Sarepta Therapeutics, Inc. (SRPT) Q4 2018 Earnings Report, Transcript and Summary

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 year, all patients showed robust microdystrophin expression, properly localized to the sarcolemma, up regulation of the dystrophin associated protein complex, an additional indication of the functionality of microdystrophin, an unprecedented drop in creatine kinase or CK levels and all showed positive functional improvement that is markedly greater than natural history would predict. While transient elevated liver enzymes, we're seeing all we managed with steroids and results. We also defined our pathway to bring our microdystrophin gene therapy to the community as rapidly as possible. First, by building out our hybrid gene therapy manufacturing approach through hiring a talent and entering into significant long-term partnerships with gold standards in gene therapy plasmid supply and manufacturing and that is of course, Aldevron, Brammer Biosciences and Paragon as well. And second, by better defining our development pathway for microdystrophin. In 2018, we also build out our gene therapy engine with additional programs, including the following, a long-term strategic investment and license agreement with Lacerta Therapeutics for rights to multiple CNS targeting gene therapy programs including our comp-agencies program. An exclusive license agreement with Lysogene for MPS IIIA, otherwise noted Sanfilippo disease, a rare and fatal inherited neurodegenerative lysosomal storage disorder. The lead program is currently dosing patients in the Phase II/III clinical trial. And a third agreement with Nationwide Children's Hospital for rights to gene therapy program to treat Charcot-Marie-Tooth or CMT neuropathy, which is the most common inherited neuromuscular disorder in the world. Turning now to the fourth quarter of 2018, we were particularly productive. Starting with our RNA platform, we had another strong quarter of sales with EXONDYS 51 standing in $84.4 million, a 47% increase over the same quarter in 2017, resulting, in 2018 sales that I mentioned of $301 million. We are also reporting today that our 2019 guidance will be between $365 million and $375 million, but, I do want to be very specific about that -- that is for eteplirsen only, that excludes any Golodirsen sales. If we are as we anticipate successful in the approval of Golodirsen sales. If later this year, we'll have to provide updated guidance that will include not only eteplirsen, but also Golodirsen . So, we are growing at a very healthy 21% to 25% in our third full-year of sales, however, we are also entering that phase where we must continue to find this understandings and its uses the accelerated approval process by some would use it as an excuse to slower by coverage for older or non-ambulant patients. For examples, some state Medicaids have mistakenly relied upon the accelerated approval path as an excuse to deny coverage. Now in 2018, CMS issued a warning to all of the states, reminding them that they do not have the right to deny coverage on the basis that a therapy has approved via the FDA's accelerated approval mechanism. Even in the phase of this warning, some states have continued to deny coverage and require patients to appeal. While states are losing these appeals at a nearly 90% rate, the approach slows down access and watch children of their right to therapy, and we will continue to fight for access for older and non-ambulant patients toward EXONDYS in 2019. Regarding our RNA pipeline, we completed our FDA submission for Golodirsen in the fourth quarter as previously promised. Golodirsen is our PMO RNA therapy designed to treat back 8% of Duchenne patients for exon 53 skipping amenable. After the close of the quarter, the FDA accepted Golodirsen for filing and granted priority review with the PDUFA date of August 19, 2019. The agency also has indicated that they currently do not intend to conduct an Advisory Committee for Golodirsen. We will also be analyzing biopsies from the ESSENCE study or casimersen, our drug designed to treat exon 45 skipping amenable Duchenne patients, another 8% of the Duchenne community. It's supported by the data we plan to submit the NDA for casimersen in 2019 with a target approval in the first quarter of 2020. If successful Sarepta will have three RNA-based therapies to treat patients in the United States by the first quarter of 2020, more than doubling the number of patients who may benefit from our PMO platform. We continue to make progress on our next-generation RNA technology the peptide-conjugated PMO platform or PPMO for short. To remind in animal models our PPMO technology exhibited greatly improved cell penetration, exon skipping and therefore dystrophin production as compared to our current PMO technology. Our first program focused on exon 51, about 13% of the community will be transitioning from a single ascending to a multi-ascending study in the very near term as previously represented. Our goal is to have insight on safety and maximum tolerated dosing by the end of 2019. Now, turning to our gene therapy platform. We made significant progress in the fourth quarter. As we have discussed in the