Good day, ladies and gentlemen, and welcome to the Sarepta Therapeutics Fourth Quarter And Full Year Twenty 18 Earnings Call. As a reminder, today's program is being recorded. And now I'd like to introduce your host for today's program, Ian Estapan, Vice President, Chief of Staff And Corporate Affairs. Please go ahead.
Thank you, Chelsea, and thank you all
for joining today's call. Earlier today, we released our financial results for the fourth quarter year end 2018. The press release is available on our website at www.sarepta.com. Joining us on the call today are Doug Ingram, Andy Mahatme, Bob combo, Gilmore O'Neill and Luis Rodino Klapac. After our formal remarks, we'll open the call for Q And 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 contained 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 such risks materially and adversely affect the business results of operations and trading prices for Sarepta's common stock. For 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 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 itself, let us put it all in 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 and 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 dine from rare genetic disease. In the full year of 2018, we achieved another successful year of EXONDYS sales with net revenue, standing at $301,000,000 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 1st 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 to 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 2008, reported unprecedented expression level results, biological marker results, and preliminary functional results in the 4 patients participated in this proof of concept cohort. As reported by Doctor. Jerry Mangalo last year, All patients showed robust microdystrophin expression, properly localized to the sarcolemma, Up regulation of the dystrophin associated protein complex and 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 that natural history would predict. While transient elevated liver enzymes were seen, all were 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 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. And 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 Lucerne 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 disease a rare and fatal inherited neurodegenerative lysosomal storage disorder. The LEAP program is currently dosing patients in a phase twothree clinical trial. And a third agreement with Nationwide Children's Hospital for Rice to a gene therapy program to treat sharcovery tooth or CMT neuropathy, which is the most coveted inherited neuromuscular disorder in the world. Turning now to form. We had another strong quarter of sales with EXONDYS 51 standing at $84,400,000, a 47% increase over the same quarter in 2017.
Resulting in 2018 sales, as I mentioned, of $301,000,000. We are also reporting today that our 2019 guidance will be between $365,000,000 and $375,000,000, but I do want to be, very specific about that. That is for attempt to listen 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 ateplirsen, but also Golodirsen.
So we're growing at a very healthy 21% to 25 percent in our 3rd 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 and 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. 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 approved via the FDA's accelerated approval mechanism. Even in the face of this warning, some states have continued deny coverage and require patients to appeal.
While states are losing these appeals at a nearly 90% rate, The approach slows down access in Rob's 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 amenable. 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 Golodir's.
We will also be analyzing biopsies for Shen patients, another 8% of the Duchenne community. If supported by the data, we will plan to submit the NDA for casimersen in 2019 with a target approval in the first quarter of 2020. If successful, Sarepta will have 3 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 50 more than about 14% of the community. We'll 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 the maximum tolerated dosing by the end of 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 1st 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 micro dystrophin 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 the fourth quarter of 2018 to gain insight and guidance on our program. And armed with that guidance, we commenced our previously ban 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 double blind 1 to 1 placebo controlled, single site study at Nationwide Children's Hospital, with a principal investigator being gene therapy legend, Doctor. Jerry Mendell, and the material being clinical supply coming from Nationwide Children's Manufacturing Facility.
By this week, Doctor. Mendell will have dosed 9 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 micro dystrophin candidate from Nationwide Children's our completing process development to yield optimization and assay development work now. Our goal is to complete that work commence a multicenter, 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 twenty nineteen and all of twenty twenty 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, will 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, we'll permit the broadest availability of our microdystrophin therapy to those patients with Duchenne muscular dystrophy. And by broad, we mean broadest age, genotype and geographic range. As a separate exercise, we are also working 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 and support mechanisms to permit dosing, even of patients who have pre existing neutralizing antibodies to RA74.
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 which we provided the results of under the umbrella of Limb Girdle Muscular Dystrophy or LGMP. As Doctor. Rodino Klapac reported, All three patients in the study showed robust expression of transduced beta sarcoglycan. Mean gene expression from the study is measured by the percentage of beta sarcoglycan positive fibers was 51% and the mean intensity of fibers was 40% 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. And in all patients expression, a beta sarcoglycan was associated with significant expression and upregulation of the dystrophin associated protein complex. And remarkably, all patients showed significant decreases of serum creatine teenager CK levels at last measure with a mean reduction of CK of over 90% from base. Is important to note that these robust expression results were observed at a dose of 5 times E than the 13th. This is a quarter of the dose used in our microdystrophin study.
