Sarepta Therapeutics Inc

NASDAQ:SRPT

Earnings Call Analysis

Sarepta Reports Profitable Quarter with ELEVIDYS Launch

Sarepta Therapeutics saw a remarkable year in 2023, celebrating their collaboration with Roche which led to substantial revenue growth from $22.5 million in 2022 to $31.7 million. This boost was driven in part by $9.2 million from manufacturing commercial ELEVIDYS supply. A first in profitability was achieved in Q4 2023, reporting a net income of $45.7 million, significantly up from a net loss of $109.2 million in the previous year. Non-GAAP net income stood at $86.6 million. Cost of sales rose to $44.2 million due to increasing demand and new ELEVIDYS sales. R&D expenses fell by $18.3 million, reflecting decreased manufacturing expenses. SG&A expenses rose due to professional services and personnel costs. Sarepta expects to maintain high profitability throughout the year following the successful ELEVIDYS launch.

Sarepta Overcomes Expectations with Gene Therapy Launch and Revenue Growth

In the story of Sarepta's latest achievements, the headlining chapter is the triumphant launch of its gene therapy, ELEVIDYS, which treated patients with Duchenne muscular dystrophy. Not only did this new treatment surpass expectations by generating roughly $200 million in revenue, but it also helped elevate the company's net product revenue to over $1 billion in 2023, marking a seminal moment in Sarepta's history and a promising entrance into 2024 with considerable momentum.

Regulatory Advancements and Revenue Metrics

Sarepta has seen significant regulatory success, as the FDA granted accelerated approval to ELEVIDYS, designed for pediatric patients with a certain genetic mutation. As the company pushes forward, they've filed an efficacy supplement, hoping to expand its patient reach. Net product revenues tell a story of demand increase for Sarepta's products, with $131.2 million from Levites and a PMO exon skipping franchise bringing in $233.8 million for the fourth quarter of 2023.

Cost of Sales and Operational Efficiency

While revenue soared, cost management remained under scrutiny. The fourth quarter witnessed an increase in cost of sales to $44.2 million, mainly due to the rise in demand and associated royalty payments for ELEVIDYS. Simultaneously, R&D expenses saw a decrease of $18.3 million year-over-year, thanks to reduced manufacturing expenses and the absence of certain upfront costs. This decrease highlights attention to cost efficiency and budgeting prudentness in the face of expansion.

SG&A Expenses and Profitability Achievement

General and administrative expenses increased to $131.7 million in the fourth quarter, reflecting investments in professional services and workforce growth. Notably, this period celebrates Sarepta's landing into profitability for the very first time, a landmark in the company's financial chronicle. A solid cash position of $1.7 billion emphasizes a strong balance sheet, poised to support further innovation and scaling.

Forecasting and Future Manufacturing Horizons

While Sarepta has not provided explicit guidance for its PMO therapies, its positive outlook is underpinned by double-digit growth in the previous year and minimal cannibalization anticipated from ELEVIDYS. Looking to 2024, confidence remains high. On an operational front, Sarepta is working on advancing manufacturing capabilities that could significantly enhance capacity and reduce costs. While this 'moonshot goal' is audacious, it reflects the organizational ethos of aiming high and delivering strong results, positioning Sarepta as an enthusiastic pioneer in gene therapy manufacturing.

Earnings Call Transcript 2023-Q4

[Unknown Executive]

[Audio Gap]

These involve risks and uncertainties, many of which are beyond Sarepta's control. Actual results could materially differ from these forward-looking statements, and any such risks can materially and adversely affect the business, the results of operations and trading prices for Sarepta's common stock. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent annual report on Form 10-K filed with the SEC as well as the company's other SEC filings. The company does not undertake any obligation to publicly update its forward-looking statements, including any financial projections provided today based on subsequent events or circumstances. And now I'll turn the call over to our President and CEO, Doug Ingram, who will provide an overview of our recent progress. Doug?

[Douglas Ingram, executive]

Thank you, Fran. By the way, everyone, it was France birthday yesterday. So happy birthday Fran and good afternoon, everyone, and thank you for joining Sarepta Therapeutics Fourth Quarter 2023 Financial Results Conference Call, led by an exceptional launch of elevates and continuing performance of our approved PMOs EXONDYS, VYONDYS and AMONDYS, we announced this afternoon, another strong quarter of full year growth and quarterly growth as we serve the patient community. As we preannounced in January at the JPMorgan conference, fourth quarter total net product revenue came in at $365.1 million, growing some 55% over the same quarter of prior year and full year net product revenue achieved $1.14 billion, growing 36% over the prior year.

In addition to continuing strong performance among our 3 approved therapies, ELEVIDYS performance was particularly impressive and reflects first-in-class launch excellence. Notwithstanding a label limited to 4- and 5-year-olds representing only about 3% or so of the total Duchenne population. ELEVIDYS net product revenue was $131.2 million for the quarter, and over $200 million for the full year. I'm exceptionally proud of the team's performance here, which speaks to our level of preparation and attention to detail, expert understanding of all aspects of launching innovative rare disease therapies and, of course, our passion for bringing a better life to those living with Duchenne. Dallan Murray, our Chief Customer Officer, will speak to this in his remarks shortly. We also continue to exercise the discipline of a fully integrated commercial stage biotech organization. We were profitable on a GAAP basis in the fourth quarter, having achieved non-GAAP profitability in the third quarter of 2023. And we exited 2023 with approximately $1.7 billion of cash, cash equivalents, restricted cash and investments on our balance sheet.