past, the service of our goal is becoming the world leader in gene therapy with an enduring gene therapy engine. We are rapidly building a first-in class Gene Therapy Center of Excellence, the greatest level of manufacturing capacity that the world has yet seen in gene therapy and bolstering our already proven commercial health economics and medical affairs genes to be the leaders in gene therapy. The foundation of our gene therapy ambitions rests first with our microdystrophin gene therapy program, the largest late-stage gene therapy program currently in development in biotech. Consistent with our prior representations we scheduled and met with the FDA in the fourth quarter of 2018 to gain insight and guidance on our program. And armed with that guidance, we commenced our previously planned to 24 patient placebo-controlled trial. We now call that trial Study 102 with the goal of further characterizing safety and expression and demonstrating the functional benefits of robust expression of our microdystrophin construct. Again consistent with our stated goal made earlier in 2018, we commenced dosing Study 102 in the fourth quarter of 2018. Study 102 is a one to one placebo-controlled single site study at Nationwide Children's Hospital with the principal investigator being gene therapy legend Dr. Jerry Mendell and the material being clinical supply coming from Nationwide Children's manufacturing facility. By this week Dr. Mendell will have dosed nine patients thus far in the study with the goal of completing all of the dosing in the second quarter of this year. With our manufacturing partners we completed the technology transfer of the microdystrophin candidate from Nationwide Children's and are completing process, development, yield optimization and assay development work now. Our goal is to complete that work and commence a multi-center, multi-country confirmatory studies in commercial supply by the end of 2019 with among other things, an interim analysis before the middle of 2020. It is also our goal to build commercial supply across the second half of 2019 and all of 2020, so that we could be in a position to have sufficient supply to fully serve the community by the end of 2020. While we are still working on the particulars of our commercial supply trial and we will take additional guidance from the FDA and other Ministries of Health before its commencement, please note that our study goal is to build a program that is successful, will permit the broadest availability of our microdystrophin therapy to those patients with Duchenne muscular dystrophy. And by broadly, mean broadest age, genotype and geographic range. As a separate exercise we are also working on solving a number of other potential issues with respect to gene therapy, both of which are in the research phase to be clear. We are conducting preclinical work in store mechanisms to permit dosing even updation to a pre-existing neutralizing antibodies to AAVrh74. Fortunately, we are currently seeing only about a 15% screen-out rate for neutralizing antibodies. However, given our mission we see even that level as too high so we are working on programs that may eventually someday address this issue. We are also conducting work on the concept of redosing in gene therapy. Now beyond microdystrophin, we have 10 additional gene therapy programs exploring 10 separate rare diseases. Earlier today, we held a webcast in which we provided the results of the first three patient cohort of our Limb-Girdle 2E program, the first of five separate rare diseases we are studying under the umbrella of Limb-Girdle Muscular Dystrophy or LGMD. As Dr. Rodino-Klapac reported all three patients in the study showed robust expression of transduced beta-sarcoglycan. Mean gene expression from the study as measured by the percentage of beta-sarcoglycan positive fibers was 51% and the mean intensity of fibers is 40%, -- 47% apologies, compared to normal control. All those drug treatment biopsies showed robust levels of beta-sarcoglycan as measured by Western blot with a mean of a very impressive 36.1% compared to normal control and in all patients expression of beta-sarcoglycan was associated with significant expression and up regulation of the dystrophin associated for e-commerce. And remarkably all patients showed significant decreases of serum creatine teenager, CK levels at last measured with a mean reduction of CK of over 90% from base. It is important to note that these robust expression results were observed at a dose of 5 times ease of the 13. This is a quarter of the dose used in our microdystrophin study and yet we're seeing the expression levels that I've just mentioned and Dr. Rodino-Klapac discussed earlier today. We anticipate significant read through from 2E program to other limb-girdle programs, that's our program MYO-102 for limb-girdle 2D; MYO-103 for limb-girdle 2C, MYO-201 from our limb-girdle 2B program or Dysferlin and MYO-301 from our limb-girdle 2L program. All of these programs involve restoration of imaging protein that makes up the dystrophin associated protein complex. And most interestingly, all or the complete gene and therefore the complete native protein the assets of which is the cause