And yet, we're seeing the expression level that I've just mentioned in the doctor Rodino Klapac discussed earlier today. We anticipate significant read through from our 2E program to our other limb girdle programs. That's our program, MYL-one hundred and two for limb girdle 2d, MYO 103 for limb girdle 2c, MYO 201 from our limb girdle 2b program or Dysferlin and myo-three zero one from our limb girdle 2L program. All of these programs involve restoration of a missing protein that makes up the dystrophin associated protein complex. And most interestingly, all are the complete gene and 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, may be a compelling basis for an expedited approval process potentially including an accelerated approval process in the United States across these programs, although to be very clear, is something that we must discuss with the agency and take additional guidance regarding. Beyond just that, each program employs the same caps in rh70 4 as does our micro dystrophin program. Each program and construct was designed by Doctor. Luis Rodino Klapac. And 3 of the 5 constructs employ the identical promoter used in our microdystrophin gene therapy program.
Current analysis suggests 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 may be as many as 76,000 to even 138,000 patients with the 5 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 and take direct and complete control overall 5 programs.
This should ensure that we can move with the rapidity that these patient populations deserve. There are 3 immediate activities that we must now accomplish for these limb girdle programs. First, we need to meet with the agency as soon as it's 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. 2nd, we need 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 You're already seeing remarkable results, which might argue against a higher dose, but on the other hand, and it does have five times either 13th, we are only 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 and the primary rate limiter is the development of commercial supply in any event. And 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. No, however, that the manufacturing process for these programs is nearly identical to our microdystrophin RIM.
We will detect transferring the process from Nationwide Children's Hospital to Paragon and then moving from a million adherent hyper stack process to a similar but far more scalable mammalian adherentisELUS process just as we have done with our microdystrophin. Beyond our microdystrophin and 5 lgfv programs, we have a number of gene therapy programs that are advancing this year, 2019. You will have seen that on February 14, 2019, we and our partner lighter gene announced that we have dosed our 1st patient in the ADVANCE trial for MPS IIIA or Sanfilippo disease. Looking toward the second half of this year, with our partner, Doctor. Zarif Sohank, at Nationwide Children's Hospital, we are preparing to dose our 1st cohort of patients.
With Charcot Marie Tooth or CMT type 1a, the most common form of the most common inherited neuromuscular disorder. Affecting over 2,800,000 people worldwide. CMT Type 1A itself affects approximately 50,000 patients in the U. S. 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 progress, And while Sarepta has more opportunity in front of it than I have seen in my nearly 25 years in Farmer Biotech, This is not a time for us to congratulate ourselves because 2019 is clearly the year of execution for us. But 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, 8 children in the United States alone will die, perhaps, needlessly.
And every month that we are delayed 33 children die, 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 a multitude of patients that they would have multitudes of genetic disease. Diseases like MPS IIIA and CMT and Pompe and our various limb girdle diseases and beyond. And so while we remain ourselves the occasional moment of pride for a job well done thus far, we are mostly driven by a singular sense of the performance. Eddie?
Thanks, sir. Good afternoon, everyone. The Myonexus transaction, which has given us full access to 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 equitable deal based on Fed terms.
Further, and because we opted in early, Sarepta generated substantial savings of approximately $50,000,000. 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 a GAAP basis. The press release is available on the 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 the fourth quarter of 2018 was $84,400,000 compared to $57,300,000 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 $58,700,000 or $0.85 per share in the fourth quarter of 2018, compared to non GAAP net loss of $13,300,000 or $0.21 per share in the fourth quarter of last year I'm sorry, of 2017.
In the fourth quarter of 2018, we recorded approximately $13,100,000 in cost of sales compared to $3,500,000 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 a one time write off work in process material. We expect our cost of sales in 2019 in increase slightly over 2018. Currently, we're projecting a range of 13% to 14% of net revenue. On a GAAP basis, we recorded $146,200,000 $44,400,000 in R and D expenses for the fourth quarter of 2018 2017 respectively, a year over year increase of $101,800,000.
