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 begin at that time. If anyone should require operator assistance during the conference, please press star then zero on your telephone keypad. As a reminder, today's program is being recorded. 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, Chelsea. 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 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 the 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 could materially differ from these forward-looking statements, as any of such risks can materially and adversely affect the business, results of operations, and trading price of Sarepta's common stock.
For a detailed description of applicable risks and uncertainties, 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 ask that you indulge me as we have much to discuss today. Before we discuss the fourth quarter itself, let us put it all in the context of the full year of 2018. I do not believe I risk hyperbole 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.
In fact, we took 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 of our next generation RNA technology, the 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 Mendell last year, all patients showed robust microdystrophin expression properly localized to the sarcolemma, upregulation 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 were seen, all were managed with steroids and resolved. 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 of 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. Second, by better defining our development pathway for microdystrophin. In 2018, we also built 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-targeted gene therapy programs, including our Pompe disease program. An exclusive license agreement with Lysogene for MPS IIIA, otherwise known as Sanfilippo syndrome, a rare and fatal inherited neurodegenerative lysosomal storage disorder. The lead program is currently dosing patients in a Phase II/III clinical trial.
A third agreement with Nationwide Children's Hospital for rights to a 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 at $84.4 million, a 47% increase over the same quarter in 2017, resulting in 2018 sales, as 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 later this year, we'll have to provide updated guidance that will include not only eteplirsen but also golodirsen.
We are growing at a very healthy 21%-25% in our third full year of sales. However, we are also entering that phase where we must continue to fight misunderstandings and misuses of the accelerated approval process by some who would use it as an excuse to slow or fight coverage for older or non-ambulant patients. For example, some state Medicaid have mistakenly relied upon the accelerated approval path as an excuse to deny coverage. 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 was approved via the FDA's accelerated approval mechanism. Even in the face 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 robs children of their right to therapy, and we will continue to fight for access for older and non-ambulant patients for 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 that 8% of Duchenne patients who are exon 53 skip amendable. After the close of the quarter, the FDA accepted golodirsen for filing and granted priority review with a 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 for the ESSENCE study for casimersen, our drug designed to treat exon 45 skip amendable Duchenne patients, another 8% of the Duchenne community.
If 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 treating 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. We 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. Turning to our gene therapy platform. We made significant progress in the fourth quarter. As we have discussed in the past, in service of our goal of becoming a 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 teams 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. Armed with that guidance, we commenced our previously planned 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. Consistent with our stated goal made earlier in 2018, we commenced dosing Study 102 in the fourth quarter of 2018. Study 102 is a double-blind, 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. Jerry 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 and yield optimization and assay development work now. Our goal is to complete that work and commence a multi-center, multi-country confirmatory study using 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, we'll take additional guidance from the FDA and other ministries of health before its commencement, please know that our study goal is to build a program that, if successful, will permit the broadest availability of our microdystrophin therapy to those patients with Duchenne muscular dystrophy. By broad, we 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 four mechanisms to permit dosing, even of patients who have pre-existing neutralizing antibodies to RH74. 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, 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. 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 for the study, as measured by the percentage of beta-sarcoglycan-positive fibers, was 51%, and the mean intensity of fibers was 47%, apologies, compared to normal control.
All post-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. In all patients, expression of beta-sarcoglycan was associated with significant expression and upregulation of the dystrophin-associated protein complex. Remarkably, all patients showed significant decreases of serum creatine kinase or CK levels at last measure, with a mean reduction of CK of over 90% from baseline. It is important to note that these robust expression results were observed at a dose of five times E to the 13th. This is a quarter of the dose used in our microdystrophin study, yet we're seeing the expression level that I've just mentioned and that Dr. Rodino-Klapac discussed earlier today. We anticipate significant read-through from our 2E program to our 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 2D program, or dysferlin, MYO-301 from our limb-girdle 2L program. All of these programs involve restoration of a missing protein that makes up the dystrophin-associated protein complex. Most interestingly, all are the complete gene, therefore the complete native protein, the absence of which is the cause of each of these diseases. This is extremely important as it means that there may be a compelling basis for an expedited approval process, potentially including an accelerated approval process in the U.S. 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 capsid, RH74, as does our microdystrophin program. Each program and construct was designed by Dr. Louise Rodino-Klapac.
