Good day, ladies and gentlemen, and welcome to the Sarepta Therapeutics Fourth Quarter and Full Year 2018 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 be given at that time. [Operator Instructions] As a reminder today's program is being recorded. And now, I'd like to introduce your host for today's program, Ian Estepan, Vice President, Chief of Staff and Corporate Affairs. Please go ahead.

Thank you Sophie. Thank you all for joining today's call. Earlier today, we released our financial results for the fourth quarter and year end 2018. The press release is available on our website at www.sarepta.com. Joining us on the call today are Doug Ingram; Sandy Mahatme, Bo Cumbo, Gilmore O'Neill, and Louise Rodino-Klapac. After our formal remarks, we'll open the call up 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 on webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, any of which are beyond Sarepta's control. Actual results can 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 of Sarepta's common stock. For a detailed description of applicable risks and uncertainty, we encourage you to review the Company's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission, 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. With that, let me turn the call over to our CEO, Doug Ingram, who will provide an overview of our recent progress. Doug?

Thank you, Ian. Good afternoon and thank you all for joining Sarepta Therapeutics for its fourth quarter and year end 2018 results, as well as our corporate update conference call. I would add that you indulge me as we have much to discuss today. Before we discuss the fourth quarter results, let us put it all in context of the full year of 2018. I do not believe, I risk, when I say that 2018 was a monumental one for Sarepta. We not only successfully met or exceeded the great majority of our objectives for the year, but we went further. We redefined and enhanced our ambition as an organization and we took steps by taking significant leaps forward in the service of our vision, to use our genetic medicine engine to rescue and greatly improve the lives of thousands of those living with and far too often dying from rare genetic disease. In the full year of 2018, we achieved another successful year of EXONDYS sales with net revenue standing at $301 million or about 98% year-over-year growth. We also met with the FDA and in collaboration with the agency, we defined an efficient pathway for our RNA-based technology. We executed our single ascending dose study on the first candidate on our next generation RNA technology that PPMO, which will be moving to a multi ascending study in the next couple of months with a readout and a read through to our other PPMO programs by the end of 2019. We commenced and we completed our proof of concept trial for our microdystrophin gene therapy. In 2018, we reported unprecedented expression level results, biological marker results and preliminary functional results in the four patients who participated in this proof of concept cohort. As reported by Dr. Jerry Mandell last…

Thanks, Doug. Good afternoon, everyone. The Myonexus transaction which has given us full access to rich fulfill LGMD candidates, cements our position as a leading gene therapy Company bringing our pipeline to 24 programs in development, 10 of which are in gene therapy. As Doug indicated on our call earlier today, the strategic and scientific rationale for the Myonexus acquisition, centers around the rapid pace at which Sarepta will seek to advance these programs through development. From a financial perspective, we believe, we negotiate an equitable deal based on fed terms. Further, and because we opted in early Sarepta generated substantial savings of approximately $50 million. Now, moving to the financials. This afternoon's press release provided details for the fourth quarter of 2018 on a non-GAAP basis as well as GAAP basis. The press release is available via SEC, as well as Sarepta's websites. Please refer to our press release for full reconciliation of GAAP to non-GAAP. I'd like to add a quick reminder here that our 2018 non-GAAP financials exclude net interest expense, depreciation and amortization expense as well as one-time expenses and stock-based compensation. Net product revenue for fourth quarter of 2018 was $84.4 million, compared to $57.3 million for the same period of 2017. The increase primarily reflects increasing demand for EXONDYS 51 in the US. We reported a non-GAAP net loss of $58.7 million or $0.85 per share in the fourth quarter of 2018, compared to our non-GAAP net loss of $13.3 million or $0.21 per share in the fourth quarter of last year -- I'm sorry, 2017. In the fourth quarter of 2018, we recorded approximately $13.1 million in cost of sales, compared to $3.5 million in the same period of 2017. The increase was driven by increases in inventory costs and royalty payments to…

