Good day, ladies and gentlemen, and welcome to the Sarepta Therapeutics Third Quarter 2018 Earnings Call. At this time, As a reminder, today's program is being recorded. And now I'd like to introduce your host for today's program in Esteban, vice president, Chief of Staff And Corporate Affairs. Please go ahead.
Thank you, Jonathan. And thank you all for joining today's call. Earlier today we released our financial results for the third quarter of 2018.
At www.sarepta.com.
Joining us on the call today are Doug Ingram, Sandy Mahatme, Bo Kumbo, Doctor. Gilmore O'Neil, Doctor. Luis Rodino Klapac. After our formal remarks, we'll open the call up 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 the slide on our 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 materially differ from these forward looking statements as any such risks can materially and adversely affect the business, results of operation and trading price Sarepta's common stock. For a detailed description of applicable risks and uncertainty, we encourage you to review the company's most recent quarterly report on Form 10 Q filed with the Securities And Exchange Commission, as well as the company's other SEC filings. The company does not undertake any obligation to publicly update its forward looking statement, including any financial projections provided today based on subsequent events or circumstances advances.
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 third quarter 2018 results and corporate update conference call. Before I comment on the quarter, I am pleased to announce that Doctor. Gilmore O'Neil has taken on an expanded role as Senior Vice President, Research And Development, as well as his previous Chief Medical Officer role. This structure will ensure that we have a seamless alignment across research through clinical development and approval as we accelerate our plans as noted previously, Doctor.
O'Neil is with us this evening as is Doctor. Luis Rodino Klapac, our Head of Gene Therapy. And now, as we will discuss this evening, we've had a very productive quarter, once again posting strong sales growth for EXONDYS 51, while we continue to advance our RNA platform and build our gene therapy center of excellence engine with a sense of purpose. Starting with our RNA platform, we had another strong quarter of sales with EXONDYS 51 standing at $78,500,000 and tracking toward our full year guidance of 2.95 of our commercial and medical affairs teams as reflected in our performance. We are focused on identifying all patients who could benefit from EXONDYS 51, and working to remove any barriers that stand in their way.
1 of those barriers has been some misunderstanding about the FDA's accelerated approval pathway and the obligation to make therapies available. We were CMS, clarify some issues and correct misconceptions regarding the obligation of state Medicaid to make access available to patients. On June 27, the CMS issued a notice to all states, reminding them of the following. First, therapies approved via the accelerated approval process have met the normal standard for safety and effectiveness and must be covered by state Medicaid programs. So long as the manufacturer has signed the standard Medicaid rebate which we did sign at the approval of EXONDYS.
And second, states that should not use the prior authorization and other utilization management methods other than to ensure the proper use of the therapy, for instance, to ensure that the therapy is used, consistent with its label. There are still children who have been kept waiting for nearly 2 years for therapy. This is unacceptable and hopefully CMS's clarification will resolve roadblocks to their obtaining. Next, we continue to build our international presence with limited but limited infrastructure but dedicated colleagues in Latin America and Europe and a managed access program or MAP now live in some 44 countries. We should continue In the quarter, we also completed the reexamination of our marketing application with the Committee for Medicinal Products for Human Use or CHMP in an effort to bring ateplirsen to the European Duchenne community in need of therapy.
While we were of course disappointed that we received a negative opinion, we obtained guidance that could provide a path forward. We will evaluate this and take advice from the European Medicine Agency in 2019. But make no mistake. We believe it is fundamentally wrong that children in Europe do not have access to therapies that are benefiting children in the United States. Our goal constrained only by science and regulatory process is to bring all of our therapies to the greatest number of patients around the world who could benefit from submission for Golodirsen, which remains on track to be completed by year end with a target approval in 2019.
Likewise, in the quarter, we met with the FDA and we obtained their guidance and their concurrence on our plan to evaluate biopsies for another therapy casimersen. If dystrophin expression results are consistent with preclinical predictions, we plan to submit our NDA for casimersen by mid-twenty 19 with a target approval by the end of 2019 to 1st quarter of 2020. To remind you, each of casimersen and Golodirsen serve approximately 8% of the Duchenne community. Which means that taken together, they should be an even larger opportunity than EXONDYS 51. If we are successful in our plan, by early 2020, we will have 3 RNA based therapies that could serve nearly 30% of the Duchenne community in the United States.
We continue to make progress on our next generation RNA technology, the peptide conjugated PMO platform or PPMO for short. To remind you in animal models, our PPMO technology exhibited greatly improved cell penetration, exon skipping, and dystrophin production as compared to our current PPMO or PMO technology. We are excited about our next generation RNA platform and our first program focused on exon 51 is progressing well in our single ascending dose study. We should be on track to have dose and safety insight by the first quarter of 2019 which will allow us to move to a multi ascending dose and accelerate development. We are also moving rapidly to complete our preclinical work and file INDs for another 5 PPMO programs, which along with our first could serve approximately 43% of the Duchenne community.
Now let's turn to our gene therapy platform. We have had we have made significant progress in building our gene therapy center of excellence engine. Before I discuss the particular gene therapy activities in the quarter, let us place this all in context of our vision to build a substantial gene therapy engine driving a stream of late stage gene therapy programs to the community. Our vision is brought into focus by considering our micro dystrophin gene therapy program, the largest late stage gene therapy opportunity that currently exists. In service of our goal of bringing this potentially transformative one time therapy to the Duchenne community around the world, 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.
Now if our microdystrophin program is successful, we will launch the program and we anticipate some number of years of enormous growth as we treat the greatest percentage possible of the prevalent population of Duchenne muscular dystrophy around the world That's a staggering 70,000 potential patients. And then we will fall back to treating the incident population approximately 3500 patients each year. While the incident population is still very significant and the value to humanity will obviously be great. We will nevertheless have excess capacity when the prevalent population is finally treated, which also means we will have expertise and ability that could be leveraged to bring a better life to countless additional patients, but that requires a vision. It requires a new model, and not in the distant future, but actually right now.
There is a solution to this. It is a gene therapy engine that through in licensing and the build of our own constructs, advances dozens of programs to surge to serve large groups of patients living with genetic based disease. This is our vision and in relation to it, consider the following. First, while this vision does not require us to serve only rare disease, the opportunity in rare disease alone is enormous. There are 7000 rare diseases, 80% of which result from genetic mutations.
And there is literally only one approved in vivo gene therapy today. The opportunity to help others is breathtaking. 2nd, If we are thoughtful and we select well characterized genetic disorders, the theoretical probability of success of each program should be far greater from the earliest days than one might anticipate from small molecule R and D. And why would that be the case? It's because gene therapy is in essence a micro engineering project.