Three of the five constructs employ 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 U.S. associated with our first five programs, about the same size as all of Duchenne muscular dystrophy. Globally, there may be as many as 76,000-138,000 patients with the five mutations we are studying, although many of them may yet be diagnosed as there are no current treatment options for any of these patient groups. Given the exceptional results that we've seen in our first cohort 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 over all five programs.
This should ensure that we can move with the rapidity that these patient populations deserve. There are three immediate activities that we must now accomplish for these limb-girdle programs. First, we need to meet with the agency as soon as is reasonably possible to discuss the 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 will decide whether to explore a 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. On the other hand. At a dose of five times E to 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 on the timing of these programs, as the primary rate limiter is the development of commercial supply in any event. Third, we need to map out the commercial manufacturing strategy and the timeline for all of these 5 programs with our partner, Paragon. Again, once we have this mapped out, we will provide an update. Know, however, that the manufacturing process for these programs is nearly identical to our microdystrophin program. We will be tech transferring the process from Nationwide Children's Hospital to Paragon, and then moving from a mammalian adherent HYPERStack process to a similar but far more scalable mammalian adherent iCELLis process, just as we have done with our microdystrophin program. Beyond our microdystrophin and five LGMD programs, we have a number of additional gene therapy programs that are advancing this year, 2019.
You will have seen that on February 14th, 2019, we and our partner, Lysogene, announced that we have dosed our first patient in the advanced trial for MPS IIIA, or Sanfilippo syndrome. 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 U.S. alone. Currently there are no available treatment options for CMT Type 1A patients.
As I have said in other forums, while we have made considerable progress, 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. To be clear, when I speak about competition, I mean this cruel disease that we're dealing with. In the U.S. alone, DMD claims the lives of 400 boys and young men every year. That means every week that we are delayed, eight children in the United States alone will die perhaps needlessly. Every month that we are delayed, 33 children die. Every quarter of delay equates to about 100 children who will be taken by this disease.
Beyond Duchenne, we are convinced that our gene therapy engine offers the opportunity to bring a longer and better life to a multitude of patients living with a multitude of genetic disease. Diseases like MPS IIIA and CMT and Pompe, and our various limb-girdle diseases and beyond. While we permit ourselves the 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 a rich portfolio of LGMD candidates, cements our position as a leading gene therapy company, bringing our pipeline to 25 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 negotiated an equitable deal based on fair terms. Further, because we opted in early, Sarepta generated a substantial savings of approximately $50 million. 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 a GAAP basis. The press release is available on the SEC as well as Sarepta's websites.
Please refer to our press release for a 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 the 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 U.S. We reported a non-GAAP net loss of $58.7 million, or $0.85 per share in the fourth quarter of 2018, compared to non-GAAP net loss of $13.3 million, or $0.21 per share in the fourth quarter of 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 for 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 a 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%-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 build-out 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 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 equivalents, and investments. This was an increase of $381 million in our cash position from the prior quarter, which is primarily driven by an 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 towards 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's 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 of our Gene Therapy Center of Excellence, and our continued global commercial expansion and build-out. Most of the expense growth will be driven by manufacturing, with gene therapy manufacturing being the most significant driver. The agreements we execute with Brammer, Paragon, and Aldevron will be in place for an entire year and will ramp up from early-stage development work to full production in order to support our expanding gene therapy portfolio for intervention in DMD, LGMD, CMT, Pompe, and MPS III disease areas. The compelling early data we are generating with both our microdystrophin and our limb-girdle programs have justified our 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 a 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 the position to be 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. Our team, the best team I've ever 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 EXONDYS 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 quarter of the previous year. 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 to our 2019 commercial strategy, we will focus on three core strategic areas. First, to build on EXONDYS 51's reach. EXONDYS 51 was a very successful launch, which is a wonderful achievement in the face of measurable and notable headwinds. 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 patients and get them into centers of excellence. We will also continue to educate on exon-skipping amenability, as well as identifying new patients through a series of targeted educational initiatives to 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 and reimbursement for all patients living with a mutation amenable to exon 51 skipping. Access and reimbursement continues to be a steady but slow climb. We have grassroots efforts actively underway to work in partnership with state Medicaid plans to ensure coverage for individuals living with DMD and who have an exon 51 amenable deletion. Our conversations are science-based and urgent.