of each of these diseases. This is extremely important as it means that there may be, maybe a compelling basis for an expedited approval process potentially including at an accelerated approval process in the United States across these programs, although to be very clear this is something that we must discuss with the agency and take additional guidance regarding. Beyond just that each program employs the same caption AAVrh74 as those are microdystrophin. Each program construct was designed by Dr. Louise Rodino-Klapac, and three of the five constructs employed the identical promoter used in our microdystrophin gene therapy program. Current analysis suggests that there are approximately 10,000 or so LGMD patients in the United States associated with our first five programs, about the same size as all of Duchenne muscular dystrophy. And global -- globally there maybe as many as 76,000, even 138,000 patients with the five mutations, we are studying, although many of them may yet be diagnosed as they are no current treatment options for any of this patient groups. Given the exceptional results that we've seen in our push toward and understanding that there is potential read through from our first program to these other programs, you saw in our earlier press release today that we have decided to exercise our option to acquire Myonexus and take direct and complete control, overall by program. This should ensure that we can move with rapidity that these patient populations deserve. There are three immediate activities that we must now accomplish, through these limb-girdles. First, we need to meet with the agency as soon as it's reasonably possible to discuss their path forward for all five of these programs. Once that meeting has taken place and we have better insight, we will provide an update. Second, we need -- we will decide whether to explore higher dose cohort with clinical supply as is currently permitted in our current protocol. This will take some analysis as we are already seeing remarkable results, which might argue against a higher dose. But, on the other hand, at a dose of five times either the 13th, we are only a quarter of the dose of our DMD program, so, there appears to be a real opportunity to safely explore higher doses. Fortunately, this decision should have no impact at all, the timing of these programs as the primary rate limiter is the development of commercial supply in there. And third, we need to map out the commercial manufacturing strategy, and the timeline for all these five programs with our partner Paragon. Again, once we have this mapped out, we will provide an update. However, that the manufacturing process for these programs is nearly identical to our microdystrophin program. We will detect transfering the process from Nationwide Children's Hospital to Paragon and then moving from immunity and here in hyperstack process to a similar, but far more scalable than here in [indiscernible] process, just as we have done with our microdystrophin. Beyond our microdystrophin and five LGMD programs, we have a number of additional gene therapy programs that are advancing this year 2019. You'll have seen that on February 14, 2019, we and our partner, Lysogene announced that we have dosed our first patient in the advanced trial for MPS IIIA or Sanfilippo diseases. Looking toward the second half of this year, with our partner Dr. Zarife Sahenk at Nationwide Children's Hospital, we are preparing to dose our first cohort of patients with Charcot-Marie-Tooth, or CMT type 1A, the most common form of the most common inherited neuromuscular disorder affecting over 2.8 million people worldwide. CMT type 1A itself, affects approximately 50,000 patients in the US alone. And currently, there are no available treatment options for CMT type 1A patients. As I've said in other forums, while we have made considerable markers and while Sarepta has more opportunity in front of it than I have seen in my nearly 25 years in pharma and biotech. This is not a time for us to congratulate ourselves because 2019 is clearly the year of execution for us. We have very ambitious timelines for our programs to stay ahead of the competition. But to be clear, when I speak about competition, I mean this cruel disease that we're dealing with. In the US alone, DMD claims the lives of 400 boys, and young man every year. That means every week that we are delayed eight children in the United States alone will die perhaps, needlessly. And every month that we have delays 33 children and every quarter of delay equates to about 100 children who will be taken by this disease and beyond Duchenne, we are convinced that our gene therapy engine offers the opportunity to bring a longer and better life to multitude of patients , but they would have a multitude of genetic diseases. Diseases like MPS-IIIA and CMT and pompe and our various limb-girdle diseases and beyond. And so while we remain ourselves occasional moment of pride for a job well done thus far, we are mostly driven by a singular sense of responsibility, that comes with believing that we have the opportunity to save lives. I will now turn the call over to Sandy Mahatme for an update on our financial performance. Sandy?

