Good afternoon, ladies and gentlemen. And welcome to the Sarepta Therapeutics Fourth Quarter and Full Year 2021 Earnings Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. [Operator Instructions]. As a reminder today’s program, is being recorded. At this time I'll turn the call over to Mary Jenkins, Senior Manager, Investor Relations. Please go ahead.

Thank you, Mel. And you all for joining today's call. Earlier today, we released our financial results for the fourth quarter and full year 2021. The press releas is available on our website at sarepta.com and our 10-K was filed with the Securities and Exchange Commission earlier this afternoon. Joining us on the call today are Doug Ingram, Ian Estepan, Dallan Murray and Dr. Louise Rodino-Klapac. After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we’ll be making a number of forward-looking statements. Please take a moment to review our slide in the webcast, which contains our forward-looking statements. These forward-looking statements 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 the 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. I’ll now turn the call over to our President and CEO, Doug Ingram, who will provide an overview of our recent progress. Doug.

Thank you, Mary. Good afternoon, everyone, and thank you all for joining Sarepta Therapeutics fourth quarter and full-year 2021 investor conference call. Among the thousands of public and private biotech companies currently existing in the United States and around the world, Sarepta sits in a select and small group of fully integrated commercial stage biotech enterprise with a proven track record of translating brilliant science into approved therapies and then supporting the patient community and physicians in gaining and maintaining access to those approved therapies. This operational focus and commitment to patients was on full display throughout 2021. We have greater than 40 programs in our pipeline of potentially life enhancing therapies focused on rare genetic diseases across multiple platforms, including RNA, gene therapy and gene editing, but more than that, in 2021, we entered a pivotal registrational trials for our lead programs in both our RNA and gene therapy platforms. Encouraging data from our momentum Part A study, we commenced Part B of the study, a pivotal trial for SRP-5051, our next generation RNA-based PPMO for the treatment of Duchenne patients with exon 51 amenable mutations. Additionally, we commenced dosing EMBARK, the pivotal registrational trial for SRP-9001. Our microdystrophin gene therapy to treat Duchenne muscular dystrophy. EMBARK, which includes sites both in and outside the United States, is currently the only truly global trial, dosing a gene therapy for the treatment of Duchenne, and we translate our development activity to approved therapies. With the approval and launch of AMONDYS 45 in February of 2021, we now have three approved therapies serving the Duchenne community. In the fourth quarter of 2021, we enjoyed our 21st straight quarter of strong quarter-over-quarter revenue growth. Fourth quarter total revenues, which consist primarily of our net product revenue, plus our collaboration revenue, reached $201.5…

Thanks, Doug. My decision to join Sarepta four years ago was driven by the strong foundation of the R&D organization and Sarepta’s unmatched dedication to science as a patient. Since that time, the R&D group has grown in breadth and depth to become a truly integrated team focused on propelling structured scientific endeavors and vast pipeline for. Today, the R&D organization totaled nearly 300 employees grounded in a mission to translate the very best science to the very best treatments for patients in the shortest time possible. I'm proud to lead such a strong and committed team of scientists. Together this R&D has achieved great things, and this is an especially exciting time for our organization. We are fostering and leveraging our internal research capabilities, capitalizing on our current strengths while also ensuring we are positioned for sustained growth into the future. As a fully integrated organization, we have expertise in the manufacturing of our RNA and gene therapy assets, all of our research grade materials produced internally and we have developed and validated the analytics to characterize and release this material. I'm particularly proud of our competency in this area as it’s a capability unique to Sarepta. We are creating efficiencies and streamlined development of our pipeline candidates using a consistent manufacturing process. We've also established internal GLP capabilities at our Genetic Therapy Center of Excellence, or GTCOE series in Columbus, Ohio. This affords us maximum flexibility, agility and speed for preclinical studies. Additionally, in the past two years alone, we've created an internal innovation engine driven by our subject matter expertise that has resulted in the advancement of over 50 therapeutic candidate constructs across gene therapy, gene editing and RNA. In collaboration with our business development and alliance management functions we are continuing to invest selectively in best-in-class…

Thank you, Louise, and good afternoon, everyone. 2021 represented an incredible year of execution, whereby our team delivered net product revenue growth of more than 30% and $150 million over that of 2020. This strong growth was driven over the course of the year by exceeding expectations in all three of our approved RNA-based PMO therapies. In 2021, compared to the prior year, we delivered nearly 8% growth of EXONDYS 51 and more than 160% growth in VYONDYS 53 in the face of a competitive market. Additionally, we recognized $68.5 million in revenue from a AMONDYS 45 after launching within just 24 hours of approval in the first quarter of 2021. This success was generated by mission driven collaboration across all of our field teams and their deep commercialization experience gained over nearly six years since the approval of EXONDYS 51. The flawless execution in the field is supported by cross-functional partners throughout Sarepta, who are all intensely dedicated to serving the serving the Duchenne community. I'll begin by highlighting some of our 2021 achievements. The team got off to a strong start, setting the stage for the entire year by successfully navigating the reauthorizations process starting in January of 2021 and maintaining more than a 90% success rate in reauthorizations throughout the year. This robust start, coupled with continued high adherence rates, serves as the foundation for four more quarters of revenue growth for EXONDYS 51 in 2021. For VYONDYS 53, we ended 2021 in a strong position in market share maintaining our leadership role in the Duchenne space and growing at a robust triple digit rate over 2020. Further, the team continued to demonstrate their operational launch excellence with the launch of our third RNA based PMO, AMONDYS 45. As we mentioned in the past, the penetration rate…