We have generated additional data that supports the benefits of the drug, and we anticipate this data to 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 a cornerstone of the 21st Century Cures Act, and how plans provide 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 golodirsen later this year. The tenets of our plan will be tailored to reach those individuals in the Duchenne community who are 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 submit 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 U.S. 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. Launch preparations are already underway. As I previously outlined, we have gained incredible experience in DMD that will serve as the foundation for a potential launch for DMD gene therapy. 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 focus 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 have 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 an 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 that 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 benefits of these medicines, especially for gene therapies that can potentially change a person's life forever in just one dose. Misvaluing these treatments could have a very real and significant consequence, putting life-altering medications out of reach for patients who have faced a debilitating and fatal disease with no alternative treatment options, while also stifling the development of future transformative therapies. Sarepta is at the forefront of this issue. 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 at 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. We are very excited for the limb-girdle community. We're doing a tremendous amount of market research on limb-girdle. Currently believe there could be as many as 6,000 patients in the U.S. and globally between 76,000 and 138,000 patients just within our five mutations that we're studying.
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 could not 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 patients' 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. With that, let's open the call to questions.
Ladies and gentlemen, if you have a question at this time, please press the star, then the number one key on your telephone keypad. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. In the interest of time, we will take only one question from each participant. To prevent any background noise, we ask that you please place your line on mute once your question has been stated. Thank you. 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, maybe I'll take a different tack this afternoon and just ask you about PPMO. I know that you have an open label extension for SRP-5051 posted to clinical trials. Just hoping to get some color on where you are in dosing, if you're at therapeutic doses with a SRP-5051, and when we might actually see some expression data. Do you think that could be a 2019 event?
A couple thoughts. One, it won't be a 2019 event. What we're really looking at in 2019, both in our single ascending dose and as we transition over to a multi-ascending dose, is safety. The real goal here is to get to a place where we know what the maximum tolerated dose for the therapy is. As many of you know, but just to remind those 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 an order of magnitude, more penetration, therefore more exon skipping and therefore more dystrophin versus the PMO. The real issue for us is a safety margin issue. Can we get to the right dosing?
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. I would be misleading you if I told you that I can give you good insight yet on the top dose, because we're not anywhere near that now. 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 could probably do some work around what that might mean from an expression level, at least based on pre-clinical models. It'll really be from there that we'll have validated the model, and then we'll create a study that actually shows the exact expression that we're getting, if that makes sense.
That will read through not just to our first program, but remember, behind that program, we have five additional therapies about, if I'm not getting it wrong, together, about 42%-43% of the Duchenne muscular dystrophy community that could be served by the PPMO.
Thank you. Our next question comes from the line of Anupam Rama with JPMorgan. Your line is open.
Hi, guys. This is Tessa filling in for Anupam this evening. Thank you for taking our questions, 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 timelines to regulatory discussions and what program updates you can be confident in 2019? Thanks so much, guys.
I think at this point that we do a lot of talking internally about the timelines, there's two sets of timelines here. One is dependent upon the clinical and regulatory pathway itself, which will require discussions with the agency. The other, of course, quite independent of that, are the commercial tech transfer and process development work. 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. For us to start discussing the exact timelines yet, it very likely has the opportunity to mislead at this point. The first thing we need to do is get to the agency. We will be doing that very soon.