This is not passive drug discovery. We are not discovering therapeutic candidates through serendipity. We are literally building constructs serve well characterized problems. 3rd, consider accelerated gene therapy timelines relative to traditional pharmaceuticals. As the FDA recently acknowledged in its gene therapy rare disease guidance in July, developers like Sarepta need translation trials.
This provides us with the opportunity to rapidly follow on our success with micro dystrophin with new therapeutic areas and new constructs and the success that we build with each program should have read through to the next program. Considering these elements, I hope you'll agree with me that our vision while certainly audacious is also quite realistic and achievable. And with that vision in mind, let me discuss the progress we've made toward it this quarter. We made great progress first in our micro dystrophin program in the third quarter. As you may recall, we faced a clinical hold in the quarter based on an out of spec finding due to the use regulatory and research jumped on this issue, completed the work necessary to satisfy the FDA, and we were able to come off clinical hold in September resulting in no delay to our program.
This has to be one of the fastest and most efficient responses to a clinical hold in history, and it speaks reems to our team's ability to execute. Shortly after the close of the quarter, Doctor. Jerry Mendell, our close collaborator and the principal investigator for our micro dystrophin program, presented results of the 4th patient in our proof of concept cohort and updated biomarker and functional data for all four patients at the World Muscle Society meeting in Mendoza, Argentina. Results were entirely unprecedented across all measures. All patients showed robust micro dystrophin expression, properly localized to the sarcolemma, all showed up regulation of the dystrophin associated protein complex and additional indication of the functionality of micro dystrophin.
All showed an unprecedented drop in creatine kinase or CK levels and all showed positive functional improvement that is markedly greater than natural history could have predicted. No serious adverse events were observed. Now our results are limited firm these results in a larger well controlled study, but certainly we are more than a little encouraged by everything that we have seen thus far. Finally, we requested a meeting with the FDA to confirm our approach to our pivotal trial and to our manufacturing plans. That meeting will take place in the fourth quarter and our goal is to commence this trial, which will be a pivotal trial by the end of this year.
Going beyond our microdiscipline program, we have built out our end with additional programs now equaling 14 and growing. As you may recall, back in May, we entered into a partnership with Myonexus. A spin out from Nationwide Children's Hospital for 5 new programs under the broad umbrella of limb girdle muscular dystrophy. There is potentially significant read through from our microdystrophin program to our limb girdle programs as they share a common inventor, a common capsid, similar disease state, and in 3 of the 5, a common promoter. We are on track to dose all of the patients in our first cohort of our beta sarcoglycanopathy or 2E program this year with biomarker results available in the first quarter of 2019.
A spin out from the University of Florida and an entity associated with 9 top gene therapy researchers in the world that gives us 3 programs all in CNS and the most advanced of which is Pompe disease. Next, shortly after the close of this quarter, we entered into an agreement with Nationwide Children's Hospital to gain access to Nationwide Children's gene therapy candidate neurotrophin III or NT3 to treat Charcot Marie Tooth neuropathy, including CMT Type Ia. CMT, a serious life limiting disease, is also the largest inherited neuromuscular disease in the world. And we are excited to work with Doctor. Zarif Sahank, a true neuromuscular and gene therapy pioneer who has been dedicated to this program for over 15 years.
And even more recently, we entered into an agreement with Lysogene to gain rights to 2 gene therapy programs, including Lysogene's late stage program, to treat MPS IIIA, also known as Sanfilippo Syndrome Taipei, a rare fatal inherited neurodegenerative lysosomal storage disorder. The pivotal trial for MDS3a is planning to commence by the end of twenty 18. As previously mentioned, our work has expanded our gene therapy platform to 14 And more than that, please understand that most of these programs are quite advanced to consider the following. We plan to commence our pivotal trial for microdystrophin by the end of twenty 18. We plan with Lysogene to commence the pivotal trial for MPS IIa, again, by the end of 2018.
We plan to complete the 1st cohort of our limb girdle 2E trial by the end of this year and to commence our pivotal trial next year. We will move with equal speed on the next four limb girdle trials. Dosing in the CMT program should begin in the first half of twenty nineteen and likewise dosing in the Pompe program will also occur in 2019. Now, our gene therapy aspirations require a robust approach protees, while also building a federation of manufacturing relationships to ensure that we can rapidly scale to serve the community at launch. Our first partnership announced was with Brammer Biosciences, a world leader in gene therapy manufacturing.
As we have previously noted, our goal with Brammers to have more gene therapy commercial capacity in about 2 years then as we understand it, all of the gene therapy capacity that currently exists in the world. We follow that up with the announcement this quarter of our manufacturing partnership with Paragon, Paragon Biosciences, another world leader committed to gene therapy manufacturer. Our relationship with Paragon significantly expands our commercial capacity, gives us a second supplier for our micro dystrophin gene therapy program, and bolsters our clinical and commercial capacity for our The approach that we are taking to manufacturing, relying as we are on the hybrid manufacturing model and a federation of gene therapy manufacturers And in our most advanced programs, a micro dystrophin and limb girdle, evolving from an adherent hyper stacks to a more robust, but still adherent approach is intended to ensure that we are moving rapidly with the highest probability of success to treat the maximum number of patients assuming a very fast launch. Healthy sense of humility as one can see by our embrace of the best and the brightest in genetic medicines. Scientists like Doctor.
Jerry Mendell and Kevin Flanagan, Barry Byrne, Zareif Sahank, Charlie Gersbach, Serge Braun, our own doctors Gilmore O'Neil and Luis Rodino Klapac, and of course, our relationships with manufacturing partners Brammer and Perrigon. And we overlay all of this with enormous sense of urgency. We insist on moving fast. Some may ask why we are so slavishly focused on speed of action. Now there are many reasons I could give.
I could talk about the fact that genetic medicine has come of age. The opportunity is right of us and we need to seize it or perhaps I could discuss the competitive value in being 1st in curative therapies. But instead, Let me use the Chen Muscular Dystrophy, the center of our culture as the example. If we catalog all of the DMD children in the world, and they are all children or at most young adults. And then we looked again in 2 years, a substantial portion of them would no longer be with us.
Death is the brutal reality of this cruel disease. And other rare diseases are similar or in the case of MPS IIIA, even worse. So if we take the leisurely If we regress to the mean of our compatriots in the industry, by the time we get around to a therapy for these children, we will have lost an entire generation. Some might accept this as the inevitable consequence of development and regulatory bureaucracy. We do not.