Thanks, Dallan. Good afternoon, everyone. This afternoon's financial results press release provided details for the fourth quarter and full year 2021 on a non-GAAP basis, as well as a GAAP basis. Please refer to the press release available on Sarepta's website for full reconciliation of GAAP to non-GAAP financial results. Beginning in the fourth quarter of 2021 due to recent SEC comment letters issued to a couple of biotech companies upfront and milestone payments associated with the company's license and collaboration agreement, settlement and license charges and collaboration revenue, along with related transaction costs incurred, are no longer excluded from non-GAAP expenses and income, although collaboration revenue slightly confounds our core business operations to conform with these updates non-GAAP financial results for the fourth quarter and full year 2020 have been updated to reflect this change for comparable purposes. For the three months ended December 31, 2021, the company recorded total revenues of $201.5 million, which consists primarily of net product revenue and collaboration revenue compared to total revenues of $145.1 million for the same period of 2020, an increase of $56.4 million. Total net product revenue for the fourth quarter of 2021 from our PMO exon skipping franchise was $178.7 million, compared to $122.6 million for the same period of 2020. For the fourth quarter of 2021, individual net product sales were $119.1 million for EXONDYS 51, $34.7 million for AMONDYS 45 and $24.9 million for VYONDYS 53. The increase in net product revenue primarily reflects higher demand for our product and the launch of AMONDYS 45. And I like to remind you as Doug mentioned earlier our 2022 product revenue guidance for our RNA franchise is greater than $800 million. In the quarter ended December 31, 2021 and 2020, we recognized $22.7 million and $22.5 million, respectively of…

Thank you very much, Ian. Now let's open the lines for questions-and-answers.

[Operator Instructions] Your first question comes from the line of Debjit Chattopadhyay of Guggenheim. Your line is now open. You may ask a question.

Hey, good afternoon, and thank you for taking my question. The prepared remarks indicated consolidated analysis of all patients who received the correct dose and then the engagement with the regulators. So would this include all 33 patients in Study 103? Will you supplement with the biopsy data from the EMBARK study? And what would be the timing of the engagement and how closely is the Roche aligned with the strategy?

First of all, everything we do is in concert with in consultation with our partner, Roche, I should say that to begin with. I'll make a few comments and then Louise, you can provide additional commentary. So obviously a couple of things to know so we have a - we have a number of different analytics and data. We want to share that information first with the agency and have some discussions, and then we will share that in a appropriate medical meeting down the road that includes additional information out of Part 2 of Study 102. The data from Study 103 and its integrated analysis that you've made reference to the integrated analysis will be - an integrated analysis looking both at safety and function for those children who were dosed at the target dose across the various studies that we have, and I will remind you that we have a wealth of insightful data, all very consistent, but just – if you just take a mark and put it to one side right now, which is, we're continuing to dose and move with, we already have across all of these studies, over 80 children that have been dosed with SRP-9001. So that's the current plan. We will package that together. We will have - we'll get we'll provide that to the agency. One of the things that you should know is that our regulatory professionals have suggested strongly to us that we share that information and have that dialog with the agency and - before we discuss it externally, so we will do just that. And then we will, of course, find an appropriate medical meeting. On the timing of those discussions, I’m - as I said before, I'm not going to provide a lot of detail around…

I think you've covered it really well. I think the only thing I would add is that there was one question around for the integrated analysis for Study 103. So there we would include the patients that are four to seven that were consistent with studies 101 and 102. To recall, we also just older non-ambulatory patients, which will certainly look at that data, but it won't be included in the one-year integrated analysis.

Thank you. Next question comes from the line of Brian Abrahams of RBC Capital Markets. Your line is now open. You may ask your question.

Hi, guys, thanks so much for taking my question. Congrats on all the progress. I guess just following up to that first question recognizing that EMBARK is the base case. I'm just sort of wondering, as you've gathered the data, whether there's been any evolution in your level of confidence in the feasibility of a faster path for approval? How the new – the change in FDA leadership and some of the pledges around the accelerated approval path might impact your views there. And then where you might stand with respect to commercial supply in terms of supplying the market if you were to get an accelerated approval versus after the EMBARK readout? Thanks.