Our CFO, Ian Estepan, will provide more color on financial performance shortly. We also advanced our pipeline in the fourth quarter. In the fourth quarter, we submitted a BLA supplement for ELEVIDYS with the goal of both expanding the label by removing age and ambulation restriction and transitioning our approval from accelerated to traditional. And in February of this year, the FDA accepted our BLA supplement for review and set June '21 as our target review completion date. In the fourth quarter, we also commenced EMERGENE, our trial for SRP-9003 to treat LGMD Type 2E. Also in January of this year, we announced the positive results of our trial MOMENTUM Part B, investigating the use of our next-generation peptide conjugated PMO, SRP-5051 to treat Duchenne patients that are exon 51 amenable. Dr. Louise Rodino-Klapac, our Head of Research and Development, will provide more color on our pipeline progress shortly.

In 2017, starting with 1 approved therapy, million in sales, a modest pipeline, a short cash runway and a little more than ambition and grit, we set out to build a sustainable, mature biotech organization, improve the lives of the greatest possible number of Duchenne patients along the way and to become the leaders in the use of RNA and gene therapy to treat rare genetic disease. If we are successful in our plans this year, we will have achieved that vision. From there, we can and we will expand our ambition and relying on our scientific and financial strength, we intend to advance our internal pipeline but also to bring in external innovation to grow from here, not incrementally but in great multiples. In short, 2024 is going to be a very important year. And with that, I will turn the call to our Chief Customer Officer, Dallan Murray. Dallan?

[Dallan Murray, executive]

Thank you, Doug, and good afternoon. The fourth quarter of 2023 represented a strong finish to an already impressive year as the team generated over $1 billion in net product revenue, a milestone for Sarepta. As previously noted, net product revenue for 2023 totaled $1.14 billion, consisting of roughly $945 million from our PML franchise and $200 million from the launch of Elevate, the first gene therapy approved for patients with Duchenne muscular dystrophy. Each of these accomplishments stands on their own merits and the performance of both surpassed our internal projections and external consensus. In the seventh year of our PMO franchise, we again grew net product revenue by double digits from the nearly $844 million in net product revenue from 2022. As with previous years, we delivered this growth organically without taking price increases on any of our approved PMO products. As such, this growth represents an increase in the number of patients we are serving, reflecting our commitment to the Duchenne community.

Turning to ELEVIDYS. We're extremely pleased with the launch of execution, exceeding our own lofty expectations. In fact, the $200 million in net product revenue surpassed the combined 2023 revenue of the other 5 gene therapy launches from the past 18 months, remarkable given the ELEVIDYS approval occurred just this past summer. The success of ELEVIDYS shows that gene therapy can be commercially viable, providing hope for those patients with Duchenne and for all those with genetic conditions with unmet need. While revenue is how we quantify the success of this launch externally, we measure ourselves on how we support patients. Our preparation was deliberate and intense and our process was put to the test with the narrow label. The team responded to that challenge with an incredible commitment to supporting all eligible 4- to 5-year-old patients. This was our fourth Duchenne launch, and our knowledge and experience played a significant role in how the team rallied, worked together and rapidly supported those patients who are approaching their sixth birthday and who are at risk of becoming ineligible for therapy, ensuring no eligible patients are left behind is what motivates us.

Let's now review the results from the fourth quarter, starting with ELEVIDYS. Net product revenue for the quarter was roughly $131 million. This represented a nearly 90% increase over Q3. We are pleased with our penetration into the very small and narrow segment of the Duchenne population. This 4- to 5-year-old label has presented a number of unique executional challenges that are relevant moving forward. Firstly, a significant proportion of the patients in this age group are not yet diagnosed. Given that the average age of diagnosis is around 5 in the United States. Secondly, those who are diagnosed have not had a lot of time to be fully educated about Duchenne, which means the patients and families need to understand that diagnosis, become aware of therapy options go through a more involved and longer pretreatment process than the PMOs, One example of this being antibody testing. And on top of this, the patients must also secure access to ELEVIDYS in this very short time window. Our team has found themselves in a race against time to help these patients.

And finally, the relatively small number of diagnosed 4- to 5-year-old patients results in a situation in which we will be working through this prevalent population quickly within the first half of the year. On the flip side, many of these dynamics are reversed once patients have transitioned over to the decline phase of the disease. This is illustrated by our real-world experience with the PMLs where we see a larger proportion treated in the older age groups, which is on top of a larger diagnosed patient pool. Because of all this, we do not expect to see significant additional growth within the existing population through the first half of this year. Notably, however, by the time of label expansion, we expect to have cleared the way for those older patients to get dosed as rapidly as possible upon eligibility. I would caution analysts therefore, to not use this current younger population as a frame of reference for our market potential in the overall population. The team is preparing as we speak, for a broad label with a focus on building upon the successful launch execution to date, and we have the access and capacity in place to execute successfully on any broader label scenario.

Let's now take a look at the PMO franchise as a whole. As previously mentioned, 2023 net product revenue of $945 million exceeded our full year guidance of $925 million. This performance represents solid revenue growth across all 3 brands, in fact, both VYONDYS 53 and AMONDYS 45 continued their double-digit growth trajectory. Looking now at the fourth quarter of 2023, the team delivered roughly $234 million in net product revenue. This is flat versus Q4 of 2022 net product revenue of roughly $236 million. As you may recall from our Q4 2022 earnings call, we cautioned around keeping the guidance of $925 million for the year due to an increase in the quarter-to-quarter lumpiness that we were observing at that time. Looking now in retrospect, it's clear the PMO has performed exactly as we expected and guided. And finally, the performance we just discussed in our PML business was achieved despite the incredible effort on the Elevates launch. Notably, we saw minimal impact on our PMO business from elevates cannibalization in 2023, given the narrow age range.

In closing, in 2023 and Sarepta set a new standard for gene therapy launches with elevates. We beat external expectations and delivered roughly $200 million. Equally important, we continue to increase the number of patients we support with our PMOs globally. I continue to be immensely proud of our mission-driven team. Combining our PMO and gene therapy businesses we exceeded $1 billion in net product revenue for the first time, and we have entered 2024 with momentum. And with that, let me turn the call over to our Head of R&D, and Chief Scientific Officer, Dr. Louise Rodino-Klapac. Louise?