I don't want to promise you, have to request the meeting and then, of course, brief the meeting and have it with the agency. 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 then around the world for each of these five programs, but also a flight path on the manufacturing process. I can tell you that we are working really hard on that. As I said earlier, I'll keep saying over and over again, when we see these preliminary results on 2A, just as we felt with our microdystrophin program, it places upon us a sense of enormous obligation to get moving.
I can tell you across the organization, the Gene Therapy Center of Excellence team, our manufacturing folks, our regulatory folks, are all working like mad to better define so that we can talk more concretely about the pathway forward for all five of these programs.
Thank you. 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. I just wanted on the time you think it'll take to complete the transfer from the HYPERStack to the iCELLis process. Also, what do you predict some of the challenges could be in that process? Thanks.
Well, again, I don't want to give hard dates right now. We just acquired Myonexus, there's a few predicate things we have to do even before we get in the process. First, we have to get INDs transferred over to us, then we've got to get a tech, which is a very straightforward thing, something that can take its own amount of time, which is to get a tech transfer from Nationwide Children's Hospital over to what, in this case, is Paragon, then over to start working on process development work and assay development work and yield optimization at Paragon. I can't give any hard deadlines. 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.
We've already, in the microdystrophin program, gone through the process of having the IND transferred to us, then tech transferring over to our partner, Brammer, then starting the process development work. Now we're fairly deep into yield optimization and assay development, and a lot of that work is going to inure to the benefit of all 5 of our limb-girdle programs. While in one sense, I'm not giving you hard deadlines right now for considering that, and some of it requires more validation before we can speak confidently about it. All of the work we're doing around microdystrophin is providing insight into what we'll be doing very soon in limb-girdle.
Thank you. Our next question comes from the line of Alethia Young with Cantor Fitzgerald. Your line is open.
Hey, guys. Thanks for taking my question. Congrats again on this morning. I have a question about Golodirsen and the launch. Do you think that the ramp speed for this Exon 53 population could potentially be a little faster since I would assume more patients are genotyped? Just was kind of curious if you would give us a little bit of framework to think about a 53 launch versus the 51 launch. Thanks.
That'd be great. I'm going to answer that question instead of Bo because he will famously try to underrepresent a number before. 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 eteplirsen that will inure to the benefit. I don't know the exact, but the 60%-70% of patients are now genotyped. Working with great patient advocacy groups like PPMD, Bo and his team have done an extraordinary amount of work, and that work will apply also to Golodirsen. There will be a ramp here just like there was a ramp with eteplirsen, but it ought to benefit from all of the great work that's been done with eteplirsen and EXONDYS, and it ought to be a healthier ramp when we get Golodirsen approved.
I can tell you that Bo's over here wildly agreeing with me. Well, the genotyping's done. We have very deep relationships with the physician communities. We've done a very good job of forging relationships with payers, that golodirsen should benefit from all of that.
Thank you. 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 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 a safety signal that we need to know about what that safety signal may be. 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 a risk?
No.
Microdystrophin.
No, I'm microdystrophin.
Oh, microdystrophin. Things are going well. Our most significant issue right now is that Dr. Mendell is working his head off to get everybody in and pre-biopsied, screened, and then dosed. Right now, I think we're doing brilliant. He's doing brilliant. Dr. Mendell is doing brilliant work with nine patients already dosed. 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. I think you asked about casimersen, if I'm not mistaken. You know, I'm getting head shakes of no on that. Apologies. Re-ask the second question. I apologize for that.
Our next question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is open.
Hi, this is Berton for Brian. 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? 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.
Thanks for that question. Apropos continuous feedback, obviously, we haven't had formal interactions with the FDA. We do notify the FDA of data. From the point of the gating of dose escalation, that is not strictly required per protocol by the FDA. As we said, we are planning to interact with them anyway. From the point of view of dose escalation, that does not require FDA approval. From the point of view of the liver function, it's really important to emphasize the fact that 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 re-escalating prednisone.