I'm going to be a little careful on the first question, because it could reveal a lot about data that we don’t yet have. I’ll just broadly say that we have an enormous amount of conviction around our program and our data safety, function and expression. I think the leadership changes with the FDA certainly, will have no to the best of our belief have no negative implication on any strategy that we might have or any faster pathway and actually might enhance it. I think. Dr. Califf is a very good choice for the Head of the FDA and has shown historically a commitment to the use of what is a tremendously valuable pathway to translate science to therapy to save lives, which is the accelerated approval pathway. And just to remind you that as the pathway to save a lot of lives over the years, both in cancer and in HIV and as well as in neurodegenerative diseases and Duchenne patients, so we're excited about that, and Louise have I missed anything here?

No, got it. Thank you.

One final, there is a final thing I think you asked about commercial material. Again, just to remind you, I want to be careful because in my enthusiasm I make you sounding like I'm pivoting off of our base case. Our base case assumption is that EMBARK will be the basis for our approval and we're moving, like mad to get that fully dosed and that will in a very short order have a readout, which will be in the middle of next year. But in the event that we had a faster pathway to an approval, we will have all of the commercial material that will need to serve the community. At that point, we will be ready in the event that we had a faster approval. Apologies, Louise, I think I might have cut you off.

Thank you.

All right.

Thank you. Okay, thank you. We have the next question comes from the line of Anupam Rama of JPMorgan. Your line is now open. You may ask your question.

Hi guys, thanks so much for taking the question. Doug, maybe more of a housekeeping question this question came up at the conference and in subsequent discussions, but where are you in terms of your contracting, your future with Sarepta? Thanks so much.

So this - by the way of background for those who might not know I joined Sarepta in late June of 2017 and I joined pursuant to a five year agreement. With that said, let me be clear, I have one of the strongest teams. I think first and certainly in Sarepta history, but more than that, I think in all of biotech. I'd say that referencing not only my direct reports, but the broader team that is Sarepta with extraordinary professionals, and I ask a lot of them. I'm asking them to be dedicated and passionate and committed to our patients and to the future of Sarepta, and I can't ask more of them than I ask of myself. So to the avoidance of doubt is my every intention to stay at Sarepta beyond my five year agreement and to continue to drive with – my colleagues towards a better life for these patients. And frankly, quite directly, where would I go with these exciting and challenging with as much opportunity to do good and do well at the same time. At Sarepta, we've got an enormous pipeline, we've got multi platforms. We're in pivotal trials in our two late stage platforms. We've had extraordinary growth. We're sitting with $2.1 billion on the balance sheet so that we can continue to execute, if you look into the future just look where we could go, right. If all is well, we'll be profitable by the end of 2024. If our late stage programs are successful and I have to say I, for one, am very, very confident on where we're heading. We will approach $4 billion in the next few years by 2025. And if you look out into the future by the end of this decade, if our pipeline performs, we could be approaching $10 billion. So I'm extremely excited about the future of the company. I'm thrilled to be working with the people that I work with. I know - a few things that are as rewarding, while at the same time challenging as working at this company and serving these patients. So I have every intention of continuing to lead this company with my colleagues. So thank you for that question.

Thank you, we have the next question. It comes from the line of Tazeen Ahmad of Bank of America. Your line is now open. You may ask your question.

Hi, guys. Good afternoon and thanks for taking my question. Doug, I was hoping to get a little bit more granular on, your $10 billion in peak sales by the end of the decade. What are the components that go into that? And how would we think about if DMD gene therapy is approved, the contribution of that versus the contribution of either PMO or PPMO? Thank you.

So I can't give a ton of detail. Because we haven't provided a lot of granularity but I’ll give you the broad strokes on this. First, know this a lot of times when people create strategic plans, they have essentially yet unidentified development programs or the light that might make up their future revenue projections and goals. That is not us. Everything that I'm talking about comes from the internal programs that we have today, even as we continue to look for new opportunities as an organization. First and foremost, the success of our plans rely on the success of SRP-9001, of which we are very excited. And if we're successful there, as I've said, together with our other programs, we'll get to approaching $4 billion by 2025. And then we have the limb-girdles in some other programs coming on behind it. Our current assumptions and I don't - and I think it's a conservative assumption and we're challenging ourselves there is that with the success of SRP-9001 gene therapy that it would have a significant cannibalizing effect on our existing RNA therapy, even though that our RNA therapy would remain viable in a lot of places and there will be different places where cannibalization wouldn't occur. So we're assuming a significant amount of cannibalization and we would still get to something around $10 billion by the end of this decade. We still get even with significant cannibalization to about $4 billion by 2025. And again, we're doing a lot of work right now to test the thesis that there is a significant amount of cannibalization in the event of SRP-9001 success because there may be a very real opportunity for accommodative benefit of RNA and gene therapy together. So that - those are kind of the broad strokes of the strategic plan for us.

Thank you. Next question comes from the line of Gena Wang of Barclays. Your line is now open. You may ask your question.