[Louise Rodino-Klapac, executive]

Thanks, Dallan. 2023 was a year of great accomplishment for Sarepta for the advancement of science and for the health and well-being of patients living with rare disease. 2023 will also be remembered as being a defining moment in genetic medicine. In June 2023, the FDA granted accelerated approval to ELEVIDYS, first gene therapy to treat Duchenne muscular dystrophy. Since that time, we've been successfully treating ambulatory pediatric patients aged 4 through 5 years with Duchenne who have a confirmed mutation in the DMD gene. And then just about 2 weeks ago, and as Doug mentioned, we were thrilled to announce that the FDA accepted and filed our efficacy supplement for ELEVIDYS. whereby they will now evaluate broadening the approved indication of ELEVIDYS by removing age and ambulation restrictions and converting the ELEVIDYS accelerated approval to a traditional approval. Should we receive accelerated approval for aluminas in the non-ambulant population in the United States, our ENVISION study, also called SRP-9001-303 and will serve as our confirmatory study for this population. Envision is a global, randomized, double-blind, placebo-controlled 2-part study, evaluating the safety and efficacy of delandistrogene moxeparvovec gene therapy in nonambulatory and older ambulatory individuals with Duchenne. This study is ongoing with all remaining patients being enrolled outside of the United States.

With U.S. enrollment completed and the remaining 85% of recruitment occurring ex U.S., we are confident in our ability to complete this trial. Moving now to our limb-girdle muscular dystrophy or LGMD programs. On January 16, we announced that screening was underway and study SRP-9003-301, also known as the EMERGENE study. We are pleased to not share that the first patient has been successfully dosed in that study. To remind you, EMERGENE is a Phase III multinational open-label clinical trial of SRP-9003 and for the treatment of limb-girdle muscular dystrophy type 2E or beta-sarcoglycanopathy. The primary endpoint of emerging is expression of beta-sarcoglycan, which is an extremely important endpoint for this program. for the other circiclycenopathies, including LGMD2D and LGMD2C and for the field of gene therapy. I'll explain why.

Beta cycloglyconopathy is characterized by a mutation of the beta sarcoglycan gene, which sits in a complex of a membrane called the sarcoglycan complex and is important for function and for preventing muscle damage during contraction. The sarcoglycan complex is a subcomplex of the dystrophin-associated protein complex or DAC. A defective sarcoglycan protein results in loss or reduced expression of the other sarcoglycans as well as other proteins in the complex such as dystrophin. Therefore, by restoring the missing proteins, such as beta-sarcoglycan, we were able to restore that functional complex at the membrane and thereby restore function to the muscle. Further, earlier this month, I had the opportunity to participate in the Speed Foundation's LGMD scientific workshop, which also featured officials from FDA, including Dr. Mark and [indiscernible] as well as patients, caregivers and clinicians among others. The key takeaways from the workshop included the perspective that traditional trial designs are not suitable for certain types of LGMD and that to ensure these therapies have the best chance of success, the totality of evidence must be considered. Doctors Mark and [indiscernible] also expressed their strong support for regulatory flexibility and a higher tolerance for uncertainty for rare diseases, such as LGMD when you're replacing the native protein as well as support for surrogate endpoints for gene therapies.

Currently, no treatments exist to effectively treat LGMD2E or the other LGMD. The EMERGENE study, which will enroll 15 participants who are ambulatory and nonambulatory, it is 4 and older, not only holds great promise for individuals suffering from LGMD2E but will lay the foundation for our other LGMD programs as well as provide a viable regulatory pathway that supports the development of future gene therapies for rare and ultrarare diseases. These data, combined with positive expression and functional data shared from our initial LGMD2E study, SRP-9003 101, which is also published in Nature Medicine earlier this year and our VOYAGE study, SRP-9003-102, which establishes safety experience across a broader patient population. Third, together as totality as evident. As a reminder, VOYAGE is a Phase I study evaluating SRP-9003 for the treatment of LGMD2E in patients ages 18 and older in the ambulant population and ages 4 to 50 in the non-ambulant population. The primary endpoints are safety and change in beta-sarcoglycan expression. We expect to have the clinical results this year.

Moving now to our RNA platform. We were also pleased to recently announce positive results from Part B of our MOMENTUM study, the SRP-5051201. Based on the data we've generated to date, we believe SRP-5051 represents a best-in-class therapy from an efficacy perspective. MOMENTUM is a global multi-ascending dose clinical trial of SRP-5051. Our next-generation peptide phosphorodiamidate morpholino older treatment, the patients with Duchenne were amenable to exon 51 skipping. As previously discussed and based on these results, we believe we have a path forward to an NDA and are planning a meeting with the FDA to discuss an accelerated approval. We anticipate that this meeting will occur in the third quarter of 2024. Regarding our post-marketing studies for the PMOs, as mentioned, we completed enrollment in the ESSENCE trial, our post-marketing requirement for golodirsen and casimersen. As a reminder, [indiscernible] is a 2-year study and is due to read out in early 2026. In addition, we are pleased to have completed enrollment in our MISSION Study, our dose-ranging post-marketing commitment for EXONDYS.

Mission is a randomized double-blind safety and efficacy dose-finding study comparing the approved dosage of eteplirsen, 30 mg per kg weekly through a dosage that provides significantly higher exposure up to 200 mg per kg weekly. Mission is a 2-part Phase III study. It was fully enrolled in October 2023 with 160 patients. We remain committed to rapidly and diligently advancing missions and sharing data as soon as it becomes available. In conclusion, the months ahead are filled with great promise to advance our mission and serve patients around the world living with rare disease. I will now turn the call over to Ian Estepan for an update on our financial results. Ian?