Thank you, Sandy. Good afternoon, everyone. I'd like to start by talking about EXONDYS 51. Over the past few years, we have watched KOL start patients on EXONDYS 51 and we know it has changed lives. We know the importance of reaching every eligible patient, getting them on and keeping them on treatment. We know that working through the complexities of access and reimbursement are real and there are patients still waiting to get on treatment and our team, the best whom I've worked with, will continue to be fully dedicated to this effort. We know this community and how important it is to them that we continue to try to make a difference in the lives of Duchenne patients around the world. That is our true mission. As a result of our efforts and commitment, we were very successful in ensuring that patients received and stayed on therapy in the first two years of the EXONDY's 51 launch and in doing so generated $84.4 million of revenue in the fourth quarter of 2018, which reflects a 47% growth over the same the quarter previous year. And our goal is to continue to advance our science-based initiatives, so that our current and future therapies reach the patients that we serve, and patients are able to access innovative medicines now and in the future. Moving toward 2019 commercial strategy, we will focus on three core strategic areas. First, to build on EXONDYS 51's reach. EXONDYS 51 was a various successful launch, which is a wonderful achievement in the face of measurable and notable headwinds. However, our work is not done. For 2019, our focus is to bring EXONDYS 51 to more patients. This is centered around a multi-step approach to patient identification and reimbursement. We will continue to identify DMD genotype…

Thank you, Bo. And with that, let's open the call to questions.

[Operator Instructions] And our first question comes from the line of Brian Skorney with Baird. Your line is open.

Hey, good afternoon guys. Thanks for taking my question. I got most of my gene therapy questions in this morning. So maybe I'll take a different type this afternoon and just ask you about PPMO. I know that you have an open label extension for 5051 posted to clinical trials. Just hoping to kind of get some color on where you are in dosing, if you're at therapeutic doses with a 5051 and when we might actually see some expression data? Do you think that could be a 2019 event?

So, a couple facts. One, it won't be a 2019 event. What we're really looking at in 2019 both in our single-ascending doses and as we transition, from all these setting dose is safety and where the real goal here is to get to a place where we know what the maximum tolerated dose for the therapy is. I think you know, just remind us on the phone, in preclinical models, we see very robust expression if we get the right dosing with our peptide conjugated PMO as much as in order of magnitude more penetration therefore more exon skipping and therefore more dystrophin versus the PMO. So the real issue for us is safety margin issue, can we get to the right dosing but I can give you some very good news right now, which is, things are going very well in our single-ascending dose study and we're going to transition to a multi-ascending dose study, but, I would be misleading you, if I told you that I can give you the green side yet on the top dose because we're not anywhere near that now. So, by the end of this year, we will have a very good idea on the maximum tolerated dose and therefore the safety margin for the therapy, and we can probably do some work around what that might mean from an expression level based on preclinical models, but it really be from there that will go into what validated the model and then we'll create a study that actually shows the exact expression we are getting in our expense. Not, what I read through, not just to our first program, remember behind that program we have five additional therapies about the guidance, if I'm not getting it wrong together about 42% to 43% of the Duchenne Muscular Dystrophy community that could be served by the PPMO.

Thank you. And our next question comes from the line of Anupam Rama with JP Morgan. Your line is open.

Hi, guys. This is Tessa filling in for Anupam this evening. Thank you for taking our questions and congratulations again from us on all the continued progress. On the limb-girdle portfolio, with the caveat, I know that meetings with regulators are on the horizon for the limb-girdle programs. Can you comment on timeline to regulatory discussions and what program updates you can be confident in 2019? Thanks so much guys.