Thank you. I have one question regarding the MD presentations in two weeks. I know you have three presentations. Just wondering specifically, regarding Dr. German Dow's presentation on the Study 102 wondering will we see two year data from the drug arm with propensity score weighting analysis with external control and also regarding the SRP-5051 PPMO Part A data, will we see longer follow up data from that data upside?

Yes. I'll let Louise answer some in detail, but let me answer the broad strokes of the first part of it. So as I've said before, we have first part of it. So as I've said before, we have a significant amount of additional analytics done and being completed after which we’re going to collect them all together and share them with our regulatory agency. And then we're going to find a medical need to have that discussion thereafter. We have been strongly encouraged by our regulatory professionals to avoid presenting any additional data until we have those discussions with the FDA for a host of technical reasons. And we certainly want to have the most accessible meeting that we can with the division when we can have it. The second issue for us is that, that having presented the main primary information and material information at JPMorgan. We want to make sure that we put this all together in one medical meeting and we don't look like we're trying to essentially promote individual pieces of data across the year. So the short answer is that Dr. Mandelas presentation will be essentially the data that you've seen before, which you can have additional commentary as you can well imagine and direct insight. And then we’re going to be in short order, gather all of our information, visual information and in Part 2, additional interesting analytics around it, the two year data Study 103, the first cohort of Study 103 about 20 patients, an integrated analysis to provide that all to the agency in the form of a well thought through briefing book. And then we'll find a medical meeting and we’ll disclose all of that information and have a discussion about where we are sometime this year as soon as it’s reasonably possible to do that with. Louise?

Yes, to just add on SRP-5051 this is - there won’t be new data from Part A. It'll be what was previously presented. This is obviously a live audience and this would be nice to be able to present and interact with people at MDA around the state. As you know, we're not rolling Part B of the study, but part a readout will be similar to what was presented previously.

Thank you, the next question comes from the line of Alethia Young from Cantor. Your line is now open, you may ask your question.

Hey, guys, thanks for taking my question. And congrats on all the progress. I just actually wanted to talk about, obviously you have that base case of drug being approved. Roughly a year or so, but if it's not, just can you talk a little bit about how you're thinking about kind of like launching into this group of people with gene therapy? Obviously, we know the cadence of your kind of launches currently as we stand, but I guess, how should we think about kind of early sets of patients that might be interested in this treatment and just how to think about the overall population in general and for you guys have been thinking about it? Thanks.

Yes. I mean, a lot of it's going to be subject to discussions with the division. Obviously, first and foremost, whether there is even a faster pathway, and that's a very much an open issue. As I've said many times, I really would - my primary investment thesis and I will say it's personally my investment thesis that everyone knows. I've been a significant investor in Sarepta personally over the years, and I bought additional stock last year. I bought on the assumption that the EMBARK is going to be wildly successful, etcetera, etcetera, on a very personal level. But we need to have additional discussions with the agency. First question is, is there a pathway that would be even faster than EMBARK? Second question is what is the size of the patient population inside of that that is going to be subject to discussions with the division? Is it a subset of patients? Is it more than a subset of patients? Those are all discussions that have not occurred yet, but we need to have them. The one thing I can say to you is that We will be well to launch the therapy under any of these various scenarios in either a subset or a larger one or of course, we will obviously be prepared for our base case assumptions. So we'll be prepared in a number of regards, we’ll be prepared commercially, Gal and his team are well aware of the various possibilities, and we'll be prepared to make the most of this therapy and to get it to patients as soon as possible, and we'll be aware, we'll be prepared from a supply chain perspective, from a manufacturing perspective and from an inventory perspective in the event. So it's difficult to say exactly what that launch would look like. First, because it's only theoretical right now, and second, because it would require additional discussions even if we were successful.

Thank you. Next question comes from the line of Colin Bristow of UBS. Your line is now open. You may ask your question.

Hi. This is Ting on for Colin. Thank you for taking our question and congrats on progress. So we have a follow up question on the ongoing or anticipated conversations with FDA. Can we know when do you expect to be in a position to provide an update on their potential filing for SRP-9001? And also, when we think of your estimates of the potential - of like your long-term goal of achieving $4 billion by 2025, how should we think of your estimates of the potential launch in time for SRP-9001? Thank you.

Yes. So let me answer the second question first. When we talk about our strategic plan and we talk about the revenue potential out of our platform, we’re assuming our base case scenario. We’re assuming that EMBARK, which is our pivotal trial, well-controlled, well-powered, 120-patient, placebo-controlled blinded study is the pathway to getting this therapy approved first in the United States and then around the world. And it is on that basis that all of our plans from our strategic plan perspective, have been built. And then the second one to the first question, we're not going to provide detail on the sort of the blow-by-blows of discussions. We obviously still have to gather information, create a briefing, book, submit that have a meeting. That meeting may be one or a few. The one thing I will say is, we'll do it, we'll do it as expeditiously as it's reasonably possible, ensuring that we have the data to have a very successful and thoughtful discussion with the agency. And when we are at a point in those discussions where we have sufficient clarity that we can provide additional color, we'll do that at that time. So I would be generally confident it will occur over the course of this year. But I can't give you more detail on the exact timing of that.