[Ian Estepan, executive]

Thanks, LRK. Good afternoon, everyone. This afternoon's financial results press release provided details for the fourth quarter of 2023 on a non-GAAP basis as well as a GAAP basis. Please refer to our press release available on Sarepta's website for a full reconciliation of GAAP to non-GAAP financial results. Before we get to the results, I just wanted to flag that beginning in the fourth quarter of 2023 and amortization of in-license rights and income tax expense or benefit are no longer excluded from non-GAAP results. The company has added income tax effect of adjustments, which represents the estimated income tax impact of each pretax non-GAAP adjustment based on the applicable effective income tax rate. Non-GAAP financial results for the fourth quarter and full year 2022 have been updated to reflect this change for comparability purposes. So for the 3 months ended December 31, 2023, the company recorded total revenues of $396.8 million, which consists of net product revenues and collaboration and other revenues compared to revenues of $258.4 million for the same period of 2022 and an increase of $138.4 million.

Net product revenue for the fourth quarter of 2023 from Levites was $131.2 million. net product revenue for the fourth quarter of 2023 from our PMO exon skipping franchise was $233.8 million compared to $235.9 million for the same period of 2 million for the fourth quarter of 2023, individual net product sales were $131 million for EXONDYS 51, $69.9 million from AMONDYS 45 and $32.9 million for VYONDYS 53. The increase in net product revenue primarily reflects increasing demand for our PMO products as well as net product revenue associated with sales of ELEVIDYS. In the quarter ended December 31, and in 2023, we recognized $31.7 million of collaboration and other revenues compared to $22.5 million for the same period of 2022. This revenue primarily relates to our collaboration arrangement with Roche.

For the quarter ended December 31, 2023, the company recognized $9.2 million of contract manufacturing collaboration revenue associated with multiple batches of commercial ELEVIDYS supply delivered to Roche with no similar activity ended December 31, 2022. The reimbursable co-development costs under the Roche agreement totaled $23.5 million for the fourth quarter of 2023 compared to $51.7 million for the same period of 2022. On a GAAP basis, we reported net income of $45.7 million or $0.49 per basic and $0.47 per diluted share and a net loss of $109.2 million or $1.24 per basic and diluted share for the fourth quarter of 2023 and 2022, respectively. We reported non-GAAP net income of $86.6 million or $0.82 per diluted share in the fourth quarter of 2023 compared to a non-GAAP net loss of $53.6 million or $0.61 per diluted share in the fourth quarter of 2022.

In the fourth quarter of 2023, we recorded approximately $44.2 million in cost of sales compared to $30.8 million for the same period of 2022 and the increase in cost of sales primarily reflects increasing demand for our PMO products, an increase in royalty payments due to ELEVIDYS sales in 2023, with no similar activity in 2022 and write-off of certain batches of our products not meeting our quality specifications in the 3 months ended December 31, 2023, with no similar activity for the same period of 2022. On a GAAP basis, we recorded $195.5 million and $213.8 million in R&D expenses for the fourth quarter of 2023 and 2022, respectively a year-over-year decrease of $18.3 million. The decrease is primarily due to a decrease in manufacturing expenses and upfront milestone and other expenses. On a non-GAAP basis, R&D expenses were $165.1 million for the fourth quarter of 2023 compared to $186.8 million for the same period of 2022, a decrease of $21.7 million.

Now turning to SG&A. On a GAAP basis, we recorded approximately $131.7 million and $120.5 million of expenses for the fourth quarter of 2023 and 2022, respectively an increase of $11.2 million. The increase was driven primarily by an increase in professional services and compensation and other personnel expenses, partially offset by a decrease in stock-based compensation. On a non-GAAP basis, the SG&A expenses were $105.7 million for the fourth quarter of 2023 compared to $86.6 million for the same period of 2022, an increase of $19.1 million. On a GAAP basis, we recorded $15.7 million in other income net for the fourth quarter of 2023 compared to $5.5 million for the same period of 2022. The change was primarily due to an increase in the accretion of investment discount net due to an increase in interest rates. We had approximately $1.7 billion in cash, cash equivalents and investments and long-term restricted cash as of December 31, and in 2023. So to conclude, we're incredibly pleased to achieve our first quarter of profitability. From a GAAP perspective, it is impressive to reach this milestone in just the second quarter of the ELEVIDYS launch and highlights the leverage in our business. for the reasons Dallan outlined, there may be some lumpiness on the bottom line in the first half. That said, with an expansion of the label, we expect to be highly profitable for the full year. Also, as I previously noted, in preparation to serve the community in the event of the label expansion we are continuing to ramp our manufacturing of elevates. This continued investment will be apparent in the first quarter financials and the remainder of the year. We are thrilled to have the resources on hand to continue to build the inventory needed to deliver elevates to the Duchenne community. And with that, I'll turn the call back over to Doug to start the Q&A. Doug?

[Douglas Ingram, executive]

TThank you very much, Ian. Shannon, let's open the call for questions.

[Operator]

[Operator Instructions] Our first question comes from the line of Gena Wang with Barclays.

[Huidong Wang, analyst]

Thank you I think operator, your voice was cut off, so I don't know how many questions I can ask. I just ask 2 very quick questions. So one is ELEVIDYS. For the proposed label, was that based on FDA feedback or was it purely from Sarepta? And the second, regarding the emerging Phase III study in Lingerdo2E. Was it confirmed with the FDA that 15 patients would be sufficient? And what protein level will be approvable?

[Douglas Ingram, executive]

Yes. Thank you very much for your questions. For the future, it is 1 question for once, but I appreciate your questions. Let me answer them. So the basis for our request to expand the label by removing both the age and adulation restriction. That is driven by the science. I want to be very clear about that. We're in the midst of a review. We're very -- we're pleased with the progress of the review so far, but it's too early right now to give you a substantive view on the division's perspective on that. But our view is that the science and the totality of the evidence supports the label expansion that we've asked for, and it's the right answer from our perspective. It's the right answer from the science. It's the right answer from a policy perspective. And most of all, it's the right answer for patients living with Duchenne for districts, which I hope will be all of our North star in this regard.