I think at this point, we do a lot of talking internally about the timeline -- and there's two sets of timelines here, one is dependent upon the clinical and regulatory pathway itself, which will require discussions with the agency and the other of course when you're dependent on that, are the commercial transfer across development work is one of the things we absolutely know based on discussions we've had with the agency late in 2018 is that we need to get to a place where we have commercial supply and commercial process material and dose patients on that supply as well. But for us to start discussing the exact timelines yet, it's very likely to have the opportunity to mislead at this point. So, the first thing we need to do, is to get to the agency. We will be doing that very soon. And I know what -- to promise you have to request a meeting and then of course, [indiscernible] the meeting and have it with the agency. But, certainly we will have later this year the ability to come back and provide better guidance on, not only substantively the pathway to a potential approval both in the United States and around the world for each of these five programs, but also flight path on the manufacturing processes. I can tell you that we are working really hard on that as, I said earlier and I'll keep saying over and over again, we see these preliminary results on 2E, just as we felt with our microdystrophin program it places upon us a sense of enormous obligation to get moving into -- I can tell you across the organization. We set our team, our manufacturing folks, our regulatory folks, all working like mad to better define so that we can talk more concretely about the pathway forward for while at these programs.

Thank you. And our next question comes from the line of Tazeen Ahmad with Bank of America. Your line is open.

Hi, good afternoon guys. Thanks for taking my question. So, I just wanted to get your thoughts on the time you think it'll take to complete the transfer from the adherence stack to the ISELS [ph] process and also what do you predict some of the challenges could be in that process? Thanks.

Well, again I don't want to give a hard dates right now we just acquired Myonexus. So, there's few predicate things we have to do even before we get it in the process. First, we have to get IPs transfered over that and then we got to tax technic is a very straightforward thing. But some of that can take its own amount of time, which is to get a tech transfer from Nationwide Children's Hospital over to, what -- this case it's Paragon and then over to start working on process development work and assay development work and yield optimization at Paragon. So, I can't give any hard -- but I can tell you this -- the one very positive thing about where we are right now is that our microdystrophin program is leading the way. So, we are already -- we've already had microdystrophin program counting to the process of having IND transfer guys and tech transferring over to our partner Brammer, then certain process development work, now we're fairly deep into yield optimization and assay development and a lot of that work is going to near to benefit of five of our limb-girdle program. So, while in one sense I'm not giving you more deadlines right now for concerned neck, some of it is requires more validation to speak confidently about it, all of the work we're doing on microdystrophin is providing insight into what will be joined very, very, very soon in limb-girdle.

Thank you. And our next question comes from the line of Alethia Young with Cantor Fitzgerald. Your line is open.

Hey, guys. Thanks for taking my question. I mean, congrats again on this morning, but I have a question about Golodirsen and the launch, I mean do you think that the ramp feed for this EXONDYS 53 population could potentially be a little faster since I would assume more patients are genotype, just was kind of curious if you give us like a little bit framework to think about a 53 launch versus the 51 launch? Thanks.

Yes. It's great. I'm going to answer that question instead of Bo, because he [indiscernible]. The truth is that Bo and his team have done a brilliant job over the last few years of defining actually a lot of the work regarding casimersen that earned benefit. So, I don't know the exact 60% to 70% of patients are now genotype, but working, we have great case established PBMD, Bo and his team have extraordinary amount work and that work will apply also to Golodirsen so, there will be, there will be a ramp here just like there was ramp in the 10%, but it ought to be, they have the benefit from all the great work that has been done with dystrophin, EXONDYS and it ought to be healthier ramp when we get Golodirsen approved. And I can tell you that Bo is over here wildly in agreement. Well, we've got the genotyping done. We have very deep relationship with the physicians we done a very good job of forging relationships with payers and so that Golodirsen should benefit from all of that.

Thank you. And our next question comes from the line of Christopher Marai with Nomura. Your line is open.

Hey. Just a quick one, I guess nine patients dosed in the microdystrophin Phase III, I was as wondering if you could provide some clarity on when we might hear about any data from that, and if you would be updating us if there were safety signal that we need to know about what that safety signal maybe? And then just quickly on casimersen any approval path forward there? Thank you.

Yeah. Fine. On Golodirsen I apologize. On Golodirsen, the question was, are there any safety signals that are at risk?

No, I'm...