Thank you, we have the next question comes from the line of Matthew Harrison of Morgan Stanley. Your line is now open. You may ask your question.

Thanks. Good afternoon. I guess I was just hoping that just clarify one point about the set of information that you're going to provide to the FDA. And I guess my question is, have you asked them specifically on the kind of information you're going to provide to them in this package? Or is this sort of solely been designed by you and your regulatory folks? Thanks very much.

Yes. It's been designed by us. Let me be clear, the briefing book and the information that we share will obviously be constructed by us. We have provided to them historically some of the statistical analysis plans that we're using. So they have a - they should have in advance a good understanding of the kind of information that we’ll be discussing, but it is essentially on us to ensure that we have a robust package that can inform our discussions. With that said, I will also - I should give enormous kudos to both our development folks, the scientists and regulatory professionals who have a very keen understanding of what might be required to ensure not that we will ultimately be successful in finding a pathway faster than EMBARK. I don't want to suggest that, but again I will say over and over again that I think everybody ought to assume that EMBARK is our pathway, and it's an exciting and very - coming up very quick path well, but that we will have a very good, well-informed and robust discussion based on what I believe to be very scientifically rigorous analytics.

Thank you. We have the next question comes from the line of Ritu Baral of Cowen. Your line is now open. You may ask your question.

Good afternoon, everyone. Thanks for taking the questions. So, Doug 2024 breakeven implies obviously some revenue from SRP-9001 and assuming you're filing on the EMBARK data that kind of gives you no time for any potential reimbursement delays, which has been super challenging for gene therapies. Can you talk about maybe lessons learned from other people's mistakes and what sort of groundwork you're laying now in advance to get reimbursement out of the gates to meet 2024 breakeven, 2025 $4 billion revenues?

Yes, I mean, I would say, broadly speaking, Dallan and team spend an enormous amount of time laying the groundwork for - laying the groundwork to ensure that we can launch this as appropriately as possible, serving this community. No one, this is going to be honest with me. But I say this on behalf of my commercial medical affairs colleagues. No one is as prepared to launch and support a Duchenne muscular dystrophy therapy as Sarepta. This is a honed team that knows what it’s doing. And, while we are still in a very nation's field of gene therapy, we do have the benefit of looking over our shoulder at what others have done, seeing what they’ve done, that's very good and mirroring and to the extent that our colleagues in other companies haven’t had the benefit of seeing others and have stumbled to be able to benefit from that and learn and certainly, I think, Novartis has done a really good job with this. [indiscernible] there's learnings in there. And I think we've had some time to get ourselves ready and to prepare for that. But, Dallan, do you have any other additional thoughts?

No, I -

Microscope on this.

Yes. No, absolutely. Everything that Doug said, and I think our forecast assumptions are based on our experience launching three PMO. So that those assumptions incorporate everything we've learned in the Duchenne market in the last several years.

I mean, one mistake we could make is to assume that launching a gene therapy is identical to launching one of our RNA therapy. But the good news is Dallan and his team don’t do that. They thought a lot about the ways in which gene therapy capacity issues, centers for excellence and the like, and all of the pre-work associated with having discussions with payers long in advance need to happen. And that's happened a bunch. I mean, we've had a significant number of interactions with payers and we have much more to come. But I will also say, I mean, look at our track record. If one wonders whether we know how to translate therapeutic approvals into meaningful therapies for patients, getting them access and keeping them maintained on access and getting great revenue growth. AMONDYS is a brilliant example of that. A lot of times a company gets an approval and then they launch a couple of months later, three months later, four months later. These folks literally launched essentially within it with either 24 or 48 hours. We had our first START form within, I think, 24 hours. And our first infusion with them on this within days, literally within days. We translated that to being into patient impact amazingly fast. And I think we have the opportunity to do the same. So I think, we have lofty goals, but I think our strategic plan is realistic.

Thank you. We have the next question it comes from the line of Brian Skorney of Baird. Your line is now open. You may ask your question.

Hey, good afternoon, everyone. Maybe departing from SRP-9001 for a minute I was just wondering on the limb-girdle programs. I think you said that the rate limiting step here has been CMC. So just wanted to see if we get an update on where you are in terms of building out a cDNA production here? And when could we possibly see initiation of a pivotal program? Thanks.