This child, in the context of serious adverse event, has now tapered off the prednisone, and the liver enzymes are at baseline and have remained so and are stable, suggesting that this is indeed a transient event. Going forward, obviously, we are modifying our glucocorticoid regime to more prescriptively call for longer dosing.
The biggest issue on the analysis of another clinical supply and the dose is really an internal question with our DSMB, which is we're seeing what we would believe to be very remarkable expression. We have also some insight, both from our preclinical models and from our microdystrophin program, that we can safely dose higher than this, and we've 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 or the flight path for bringing this therapy to the community.
Thank you. 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 limb-girdle Type 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 in all of this?
Yeah. Let me say one thing, then I'll leave, and Louise Rodino-Klapac 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, of course, Dr. Louise Rodino-Klapac, I hope she'll be modest about this, was the designer of all five of these programs. The same thoughtful approach to the design of these programs, and selection of promoters and the like, was the same across both our microdystrophin program and all five of these. All five of them, very importantly, are RH74. All of them deal with the dystrophin-associated protein complex. They're all single gene mutations. They all aim to do a very similar thing, which is to have the full-length gene and therefore the native protein that is the cause of the injury.
I'll let Louise go into detail. 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 Louise, in the first two report outs that we have, is giving us a lot of confidence around the productivity of that promoter. One of the five, I should note, and Louise should comment on that, does have something that's a little different, which is it's a dual vector construct and slightly different only in that regard. With that said, maybe a little more detail from you, doctor.
Sure. I think Doug covered it well that all of these programs are using RH74, so there's read-through to all of the five programs. In addition to Type 2E, we're using the MHCK7 promoter in the LGMD2B and LGMD2C programs, which also have significant cardiac involvement. The other two programs, LGMD2C and LGMD2L, we're using a PMC kip promoter, which also expresses very highly in skeletal muscle, but not as much in the heart, where we don't necessarily need it in these programs. We were thoughtful in the way that we designed which promoter to use for which study, but we have robust preclinical results in all. To the point of the LGMD2B program, we're using a novel dual vector approach where we reconstitute the entire protein using two different vectors. This is also delivering the full-length gene.
In a sense, all of our programs, again, are delivering the native full-length gene and corresponding protein.
Thank you. Our next question comes from the line of Danielle Brill with Piper Jaffray. Your line is open.
Hi, guys. Thanks for the question, and 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. Let's be clear, there's two answers to that. In the current trial, there are exclusions for certain of the earlier exon than a couple of the later exon. That is not our long-term goal. I don't want to create the false impression that we envision a label at the end that would have those exclusions. We intend, in connection with our next trial or set of trials associated with commercial material to address those issues and remove some of the restrictions that out of an overabundance or an abundance of caution existed in the protocol for what we call Stage 1 and now Study 102. Our ultimate goal is to have the broadest possible coverage, both of patients, age groups, geography, but also genotype as well.
Let me just clarify, we're not excluding 18 to 58. It's the corollary. It's the one to 17 and the 15 to 19. We're including 18 to 58. As Doug says, the plan is to expand 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.
Hi, thanks for taking the question. This is Ross for Salveen. One quick question on the microdystrophin program. Can you just provide an update on the status and the timelines associated with beginning the commercial supply program?
The goal remains the same. We've got a lot to do, but we're deep in the process. There are two things we need to do to start the commercial supply trial. One is the design of the trial. That should not be at all a gating item. We're doing some interesting work to make sure that we've got a really thoughtful program there. 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 release assay and other assay development stage. Our goal remains the same. In the second half of 2019, likely a little bit later in the second half of 2019, our goal is to commence a multi-center, multi-country site study with a commercial supply, and we're 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. Then also, will you be willing to test suspension cells for better scalability in the future?