No, things are going well. Our most significant issue right now is Dr. Mendell is working his head off to get everybody in and about three biopsies strained and then dose, so right now I think we are doing brilliant -- he's doing brilliant, Dr. Mendell quite brilliant worked with, nine patients already dosed. So our biggest issue right now is just making sure that we hit our Q2 goal of having all 24 patients dosed. Things are going very well there. And then I think you've asked about casimersen, if I'm not mistaken. Jeff -- I'm getting him chunks of no on that. Apologies, re-ask the second question? I apologize for that.

And our next question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is open.

Hi. This is Bert on for Brian, and congratulations again on the Limb-Girdle data from this morning and thanks for taking our question. I just wanted to clarify whether you've been getting any ongoing feedback from the FDA during the Limb-Girdle 2E study and do you have any sense of their comfort with your plan to manage or prevent the liver toxicity that you saw? And related to that, is FDA sign off a gating factor for dose escalation in this study, or is that more just up to Sarepta and the DSMB? Thank you.

So, thanks for that question. I propose continue to see back. Obviously, we haven't had formal interactions with the FDA, we do not file the FDA of data. From what you've been gazing of dose escalation, that is not strictly required by protocol by the FDA. But, as we said, we are planning to interact with them anyway. But from the point of dose escalation, that does not require FDA's approval. I think from the point of view of the liver function, I think it's really important to emphasize the fact that this was -- if these were transient bumps even in the context of the serious adverse event where the child was admitted, it was a very transient bump, it responded very rapidly within days of reescalation of prednisone, this child as constitutes as prevented off, has now tapered off the prednisone and the liver enzymes are at baseline and have remained so and are stable. I suggest this is indeed a transit event. And then going forward, obviously, we are modifying our glucocorticoid regime to more prescriptively call for longer dosing.

So, the biggest issue on analysis of this sector, now this clinical supply of glucocorticoid and the dose is really an internal question, I mean in you know, you guys have the meaning which is -- we are seeing what we would believe to be the remarkable expression. We have also some insight both from our preclinical models and from our micro-dystrophin program that we can safely dose higher than this and we got to make a decision about what the right answer for that is. As I've said before, neither of those answers either direction will have any material impact on the timelines of the fly path in bringing this therapy to the community.

Thank you. And our next question comes from the line of Ritu Baral with Cowen. Your line is open.

Hey, guys. Thanks for taking the question. Which programs do you think have the most positive read through from the micro -- I'm sorry from the Limb-Girdle 2E data this morning? Which of those constructs are most parallel, I guess Doug you mentioned three out of the five have the same promoter, which are those? And how should we think about, maybe, Charcot-Marie-Tooth and that construct and all of this?

So, let me say one thing and then I will leave it to Louise, who will give you more detail. In the broadest of strokes, there is significant read through of all of these programs for a number of reasons. First, chiefly among them are these, first of all, for us, [indiscernible] we should give it right back, she will be modest about this with the designer of all five of these programs. So, the same thoughtful approach to the design of these programs, and special promoters and like was the same across both our microdystrophin [ph] program in all five of these. All five of them very importantly are rh74. All of them deal with dystrophin associated proteins complex, they are all single gene mutations. They are all aimed to do a very similar thing, which is to have a full length gene and therefore the native protein cause of the injury. Now, let, moving into the details, you're right, three of the five, the ones that are associated with a desire to have an increased benefit in the heart use this MHCK7 promoter, which recently pursued reported out that we have is giving us a lot of confidence around the productivity of that promoter and then one of the five I should note we should comment on that is those have something, there is a little different, which is individual vector construct and slightly different only in that regard, but we got to say, maybe a be little more detail from you doctor.

Sure. I think, Doug covered it well, but all of these programs are using rh74, so those are reasons to all the type program. In addition to 2E, we're using MHCK7 promoter and the LGMD 2B and 2C programs, which also have significant cardiac involvement. On the other two programs, LGMD 2E and LGMD 2L, we're using a PMCK -- promoter which also expresses very highly in skeletal muscle, but not as much in the heart, where we don't necessarily need any of these programs. So, we're very thoughtful in the way that we design which promoters to use for which study that we have or (technical difficulty). The point of the LGMD 2E program, we're using a novel dual vector approach, where we reconstitute the entire protein using two different vectors. But this is also delivering a full length gene to understand all of our programs again are delivering the native full length in gene and corresponding protein.