So, do those who wonder why we agitate? Why we count our timelines in hours and days and not months and years, I say this? Meet a family living with Duchenne muscular dystrophy. I will now turn the call over to Sandy Mahatme for an update on our financial performance. Cathy?
Thanks, Doug. Good afternoon, everyone. Over the past year, we've executed on our business development strategy to become the leaders in gene therapy. With patients in mind, we have judiciously used our resources to rapidly expand our gene therapy pipeline 14 compounds in development to treat devastating diseases, while simultaneously potentially positioning investors for a return on investment that dwarfs industry standards. Diluted by this philosophy, we will continue to forge strong partnerships with leaders in gene therapy over the coming months.
We have also put our balance sheet to work to ensure that we not only develop the best drugs, but also have the manufacturing capabilities to supply them to patients. We signed 2 exclusive partnerships to become the largest gene therapy supplier in the world. This gives us significant manufacturing capability, but also from a capacity standpoint puts us at multiples over what a 2000 liter reactor can deliver. We believe that these investments lay the foundation for building shareholder value for many years to come. Now moving to the financials This afternoon's press release provided details for the third quarter of 2018 on a non GAAP basis as well as GAAP basis.
The press release is available on the SEC as well as Sarepta websites. Please refer to our press release for a full reconciliation of GAAP to non GAAP. I'd like to add a expenses in connection at one time items as well as stock based compensation. Net product revenue for the third quarter of 2018 was $78,500,000 compared to $46,000,000 for the same period of 2017. The increase primarily reflects increasing demand for Axonics 51 in the U.
S. We reported a non GAAP net loss of $37,100,000 or $0.56 per share in the third quarter of 2018 compared to non GAAP net loss of $10,700,000 or $0.17 per share in the third quarter of 2017. In the third quarter of 2018, we recorded approximately 8,700,000 in cost of sales compared to $3,100,000 in the same period last year. The increase was driven by higher inventory costs related to increasing demand for EXONDYS 51 during 2018 and as well as an increase of $1,700,000 in royalties payable to BioMarin as a result of the settlement and license agreement we entered into with BioMarin in July of last year. We expect our cost of sales in Q4 2018 to be consistent with this quarter.
On a GAAP basis, we recorded $86,600,000 $34,200,000 in R and D expenses for the third quarter of 2018 2017, respectively, which is a year over year increase of 52,400,000. The year over year increase in GAAP R and D expenses 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 as well as an expansion of our research and development pipeline. On a non GAAP basis, the R and D expenses were $64,200,000 for the third quarter of 2018 compared to $31,500,000 for the same period last year, which is an increase of $32,700,000. Turning to SG and A. On a GAAP basis, we recorded $53,000,000 28,200,000 expenses for the third quarter of 2018 2017, respectively, a year over year increase of 24,800,000.
On a non GAAP basis, the SG and A expenses were 42.5 for the third quarter of this year compared to $22,200,000 for the same period last year, an increase of $20,300,000. The year over year increase was primarily driven by continued build out supporting our global expansion. On a GAAP basis, we recorded $7,000,000 in net interest expense for the third quarter of this year, compared to $200,000 for a of net interest income for the same period last year. The unfavorable change is driven by higher interest expense in Q3 of twenty eighteen, which is related to our debt instruments that we entered into in the latter half of last year. Turning to our cash position, we ended Q3 with approximately $794,000,000 in cash, cash equivalents and investments.
This was a decrease of $156,000,000 in our cash position, from the prior quarter and was driven primarily by a $68,000,000 expense related to new business development deals as well as our manufacturing activities, and $33,000,000 related to the payoff of our term loan, as well as related interest expenses. In addition, we have prepaid approximately $54,700,000 towards future manufacturing expenses in connection with our gene therapy and RNA program. From a cash perspective, we are well positioned to execute on our corporate objectives. With that, I'd like to turn the call over to Beau for a commercial update. Bo?
Thank you, Sandy. Good afternoon, everyone. We've now completed 2 full years of the EXONDYS 51 launch. And I would like to take a moment to say thank you to the entire Sarepta team for all their hard work, dedication, and passion to bring EXONDYS 51 to the individuals who need it. We've taken our key learnings over the last 2 years and are preparing to launch 2 additional exon skipping products.
Golodirsen and casimersen, as well as multiple new gene therapy prize for Duchenne and Limb Girdle Muscular Dystrophy over the next few Similar to previous quarters, we had a solid 3 months and remain on track to achieve our full year guidance of 2.95 to $305,000,000. The team has been able to successfully navigate challenges since approval and maintain patients on therapy without significant disruptions. As we move into our third year of commercializing EXONDYS 51, The majority of our efforts are focused on identifying patients amenable to EXOND 51 skipping, while continuing active dialogue with payers to for broad coverage and reimbursement decisions. We will continue to work with key offices to help educate around the importance of patient identification early diagnosis and treatment potential treatment options. Top tier centers continue to receive referrals or identify new patients amenable to EXOND 51 skipping and submit start forms as appropriate.
We continue to call on the top tier centers but have purposely expanded our efforts for the future. A portion of our educational endeavors have shifted to large pediatric off is within key states where we are helping to educate on the importance of early identification for children who have not yet been diagnosed with Duchenne. These efforts are now focused on supporting early testing and diagnosis and will ultimately shorten the timeframe of referrals from pediatrician offices to neuromuscular specialists. From an adherence and persistency perspective, throughout the last 2 years, we have seen high compliance rates and minimal discontinuations. We have also transitioned greater than 50% of patients to home infusion, which we believe as health patients stay on therapy over time.
Our national accounts and medical affairs team continue to have ongoing engagement with both commercial government level payers around Duchenne, EXONDYS 51, and the new CMS guidance letter on the obligation of state Medicaid to make accelerated approval treatments available to patients. In 2018, we have continued to see an increase in patients covered by Medicaid, which has increased the payer coverage mix to 50% commercial and 50% government. Previously, the mix was approximately 55% commercial and 45% government. Over the course of the last two years, we've continued to adapt our approach to the market and have had the flexibility to quickly resolve potential obstacles. We believe this is a strength of ours as we head into future launches and prepare for potential RNA and gene therapy approvals.
As Doug highlighted, Sarepta's mission is to develop a precision genetic medicine engine, where we can help worldwide, continuously striving to advance our multi platform pipeline and keeping patients at the center of all conversations. We currently have 20 ensuring treatment access for patients. We are putting the framework in place from distribution networks market access, sales, medical affairs and patient support, which will allow us to reach patients globally. We have continued to strengthen our global presence in Europe, Brazil and MENA by engaging with key opinion leaders and advancing our distribution networks. We have also started meeting with key opinion leaders throughout Japan to understand the landscape and assess the thinking of our commercial and medical affairs teams to ensure we remain flexible and adaptable in diverse markets.
