. I will just quickly say, we see the enrollments in Scholar Rock Supports representing label more than the phase III trial, and we are gratified by that. It is really, the volume and the breadth has been very encouraging. Keith can comment on what the subcu might offer somewhere down the line, but we sure are, again, encouraged by what the ISEMBYLD that is approved, the IV version, every 28 days is going to be able to offer to the community. Keith?
Yeah. I guess I would first say that, as we have said, the breadth of the patient type that we are enrolling is so much broader than what we really see in the phase III. So, I already referenced a patient that was greater than 60 at a community neurologist. That is not the only person of age that has been enrolled in the program. So, no, we are not seeing just the 2- 12, and I would not even say that 2- 12 is dominating the enrollment. As far as ambulatory to non-ambulatory, in the study, we studied non-ambulatory. That is not in our label, and we are seeing these enrollments that are much more consistent to what we see in label.
Now to subcu, I think that the unmet medical need in SMA that exists today and the fact that we are the first and only muscle-targeted therapy for the majority of people that are suffering with SMA, they are going to want to utilize ISEMBYLD IV Q4 weeks because of the difference that it can make and the fact that right now, they have limited function, which can also limit their independence. When we have a subcu program available, do I think we would have switch-overs? Yes. Is it possible that we would actually see additional patients? My answer is yes. I say that because you can see where EVRYSDI has expanded the market because they are an oral therapy, and although they did not hit stat sig on the Hammersmith Scale, they are still the largest-selling SMN-targeted therapy that exists, and that is partially because of convenience.
The subcu that we are able to deliver that could be potentially administered at home by a caregiver, that could open up a convenience that we think could even grow the adult population for ISEMBYLD.
Overall, just a complete plan around life cycle management that we think gives us plenty of legs of growth for many years to come. Maybe one more final question.
Our next question will come from the line of Basma Radwan of Leerink Partners. Your line is open, Basma.
Thank you. Good morning, and congrats on the progress, and thank you for taking my question. I know it's early, but any commentary you could provide to us about the prior auth approval rates? In case of denial, what is the key contributor to the denial? Is it the patient criteria not being similar to the clinical trial population or something else? How long does it take for the appeal process really to complete?
It's a great question, Basma. There's a lot of kinetics between enrollment form to ultimate infusion. I think you're highlighting that. Keith and I see right now, probably the number one reason why there might be a denial is because ISEMBYLD's not in the system, and there's not a medical policy, and they need to kind of figure out patient by patient how to deal with it. I think that's actually kind of gratifying to us and why we see this as a matter of when and not if those patients on label in the program are going to receive coverage and reimbursement for ISEMBYLD. Keith?
Yeah. I would just call out on the prior auth, remember, this is not exclusive to ISEMBYLD because we're new. Your SMN-targeted therapies, if you look at the Cure SMA data, 98% of the time, there is a prior auth that is required for them to go on therapies that have been out and available for as many as 10 years now. It's not something that I think that's going to go away. I think it's something that you're going to see improvement over time as there's a better understanding of what is being required from each of the various insurance companies from a prior auth and the ease and the ability to fill this out. Remember, though, this SMA community has not only been familiar with prior auths, and I'm talking about the healthcare professionals, but also the patients and the caregivers, right?
They are familiar with having to deal with prior auths. They're familiar with having to deal with denials, and they also are familiar still to this day, no matter how long they've been on an SMN-targeted therapy, about being reauthorized every 6- 12 months. This is a community that is very persistent from both the healthcare side and the patient side.
I guess what I would end with is, we're facing the dynamics that are quite typical in a launch, and we will work through this, and we've got a great resource to do so in the SMA community, but also in my Scholar Rock teammates, because this team has been built on people that work and have worked in rare disease for many a years, and you know that you have to fight for each and every patient to get through the system and ultimately be able to benefit from product.
Maybe in closing, there just hasn't been anything on the access side that has been unanticipated on our side. It's sort of steady as she goes, and again, we're very encouraged by these early metrics and early observations here in the launch. We'll keep everybody apprised. Thank you all for your questions. We'll hand it back to the operator.
And this concludes today's program. Thank you for participating. You may now disconnect.