The year over year growth in GAAP R and 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 PPMS platform and an expansion of our R and D pipeline. On a non GAAP basis, the R and D expenses were approximately $77,000,000 for the fourth quarter of 2018 compared to $41,000,000 for the same period of 2017. An increase of $36,000,000. Turning to SG and A.
On a GAAP basis, we recorded $64,200,000 $32,200,000 of expenses for the fourth quarter of 2018 2017, respectively, a year over year increase of $32,000,000. On a non GAAP basis, the SG and A expenses were $52,900,000 for the fourth quarter of 2018 compared to $26,200,000 for the same period of 2017. An increase of $26,700,000. The year over year increase was primarily driven by continued build out supporting our global expansion. On a GAAP basis, we recorded $2,300,000 in net interest expense for the fourth quarter of 2018, compared to $2,700,000 net interest expense for the same period of 2017.
The decrease in interest expense is primarily driven by payoff of certain debt instruments during third quarter of 2018. Turning to our cash position. We ended Q4 with approximately $1,174,000,000 in cash, cash equivalents and investments. This was an increase of $381,000,000 in our cash position from the prior quarter, which is primarily driven by an equity raise of $513,000,000, offset by $42,600,000 related to new business development deals and $36,000,000 to our manufacturing initiatives. In addition, we have prepaid approximately $92,700,000 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 up 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 IIIA disease areas. The compelling early data we're generating with both our microdystrophin and our limb girdle programs have justified RB 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-twenty 19, and continue to build out our footprints in market 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, but it allows us to not invest appropriately in our current pipeline, but also to remain in a 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've watched KLL 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 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 1st 2 years of the EXONDYS 51 launch. And in doing so, generated $84,400,000 of revenue in the fourth quarter of 2018, which reflects a 47% growth over the same quarter of the 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, will focus on 3 core strategic areas: 1st, to build on EXONDYS 51s reach, Exama-fifty one was a very 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 patients and get them into centers of excellence. We will also continue to on exon skipping availability, 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 and reimbursement for all patients living with the mutation amenable to Exxon 51 skipping.
Access and reimbursement continues to be a steady but slow climb. We have grassroots efforts actively underway to work in partnership with Safe Medicaid Plans. To ensure coverage for individuals living with D And D and you'll have an Exxon51 amenable deletion. Our conversations are science based in 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, 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
19, that the FDA has accepted our NDA for golodirsen, or SRP 4053. The FDA also granted Golodirsen priority review status with the PDUFA date of August 19, 2019. In light of this, development we will be ready to launch golodirsen later this year. Who are exon 53 5th 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-twenty 19. With a target approval for the first quarter of 2020. If approved, casimersen will serve approximately another 8% of the Duchenne's beauty. What this means is by early 2020, we could have 3 approved drugs out of our RNA platform doubling our PMO based opportunity in the United States. Our 3rd major strategic area of focus is to prepare and Limb girdle muscular dystrophy forever.
Microdystrophin has the potential to be the most successful rare disease launch ever. And launch preparations are already underway. As I previously outlined, we have gained incredible experience in D And D, that will serve as the foundation for 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 3rd 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 7000 rare diseases currently in existence, and the over 400,000,000 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 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 for payers and manufacturers for one time therapies. Up to now, models assessing value, such as Eiserv, 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.
Miss valuing these treatments could have a very real and significant consequence, including life altering medications 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 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 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 6000 patients in the U. S. And globally between 76,138,000 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 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 wrapped up. I will turn the call back over to Doug for
Thank you. And our first question comes from the line of Ryan 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 tax 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 505 1. And when we might actually see some expression data, do you think that could be a 2019 event?
So a couple of thoughts. 1, 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 over, well, the ascending dose is safety. The real goal here is get to a place where we know what the maximum tolerated dose for the therapy is, as I think you know, but just to 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 an order of magnitude more penetration therefore, more exon skipping and therefore more dystrophin versus the PMO.
So the real issue for us is a safety margin issue. Can we get to the right dosing? That 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 trash a multi ascending dose study, but 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.