We have the right people, individuals who are highly motivated and proactive, who work with a sense of purpose and possess the agile thinking success of EXONDYS 51 over the last 2 years has provided Sarepta the framework, the infrastructure and the resources to support future global launches. Executional success globally. Thank you for following our important mission. I will now turn the call back over to Doug.
Thank you, Beau. As you all may recall, as we tracked into 2018, we had a significant number of important inflection points in front of us. As we track to the end of 2018 and into 2019, the number of important milestones and inflection moments has only multiplied considerably. Over 2018, we have over doubled the number of talented and passionate Sarepta employees dedicated to this mission. We have increased our pipeline to some 24 RNA and gene therapy programs, In fueled by encouraging data, we have brought into sharper focus our strategic vision and charted out the path we intend to carve to achieve that vision.
Precision Genetics medicine is driving a revolution now in health care and we intend to be the leaders of that revolution to the benefit of countless patients formerly bereft of potentially transformative therapies. With that, we will open
you. Our first question comes from the line of Salveen Richter from Goldman Sachs. Your question please.
Good morning. Thanks for taking my question. So with regard to the CMT program, can you just comment on the proportion of the opportunity targeted here in the Type 1A program? And then the construct, if you could just describe it for us and whether the G needs to be truncated And then finally, the endpoints and biomarkers we should be looking for here to determine clinical benefit. Thank you.
I'll pass it over to Luis to answer at least the last 2. Luis?
Sure. CMT, as a group is 1 in 2500. And CMT1A is the most common form which is about 1 in 10,000 individuals. So our program or Doctor. Sahenk's program at Nationwide Children's uses NT3, which fits into AV.
So it's not truncated. And this is a secreted molecule. So what she's doing is injecting directly into the muscle and using the muscles of factory to create and generate NT3. And this allows for sustained circulating levels of NT3 producing a therapeutic effect. So NT3 is important for neurodegeneration, and therapeutic effect, which she showed pre clinically, as well as an earlier phase 1 trial with just a recombinant and T3 molecule.
So in this 1st phase 1 trial of 9 subjects, we'll be looking for, endpoints using the CMP pediatric scale, the one hundred meter time test, electrophysiology CMAP potentials as well as circulating and T3 levels.
Okay.
Thank you. Our next question comes from the line of Alethia Young from Cantor. Your question please.
I just wanted you to maybe talk a little bit about, I get a lot of questions about kind of thinking about the pivotal design, for the gene therapy. So you just you help maybe frame for us what the potential base case could be? And just a quick one question on, have you guys had the conversation with the FDA yet? Thanks.
So I'll answer the second one first and the answer is we have it scheduled. It'll be this quarter. So we'll definitely have our meeting with the FDA in this quarter. And as I said during this, the opener, our goal is to commence the pivotal trial this year. As it relates to the pivotal trials, broadly speaking, it's consistent with what we've said in the past.
We are proposing a 24 patient study 1212 placebo, double blinded study, 1 year on function, and we'll look at obviously, we look at biomarkers as well as including expression levels. And we're going to look at it in two ways. So our base case is that we could get accelerated approval. This will certainly be the one of the issues we'll discuss with the FDA, but accelerated approval on the basis of expression But also powering the study in the hope that we would also see a functional benefit at the 1 year mark So we would actually confirm the accelerated approval at the end of the study and we'd get approval that wouldn't just be accelerated. And the only reason I say hope in that is that we have seen really, really exciting results out of the first four patients, but of course, These results are entirely unprecedented.
And so, as we track into the pivotal trial, we want to that we have both the opportunity to get approval on an accelerated basis as well as the potential to get an approval on a functional basis. Well, then let me say one other thing as long as I'm talking because the question then may come up. What about, what about the age range in the label? And the answer is going to be that our goal is to the broadest age range possible, hopefully no limitation whatsoever on age. And the way we're going to do that is we have a main study of 24 patients focused on a very pipe group of four to seven year olds consistent with the original proof of concept cohort that we did.
And then we're going to separately have a cohort to look at expression and safety in younger children, in older and heavier children, as well as some additional of the earlier exons that may be excluded from the main study. So our goal at the end is to cover the maximum number of patients available. The one limitation we will almost certainly have is of course that there may be screen out for pre existing antibodies. The good news for us right now as we sit here, we've screened a lot of patients. And what we're seeing right now across all age groups is about a 15% screen out rate.
We wish there was 0, but 15% is much better than the literature would would anticipate for other vectors humanized vectors like AAV9 and the like.
Great. Thanks. Thank you. Our next question comes from the line of Christopher Marai from Nomura Instinet.
Hi. This is Jackson Harvey on for Christopher. I was just hoping if you could expand a little bit on how we should expect the LGMD data to be released in first quarter of 2019. Will that be through a call or will it be presented at a conference? And then I have a follow-up question?
Sure. Well, the short answer on that is that we haven't made decisions on the form of release of that data. What I can tell you is that at our goal to have the entire first cohort, fully dosed this year and to have the available data by the first quarter of year, but exactly how to what extent that gets released is something we're going to have to decide later.
Got it. And the decision to work with Lysogene and this direct to brain approach. Now do you see an opportunity for systemic dosing with brain penetration. And also what was the rationale for exploring these direct to brain approaches? Thank you.
I can pass this over to Luis if you want to touch on this briefly.
Sure. MPS IIIA, which is, the primary, target for Lysogene, is primarily a CNS disease that has profound mental retardation, but and minimal somatic, manifestations. So Lysogene tested this. They looked at targeting a white matter directly, intrapurincomole injection versus, intraventricular intravascular and found that it resulted significantly higher expression and broadest distribution throughout the brain. So that was the rationale for that decision.
Now, however, this does leave the door open for later systemic delivery for the somatic, defects as well?
Thank you. Our next question comes from the line of Nupam Rama from JP Morgan. Your question please.
Hi guys. This is Tessa filling in for Anupam this evening. Thank you for taking our questions. So now thinking about the limb girdle program as we are thinking towards the early 2019 update, help us FedEx patients here for the scope of the data that we will see and how we should be thinking about the benchmark for a clinically meaningful change inteen expression in the 60 day biopsy data? And then maybe relatedly, what can we expect to see on any other biomarkers or potential functional endpoints in the initial look?
Thanks so much guys.