Yes, so you're exactly right. The rate limiting step for the commencement of a pivotal trial, I mean, it is - we still have to have further discussions with the agency to confirm and agree on the development program itself. But the predicates to all of that is the CMC. And in relation to the CMC, it's really more than anything else assay work. You've got additional assays that still need to get built. They will get built. It just takes time. It reminds me a lot of sort of where we were with SRP-9001 in 2019. You'll recall in 2019, I was telling people, we're building our manufacturing process, but we don't have the for them - this is not the case with SRP-9003, but the SRP-9003, is just about building assays for the most part. But with SRP-9001, you'll recall I was telling the external world, the yields aren't yet where we need them to be for a manufacturing process perspective, but we're going to get there. It's the same answer with these assays. We have additional assay work to do. It's an engineering and empirical process. We don't have any significant inventive steps here. We know exactly how we need to get there. It just takes some time. So once we have that CMC complete, we've the assays complete then we can have a discussion with the agency and start what we would hope to be the pivotal trial for this - for 2E. Beyond 2E, I can tell you a couple of additional things. We're working really hard on the other sarcoglycan and trying to get them in a place where they could be as close to 2E as possible. That's a big effort for us right now. And we will also start a pilot program for 2B, which is dysferlinopathies, if I'm not mistaken, Louise, by this year we'll start our pilot program, which could be really, really interesting. We're doing a pilot program because dysferlinopathy is a little bit different than the other programs, including the sarcoglycans. It's a dual vector approach, so it has that difficult - that different technical aspect to it. And we want to do a pilot program and see its effect before we move into a pivotal trial. But we've got a lot going on with one of the reasons we raised additional resources last year was number one to ensure that we were well funded, but also to ensure that we were moving limb-girdles along, as well as with the success of SRP-5051, ensuring that we're moving the other PPMOs along as well as we are.

Thank you. Next question we have from the line of [indiscernible] Gigori of Oppenheimer. Your line is now open. You may ask your question.

This is [indiscernible] Gigori dialing in for Hartaj Singh. Thank you for taking and cover our question. One from us on the limb-girdle muscular dystrophy program also. So some key opinion leaders we have spoken with have emphasized that the natural history for LGMD is poorly defined and that there's a strong unmet need with the lack of trials as well as difficulty of conducting trials in the ultra-rare disease. Our question is if you could elaborate on this points and also on your conviction as it interrupt as an entire LGMD portfolio. Thank you.

Sure. Louise, do you want to take this one?

Sure. I'll emphasize that we are currently doing a natural history study in limb-girdle called JOURNEY and as for the sarcoglycan 2E, 2G and 2C to help them inform that. We do have natural history data in 2E for example we've previously shared data where we've shown the comparison of our 101 patients in comparison to natural history. We're certainly for some indications, like visceral [indiscernible], there's actually a wealth of natural history data. So where there is an absence of data, we're making sure that we are doing studies and it's well informed. It's certainly a newer field than Duchenne in terms of natural history, but we are making sure that we're making the best decisions for patients and gathering natural history data where we need to, and then being creative in terms of our approach to making every patient count in our trials and maximizing the amount of information we get from that. Thank you for that question.

Thank you. We have the next question comes from the line of Gil Blum of Needham and Company. Your line is now open. You may ask your question.

Good afternoon, and thanks for taking our question. So maybe focusing a little on the PPMOs here. So, you guys have never taking a price increase on your PML franchise. But considering the potential for an improved clinical benefit with SRP-5051, would there be discussions around this? Is this isn't something you're considering? Thank you.

Well, we haven't gotten to a point where we thought about the exact pricing for the PPMOs. And certainly, if it is successful, could be a significant and profound benefit to patients even over our current PMOs in a number of regards, of course. Just to remind everybody what we've seen so far in our performance, obviously they are borne out in our pivotal trial, which is MOMENTUM Part B. Just to remind you, we saw 6% dydystrophin, which are 18 times more exon skipping, about eight times more dystrophin in EXONDYS, we saw it in half the time and 20% of the dose. So the product profile could be significantly different. Now, with that said we haven't made those decisions and we’ll look at that carefully. I can give you our current general philosophy, which doesn't speak exactly to what our pricing will be for PPMO, but should give everyone a steer on that who we are as a company. We’re a company that believes in pricing our therapies appropriately to ensure that programs like this can be successful for patients and will spur additional innovation. But once launched, we don't believe in trying to meet our goals, for instance, by unnecessarily or inappropriately raising price. And that’s why, to your very good point, we’ve launched EXONDYS what will this year be six years ago and we have never taken a single price for EXONDYS. Then we got AMONDYS and VYONDYS approved, and there was at least an argument that could be made for pricing them at a premium to EXONDYS, maybe in part because they are smaller patient population. And we didn't do that, we priced them all at parity. So generally speaking, our goal was to price our therapies appropriate at inception and to not use - to use our performance and our commitment to the patient community and serving the community as the basis for our success and not using things like unnecessary or, gratuitous price increases as a way of satisfying our obligation. And so far, it's worked just by the way. And I’ll go back and I want to give an enormous credit to our commercial and medical affairs group and everyone that supported them because we've had 21 quarters of consistent sequential, strong, quarter-over-quarter growth. We've grown 40% CAGR over the last five years. We'll do over $800 million in product net product revenue this year. And so I think that the philosophy that we have has worked well for us now. With the exact price where the PPMO will be is something that we'll decide when we get closer, but one should assume it will be, we'll take - we're not going to take advantage of the benefits of the PPMO. We'll make sure that we price it appropriately to serve the community and justify future innovation.