So by the end of this year, we will have a very good idea on the maxim tolerated dose and therefore the safety margin for the therapy and we could probably do some work around what that might mean from a expression level based on preclinical models. But it'll really be from there and then we'll go into we'll have allocated the model and then we'll create a study that actually shows the exact expression that we're getting. That makes And that will add read through, not just to our first program, but remember, behind that program, we have 5 additional, therapies about devices, if I'm not getting it wrong, together, about 42% to 43% of the Duchenne Muscular Dystrophy community that can be served by the peak
Thank you. And 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 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 program Can you comment on timelines to regulatory discussions and what program updates you can be confident in in 2019? Thanks so much guys.
I think at this point that we do a lot of talking internally about the timelines and there's 2 sets of timelines here. 1 is dependent upon the clinical and regulatory pathway itself, which will require discussions with the agency and the other of course, why independent of that are the commercial tech 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 go to a place where we have commercial supply and commercial process material and those patients on that supply as well. But for us to start discussing the exact timelines yet, it very likely has the opportunity to mislead at this point. So the first thing we need to do is get to the agency. We will be doing that very soon.
I don't want to promising the request meeting and then of course breach 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 vote in the United States and around the world for each of these 5 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, and I'll keep saying over and over again, we see these preliminary results on 2E just as we felt with our micro dystrophin program, it places upon us a sense of enormous obligation to get moving can tell you, across the organization, the lease entertainment, our manufacturing folks, our regulatory folks are all working like mad to better defined so that we could talk more concretely about the pathway forward for all five of these programs.
Thank you. And our next question comes from the line of Tazeen Ahmad with Bank of America.
Hi, good afternoon guys. Thanks for taking my question. So
I just wanted to touch
on the time you think it'll take to complete the from the adherence back to the iCELLis 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 the hard dates right now. We just acquired by an exit. So there's a few sort of There's a few predicate things we have to do even before we get in the process. First, we have to get IDs transferred over to us, and then we've got to get tactics, a very straightforward thing, but it's 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, 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 heart there.
Like I can tell you this, the one very positive thing about where we are right now is that our micro dystrophin program is leading the way. So we're already, we've already had the micro dystrophin program come through the process of having the transferred us and then tech transferring over to our partner Brammer than certain process development work. Now we're fairly deep into yield optimization and assay development. And a lot of that work is going to give years the benefit of all 5 of our limb girdle program. So while in one sense, I'm not giving you more deadlines right now for conserving that, some of it is, requires more validation before we speak confidently about it.
All of the work we're doing on micro dystrophin is 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.
And congrats again on this morning. But I have a question about golodirsen and the launch. I mean, do you think that the ramp speed for this EXOND 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 of framework to think about a 53 launch versus the 51 launch.
Yes, that'd be great. I'm going to answer that question instead of Bo, because he's he will famously try to underrepresent a number before The truth is that Boeing and his team have done a brilliant job over the last few years of defining actually a lot of the work regarding a published in that mill and near to the benefit. So I don't know the exact the 60% to 70% of patients are now genotypes. But working with great patient advocacy groups like PPMD, both his teams had an extraordinary amount of work. And that work will, will apply also to Golodirsen.
So, so there will be a ramp here just like there was a ramp in the Tupper City but it ought to be, it ought to benefit from all the great work that's been done with the Tempuris and EXONDYS and it ought to be a healthier ramp when we get Golodirsen approved. And I can tell you that those over here widely agreed. But it will. We've got the genotyping is done we have very deep relationship with the physician communities. We've done a very good job of forging relationships with payers.
And so that golden earth should benefit from time.
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 9 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 safety signal may be? And then just quickly on casimersen, any approval path forward there?
Yes. On Golodirsen, if you, I apologize, on Golodirsen, the question was, are there any safety signals that are at risk?
No, I'm sorry.
Oh my goodness. Things are going well. Our most significant issue right now is that Doctor. Mendell is working his head off to get everybody in and bought pre biops, you'd screened in the dose. So right now, I think the Doye brilliant, he's Doye brilliant, Doctor.
Mendell's Doye brilliant worked with 9 patient 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 if you asked about Casimersen, if I'm not mistaken, if you're giving him Jake some 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. 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 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. Apropos continued feedback. Obviously, we haven't had formal interactions with the FDA. We do notify the FDA of data from what is the gating of dose escalation that is not strictly required per 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 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 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 prednisone. This child in the cancer serious adverse event is off 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 trans defense. And then going forward, obviously, we are modifying our our glucocorticoid regime to more prescriptively call for longer dosing.