Thank you. And our next question comes from the line of Danielle Brill with Piper Jaffray. Your line is open.

Hi, guys. Thanks for the question. Quick one from me. In the DMD trial, are you targeting all patients or are you excluding those with mutated exon 18 to 58?

This is Doug. So, let's be clear. There is two answers to that. In the current trial, there are exclusions for certain earlier exons and get on the later exon, that is not our long-term goal. So, I don't want to create the false impression that we envision a label at the end they have those exclusions -- we intend in connection with our next trial, or set of trials associated with the commercial material to address those issues and move some of the restrictions that out of an over-abundance or abundance of caution existed in the protocol for -- in cause of Stage 1 in our study one and two. So therefore our ultimate goal is to have the broadest possible coverage both of patients age groups, geography, but also gene and factors involved.

And let me just clarify, we are not excluding 18 to 58 it's the corollary, 1 to 17 and the 59 set back, we are including 18 to 58. As Doug said the plan is to expand sort of -- in a planned manner in our development plan.

Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is open.

Thanks for taking the question. This is Ross on for Salveen. Just one quick question on the micro-dystrophin program. Can you just provide an update on the status and the timelines associated with beginning of the commercial supply program?

Yeah. So the goal remains the same. So, we've got a lot to do, but we are deepening the process. The biggest gaining item -- there are two things we need to do first to start the commercial supply trial. One is the design of the trial that should not be at all, in gaining item, we are doing some interesting work to make sure that we got really thoughtful program there, but the other is, of course, the commercial supply itself. As I've mentioned before, we are deep in the process development work, in fact we're in the yield optimization stage and the released assay and other assay in development stage, so our goal remains the same and in the second half of 2019, like we toward -- little bit later in the second half of 2019, our goal is to commence a multi-center, multi-country site study with commercial supply and we are continuing to work in that direction.

Thank you. Our next question comes from the line of Gena Wang with Barclays. Your line is open.

Thank you for taking my question. Just one regarding manufacturing. Wondering if you can walk through the additional steps that will be required for Brammer Bio to produce initial commercial product. And then also will you be willing to test suspension sales for better scalability in the future?

So, let me take the second question first. On suspension, there are a lot of really interesting ways to go about commercial supply; there is, what we do right now is sell those units there's suspension, people talk about potential efficiencies associated with bacteria or virus or insect based approaches of those familiar approach. We have chosen and we've got a lot of programs right now, we have 10 gene therapy programs. We will have more than those in the future and in connection with our goal of becoming the world's leader in gene therapy to treat rare disease, we will be looking on lot of things including suspension and perhaps even back virus. We have a very interesting relationship with Lacerta and they something called the one back system, but with respect to our Duchenne Muscular Dystrophy Program, (technical difficulty) initial limb-girdle programs and probably all of limb-girdle programs. We had chosen to go to our sellers, we've done that for a very specific reasons. And that is because it is the closest to what we have at Nationwide Children's Hospital. Nationwide Children's Hospital has a million based inherent system, but it's on high hyper stacks and not easily scalable and I sell the share much in common it is also inherent. It is also in the million, but it is, a three dimensional structure and therefore, it's much more scalable. What is good about is that I sell is versus suspension is very scalable, so we get very good productivity, out of ISELS that competes with suspension and beyond that as we sort of cost it out with cost of goods perspective, we feel very confident and comfortable with where we're tracking. So I would suspect that we will not be moving to suspension with respect to our…

Thank you. And our next question comes from the line of Joel Beatty with Citi. Your line is open.

Hi, guys. Thank you for taking my question. This is Shawn Egan on for Joel. Could you provide a little additional color on the interim look for the confirmatory commercial supply trial in DMD? Specifically, the number of patients, you expect to have at that interim look -- the timing and points that are needed to support manufacturing comparability?