Well, generally speaking, Luis, you can follow-up on this as well to try to speak, but broadly, we'll be looking at expression levels from a 2 month biopsy. You'll note that in our microdystrophin program, we looked at 3 month biops sees. This is a self complimentary construct. So it's more efficient than 2 months actually seems like the appropriate time. It will be expression levels.
And there'll be both expression levels of the protein and interest. We'll probably look at other ones as well, including the dystrophin associated protein complex. And I believe also dystrophin itself, it can be at least in preclinical models, and this has been, Louis has already published this, in preclinical models, the restoration of the protein of interest also upregulates generally the, the dystrophin associated protein complex and up regulates driven as well. Luis, did I miss anything there?
No, I think you covered it all mainly primarily looking at expression and restoration of dystrophin and vector copies as we would, similar to micro dystrophin.
Thank you. Our next question comes from the line of debjit Chattopadhyay from H. C. Wainwright. Your question please.
Hey, thanks for taking the questions. Just a couple. Firstly on NPMPS program, the construct that's heading into the pivotal studies is different from the original construct that was studied in specifically the transgene is different and the promoter is different. So any thoughts on what caused the changes and how do you expect that to translate into maybe a more pronounced effect?
I'll touch it briefly and then Louise can give you probably a better, more nuanced answer. The short answer is that the thing, the 2 most significant changes that move from the prior cohort to the current pivotal is first the use of a more efficient promoter, a promoter that appears at least in animal models to be more than three times more efficient than the prior promoter that was used. And then secondly, the dose itself informed by the prior cohort that the dosing is actually going to be a full order magnitude higher. So taken together, it's a potentially 30 times more efficacious therapy, at least 30 times more potent therapy. With that, Luis, what I'm sure I've missed some of the nuance there?
No, actually you covered it well. So the promoter itself driving higher levels of expression, were significantly anticipated a much higher effect from this new construct.
Great. And then on the CMT related stuff, kind of as you try to narrow down the patient population, that's most likely to benefit from gene therapy. Any thoughts on the NT3 as a target for a whole range of other neurologic or neuromuscular indications? Thank you so much.
I think there is a lot of potential opportunity that we're exploring with that. We're talking to Doctor. Sahenk about that, even as we speak, Thank
you. Our next question comes from the line of Matthew Harrison from Morgan Stanley. Your question, please.
Great. Thanks for taking the question. I will ask only one I just want to follow-up, Doug, on a comment you made earlier related to the pivotal program for DMD. So the what I'll call peripheral studies in four or seven year olds and the younger cohort and the older cohort and maybe some of the other exons Are you expecting them all to start at the same time and have data around the 1 year mark with the with the sort of pivotal cohort or are these going to be later studies? And I guess, how would that impact your filing plan?
So they'll they will start a little bit later than the commencement of our initial study, but they will be comfortably completed before the end of our study and the submission and the approval of our study, which obviously, I think as we've said before, our ambition is to try to get an approval by the end of 2020. And you may see how is that the case because where those patients, our proposal is not to run full year study for those, but actually since those are really safety studies and expression related studies to look at 3 month biopsies on this space. If we look at safety, look at 3 month biops and follow the patients. So, if we get good concurrence from the agency on that, then obviously, these cohorts can all be completed comfortably within the timelines as we sort of build out our flight path to an approval in the United States and around the world.
Our next question comes from the line of Gena Wang from Mark Your question please.
Thank you. I will also only ask one question. So regarding the manufacturing, I know you signed a contract with both Bremerbau and the Paragon. Just wondering, how will these two companies share experience when they during their optimization process? And will both of them focusing on adherence cells and how will the manufacturing capacity be split in the future?
Well, as it stands right now, so remember, we, Paragon is a is a secondary manufacturer, to Brammer. So we've already tech transferred out to Brammer, and we're actually completing the process development work with Brammer. And that'll all go to the benefit of, text transferred to Paragon as well for our micro dystrophin program. Remember, with our Brammer program alone, our goal was on a standalone basis to have sufficient, manufacturing capacity to fully serve well both in U. S.
As we move around the world. And then, of course, remember, beyond that, Paragon has the opportunity to provide us with capacity far beyond Duchenne muscular dystrophy, most acutely in limb girdle and 2E and the like. And then, and of course, it will be the plan, both repairagon and for Brammer for both limb girdle and for Duchenne Muscular Dystrophy micro dystrophin is, is adherent. It's a CELUS units as Sandy discussed during his discussion. And of course, the reason for that is that we can create capacity with a much lower risk with reducing the numbers of unknown steps.
So I think that's the way we're approaching that. And then also remember one thing, how do we, how do we stick together sort of Brammer on the one hand, Paragon, the other, perhaps another partner down the road. And the answer is that we have a hybrid manufacturing model. We are not simply is essentially contracting with contract manufacturing organizations that entirely outsource everything. We actually are building our own expertise And we look to Brammer and we look to Paragon and we'll look to others not to be outsourced service providers, but to actually be partners with us, with our employees with our experts sharing information.
So it'll all endure to the benefit of the entire federation of manufacturers and to our own internal experts. Driven by Polani, our Head of Manufacturing.
Thank you. Our next question comes from the line of Vincent Chen from Bernstein. Your question please.
Great. Thanks for taking the question. So thinking toward the upcoming PPMO readout wondering if you could provide a bit more detail on the cadence and progress of the PPMO dose escalation study. For example, how many doses do you intend to evaluate how many patients are treated each of these different dose cohorts? What degree of run out is required at each dose?
What safety assessments are done? What toxicities would you consider dose limiting? Potentially halt for the progression. What needs to happen for each additional dose core to be opened and how quickly would you expect to progress to the next dose after one of those cohorts opened? And finally, if you can, where are you in this study?
That was on the top of your head. It's a traditional 3x3 single ascending dose study. To be entirely frank, I would have liked to have a more exotic approach to our single ascending dose study, but unfortunately, I did not have the benefit of Doctor. Gilmore O'Neil, when it was originally designed. And I think we would be a little more creative in that approach today.
But we're progressing well. I'd say we haven't really discussed the exact doses we've gotten to. We haven't hit any kind of serious adverse events or anything concerning and we should have dosing insight by year. But with that said, perhaps Doctor. Ernie, you could provide some additional insights.
So I think your question is,
define or reveal a familiarity with a dose escalation in phase 1. We are, as Doug said, we will have insights in the first quarter of this year of next year, I should say. We are actually evaluating other ways to accelerate, our dose expiration and move into patients at potentially therapeutic ranges. In the next year. But I think the key thing to say also is that we know about the target organs based on our nonclinical tox are.