With respect to EMERGENE or EMERGENE, I should say, that -- the protocol for that has been shared with and reviewed with by the FDA, and they have on the basis of there were discussions, including the end of the study, given us their blessing to commence that study and we'll provide additional information on the level of expression likely to predict the clinical benefit at a later date. I would note in our prior studies, we've got 2 cohorts. We've seen very robust expression of the [indiscernible] protein, the absence of which is the sole and exclusive cause of the degeneration in patients who have LGMD type 2.

[Operator]

Our next question comes from the line of Tazeen Ahmad with Bank of America.

[Tazeen Ahmad, analyst]

I just wanted to get a sense as you look for the expansion of label and how to model COGS, especially as more patients get on therapy over time and the weight of the patients presumably will go higher as you get to older patients? What's the reasonable range of COGS that we should be assuming?

[Douglas Ingram, executive]

Yes. Ian, I'll turn this to you.

[Ian Estepan, executive]

Sure. So from a cost perspective, we've been pretty clear that we're targeting 80% obviously from our financials that we reported today. You see it's much higher than that. But over time, as heavier patients get on the therapy and obviously, our pre-expense inventory is exhaustive you'll see the COGS obviously starts to increase and our margins to start to decline more to that 80% range, which we've been guiding. Obviously, we can't give complete clarity around that because we have a suspension, which could be coming online with a much higher yielding process and time for some of the old or heavier patients to be coming on which would offset their weight. So as we said over time, you see some erosion of the margin from where we currently are, but modeling it around 80% is probably reasonable.

[Operator]

Our next question comes from the line of Joseph Schwartz with Leerink Partners.

[Unknown Analyst]

This is Will on for Joe. Congrats on the great quarter here. So one question for us in manufacturing with the recent acquisition of Catalent by Novo and the expected exploration of your agreement with Catalent at the end of this year. How are you guys thinking about manufacturing moving forward -- and then in terms of capacity, the potential for an expanded label this year, are there any potential for supply constraints in the near term?

[Douglas Ingram, executive]

Yes, essentially for your questions. Well, first of all, I think there might be a misunderstanding of some sort. Let me be very clear. Our agreement with Catalent does not end at the end of this year. We have a long-term relationship with Catalent. They've been very good partners of ours. So there will be, from our perspective, no impact from the acquisition of Catalent by Noble Holdings as we understand it, Noble Holdings would be acquiring the entity as a whole, the GLP-1-related manufacturing, I think, is going to be sold down to Novo Nordisk and then the Novo Holdings will hold the rest of Catalent and it'll be run the way it's run today. And we've had -- I had had direct discussions with the senior management at Catalent. I'm quite confident that it is business as usual with them. So we're feeling very good about that. And generally, from a supply perspective, I will say what we have done together over the last in 2018 at the beginning of this journey from a manufacturing and CMC perspective would be nothing other than miraculous if it wasn't for the fact that it's science and hard work driven. As we sit here today, we're doing a really brilliant job of serving the community, and we'll be continuing to do a brilliant job of serving the community over the course of this year with our partner, Catalent and we're feeling very good about where we are.

[Operator]

Our next question comes from the line of Gil Blum with Needham & Company.

[Gil Blum, analyst]

So I know this may be knowable. But can you remind us what the population divided between ambulatory and nonambulatory patients? And what is kind of the median age for loss of ambulation?

[Douglas Ingram, executive]

So I can give you the broad coke. It is about every neo logically about 50-50 between ambulatory and nonambulatory patients. And Dallan, do you have the recent estimates of the of ambulation.

[Dallan Murray, executive]

You cut out there for a second. Did you say the diagnosed patients?

[Douglas Ingram, executive]

Now I said what is the average age of loss of ambulation.

[Dallan Murray, executive]

Average age of loss of ambulation, I think Louise will probably have better data than me, but it would be -- depending on different publications in the 11% to 12% range. Louis, is that sound right for?

[Louise Rodino-Klapac, executive]

Yes. Some are slightly earlier. To your point, there are some differences.

[Operator]

Our next question comes from the line of Brian Abrams with RBC Capital Markets.

[Unknown Analyst]

This is [indiscernible] on for Brian. So maybe I'll ask 1.5 questions, if that's okay, not quite so. So I guess, can you clarify the application process with respect to ELEVIDYS, I guess, is the conversion to a full approval and the label expansion, 2 separate questions before the FDA that have potentially separate time lines, reviews, discussions around them? Can they be separated? And then I guess just related to that, you mentioned in the prepared remarks you're thinking through broad label scenarios. So -- and you mentioned if you get an accelerated approval in the non-ambulatory setting, I guess, is that part of those scenarios? Is that something you've heard from the FDA? Or is this just preparing for all the possibilities?

[Douglas Ingram, executive]

So a couple of things. Yes, there are essentially 2 issues at the agency at the same time. One is modifying the label to expand the label and to provide access to a much broader population of patients and as we said that there's repeating our BLA supplements requested the removal of all Asian ambulation related restrictions from the label because we believe that's founded on science. And of course, the second question then is this -- the view that we have satisfied the requirements for our confirmatory trial and the entire approval should be translated from accelerated to a traditional approval. There are many different scenarios there. There's obviously going to be dialogue about the breadth of the label? And then, of course, there'll be the dialogue about what portions of that are confirmed for traditional approval and what portions in that are confirmed for will remain an accelerated approval -- so there are many iterations. We have a strong view on what we think the science justifies. So first, from an administrative perspective, the time lines are identical.