So, we're at a stage right now. I don't want to provide you even ranges of numbers right now because, again in order we are going to start with girdle -- we need to take. We need to come up with some views. We have some preliminary views and we need talk to the FDA. So we are very clear, we are -- we need to work in close collaboration with the agency, and ensure that everything we are doing are is exactly as the agency received. So, we do have a view that are more like a quite drive and will have interim look, our goal have an interim goal in some number of patients after what we would envision to be three month biopsies because that's what we were looking at it seems to be working quite well. And then what comparability across the two suppliers both commercial and clinical. But the exact number is going to require additional discussions for the agencies before it feel, I feel confident for my -- within the partner.

Thank you. Our next question comes from the line of Tim Chiang with BTIG. Your line is open.

Hi, thanks. Doug, what do you think about enrolling non-ambulatory patients in some of the gene therapy studies, I mean of course, you're seeing pretty good results in younger patients at this point? But, at some point do you think you'll be looking to dose older patients as well?

Couple of thoughts on that. The first is I just said, you know, by way and background in our limb-girdle program we have all the mix, they are ambulatory, but they are 13 years result. So, we have already begun with our gene therapies, looking at older patients. As it relates specifically to the Duchenne program, let's go to the end. It is crucial that the program has -- is build so that their is access to over a non-ambulatory patients who, if we are grudge our thesis and if -- early evidence bears out will benefit enormously, qualitatively an extension of live from our Duchenne muscular dystrophy program. Our current program with Dr. Mendell of course, has narrow age range, but let us be clear, the reason it has a narrow age range is they are using it has our age range is to ensure this disease, that is -- is degenerative and of course different markers and different functional outputs depending on age, we need to have it narrowed so that we actually can prove the functional benefits correlated to expression. In our next group of studies, we are going to look very thoughtfully and carefully at how we ensure that we can address older and non-ambulatory patients in a way that not only gets us a label that ensures this has -- much better access for older patients, but then we have data that is compelling, we are payers in the United States and also for HDAs and others around the world. So this is going to be a big part of our next study.

Thank you. Our next question comes from the line of Vincent Chen with Bernstein. Your line is open.

Thanks for taking the question. Thinking about the commercial confirmatory study, what would you expect the powering of SA to look like recognizing you'll be fairly unconstrained from a manufacturing and patient enrollment perspective and that was a broad populations of folks you like to enroll? How many patients are you likely to target?

Well, we don't have the exact numbers now their will be significantly higher than the 24 patients that we have with Dr. Mendell for a host of reasons, one of which is we want a multi-center trial to start with that alone, we want a multi-center trial, we currently want multi-center and very likely multi-country trial. So, there will be an opportunity to have much larger and actually still because of the number of sites rapidly enrollment, right. You want to use with Dr. Mdendell is, he is working like mad and every additional patient innovation to Dr. Mendell right now, who as to treat following so they had service rates, well we are unconstrained in second trial as regards to that. So, I don't have the exact numbers, it will be significantly larger than the 24 patient study that we have. Today because in addition to -- in addition to that and empowering we have to think about some of the other patient populations to ensure that we're addressing that into the next study.

Thank you. And our next question comes from the line of Hartaj Singh with Oppenheimer & Company. Your line is open.

Great. Thanks, everyone. Thank you for the question. I just had quick question on the expenses. Sandy you've provided a lot of color and granularity in your comments and on the press release. Can you just give us a little bit of an idea whether the fourth quarter, which I know generally tends to be heavier on expenses. So maybe that's not the right way to think about, but can you just give us any thoughts on how to think about expenses going into 2019 and with the potential launch of Golodirsen, if you do that in the second half, the manufacturing, could, -- we see a heavier, second half versus first half? Thank you very much for the question.