So the biggest issue on dialysis of the second of another clinical supply code wherein And the dose is really an internal question I made with our DSME, 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 micro dystrophin 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 fly path for bringing this therapy to the community.
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, which programs do you think have the most positive read through from the micro, I'm sorry, from the limb girdle to E data this morning, which of those constructs are most parallel? I guess, W mentioned 3 out of the 5 at the same promoter, which are those And how should we think about maybe Sharpen Marie Tooth and that construct in all of this?
Yes. So let me say
one thing and then I will I'll leave them at least, 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, amongst MRDs, 1st of all, of course, Doctor. Louise would either play back, she'll be modest about this. Was the designer of all 5 of these programs.
So the same, thoughtful approach to the design of these programs and selection of promoters in the like was the same across both our microdystrophin program and all five of these. All five of them very importantly are rh7 for all of them deal with the dystrophin associated proteins complex. They're all single gene mutations. They've all aimed to do a very similar thing, which is to have the full length of gene and therefore the native protein is the cause of the the injury. Now I'll let Luis go in the details.
You're right. 3 of the 5, the ones that are associated with a desire to have an increased benefit in the heart, use this MHTK7 promoter, which we see in the first two report outs that we have is giving us a lot of confidence around the productivity of that promoter, then one of the 5 I should note, but we should comment on that is, does have something that's a little different, which is it's a dual vector construct and slightly different only in that regard. But with that said, maybe a little more detail from you, Doctor.
Sure. Thanks. Doug covered well, but all of these programs are using RS74. So there's read through to all of the five programs. In addition to 2E, we're using MHTK7 promoter in the LGMD2B and 2C programs, which also have, significant cardiac involvement.
The other programs, LGMD2C and LGMD2L, we're using a PNC kip promoter, which also expresses very highly in skeletal muscle, not as much in the heart where we, we don't necessarily need it in these programs. So we're thoughtful in the way that we design which promoters to use for which study, but we have more about clinical results at all. The point of the LGMD2B program, we're using a a novel dual vector approach where we reconstitute the entire protein using 2 different vectors. But this is also delivering the full length genes and all of our programs again are delivering the native full length, gene and corresponding protein.
And our next question comes from the line of Danielle Brill with Piper Jaffray. Your line is open.
Hi guys. Thanks for the question. A 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's 2 answers to in the current, trial, there are exclusions for certain of the earlier exon, like a little bit 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 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, move some of the restrictions that out of an overabundance or a abundance of caution, existed in the protocol for what we call stage 1 and now study 1. So that's our ultimate goal is to have the broadest possible coverage, both in patients, age groups, geography, but also gene impact as well.
And let me just clarify. We're not excluding 18 to 58. It's the corollary. Is the $1,000,000 to $17,000,000 and the $59,000,000,000 to $58,000,000. And as Doug says, the plan is to expand is sort of in a planned manner in our development job.
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 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 the commercial supply program?
Yes. So the goal remains the same. So we're we've got a lot to do, but we're we're deep in the process. The biggest gating item, there are 2 things we need to do for, to start the commercial supply trial. 1 is the design of the trial.
That should not be it at all. A gating item, we're doing some interesting work to make sure that we've got a 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 at we're in the yield optimization stage and the, the released assay and other assay development stage. So our goal remains the same.
In the second half of twenty nineteen, likely towards the later in the second half of twenty nineteen, our goal is to commence a multicenter, multi country, site study with commercial supply. And we're continuing to work in that direction.
Thank you. Our next question comes from the line of Gina 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 cells for better scalability in the future?
Suspension, there are a lot of really interesting ways to go about commercial supply. There's what we're doing right now is sellers units, there's suspension, people talk about potential efficiencies associated with backlitomirus or an insect based approach as opposed to a 1,000,000 approach. We have chosen we've done 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 back refiners.
We have a very interesting relationship with LaSerta and they have something called the 1 MAC system. But with respect to our Duchenne muscular dystrophy program, and at least with our initial limb girdle rooms and probably all of our Limb girdle programs. We had chosen to go to Icellus units, and we've done that for a very specific reason. And that is because, it is the closest to what we have at Nationwide Children's Hospital. Nationwide Children's Hospital has a mammalian based inherent system, but it's on hyper stacks and not easily scalable.