So we have a target completion date that is for both of those issues. So we'll address both of those issues with June 21. And we're very pleased with June 21, as you know, because we had been guiding people to end of August from a from that perspective. On the substantive issues or what's going to happen. And the review that's going to be subject to the review and we're in the early days. Again, I'd say we're very pleased at least with the engagement of the division thus far, but we have more work to do and more discussions to be had and I don't want to overpromise before the end of this. I will also say there are a lot of different iterations from our perspective. Priority #1 is the broadest possible label. So as between the 2 issues that we're discussing, we are first and foremost focused on the broadest possible label, given the potential of access and hopefully a better life the greatest number of patients. And then, of course, we also -- it's important to us, but the secondary issue is translating this from accelerated to traditional and the breadth of that will be a separate discussion. But we have more work to do and more discussions and work to do with the agency and June '21 will be our return date on all of that.

[Operator]

Our next question comes from the line of Kostas Biliouris BMO Capital Markets.

[Konstantinos Biliouris, analyst]

Congrats on the impressive progress. So 1 quick question from us. If we assume that your label will expect levies used to ambulatory patients only for all 80s. How straightforward would it be for physicians and importantly, payers to clearly determine whether someone is ambulatory or not, given that patients are losing copulation progressively -- so there may be a state where the ambulation status is unclear. So would it be clear for physicians and payers to determine if someone is eligible or not.

[Douglas Ingram, executive]

Okay. Thank you very much for your question. First, let me be clear. I resist the assumption that we've been able to get ambulatory alone, of course, because we are, at this point, seeking the removal of the ambulatory restrictions. But to your point, ambulation is in the label today. And the question then is what is -- how do the physicians determine what angulation means? The short answer is that, that is left to the medical judgment of physicians, but there is good guidance in medical practice for that. It is based on functional assessments and functional tests. There are well-defined approaches probably the most common perhaps the most gold standard approach is the definition from synergy, which is that there is a patient reported continuous use of a wheelchair without ambulation. And then that is verified by the physicians, by the inability of the patient to walk meters unassisted. So that would be a typical functional assessment that a physician would use to determine ambulatory status. So this isn't an enormously difficult functional assessment and conclusion to make by physicians.

[Operator]

Our next question comes from the line of Neena Bitritto-Garg with Deutsche Bank.

[Neena Bitritto-Garg, analyst]

Just a follow-up on the last question. Can you just remind us what data was included in the filing on patients with -- that are nonambulatory, if any, just to kind of clarify that.

[Douglas Ingram, executive]

Yes. We had data from children up to 20 years old from a separate study that we go study 103 that went in with it. We obviously also have an ongoing study Envision, which is a study for non-ambulatory patients. Now that is an ongoing placebo-controlled trial, but the safety from that study is obviously made available to the FDA on a continuous basis. And all of that supports our BLA supplement.

[Operator]

Our next question comes from the line of Tim Lugo with William Blair.

[Tim Lugo, analyst]

Can you discuss the level of warehousing currently occurring in the DMD commuting and maybe any subpopulations that are ahead of this potential expansion in the summer, which we should be aware of. I know we all focus on ambulatory and age related. Is there anything else there that we should be also looking at the function or other subpopulations?

[Douglas Ingram, executive]

Well, I don't I'm not 100% sure what we mean by warehousing to be honest. There is going to be an exceptional amount of demand for this therapy when the label is expanded both from the physician community but from families with Duchenne muscular dystrophy, and we stand prepared to build the material and have lots available to fully serve that demand over the course of 2024. But Dallan, do you have other thoughts on the warehousing question itself.

[Dallan Murray, executive]

Yes. If it's related to the PMOs and warehousing with the PMOs in anticipation of the gene therapy we were worried about that leading up to the initial launch, and the team did an exceptional job of making sure that, that did not happen. And we don't we don't see widespread warehousing where patients are getting delayed or really any warehousing where people are foregoing PMO in anticipation of the gene therapy. So I think, as I mentioned in the script, we were one of the things we're particularly pleased with this year is the continued incredibly excellent execution of the PMO team for patients who were not eligible for for the gene therapy for ELEVIDYS.

[Operator]

our next question comes from the line of Uy Ear with Mizuho.

[Uy Ear, analyst]

So just going back to the [indiscernible] skipping products. Could you I'm not asking full guidance or anything to that effect. Maybe just help us understand the first half of the year. In the prior quarter, growth -- year-over-year growth was relatively strong in the first half. Just wondering how we should sort of think about the first half of 2024 for those 3 products.

[Douglas Ingram, executive]

We haven't provided guidance on the PMOs for this year, but we're doing very well. I think you saw very good performance of all 3 of the PMOs last year, in fact, modus and by August, we're still growing at double digits. And 1 of the things that's interesting is that we are not seeing right now and probably won't see a significant amount of cannibalization from ELEVIDYS over the course of 2024 that will have a significant impact on the P&L. So we feel very good about where we are with our RNA-based therapies in 2024.

[Operator]

Our next question comes from the line of Salveen Richter with Goldman Sachs.

[Unknown Analyst]

This is Lee on for Salveen. So if the label for elevates is expanded and the broader population opens up -- how do you think that physicians might prioritize which patients to treat first in the context of site constraints.

[Douglas Ingram, executive]

Yes. That will be an issue that physicians are going to have to grapple with the -- there are a number of constraints. One of the things that you have to recall or remember is that we need to ensure that we are always prioritizing great outcomes and safety over, for instance, short-term revenue. So we need to make sure that physicians and physicians will know this, and they're going to certainly consider this. They need to make sure that they can not only in use patients but follow up appropriately. And so that will likely require them to prioritize patients as they consider this therapy. The short answer is that we are -- we can't invade the practice of medicine and decide for them what to do. There is a compelling arguments on both across the spectrum. On the 1 hand, there may very well be physicians who want to prioritize very young children to get in and intervene before damage is done. On the other hand, for the nonambulatory patients and later patients. There is a race against time for those patients. And so getting to those patients and stopping damage before it's too late is extraordinarily important. So these are going to be difficult decisions physicians are going to have to work that out, and I'm sure there'll be white papers and discussions among thought leaders on that topic.