We are monitoring those closely, not just looking for tolerability, but actually monitoring chemically for those known target organs. We've not seen anything to date.
Thank you. Our next question comes from the line of Tazeen Ahmad from Bank of America. Your question please.
Good afternoon. Thanks for taking my question. Doug, in your prepared statements, you talked about some of the programs that you plan on moving clinic, one of them was for Pompe. You would also say that it's important to try to be as fast as possible to get drugs to market and the importance of being first. So given that there are quite a number of companies already that have talked about their plans to move in the clinic for their own Pompe assets.
How were you thinking about, seretive chances there? And what do you think would distinguish your ability to develop a drug versus anything else that might also be in development? Thanks.
I will turn this over to Doctor. O'Neal to comment. But before I do, let me say this, we are taking a unique approach to Pompe. The approach that we're taking to Pompe and CNS driven, that is, that is different than the other programs that exist out there. So we are this is a differentiated program.
Would that?
Yes. So I think Doug has actually actually said giving you the key differentiating answer. In some cases, speed? Well, 1st of all, speed matters because there are these are sick patients who actually are waiting for the drugs think the second obviously is where the differentiation is clear. It's actually also very important.
But I think where there is clear differentiation, then I think there is room. And certainly, 1st of all, we are moving aggressively. And secondly, there is cure differentiation because this is CNS delivered. And I think it's important to remember the Pompe's is not a purely muscular disease. In fact, it's a neuromuscular disease, with a significant impact, upon pays on the anterior horn cell and motor neurons, which is why we believe that this differentiated approach to CNS delivery is a critical and possibly very probably likely to be the most meaningful delivery approach that we can bring to this disease.
So that's why we believe that we have that edge here and can, bring real value to patients.
I think one other thing to remember, another potential differentiator for us is that we have Doctor. Barry Burr, who is the inventor and the driver behind this. One of the things that I've said many times, including tonight is that we are going to approach the mission ahead of us with an enormous sense of humility, leaning heavily on the experts around the world. To that end, as you may remember, we stole from Nationwide Children's Hospital, as much as it paints Doctor O'Neill every time I use the word steel. I talked to Louise Rodino Klapac and her lab and Doctor.
Barry Burns is one of the world's experts in gene therapy, which gives us an enormous additional level of confidence that we have something with the Pompe program. Okay.
Thanks. And do you think that would help your rate of enrollment being CNS delivered as well?
You know, I don't know if we've really considered that, you know, frankly, so I don't have an answer one way or the other. Apologies for that.
Okay. Thank you.
Thank you.
Our next question comes from the line of Joseph Schwartz from Leerink Partners. Your question please.
Great. Thanks very much. So I was wondering if you could quantify how much misconceptions about reimbursing drug which were approved in an accelerated manner have held back EXONDYS sales. How many DMD patients would you estimate have not been able to access it's on this as a result? And have you noticed any change since the CMS clarification?
So it's still a little bit early days in the process slow as state Medicaid, to be fair. It is a very state by state related issue. Some states basically, some of the larger states have very good policies and have done a brilliant job of getting patients on therapy, states like Texas and California and Florida have had very good policies. And actually, those are some of the larger states as well. But there are definitely been, a significant number of states and patients.
It's not the majority, but a significant number that have had misconceptions. And I think a lot of it is driven by misconceptions. We want an accelerated approval is, notwithstanding the fact that accelerated approval is a concept that's existed, in the regulations for a very, very long time. And therefore, We're fully cognizant of the requirement of state Medicaid to provide access to drugs approved through the accelerated approval process and not to unduly delay that. So I'd say we haven't had it hasn't been an enormous impact, but over time, it will be.
And I think it'll and it's all to the benefit of patients, many of whom frankly minority, but many of whom have been waiting since the very approval of EXONDYS to get on therapy.
Great. Thanks for taking my question.
Thank you. Thank
you. Our next question comes from the line of Ritu Baral from Cowen. Your question please.
Hey, guys. Thanks for taking the question. Mine is on the MPS III Sensilippo program. One, it represents a little bit of a departure from your neuromuscular focus being a lysosome storage neurological disease. What does that say to your overall, I guess, near term clinical focus?
And 2, what is that pivotal trial going to look like as especially given the controversy around, what pivotal endpoints can be and what neurotrog scales are acceptable?
Okay. I will I'll let Luis answer the trial and endpoint related questions. But what it says about our approach is meaningful. And what it says is that we are going to build this gene therapy center of excellence and then this gene therapy engine and we're going to focus on what we know and we're also going to focus on adjacencies to the areas that we're in. So if you think about it, we start with DMD, so we're neuromuscular.
So when we move beyond DMD and moving to moving to other neuromuscular diseases, something like limb girdle muscular dystrophy is a brilliant next step. But if you think about neuromuscular generally, then obviously thinking about CNS is not a significant departure. It is different than neuromuscular, but not an enormous departure. We started with Pompe, which is a CNS approach to a neuromuscular manifestation. And then of course, going to Lysogene is one step further CNS driven and we'll do more things opportunistically like that.
And that's the way we're going to grow over time. As I've said before, we have 14 gene therapy programs today. I think over time, probably the next few years, it would not surprise me at all that we have as many as 30 gene therapy programs, which will, as stands right now. We're really focusing in on in licensing, but, we are building a gene therapy center of excellence around the least in their lab in Columbus, Ohio, and they will be creating their our own constructs as well. I think between the mix of in licensing and And our own constructs, I think, is really very possible in the next couple of years we have as many as 30 programs fueling this engine that we have with hopefully near term results and a series of launches.
And it will be neuromuscular. It will be CNS. And, it will be in kind of an evolutionary way moving into adjacencies to both of those areas over time, because if you think about it, gene therapy is the expertise in gene therapy is significantly focused on delivering This is a this is the delivery like a rocket ship of a payload and we can build new payloads and we have increasing expertise around the rocket ship itself and we will start building payloads in CNS and neuromuscular and I'm quite confident over time beyond that.
Thank you. Our next question comes from the line of Joel Beatty from Citi. Your question please.
Hi, thanks for taking the question. It's on the pivotal trial of the microdisciplined gene therapy program. Could you share some thoughts on what the magnitude of benefit of the trial is powered to detect on both the biomarker endpoints and the functional endpoints?
Well, I'm really sorry, I missed that. But Paul, just can just repeat the question one more time. I apologize for that.
Sorry. For the micro dystrophin gene therapy program, what magnitude of benefit is a trial powered to detect on the biomarker endpoints and the functional endpoints?