Thanks, Hartaj. So we are not guiding specifically on expenses for 2019. What I would like to use to exist is to look at our Q4 expenses and use that as a trend to project on what are the expenses will be for this year. And for perspective, in Q4, we spend approximately $130 million for our OpEx on a non-GAAP basis versus about 85.5 -- $84.5 million of revenue. So, we do not have a significant cash burn from our operations. Most of the borrowing was from one-time events that either hit the balance sheet or were pro forma items. We had approximately $100 million of cash expense and most of that was from business development deals and our gene therapy manufacturing prepayments, as well as a large amount for our CapEx much of that too was for gene therapy and RNA manufacturing. So, I think, I'm guiding toward our Q4 expenses to use that as a trend obviously, to slope upwards, and that I add a little bit more for our potential launch for Golodirsen as well as for our ex-US ramp especially in Brazil and Japan as well as in Europe.

Thank you. And our next question comes from the line of Timothy Lugo with William Blair. Your line is open.

Hi. MILES Mitch on line for Tim. I'm just wondering whether you can comment on where you I was thinking some additional guidance from the AMI regarding [indiscernible] approval in the EU. And if you see a similar headwinds to potential approval pathway for golodirsen and casimersen there or if you're still thinking about potentially unblinding promo if your in ESSENCE trial and if that would help you in that manner? Thanks.

Yes. Thank you. So, first with respect to eteplirsen, it is our goal to take additional scientific advice in fact we've been encouraged by the EMA to take scientific advice. So, we'll -- I will never promise that will have an update in 2019, on the potential pathway for eteplirsen in Europe, as I have now as we -- we did a lot of work in 2018 with the goal of bringing eteplirsen to the European patient community and we haven't -- we weren't successful in 2018. But, we remain committed possible to find pathway to Europe, if you think it only fair to patients in Europe have access to therapy that is -- from our perspective benefiting patients with exon 51 in that ability of the US. As it relates to golodirsen and casimersen, we have the ESSENCE trial and it is very likely that will be the pathway for approval, that is a placebo-controlled blinded study. We couldn't unblinded it, let us be clear about that, we couldn't unblinded as a basis for seeking approval somewhere else because that trial, assuming that we are approved for golodirsen and then for casimersen the very beginning of next year will serve as the confirmatory trial for both of those approval. So it has to remain intact and viable and blinded as well. So, ESSENCE will almost certainly be the pathway to potential approval in Europe for golodirsen and casimersen and will have better insight once we take scientific advice -- additional scientific advice from the EMA on eteplirsen later this year.

Thank you. And our next question comes from the line of Liisa Bayko with JMP Securities. Your line is open.

Hi, there. Thanks for taking the question. You sort of touched upon a topic that I've been pondering a lot myself and that's the whole pricing models around gene therapy and I'd be curious as sort of a leader in this conversation, and then really at the forefront of what's going on. Can you maybe talk about what are some of the kind of what's rising to the surface as the most reasonable pricing models and then, is there -- there are some sort of consistency or do you think it will be, and I'll be the same across different payer types. For example, the one payer systems like in Europe or kind of the private payer and multi-payer systems like in the US. Can you maybe just speak to those two things. I guess that sort of idea of one common payment system for gene therapy globally, and then also what sort of emerging as the -- the best payment models are? What's most topical at this point in time? Thanks.

Yes, it's a fascinating issue because we are doing a ton of work right now. Your good point it's our goal to be a leader in gene therapy, and one of our goals to be a leader is beginning to saw in the structure issues associated with assets. Gene therapy, I suspect that won't be one overarching structure because I don't think there will be even one overarching structure in the United States. United States is been were exploring a number of things, but let me step back for a second and put this in comment. There are really two issues with the gene therapy. One question, that people have is just the value itself, well, the pricing value in gene -- I posit that putting aside distraction, public relation, issues in reality, the value of transformative gene therapies, which is exactly what society want which are one-time significant transformative moments in to there. This is not actually a value proposition issues associated with gene therapy. But, in this -- let's start with US, which will be some of the test case that will be bringing around the rest of the world. There are fundamental structural issues that we need to address and financials for and there are obviously answers for. So things like payments over dealing with payers, payments overtime issues or subscription models, I can tell you that Bo and his team is actually in reimbursement, our government affairs group are all working together with a number of really and little in a bit of outside folks, looking at these issues and coming to views and which of these various models which menu of these models, will work fast and there's most the medical, because most of this what is best for the payers. We are having -- we're already having advisory genetic meetings and discussions with a number of private payers who will begin the dialog with state Medicaids and CMS as well that's a little bit behind private payer discussions. So, I think by, I would say from Sarepta perspective, by the end of this year into early next year we will have very -- almost certainly landed on, one couple of perspectives on what we would do in the United States. Then -- then subset of those around the world to address the access issues and ensure that there is maximum access in basis rapidly when this therapies are approved, I thing, most likely alternatives, which is just lumpsum payment is, payments overtime and probably inside of that risk-based payments, and I will say that so on is the value proportion is there Sarepta remains committed any of those models and we're looking at all of them right now.