The issue today is a slightly different one. The prioritization today, given the label that we have is to ensure that we get kids on the label, and this really comes from the physician more than from us to get kids on the label before they age out and the therapy won't be available to them. So if you look at the bias here, the bias tends to be to the -- in this tight age range of 4 and 5 to be in the later ages because they're really trying to get to those kids who if they don't get through the administrative process will age out to 6 years old. The good news is that if we can expand this label that issue goes to the side, and then we'll have to deal with the other issues about prioritization and the like. But it ultimately will be a physician decision and the issue of the practice of medicine for physicians.

[Operator]

Our next question comes from the line of Ritu Baral with TD Colin.

[Ritu Baral, analyst]

I want to -- just to follow up on the sort of guidance given. Your comment on how not to expect additional growth in elevates through the first half of the year, at least until the PDUFA. Is that a comment or a reflection on just the fact that you've reached sort of a run rate on to 5-year-old or is that a comment on sort of capacity of the systems throughput? Are you getting through as many patients as possible? And can you comment on what that sort of throughput capacity of like the center is at this point for when hopefully the label expands.

[Douglas Ingram, executive]

Yes, this really isn't a capacity issue right now. So I think as Dallan commented in his opening remarks, the label that we have today in this population is it's really a fairly unique population. First, as we all know, it's a very narrow age range, 4 to 5 years old. But that alone doesn't really describe the unique nature of this population because beyond that, there is a significant percentage of those patients that are not yet diagnosed. And so that makes it unusual. And then when they are diagnosed. Remember, they're not all getting diagnosed on 4 years in 1 day. Some of these kids are getting diagnosed deep into their 5s. And so what does that mean? It means that the family is based with what is very likely the most devastating piece of news so far in their life has to come to grips with that news, then understand it well enough and then go through the administrative process that exists to get approval, to get antibody tests to get an infusion data to get infused. So this is a really unique population.

In light of that, just to give a shout out to the team, it is particularly impressive when 1 considers that we did $200 million in that product revenue this year. So what Dallas really talking about when we talk about this is just simply that as we work through the prevalent population, this is a really unique population and much narrower than you might imagine the 4% to 5%. And so by the middle of this year, assuming the label expansion, you would get to a place where you begin to be treating the incident population as opposed to some bolus prevalent population in this group. Now the good news is that we have a June 21 date for our request for a label expansion. So hopefully, by July, we'll have a broader label and we'll be able to serve a much greater percentage of the population.

[Operator]

Our next question comes from the line of David Hong with Citigroup.

[David Hoang, analyst]

I just wanted to ask a little bit more about the pension culture manufacturing you have in the works. How fast did something like that come online? And once that is operationally how might that improve your margins?

[Douglas Ingram, executive]

So we're very excited about where we are from a suspension perspective. There's still a ton of more work to do, but A couple of things to think about. We are very advanced actually in the suspension work that we're doing, not just with 9001, but we're actually getting great results from a suspension perspective with our some of our limb-girdle programs. A couple of our sarcoglycan programs to actually transition to a suspension and we're making great progress there. When we focus specifically on ELEVIDYS we are in engineering runs right now on suspension. We've done 500 liter. We're doing another 500 liter. We'll do -- will start in the next month or so, 2,000 liter. We're so far getting not only really tremendous enhancement on yield but really good product qualities.

If all goes well, our goal is to have this suspension process available commercially by 2026. Now that's a moonshot goal on our part and then with keeping the patients front and center. We're going to try to move as fast as possible. But hopefully, we have the history to prove that we can make -- we can come up with audacious plans and serve them. So we're really excited about that. as far as what that might do, both from a capacity perspective as we go around the world with our partner, Roche, and a COGS perspective, that's going to require more work and more clarification as we get these runs done, but it won't be modest. It will be multiples. And we are seeing multiple times greater yields with suspension than we get with our iCELLis process, which as Ian mentioned, still drives right now an 80% margin. So we're -- I mean you probably hear in my voice, a certain amount of enthusiasm for our manufacturing approach and our suspension approach. And this is -- it is still early days, and we're just in engineering rents right now, but we're very, very excited about what this could mean for our ability to bring this therapy across the world and at a lower cost of goods as we go across the world.

[Operator]

Our next question comes from the line of Mike Ulz with Morgan Stanley.

[Michael Ulz, analyst]

Maybe just a quick 1 on timing since the PDUFA date was granted 2 months ahead of expectations. Just curious if the thinking now is you'll probably get a decision close to the PDUFA date? Or is the FDA still really committed to rapidly reviewing and might get an answer sooner?

[Douglas Ingram, executive]

Well, I have no reason to believe that the FDA isn't committed to rapidly reviewing this. With that said, there's still a lot of work to be done, and I think it would be prudent for all of us to assume that our target completion date of June 21 as the date on which we're going to get the answer we're planning for June '21, even though we are -- I don't think anyone thinks we said, well around, we try to move as fast as possible. But we're assuming June '21, that's when we're going to get on label expansion request answer.

[Operator]

Our next question comes from the line of Danielle Brill with Raymond James.

[Unknown Analyst]

This is Alex on for Danielle. I know the PMO confirmatory trials are fully enrolled. Could you just remind us whether -- where we should expect data for admission this year?

[Douglas Ingram, executive]

No, we shouldn't -- it doesn't read out for 2026.

[Operator]

Our next question comes from the line of Brian Skorney with Baird. Brian Skorney with Baird.