Well, it's powered to see a statistically significant difference, both on the biomarkers, obviously on distro than expression, which I don't think anyone's going to believe is a difficult powering. And also on Funk as well. So based on informed by what we see in the first four patients, it is powered to see a statistically significant difference on functional difference. One thing I will I would like to go back and do because it didn't get answered in the last question was, I think, the endpoint related question then maybe Doctor. O'Neal, you want to touch on?
Yes. So I think we actually I think it was either myself or our Doctor. Rigel KAPAC, but I think that the prior questioner had asked about the outcomes for the MPS II or the Sanfilippo. And so we'll be looking at sleep agitation and other behavioral outcomes. I think we believe that we can actually see, we'll be able to actually demonstrate clear benefit, with that approach.
And obviously have had our partners have had the opportunity to discuss with regulatory agencies. I think between the discussions that have regulatory agencies and the potency of their approach, I think that there's a very this is a very reasonable approach with a good likelihood of success. So sorry for hijacking your question to go back to the prior question, but
That's fine. Thank you.
Thank you. Our next question comes from the line of Lisa Bayko from JMP Securities. Your question please.
Hi, yeah, total departure question and one more for Sandy. Can you just give us some color on how to think about R and D and SG and A spend, you know, next quarter and into next year. Thank you. I mean, next year, actually. Thanks.
Yes. So you should see a quarter over quarter increase going into next quarter as, increasing number of programs come online, especially in PPMO. Next year, we haven't really come up with our long term strategic plan as yet. So we'll be in a much better place to guide on it. Early next year, Lisa.
But you should see an increase there as well simply because of the number of people, as Doug indicated, we have almost doubled the size our employee base, both in the U. S. As well as in some foreign locations. And then as our gene therapy programs start increasing in size, you should see an increased spend on manufacturing in that area as well. But again, it's a little too early to guide on that.
Thank you. Our next question comes from the line of Marty Oster from Credit Suisse. Your question please.
Hey guys, thanks for taking the question. Congrats on all the BD activity this quarter. I had a question for you about just kind of curious about the competitiveness of some of those recent gene therapy deals and kind of whether you're what you're seeing is kind of your differentiation kind of landing some of these assets. And then also wanted to know if you have any appetite for kind of more advanced clinical stage gene therapy assets that have had some clinical data already produced Thanks.
Yes. So a couple of things on that. It's very interesting. So one of the things we're doing right now to use a silly overused bromide is making hay white while the sun shines. We have the ability to, to in licensed programs that are comfortably within our balance sheet and very late stage.
And one of the things that's interesting about that is that some of these have been quite competitive and we were not the high bidder. And the reason for that, I think, is a couple of fold. 1, I think if you want to talk to Lysogene as one example, they they see our shared vision. They see that we not only have built quickly and expertise in gene therapy. We have a vision for doing things rapidly, in gene therapy and we're very committed to these programs.
I think that gives us a competitive edge. I think the second thing that gives us a competitive edge is that we are a very good partner. It is a it is not a secondary thing. It is literally part of our strategy to be a good partner. If someone was looking to do in license or other deal with us and they cared about the app it.
They had, for instance, like Doctors Hanks worked on something for 15 years. And they were going to do diligence on us. And they called someone like a Doctor. Jerry Mendel, I'm quite confident that he would sing our praises about the ability not only to advance things and move with the urgency that he would expect but also that we work with him, that we're respectful of him, that we understand his expertise and we align with his mission. And I think because of that, we really frankly had an outsized, outsized level of success so far.
The 2 other things I'd say on that. So then let's talk a little bit about whether we would do like a bigger deal or with another public company. The issue there interestingly enough I'm not saying we never would, but the interesting thing that we're getting from some of the in licensing right now are very late stage assets at a fraction of what one might get if we went out to a company that was, for instance, had already done an IPM was public. 1 of the unusual things about gene therapy I think right now is the following. So if you we were in a typical small molecule based company, we wouldn't be an academic in license or a company that just spun out from an academic institution.
We would be in licensing a program that was 12 or 14 years potentially from the market with the probability of success in the single digits at best. But gene therapy is not like that. We go and do something like we would do in myonexus. Myonexus was just freshly spun out of Nationwide Children's Hospital. And we'll have our entire cohort of our first cohort at what we believe to be therapeutic doses done this quarter.
So the ability to actually in license assets that are, that are later stage with a fairly significant probability of success is inconsistent versus history. And I think we're taking advantage of that right now. What that's not going to continue forever, right? So the competition is going to increase over time. We are kind of taking advantage of what seems be a fairly inefficient market in that regard.
That won't remain the case forever. But the good news for us is that we are building our center of excellence We'll be building our own constructs. We'll be the masters of our own destiny at that point. We'll certainly always be looking into other business development and licensing. I think we have a core competence in that.
But we don't have to rely solely on that as we get our gene therapies and our medicines propped up. And that'll be in by February of 2019. Yes, sure.
Thanks for the insights on that. I appreciate it.
I think Sandy had something else to add.
Just to add to that. I mean, answer your question, some of those deals were bitterly competitive and it went to the very end. And we were very pleased with our ability not just to compete with other public biotechs, but also big pharma. And I think it's primarily for, 2 or 3 different reasons. Firstly, our manufacturing expertise that we have and our ability to be able to supply our partners with the drug that they need.
And that really differentiated us in a very big manner. That also referred to the speed of execution of the entire team from clinical, legal, and obviously business development to get these deals done. And then lastly, as we've said before, we continue to forge strong partnerships to become the leaders in gene therapy. But what has occurred now is because of our relationships with the various KOLs and our success in business development, we're getting a lot of inbound inquiries that lets us both be more selective in terms of the quality of the deals that we want to do, but also ensures that the cadence of business development deals that we are getting keeps increasing. So you will see us continue forging these partnerships over the upcoming months and years.
Thanks.
Thank you. Our next question comes from the line of Brian Abrahams from RBC. Your question please.
Hi. This is Bert on for Brian. Thanks for taking our question and congratulations on all the progress. My question is on the DMD gene therapy program. So given the known effects of increased activity in on CK level, do you see CK levels as kind of the best way to measure the durability of the gene therapy, or do you think more focusing on the functional gains or even repeated biopsies would be a better way to change the durability?
That's a great question. So I think that there is that enormous there's an enormous compounded variables with the use of CK, first CK is variable as an example. You look at there are, phenotypically, non muscular dystrophy, Becker's patients that show they'll show significant spikes in CK. So it's already a bit of a variable endpoint. And then on top of that, to your very good point, we have seen a pretty strong correlation between, increases in exercise these kids appear to be.