Let me take the second question first. On the suspension, there are a lot of really interesting ways to go about commercial supply. What we're doing right now with iCELLis units, there's suspension. People talk about potential efficiencies associated with baculovirus or an insect-based approach as opposed to a mammalian approach. We've got a lot of programs right now. We have 10 gene therapy programs. We will have more than those in the future. In connection with our goal of becoming the world's leader in gene therapy to treat rare disease, we'll be looking at a lot of things, including suspension and perhaps even baculovirus. We have a very interesting relationship with Lacerta, they have something called the OneBac system.
With respect to our Duchenne muscular dystrophy program, at least with our initial limb-girdle programs and probably all of our limb-girdle programs, we have chosen to go to our iCELLis units, we've done that for a very specific reason. That is because it is the closest to what we have at Nationwide Children's Hospital. Nationwide Children's Hospital has a mammalian-based adherent system, it's on HYPERStack. They're not easily scalable. Our iCELLis shares much in common. It is also adherent. It is also mammalian, it is a three-dimensional structure, therefore it's much more scalable. What is good about it is that our iCELLis versus suspension is very scalable. We get very good productivity out of the iCELLis that competes with suspension.
Beyond that, as we sort of cost it out from a cost of goods perspective, we feel very confident and comfortable with where we're tracking. I would suspect that we will not be moving to suspension with respect to our Duchenne muscular dystrophy microdystrophin program or at least right now in our limb-girdle programs. On the pathway, the pathway is as I've said before. We have a number of things to do, and I can tick off which ones have been done and which ones remain to be done. The first thing we had to do was get an IND in our hands and then go through the process of tech transfer information, Nationwide Children's Hospital with our Duchenne program to Brammer Bio sites. That is long done and done and dusted. We've completed that work.
The next thing to do was to start working with the iCELLis units and do process development, we are deep in that process. In fact, we're more than deep in that process. We've actually started the next phase, which is yield optimizations. We've started getting runs and doing yield optimizations, and we're very deep into that as well. The next thing we're doing, and we're doing many of these 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 bespoke, that need to be developed to ensure that we have the right commercial process and the right release process for material. We're sort of deep into those as well, and we've got a very good team and a very good partner with Brammer as well in that development.
That's kind of where we are right now. That should, if everything goes brilliantly, lead us to a place where, parallel from that, we'll be working on the exact design and getting sites up and ready to go for this commercial supply trial. Before the end of this year, in the second half of 2019, it is our goal to commence the commercial supply trial.
Thank you. 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 Sean Egan 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?
We're at a stage right now that I don't want to provide even ranges of numbers right now, because again, similar to what we said with Myrtelle, we need to come up with some views. We have some preliminary views. I think we need to talk to the FDA. We're very clear. We need to work in close collaboration with the agency and ensure that everything that we're doing on is exactly as the agency would see it. We do have a view that our commercial supply trial will have an interim look. Our goal is to have an interim look on some number of patients after what we would envision to be three-month biopsies, because that's what we've been looking at. It seems to work quite well. Then look at comparability across the two supplies, both commercial and clinical.
The exact number is going to require additional discussions before the agency, before I feel confident providing you with a view on that.
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? Of course, you're seeing really good results in younger patients at this point. At some point, do you think you'll be looking at those older patients as well?
A couple of thoughts on that. First, just so you know, just by way of background, in our limb-girdle program, we have older patients. They are ambulatory, but they are 13 years old. 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 is built so that there is access to older and non-ambulatory patients who, if we are correct in our thesis and if our early evidence bears out, will benefit enormously qualitatively in an extension of life from our Duchenne muscular dystrophy program. Our current program with Dr. Mendell, of course, has a narrow age range.
Let us be clear, the reason it has a narrow age range is to ensure in this disease that is degenerative and requires different markers and different functional outputs depending on age, we need to have it narrow enough 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 that we have data that is compelling for payers in the U.S. and also for HTAs and others around the world. 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 that study to look like, recognizing you'd be fairly unconstrained from a manufacturing and patient enrollment perspective, and that there's a broad population of folks you'd like to enroll? How many patients are you likely to target?