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 BioMarin, primarily related to increasing demand for EXONDYS 51 during 2018, as well as the one-time write-off of work-in-process material. We expect our cost of sales in 2019 to increase slightly over 2018. Currently, we are projecting a range of 13% to 14% of net revenue. On a GAAP basis, we recorded $146.2 million and $44.4 million in R&D expenses for the fourth quarter of 2018 and 2017 respectively, a year-over-year increase of $101.8 million. The year-over-year growth in GAAP R&D expense was driven by upfront and milestone payments, increased patient enrollment in our late-stage clinical trials, a ramp-up of manufacturing activities for our PPMO platform and an expansion of our R&D pipeline. On a non-GAAP basis, the R&D expenses were approximately $77 million for the fourth quarter of 2018, compared to $41 million for the same period of 2017, an increase of $36 million. Turning to SG&A. On a GAAP basis, we recorded $64.2 million and $32.2 million of expenses for the fourth quarter of 2018 and 2017, respectively, a year-over-year increase of $32 million. On a non-GAAP basis, the SG&A expenses were $52.9 million for the fourth quarter of 2018, compared to $26.2 million for the same period of 2017, an increase of $26.7 million. The year-over-year increase is primarily driven by continued buildout, supporting our global expansion. On a GAAP basis, we recorded $2.3 million in net interest expense for the fourth quarter of 2018, compared to $2.7 million net interest expense for the same period of 2017. The decrease in interest expense is primarily driven by the payoff of certain debt instruments during the third quarter of 2018. Turning to our cash position. We ended Q4 with approximately $1.174 billion in cash, cash equivalents and investments. This was an increase of $381 million in our cash position from the prior quarter, which is primarily driven by equity raise of $513 million, offset by $42.6 million related to new business development deals and $36 million to our manufacturing initiatives. In addition, we have prepaid approximately $92.7 million toward future manufacturing expense in connection with our gene therapy and RNA programs. From a cash perspective, as we focus on this year, several factors will drive Sarepta expenses higher in 2019 versus prior years. Investments in developing our pipeline will continue in 2019. This is due to the continued expansion of pipeline, current programs moving from smaller early stage trials into late-stage development, the opening up of our Gene Therapy Center of Excellence and our continued global commercial expansion and buildout. Most of the expense growth will be driven by manufacturing. The gene therapy manufacturing being the most significant driver. The agreements we executed with Brammer, Paragon and Aldevron will be in place for an entire year and will ramp up from early stage development work with full production in order to support our expanding gene therapy portfolio for intervention in DMD, LGMD, CMT, Pompe and MPS IIIA disease areas. The compelling early data we are generating with both our microdystrophin and our limb-girdle programs are justified, are being more aggressive in the scale necessary to meet the growing needs of the patient community. Separately, we are also preparing for the potential approval for Golodirsen by the FDA in mid-2019 and continue to build out our footprints in markets in Europe, Latin America and Asia. From cash position, we remain well positioned to execute our plan and invest in our business. Our philosophy of having a very strong cash balance remains an asset and it allows us to not only invest appropriately in our current pipeline but also to remain in a position to get off on the front-footed strategy in our field. With that, I'd like to turn the call over to Bo for a commercial update. Bo?

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 to patients and get them into centers of excellence. We will also continue to educate on exon's skipping inability as well as identifying new patients through a series of targeted educational initiatives, help support families desperately seeking information. Identifying patients and getting them into care is only the first step. We need to continue to fight for access for reimbursement for all patients living with the mutation amenable to exon 51 skipping. Access and reimbursement continues to be a steady but slow coin. We have grassroots efforts actively under way to work in partnership with safe Medicaid plans to ensure coverage for individuals living with DMD and you have an exon 51 amenable position [ph]. Our conversations are science-based in origin. We have generated additional data that supports the benefits of the drug and we anticipate this data will be published soon. This data, along with the EXONDYS 51 experience at the KOL level, will help continue to support reimbursement. We are continuing to build an appreciation and understanding around the accelerated approval process, which is the cornerstone of the 21st Century Cures Act and how plans provide the coverage for Accelerated Approval Products. As they were reminded by CMS in 2018, states are forbidden to deny coverage of any therapy made available through the FDA's Accelerated Approval Process and we will continue to have discussions with states on accelerated approval pathway and why they need to provide coverage for every child amenable to EXONDYS 51. Our second strategic area of focus for 2019 is to advance our RNA franchise. As Doug mentioned, we announced on February 14, 2019, that the FDA has accepted our NDA for Golodirsen, or SRP-4053. The FDA also granted Golodirsen priority review status with a PDUFA date of August 19, 2019. In light of this development, we will be ready to launch the Golodirsen later this year. The tenants of our plan will be tailored to reach those individuals in the Duchenne community through our exon 53 skip amenable. We will leverage our knowledge and experience of EXONDYS 51 to deliver this drug to patients as fast as possible. Continuing with our RNA therapies, we are currently on track to cement our NDA for casimersen by mid-2019 with a target approval for the first quarter of 2020. If