Thank you. Our next question comes from the line of Yun Zhong with Janney. Your line is open.

Hi, thank you for taking the question. So this is a follow-up question on casimersen because I don't believe I heard you answer your previous question, so I wonder if you can confirm the status of the biopsy analysis and do you plan to announce that biopsy data before you submit the NDA and also is there a specific level of protein expression you'd like to see, to feel comfortable before moving into an NDA submission? Thank you.

Yes. We don't have, so there is -- the short answer is that the biopsies will be analyzed in the coming 60 -- 30 to 60 days maximum. So, we will have -- we don't have the data now. We'll have that data and then two things; one, we certainly will -- we'll certainly share with the investment community the results of that, add over before we will make a submission to the agency on that. As far as the amount, I can only tell you what the preclinical models predicts. The preclinical models that which have been fairly accurate in their predictions as an example predicting when we work to golodirsen, then golodirsen it would be somewhere in the two to three times more expressions that we have with the eteplirsen in whole its about 2.4 times more expression than eteplirsen and the preclinical models predict that casimersen will be sort of in the hurt of golodirsen maybe modestly below golodirsen and at least some all of our discussions with the agency and precedent that would be in a position that which we comfortably support the submission for casimersen in the significant biopsies are as preclinical models suggested.

Thank you. And our next question comes from the line of Edward Nash with SunTrust Robinson Humphrey. Your line is open.

Hey. Thank you for taking our question. This is [indiscernible] for the Edward Nash. A quick question on the MPS IIIA programs and since we already started pivotal trial, have you guys define or Lysogene has discuss based the revenue agencies regarding what's the bar for approval. And secondly, can you share us a reminder, is what are the Phase I/II data looks like? Thank you.

Sure. I will turn this to Doug again.

Thanks for that question, their have been interactions with agencies in the design and planning of this study, but I don't feel that, I want to sort of disclose details of that right now. And the prior data basically, I think most of the data, the prior Phase I data use different constructs. I think it's important to understand. The construct thing used in this current study was actually significantly optimized construct which enabled in the non-clinical setting, a substantial enhancement in both delivery and expression, and is it that construct that is in our current study, a pivotal study that prepared by LYSOGENE.

Thank you.

One interesting thing about MPS III program, it has an interesting read through some of our programs. In the preclinical models with MPS III, early models, they used a particular promoter and they switched promoters and found a 300% increase in expression levels. You think about that, and then you look across to our programs and you look across to our micro-dystrophin program and then you look at our push to enroll program, which is a quarter of the dosing that we're still seeing really robust expression even in a quarter that does. It does begin to get along with a view that there is a particular promoter that we've chosen that make CK7 heavy chain promoter and it appears to be very productive. We've seen -- it speaks to what could happen with our growth programs and obviously as a [indiscernible] microdystrophin program.

Thank you. This concludes today's question-and-answer session, and I would now like to turn the call back to Doug Ingram, Chief Executive Officer, for closing remarks.

Thank you all for spending the evening with us. Thank you doubly for those who were with us this morning for our webcast. I appreciate it obviously as I said in other forums 2019 is the year of execution. We have much to do as we track through the year and we execute, we'll obviously be providing additional guidance on all of our programs, certainly including our Duchenne Muscular Dystrophy program as well as all of our Limb-Girdle programs. So thank you all and have a lovely…

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program. You may all disconnect. Everyone, have a great day.