[Unknown Analyst]

This is Charlie on for Brian. So we were just wondering if you've heard anything from Roche regarding time lines with the EMA as well as if the European opportunity were to come online, would there be any supply limitations resulting from that? I know you're very comfortable with the expansion of the label but bringing on a whole another content. Do you think you have to do any prioritization between regions?

[Douglas Ingram, executive]

Well, Roche is publicly saying that their goal is to submit in 2024. And then as it relates to supply, our supply plans include our partner, Roche.

[Ian Estepan, executive]

And just 1 quick follow-up just to the previous question around mission and the timing. Just 1 thing to remind everyone is that this is a dose compared to doses of the drug. And so the data which we'll read out will be comparative from the 30 mg per kg compared to either the 100 mg or 200 mg per kg, and there's no risk of the drug being pulled off the market.

[Operator]

Our next question comes from the line of Kristen Kaska with Cantor Fitzgerald.

[Unknown Analyst]

This is Rick Miller on for Kristen. Since launching, are you able to talk about if and how the profiles of DMD patients that you're that are looking to get on the levies have changed? Or to put it in another way, I imagine you had highly engaged caregivers who are ready on for ELEVIDYS on day 1. So are you seeing more patients coming forward now after a few months of commercial experience or caregivers to get their child in line for ELEVIDYS?

[Douglas Ingram, executive]

Yes. I would say in the broadest of strokes, there is going to be a substantial demand for this therapy. I don't think that's changed. I think it's what we anticipated before launch, I don't think it's changed after launch. Duchene muscular dystrophy a devastating disease and the opportunity that's offered by ELEVIDYS is an important one. I think physicians understand that families with Duchenne muscular dystrophy the way I understand that as well. But Dylan, if you have any additional color on this or your views, please share them.

[Dallan Murray, executive]

No, I think broadly speaking here, exactly right, Doug. It's -- we're not seeing a real a real major change in terms of the patients coming in. It is as we set up on a small population. And so as soon as they're getting diagnosed and they've had their discussions with the docs, they're coming in through the enrollment forms. And so we're just working through those patients as fast as they can -- as we can prior to them aging out. But no major differences in -- for example, there wasn't a big kind of bolus of patients that initially came in, and now that's different. It's just -- it's been a steady clip essentially.

[Operator]

Our next question comes from the line of Anupam Rama with JPMorgan.

[Anupam Rama, analyst]

At the conference in January, you talked about 70 sites being active and about half of those sites had dosed patients. Can you give us a sense of where you are kind of now in the first couple of months of the year?

[Douglas Ingram, executive]

Yes. I believe that, that remains the accurate answer. But Dallan, you can give us an update if there's any change in that?

[Dallan Murray, executive]

No, Anupam, that really hasn't changed all that much. There's obviously more than there was then. And there's a higher proportion of sites that have dosed, but we're actively looking at this on a daily basis, and we have this flexible model where we can bring on new sites, get them trained and up and ready as needed. So we've got more than enough sites up and running, and we threw out -- we've got great geographic coverage, but the team is also ready to support and serve as needed out there.

[Douglas Ingram, executive]

I really do want to give kudos to this team for where we are. The -- I think everybody knows, the goal was to try to get to 50, not just 50 sites in 2024 -- 2023, by the end of 2023, which would have been would have been record smashing for a gene therapy launch and that there was going to be this aspiration that maybe someday we could get to 70 sites that would be trained and up and running. And this team got, as you know, over 70 sites in 2023. But also the way they got there is something that gives me an enormous amount of pride, which is, as I said earlier in this call, we don't we don't prioritize revenue over patient safety and great outcomes far more important for us to ensure great outcomes. And this team has done a ton in that direction. These 70 sites that are activated or activated because they've all been well trained. They're in good shape to be able to safely infuse this therapy and get good outcomes and consistent outcomes which is important. We have a very laudable safety profile for full-body infusion gene therapy, and we want to ensure that remains the case over the long term, not in the short term. And then, of course, there's a lot of other programs around that, the ability to access experts so that every physician has an opportunity to get the right kind of information to inform the way they not only infused that monitor patients and react to something that has been -- that is unique. I'm not sure anyone else has ever done the kind of work we've done. So we're in great shape right now to serve this community and serve it responsibly. So I'm really proud of where the team is right I think -- and frankly, it also explains our revenue in 2023.

[Dallan Murray, executive]

Thanks, Doug. And as you were speaking, that team did get us just a direct answer to Anupam's question, and we're closing in on 60% of the sites have dosed. So it just exactly as you said, it's just increasing as we go.

[Operator]

Thank you. I'd now like to turn the call back over to Doug Ingram for closing remarks.

[Douglas Ingram, executive]

Thank you, Shannon. Thank you all for joining us today, and thank you for your insightful questions. We appreciate it. At the risk of repeating myself, I think 2023 was an extraordinarily important year for Sarepta. We -- a lot of folks on this team in concert with the patient community and investigators and physicians, frankly, moved heaven or to get us where we are today. which is, I think, a fast-maturing fully integrated biotech organization committed to bringing a better life to patients with Duchenne muscular dystrophy, limb-girdles and other serious rare diseases. 2024 is actually going to be even more significant if we are successful. And that's going to put us in a position where we can do a lot of good for a lot of rare disease patients and where we can reward those who have stuck with us and invested in a better life for these patients. So I will remind you, if we are successful this year, and we brought in the label for 11 we can meet our goals this year. We are going to leverage our acumen and our financial strength and the talent of this team and through both advancing our internal pipeline, but looking to external innovation, we will have the goal of growing even after a levies not incrementally but in multiples. So we're going to build for ourselves a very big ambition if we are successful in 2024. With that said, we need to focus on 2024 and be successful and the team is prepared to do that. And I look forward to updating you along the way as well. So thank you, and have a lovely evening.

[Operator]

This concludes today's conference call. Thank you for your participation. You may now disconnect.