We don't have the exact numbers now. They will be significantly higher than the 24-patient study we have with Dr. Mendell for a host of reasons, one of which is we want a multi-center trial. Let's just sort of start with that alone. We want a multi-center trial. We frankly want a multi-center and very likely multi-country trial. There will be an opportunity to have a much larger end, and actually still because of the number of sites rapidly enrolling, right? One of the issues with Dr. Mendell is he is working like mad, and every additional patient is a patient that Dr. Mendell right now has to treat and follow on. That has its own constraints. We'll be unconstrained in our second trial as regards to that.
While 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 that and powering, we have to think about some of the other patient populations and ensure that we're addressing that in connection with the next study.
Thank you. Our next question comes from the line of Hartaj Singh with Oppenheimer & Co.. Your line is open.
Great. Thanks, everyone. Thank you for the question. I just had a quick question on the expenses. Sandy, you had 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 it, but 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 of the manufacturing, could we see a heavier second half versus first half? Thank you very much for the question.
Thanks, Hartaj. We're not guiding specifically on expenses for 2019. What I would guide you towards is to look at our Q4 expenses and use that as a trend to project out what our expenses would be for this year. And for perspective, in Q4, we spent approximately $130 million for our OpEx on a non-GAAP basis versus about $84.5 million of revenue. We did not have a significant cash burn from our operations. Most of the burn 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 for 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.
I think I'd guide you towards our Q4 expenses to use that as a trend. Obviously, it'll slope upwards. Then I'd add a little bit more for our potential launch for golodirsen as well as for our ex-U.S. ramp, especially in Brazil and Japan, as well as in Europe.
Thank you. Our next question comes from the line of Timothy Lugo with William Blair. Your line is open.
Hi, Myles Minte r on the line for Tim. Just wondering whether you can comment on where you are with seeking some additional guidance from the EMA regarding eteplirsen approval in the EU, and if you see similar headwinds to a potential approval pathway for golodirsen and casimersen there, or if you're still thinking about potentially unblinding a PROMOVI or an ESSENCE trial and if that would help you in that manner. Thanks.
Thank you. 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. I don't want to overpromise, but we'll have an update in 2019 on the potential pathway for eteplirsen in Europe. As everyone knows, we did a lot of work in 2018 with the goal of bringing eteplirsen to the European patient community, and we were unsuccessful in 2018, but we remain committed, if possible, to find a pathway to Europe. We do think it only fair that patients in Europe have access to this therapy that is, from our perspective, benefiting patients with exon 51 amenability in the U.S. 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 unblind it. Let us be clear about that. We couldn't unblind it as a basis for seeking approval somewhere else because that trial, assuming that we are approved for golodirsen and then for casimersen at the very beginning of next year, will serve as the confirmatory trial for both of those approvals. It has to remain intact and viable and blinded as well. ESSENCE will almost certainly be the pathway to a potential approval in Europe for golodirsen and casimersen, and we'll have better insight once we take additional scientific advice from the EMA on eteplirsen later this year.
Thank you. 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. I'd be curious, as sort of a leader in this conversation and really at the forefront of what's going on, can you maybe talk about what's rising to the surface as the most reasonable pricing models? Is there some sort of consistency, or do you think it'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 U.S. Can you maybe just speak to those two things?
I guess the sort of idea of one common payment system for gene therapy globally, also what's sort of emerging as the best payment models, or what's most topical at this point in time? Thanks.
Yeah. It's a fascinating issue because we're doing a ton of work on it right now. To your good point, it's our goal to be a leader in gene therapy, and one of our goals is to be a leader in beginning to solve some of the structural issues associated with access to gene therapy. I suspect there won't be one overarching structure because I don't think that there'll be even one overarching structure in the United States system. We're exploring a number of things. Let's step back for a second and put this in context. There are really two issues with the gene therapy. One question that people have is just the value itself. Well, the pricing and value of gene therapy.