Again, I want to be careful and label, but they appear to be very active relative to a matched Duchenne child and we definitely see exercise related increases in CK and then we see them fall right back down when the kids rashed. And so it does make it difficult. We're these early days and we're pondering, but it does make it difficult to use CK for instance as a reliable endpoint. We're going to have to there's definitely be a secondary endpoint in the trial, but
Yes. So given Roni here, I think that there are a couple of points to make. 1st of all, the CK What we do see is the overall trend, or not just more than trend puts us down in the range of the records, including with the spikes. So I think that's an important point, and that's actually very reassuring. I think the second thing is that no one would ever want to design a study where it's contingent on one outcome measure And then with regard to durability, I think there are multiple ways that we'll be able to look at that and that we're actually designing into our program, which I think you've outlined but function CK trend possibly controlling actually also for activity levels prior to CK, etcetera.
These are all approaches we will use. But overall, the most important thing will be functionality. And we've actually been surprised. And I shouldn't say surprises around more pleasantly cantilized by the data, the really robust data we've seen so far in the 4 subjects from a functional point of view. So I think all of that helps us makes us feel confident about how we design our trial using functional outcomes for looking at durability, but we will be looking at the totality of the data.
And durability is a very important issue in the long term. The good news, however, the preclinical models give us a lot of confidence on durability. We've seen both the obviously starting with the mouse model and then moving on to go to retriever models and moving all the way up to non human primate models, we've seen significant multi year durability, very node diminutions and durability over very long periods of time. And then when you couple that with the kinds of expression that we're seeing, there seems to be a very high probability that we're going to have a very, very durable product, but of course, that all has to be looked at over time.
Great. Thanks so much.
Thank you.
Thank you. Our next question comes from the line of Tim Chang from BTIG. Your question please.
Hi, thanks. Hey, Doug. Has the age of the patients taking EXONDYS 51 changed at it's still around thirteen years of age?
It's 12.9.
And just one follow-up. I think you guys mentioned there was slight change in the commercial government payer mix. What was the change?
Now fifty-fifty split between commercial and government, which is when I say government, it's almost all Medicaid And it's just increased number of patients that are coming on board, from Medicaid plans.
I mean, do you guys expect that to basically be the split going forward pretty much fifty-fifty?
Yes. We actually expected the split to be fifty-fifty 2 years prior to launch. And then, at launch, it was sixty-forty and it's moved up. And it's just And this is how every one of my launches have ever been Medicaid flag commercial plans at the beginning of the launch and then they catch up. So this is exactly what we thought would happen 2 years ago and we're seeing it play out.
Okay, great. Thanks.
And then probably ironically, particularly with the CMS letter gives us some opportunity over the coming couple of years.
It could get a little a little bit more to Medicaid on average fifty-fifty.
Thank you. Our next question comes from the line of Tim from William Blair. Tim, your line is open.
Hi, hopefully you can hear me. Ask maybe commercially how you're laying the groundwork for gene therapy in the industry is obviously seeing more scrutiny around pricing. This will obviously be a premium priced product. How are you prepping for payer discussions and maybe some of the pushback from, what should be a robust demand?
So we're doing a lot the short answer is a lot of work. So we're not only working on the models itself. We're reaching out beginning to have dialogue with payers and governments and others along the way. The really the interesting thing about gene therapy, I'd like to be clear, thinking about gene therapy as it is. And one of the things we're working on as an organization is the following.
The fact is that that from a typical health economic perspective, if you run our gene therapy program or any gene therapy program that would look like ours through a model, it will be very easy to get to the, to have a good number, a very good number for us. If you know, I serve as an example themselves, did a theoretical gene therapy analysis at a recent meeting and they had enormous numbers in the millions of dollars for a gene therapy, that was sort of a theoretical gene therapy that was transformative that would take the place of a therapy that was $200,000 a year. And when they did that, ran the math on that from even an Easter model, it was an enormous value. The issue that we're going to work on over the next 2 years is not the typical value proposition that you have to struggle with, but rather to structurally the real issue is there's not that whether the value is there, I think that's going to be fairly easy. That's just a mathematical side.
And I think we're going to do brilliantly in that. But this is the structure ready for big transformative, moments that will benefit as all health economically and benefits society, but they come in one form as opposed to chronic therapy. So the irony is if we don't put a lot of thought into this, our system is built around chronic therapies, What we all want as a society is big transformative potential cures, but our structure may not be brilliantly adapted to it. The if you're going to be the leader in gene therapy as we believe as our destiny is to be, then we've got to play an enormous role in helping to figure that out. And we're doing a lot of that work even right now and having a lot of dialogue with folks right now, including being able to have dialogues with government payers.
Frankly, those people have put a lot of thought already into models and the like. So it's a work in progress, but it's something that we're very deeply involved in right now as an organization.
Yes, Tim. I'll just follow-up with Doug said, it's, we're actively thinking about this and doing work now. We're going to keep everything very close to the chest. So we're in competitive situation. And we're planning on making sure that Sarepta's microdystrophin drug gets to all the kids first.
Thank you very much.
Thank you. Our next question comes from the line of Eun Chung from Janney. Your question please.
Hi, thank you for taking the question. I wanted to ask about the Europe for EXONDYS 51. Is there any data specific data that your mind could potentially help you to pursue approval, again? And, or do you think that the microdisciplined gene therapy program can have a better chance to get there first?
Well, the good news is we're not going to choose between them because we're going to go like that on both in we're going to go like Matt on Golodirsen and Casimersen as well and then other gene therapy programs. As it relates specifically to Tupperson, did get some guidance from CHMP. That's been very helpful. We're being a little careful about sharing various hypotheses right now for the simple reason, to be honest, we don't wanna die a 1000 deaths as we think this issue through and work with it. But we I will say that the as disappointed as we are and I don't wanna like we weren't disappointed with the outcome of the reexamination.
Of course, we were for more than anything else for patients in Europe that are waiting for this therapy. We did get good guidance from our repertoires and from CHMP. And based on that, we're going to take scientific advice from EMA in 2019. And I think we'll have a better understanding of what the pathway looks like and it And there might be opportunities that could be more efficient than for instance, another study or waiting for the outcome of a long term study.
Thank you.
Thank you very much.
Thank you. This does conclude the question and answer session of today's program. To Doug and Grew for any further remarks.
Thank you all very much. Thanks for your good questions and for sticking with us this evening. We have a lot to do over the coming months and years, but we've got the right team in place. We're focused. And we're going to not only think big, but we're going to focus on execution over the coming quarter and then the following year and then years beyond that.
So thank you all very much for for your questions this evening.
You may now disconnect.