And I sell a share as much in common, it is also inherent It is also mammalian, but it is a three-dimensional structure and therefore it's much more scalable. What is good about it is that I sell versus suspension is very scalable. So we get very good productivity out of the cell that competes with suspension. And 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. So I would suspect that we will not be moving to, to suspension with respect to our Duchenne micro dystrophin program or the scans right now in our limb girdle programs.
And on the pathway, the pathway is, as I said, before. So we had a number of things to do and I can tick off which ones have been done and which ones are made to be done. The biggest first thing they had to do is get an IND in our hands and then go through the process of tech transfer information when children's hospital with our Duchenne program to Brammer Biosciences. That is long and done and done and thus we've completed that work. The next thing to do is to start working with the icellis units and do process development.
And 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.
And then the next thing we're doing and we're doing many of these things in parallel is assay development. 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. Is for a material.
And so 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. So that's kind of where we are right now. That should, if everything goes brilliantly, we just took place where, and parallel from that, we'll be working on the exact design and getting sites up and ready to go for this commercial supply trial. And then by before the end of this year, in the second half of twenty nineteen, 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.
You for taking my question. This is Sean 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 even, ranges of numbers right now because again, similar to what we said with Myrtle, we need to take, we need to come up with some views. We have some preliminary views. I think we need to talk to the FDA. So we're very clear we are, we need to work in close collaboration with the agency and ensure that everything that we're doing on exactly as the agency would see it.
So we do have a view that our, commercial supply drive 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 3 month biopsies because that's what we've been looking at. It seems to work quite well and then look at comparability across the the, the 2 supplies, both commercial and clinical. But the exact number is going to require, additional discussions before the agency before it fill I feel confident providing 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 in some of the gene therapy studies. I mean, of course, you're seeing really 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. 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 thirteen years old. So we have already begun with our gene therapies looking at the older business. As it relates specifically to the Duchenne program, let's go to the end.
It is crucial that the program has is, built so that there is access to older and non ambulatory patients. Who, if we are corrected our thesis and if our early evidence bears out, will benefit enormously qualitatively and an extension of life from our Duchenne muscular dystrophy program. Our current program with Doctor. Mendell, of course, the narrow age range, but let us be clear, the reason it has a narrow age range is to ensure this disease that is is the generative and that requires different markers in different functional outputs depending on age, we need to have it narrowed 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, has much better access for older patients.
But then we have data that is compelling for payers in the United States and also for HD 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.
Powering of that site 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?
Well, so we don't have the exact numbers down. It will be significantly higher than the the formation study we have with Doctor. Mendell for a host of reasons, one of which is we want to multi center trials. Let's just sort of start with that alone. We want to want a multicenter trial.
We frankly want a multicenter 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 enrolling. I mean, one of the issues with Doctor. Mendell is he is working like that and every additional, patient is a patient of Doctor. Mandel right now, has to treat the following.
So that has its own constraints. We'll be unconstrained in our 2nd 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 that empowering, we have to think about, some of the other patient populations and ensure that we're addressing that in connection with next study.
And our next question comes from the line of Hartaj Singh with Oppenheimer And Company. 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, the manufacturing could we see a heavier second half versus first half? Thank you very much for the question.
So we're not guiding specifically on expenses for 2019. What
I would like you towards is
to look at our Q4 expenses and use that as a trend to project our water expenses would be for this year. And for perspective, in Q4, we spent approximately $130,000,000
for our OpEx on a
non GAAP basis versus about $85,500,000 $84,500,000 of revenue. So 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 form a items. We had approximately $100,000,000 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've guided towards our Q4 expenses to use that as a trend. Obviously, it'll slope upwards. And then I'll add a little bit more for our for a potential launch for Golodirsen as well as for our ex U. S. Ram.
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, Myles, Spencer on the line for Tim. I'm just wondering whether you can comment on where you are with seeking some additional guidance from the AMA regarding Eteplirsen approval in the AU. 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 promo trial? And if that would help you in that manner?
Thanks.
Yes. Thank you. So first with respect to a 10% 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 went over promised that we'll have an update in 2019 on the potential pathway for a teprotersen in Europe.