Thank you. Next question comes from the line of Joseph Schwartz of SVB Securities. Your line is now open, you may ask your question.

Hey, thanks very much. Could you provide us with any phase 3 enrollment statistics for SRP-9001, such as the proportion of sites that have been activated or patients that have been enrolled in dose so far, and maybe also describe the impact that your new inclusion and exclusion criteria has on head on enrollment. What percentage of patients due to seek screening out on this criteria?

Yes. So I’ll give you the broad strokes who is going to give any of the - I think best [indiscernible] and brightest of strokes, and we’re not giving details on numbers of price activated yet or patients dose other than to say we’re dosing patients. I think someone has asked me recently if we were dosing patients in the US yet, but I’ve been asking for a lot of people a significant challenge and short answer is yes, we’re dosing patients in the US. We are on track to complete the dosing of our study in the middle of 2022, which is our goal. So that's great. We've got more sites to initiate and we’re working well to do that and outside the United States and even some additional sites in the United States. So we got more work to do, but the team is executing well and we’re on track to hit our goals. On the exclusion criteria, Louise can give some of the data on which she think the percentage of patients that might be excluded from that might be. But broadly speaking, there’s such an extraordinary need and demand for this therapy, both from families and investigators are well aware of this that, I don’t believe that there's going to be an impediment to robust enrollment in this study. Louise?

Yes, that's correct. We've not seen a significant influence of the revised inclusion exclusion criteria for Study 301 accelerated forms on our earlier study. The demand is high and recruitment is on track.

Thank you. We have the next question comes from the line of Judah Frommer of Credit Suisse. Your line is now open. You may ask your question.

Hi. Thanks for taking the question. And just to follow up on the last one, just kind of given the, continued clinical holds placed on AAV gene therapies, any impact, positive or negative, you can sense and enrollment sites, any hesitancy maybe from investigators or patients, obviously, kind of different AAV here. And then tied to that somewhat within the long-term guidance, can you make any comments on competition for your gene therapy?

So I will say a couple, on the last one, let me say that the long - our long-term strategic plan base case assumes robust competition, whether or not that's accurate or not. Something we’ll all find out over time, but we're trying to be thoughtful and conservative in our strategic plan approach, so we actually assume in our plan and our revenue assumptions robust competition for our therapies, even including our gene therapy. So that's built-in. On the first part of the question, I don't believe, but Louise you can correct me that there has been any significant impact from the issues that have occurred with our colleagues at other companies, both Pfizer and Solan with respect to AEs, SAEs and the like and the most recent, very difficult situation that occurred with Pfizer. I think that investigators are fairly well informed that SRP-9001 is substantially different than those others and has performed different than those others from a safety perspective, and I think patients are generally pretty sophisticated in this space and generally are aware of that, but Louise you might have more color on this than me.

Yes. I agree with everything you said. The physicians are eager as well as the patients for Study 301, they ask good questions. I think one thing that we're seeing is that PI is becoming increasingly sophisticated and ask the right questions, which is good to see as we're tracking along development as well as IRBs they're asking the right questions. So I think we're in a good space in terms of education of the community, of knowing the right questions to ask and being informed. So it's a positive from our perspective.

Thank you, the next question comes from the line of Salveen Richter of Goldman Sachs. Your line is now open. You may ask your question.

Hi, thanks for taking the question. This is [Tommie] on for Salveen. Our question is on the genetic collaboration. Seeing your non-viral delivery has had some setbacks in the past. What is giving you confidence that their platform could be successful? Thank you.

Louise, you might want to take this one.

Yes, thank you for that question. I think, as I mentioned with non-viral deliveries, one of the challenges is getting to muscle in the first place. So these - the non-viral delivery mechanisms have been very efficient of going to places like the deliver, as you would expect. And so one of the hurdles to get over this was to efficiently deliver to muscle and so while we delivered which is not systemically inside expression in muscle we're thrilled with the progress on that. Now we have a ways to go. It's early, but where this is the first time we really saw a measurable expression level [ph]. So we're excited about where that could go. Again, it's early, its research, but we're excited.

Thank you.

No I had one probably. It’s a very good question, one thing you should know is that we're taking a number of different approaches simultaneously because as you pointed, it's very this is a very challenging concept in our AAV, AAV has been successful, there are lots of interesting opportunities. If one could either enhance AAV something we're working on or find an alternative to AAV. But it's challenging. So this - it's a genetic is exciting. There are other approaches we're taking as well in the hope that we can advance the science of genetic medicine.

Thank you. We have the next question - sorry, go on.

No, Mel, go ahead. Sorry I'm interrupting you.

Okay. Sorry about that. Thank you. So, on for the next question we have from the line of Yun Zhong or BTIB. Your line is now open. You may ask your question.