I posit that putting aside distraction and public relations issues, in reality, the value of transformative gene therapies, which is exactly what society wants, which are one-time significant transformative moments, is there. This is not actually a value proposition issue associated with gene therapy. Let's start with the U.S., which will be some of the test cases that we'll be bringing around the rest of the world. There are fundamental structural issues that we need to address and find answers for, and there are obviously answers for them. Things like dealing with payers, payments over time issues or subscription models.
I can tell you that Bo and his team in access and reimbursement and our government affairs group are all working together with a number of really innovative outside folks, looking at these issues and coming to views on which of these various models or which menu of these models will work best and is most amenable, because most of it's what is best for the payer. We're already having advisory committee meetings and discussions
With a number of private payers, and we're beginning a dialogue with state Medicaids and CMS as well. That's a little bit behind the private payer discussions. I think, I would say from a Sarepta perspective, by the end of this year into early next year, we will have almost certainly landed on the one or couple of perspectives on what we would do in the United States, then a subset of those around the world to address the access issues and ensure that there is maximum access to patients rapidly when this therapy's approved. I think the most likely alternative to just a lump sum payment is payments over time, and probably inside of that, risk-based payments. And I will say that, so long as the value proposition is there, Sarepta remains committed to 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. This is a follow-up question on casimersen because I don't believe I heard you answer a previous question. 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? Also, is there a specific level of protein expression you would like to see to feel comfortable before moving into NDA submission? Thank you.
The short answer is that the biopsies will be analyzed in the coming 30 to 60 days maximum. We don't have the data now. We will have that data, then two things. One, we will certainly share with the investment community the results of that at or before we would make a submission to the agency on that. As far as the amount, I can only tell you what the preclinical models predict. The preclinical models, which have been fairly accurate in their predictions. As an example, predicted when we went to golodirsen, that golodirsen would be somewhere in the two to three times more expression than we had with eteplirsen. Lo and behold, it was about 2.4 times more expression than eteplirsen. The preclinical models predict that casimersen will be sort of in the hunt of golodirsen, maybe modestly below golodirsen.
At least from all of our discussions with the agency and precedent, that would be in a position that would very comfortably support a submission for casimersen, assuming that the biopsies are as the preclinical models suggest.
Thank you. 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 Fang Lang for Edward Nash. A quick question on the MPS IIIA programs. Since you already started the pivotal trial, have you guys discussed or Lysogene has discussed with the regulatory agencies regarding what is the bar for approval? Secondly, can you share with us, remind us what are the phase I, II data looks like? Thank you.
Sure. I'll turn this to Dr. O'Neill.
Right. Thanks for that question. There have been interactions with agencies in the design and planning of this study. I don't feel that I want to sort of disclose details of that right now. The prior data, basically, I think most of the data, the prior phase I data used a different construct. I think that's important to understand. The construct that's being used in this current study was actually a significantly optimized construct, which enabled, in the non-clinical setting, a substantial enhancement in both delivery and expression. It is that construct that is in our current study, the pivotal study that's being run by Lysogene .
Thank you.
I will say the one interesting thing about the MPS III program that has an interesting read-through to some of our programs is in the preclinical models with MPS III, early models, they used a particular promoter. They switched promoters and found a 300% increase in expression levels. When you think about that, then you look across to our programs, and you look across to our microdystrophin program, then you look at our first limb-girdle program, which is a quarter of the dosing, yet we're still seeing really robust expression, even at a quarter of the dose. It does begin to give one the view that the particular promoter that we've chosen, this MHCK7 heavy chain promoter, appears to be very productive. Which speaks reams to what could happen with our other limb-girdle programs and obviously gives us additional comfort with our Duchenne muscular dystrophy program.
Thank you. This concludes today's question and answer session. 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. Certainly thank you doubly for those who were with us this morning for our webcast. 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, but certainly including our Duchenne muscular dystrophy microdystrophin program, as well as all of our limb-girdle programs. Thank you all.
Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program. You may all disconnect.
Thank you.
Everyone, have a great day.