As everyone knows, we We did a lot of work in 2018 with the goal of bringing ateplirsen to the European patient community, and we have we were unsuccessful in 20 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, you know, benefiting in patients with exon 51 or 9 ability in the U. S. As it relates to golodirsen and casimersen, we have the SSENSE 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, but 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. So it has to remain intact and viable and blinded as well. So ESSENCE will almost certainly be the pathway to a potential approval in Europe for golodirsen and casimersen we'll have better insight once we take scientific advice, additional scientific advice from the EMA on Entellusimm later this year.
Thank you. And our next question comes from the line of Lisa Baker 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 really at the forefront of what 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 some sort of consistency or do you think it'll be the same across different payer types for example, the 1 payer systems like in Europe or kind of the private payer and multi payer systems like in the U. S. You maybe just speak to those 2 things? I guess the sort of idea of one common payment system for gene therapy globally? And then also what's sort of emerging as the, the, the best payment models or what's the most topical at this point?
Thanks.
Yes, it's a fascinating issue because we're doing a ton of work on right now. You're good point. 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.
States in the United States system. We're exploring a number of things. But let's step back for a second and put this into context. There are really 2 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, you know, 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, as the gene therapy. But in the let's start with the U. S.
Which will be the, 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 it. So, things like payments over dealing with payers, payments over time issues or subscription models. I can tell you that Bo and his team announced reimbursement in 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 as most amenable, because most of it's what is best the payer.
We're having, we're already having advisory committee meetings and discussions with a number of private payers and we're beginning the dialogue with state Medicaids and CMS as well. That's a little bit behind the private payer discussions. So I think by, I would say from a Sarepta perspective, by the end of this year into early next year, we will have, very, almost certainly landed on the 1 or couple of perspectives on what we would do in the United States, then, or then, you know, subset of those around the world to address the access issues and ensure that there is maximum access to patients rapidly when these therapies are approved. I think the most likely alternative to just the lump sum payment is payments over time and probably inside of that risk based payments and 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.
Our next question
comes from the line
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 would like to see to feel comfortable before moving into NDA submission? Thank you.
Yes. So we don't so the short answer is that the biopsies will will be analyzed in the coming 60 to 60 days maximum. So we'll have we don't have the data now. We'll have that data. And then 2 things.
1, we certainly will, we'll certainly share with the investment community. The results of that ator before we would make a submission to the agency, on that. And as far as the amount, I can only tell you what the preclinical models predict. The preclinical models, which have been fairly, fairly accurate in their predictions. As an example, predicted when we went to Golders and the Golders, it would be somewhere in the 2 to 3 times, more expressions than we had with the teprosymia level, it is about 2.4 times more expression than a teprosymia and the preclinical models predict that casimersen will be sort of in the hunt of golodirsen, maybe modestly below golodirsen and at least from all of our discussions with the agency and precedent, that would be in a position that would, with, would very comfortably support a submission for Casimersen significant biopsies or additive preclinical models suggest.
And our next question comes from the line of Edward Nash with SunTrust Robinson Humphrey. Your line is open.
Thank you for taking our question. This is Fang Ke Huang for Edward Nash. A quick question on the MPS IIIA programs. And since you already started periodal trial, have you guys discussed or Lysogene has discussed with the regulatory agencies regarding what's the bar for approval? And secondly, can you share us a reminder as what other Phase III data looks like?
Thank you.
I'll turn this to Doctor. Adrienne.
All right. So, thanks for that question. There 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 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 nonclinical setting, a substantial enhancement in both delivery and expression And it's just that construct that is in our current study, the pivotal study that's being run by
Thank you.
I would say the one interesting thing about the MPS III program, has had an interesting read through to some of our programs is the preclinical models with MPS III, early models, they use the particular promoter. They switched promoters and found a 300% increase in expression models. And when 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, our 1st and neural 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 get one of the few that the particular promoter that we've chosen is MHCK7 heavy chain promoter appears to be very productive, which speaks to reasons to what could happen with our other limb girdle programs and obviously gives us additional comfort with our Duchenne muscular dystrophy.
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. Certainly, thank you, Emily, for those who were with us this morning for our webcast. Appreciate it. Obviously, 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 we'd be providing additional guidance on all of our programs, certainly including our Duchenne muscular dystrophy micro dystrophin program as well as all of our limb girdle programs.
So thank you all. Have a lovely evening.
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.