Hi, thanks very much for taking question. So my question is a follow-up one PPMO platform and was a better clinical profile. How possible do you think the platform can potentially expand the patient population, convincing those patients who are not committed to receiving exon skipping therapies to get on treatment and given that you said then exon, EXONDYS 51 and maybe even VYONDYS 53, the sales are nearing plateauing? So - I know that you're very confident in the gene therapy program, but if you do decide to work on additional candidates, how fast do you think you can move the next one into the clinic?

Well, we're moving from a preclinical perspective, we're moving as fast as we can, and obviously everything takes more time than one would like when you’re dealing with a often ferocious neurodegenerative diseases like Duchenne muscular dystrophy, but we're moving fast as far. As the potential opportunity for the PPMO and PK anonymous people anonymous in many ways. First, remember, with our first three therapies, we treat about 29% of the Duchenne muscular dystrophy - the Duchenne community. We can both with our PMOS or PPMOs treat easily 50% of the patients so theoretically, up to over 80%. There's, challenges when you get to the really rare exons, but we can treat a significant number of patients and we can make a bet on the PPMO platform that gets us to a significantly greater percentage of patients than just 29% beyond just that the, our ex-U.S. is on a named patient basis. The Managed Access Program very much a responsive program and while patients do benefit from our therapies outside of the United States, the vast majority of all of our sales will happen inside the United States with our PMOs. And that relation in significant ways to start some of the history of the PMOS, the way they were approved and the like. I think with the PPMO and certainly with the therapy that, if successful, could make, 10% or so over the course of a year truncated but functional dystrophin, which literature would say would be a profound change in trajectory of disease. Potentially, I think the ex-U.S. opportunity becomes far more viable and that would really expand the potential for this therapy to treat patients around the world. And then therefore, as a result of that benefit, I think would really greatly enhance the long-term revenue associated with the PPMO. So there's a lot of exciting opportunities in the PPMO, and then we're moving as fast as we can with respect to that.

Thank you. We have the next question comes from the line of Zhiqiang Shu of Berenberg. Your line is now open. You may ask your question.

Great, thanks very much. Good afternoon. I want to ask about your 2025 revenue aspiration of $4 billion. I think if you just look at the consensus right now its $2.2 billion, $2.3 billion. What do you think is really is missing here? And what do you think that - the delta can be accounted for? Thank you.

I'm not 100% sure where they're deriving their number. I can tell you where we're deriving our number with an understanding of the prevalent population that is - that’s much better than certainly the literature. And it's a very thoughtful bottoms-up approach to building our revenue guidance. They might be assuming complete cannibalization of the RNA franchise with the launch of SRP-9001 that would be, I think, an inaccurate assumption. So I can't say with precision, I suspect, frankly, that we've just done significantly more modeling than one would expect from folks which is all we do is with these genetic medicines.

It's also partially being driven by probability of success.

Okay.

Thank you. The last question comes from…

They may just be discounting, and that's a good - point.

Sorry about that. So we have the last question comes from the line of Debjit Chattopadhyay of Guggenheim. Your line is now open. You may ask your question.

Hey, thanks for letting me back in again. So any progress with EMA, with respect to SRP-5051 and the threshold of dystrophin expression for potential EMA submission also, are you expecting top-line by the end of this year?

Louise, do you want to take this question?

There is certainly something that with SRP-5051 in terms of the levels that we expect that we will revisit and have discussions with regulators in the United States and with the EMA. The study will be enrolled this year. And so, we'll look towards dystrophin expression at 20 weeks thereafter. So we'll provide guidance as we track towards that.

I will say that having been personally involved in and involved in the discussions with CHMP and EMA, and I do think we would have a different I suspect anyways, I should say it'll all be subject to discussion. I think we would have a different dialogue with the division with EMA and then ultimately CHMP with a therapy that was making 6% to 10% dystrophin. I think the probability of success would be much higher for an approval or a conditional approval.

Thank you. I am showing no further question at this time. I would now like to turn the conference back to President and CEO, Doug Ingram, sir?

Thank you very, very much. So I'll be brief, yesterday was Global Rare Disease Day. It is a time when we reflect on those around the world who are living with a rare disease, very often a rare genetic disease. The external world can often seem chaotic and uncertain, particularly these days, and that can be particularly distracting, but reflecting on Rare Disease Day and in our mission to bring a better life to our patients and their families that live with rare degenerative disease, it reminds us that we don't have the luxury of getting distracted. And fortunately, we don't have to be distracted. We have the team, we have the science, we have the programs, we have the revenue, we have the balance sheets and we have talent to stay focused and to execute our plans for the benefit of our patients and thus to the reward of those of our investors who place their trust and their resources with us. We will continue to execute in 2022, and I look forward to additional updates with you across this year. And with that have a good evening and thank you for joining us today.

Thank you. Ladies and gentlemen, that concludes today's conference call. Thank you all for participating. You may now disconnect.