approved, casimersen will serve approximately another 8% of the Duchenne community. What this means is, by early 2020, we could have three approved drugs out of our RNA platform doubling our PMO-based opportunity in the United States. Our third major strategic area of focus is to prepare for the future. To state the obvious, gene therapy is poised to hopefully transform Duchenne and Limb-Girdle Muscular Dystrophy forever. Microdystrophin has the potential to be the most successful rare disease launch ever. And launch preparations are already under way. As I previously outlined, we have gained incredible experience in DMD that will serve as the foundation for potential launch for DMD gene threapy. However, there will be new areas of focus, which include innovative pricing models, access, site readiness, assay development and engagement of key stakeholders worldwide. A critical part of this third strategic area of progress is gene therapy pricing. Gene therapies have the potential to profoundly transform the course of previously untreatable diseases. For the over 7,000 rare diseases currently in existence and the over 400 million patients that these diseases impact, there is only one approved gene therapy on the market today. We, at Sarepta, has every intention to increase this number of approved drugs dramatically in the future. At Sarepta, we believe that the advancement of human health begins with bold steps and audacious goals, which is why a critical component of our efforts in 2019 will focus on playing active role in creating new payment and reimbursement models for life-altering gene-based medicines. Sarepta is working with thought leaders in public health and health economists to create a new framework for the way in which treatments for rare diseases are assessed. Additionally, Sarepta is working with economists and payers to create new reimbursement models then address one-time potentially curative therapies. The goal of these reimbursement models is to support patient access, while creating a sustainable model for payers and manufacturers for one-time therapies. Up to now, models assessing value such as ICER do not accurately capture the full benefit of these medicines, especially for gene therapies that can potentially change a persons live forever in just one dose. Miss-valuing these treatments could have a very real and significant consequence, putting life-altering medication out of reach for patients who have faced a debilitating and fatal disease with no alternative treatment options. While also cycling the development of future transformative therapies, Sarepta is at the forefront of this issue and we will remain there. We will continue to lead discussions on gene therapy pricing and payment models and take a seat at the table as decisions are being made, so that once-in-a-lifetime technologies and potential curative therapies will have a chance of becoming reality to treat as many rare and ultra-rare diseases as possible, ensuring that true innovation continues. This work will also establish a foundation for our ever-growing gene therapy portfolio. The data presented today on Limb-Girdle Muscular Dystrophy Type 2E is quite promising and we are very excited for the limb-girdle community. We're doing a tremendous amount of market research at limb-girdle and currently believe there could be as many 6,000 patients in the US and globally between 76,000 and 138,000 patients just within our five mutations that were studied. Unlike Duchenne, genetic testing is not as prevalent within this community and we need to focus on this initiative even more so than we did with Duchenne. In addition to our market research, genetic testing will help us get a better understanding over time of the total number of eligible patients in our key markets. We cannot be more excited to not only lead the field in the development of potentially life-altering therapies, but also pave the way for patients to access these treatments. Our work will not only help patients who have diseases that we are developing therapies for, but also for all patients who stand to benefit from potentially curative one-time therapies in the future. This is an incredible responsibility, but one we look forward to solving with our committed partners over the coming years. We are currently standing at a rare moment in time, a moment that will shape the future of healthcare and patient lives forever and we are proud to do this at Sarepta. I will turn the call back over to Doug for remarks.

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 Duchenne Muscular Dystrophy microdystrophin program or it just stands right now on our limb-girdle programs. And on the pathway -- the pathway as said before, so we had a number of things to do, and I can tick-off which ones have been done which ones remains to be done. The biggest, the first thing you have to do is get an ID&R and demand goes through the process of tech transfer information from Nationwide Children's Hospital with our Duchenne program to Brammer Biosciences that is long done and done and dusted, we completed that work. The next thing to do is to start working with ISELS units in process development and we are deep in that process segment or you've been there for us as we've actually started the next phase, which is yield optimizations, we started getting runs into yield optimization and we very deep into that as well. Then the next thing we are doing and many of this things in parallel is assay development work. There are a number of assays, some of them are off the shelf, some of them have to be disposed that need to be developed to ensure that we have the right commercial process, and the right release process for material and so we're deep into those as well and we've got a very good team and a very good partnering with Brammer as well in that development. So that's kind of where we are right now and that should if everything goes brilliantly, we can still place where in parallel from that will be working on the exact design and getting sites up and ready to go for its commercial supply trial and then by before the end of this year, second half of 2019. It is our goal to commence the commercial supply trial.

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.