Good day, ladies and gentlemen, and welcome to the Sarepta Therapeutics First Quarter 2020 Earnings Call. At this time, all participants are in a listen-only mode. After the speaker presentation there will be a question-and-answer session. [Operator Instructions] As a reminder, today's program is being recorded. And now I would like to introduce your host for today's program, Ian Estepan, Senior Vice President, Chief of Staff and Corporate Affairs. Please go ahead.

Thank you all for joining today's call. Earlier today, we released our financial results for the first 2020. The press release is available on our Web site at www.sarepta.com, and our 10-Q was filed with the SEC earlier this afternoon. Joining us on the call today are Doug Ingram, Sandy Mahatme, Bo Cumbo, Dr. Gilmore O'Neill, and Dr. Louise Rodino-Klapac. After our formal remarks, we'll open up the call for Q&A. I'd like to note that, during this call, we'll be making a number of forward-looking statements. Please take a moment to review our slides on the webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, any of which are beyond Sarepta's control. Actual results could materially differ from these forward-looking statements, and any such risk can materially and adversely affect the business, the results of operations, and the trading prices for Sarepta's common stock. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent annual 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. And 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 us for Sarepta Therapeutics' first quarter 2020 financial results conference call. Let us begin with a topic that is on all of our collective minds, COVID-19. I am very proud that the Sarepta team is still rapidly responding to this crisis, focusing on the safety and welfare of our patients and our workers, while ensuring that our operations run smoothly, and that our programs proceed. We are able to do this not only due to our execution-oriented ability to adapt and remain focused, but also because of good advanced planning. Numerous of our functions, including in particular, our information technology group, our clinical operations function, and our commercial organization began contingency planning as early as January of 2020 in the event that what came to be COVID-19 became a crisis. For that reason we were able to rapidly respond [technical difficulty] situation unfolded. By Friday, March 13, I had ordered that all but a small but dedicated facility-dependant staff would work from home, and because of our advanced preparations and the systems and the infrastructure in place to seamlessly transition, execute, and remain connected as we commenced work in that Monday morning. About 10% of our workforce is designated as facility-dependant, and we have worked to keep them safe and comfortable as they come in to the facility to run labs and experiments, continuing our manufacturing activities, and the like. We also immediately reached out to our partners, suppliers, and other important third parties to assess new working arrangements with them and to assure that they and we would continue to deliver, and we reached out to our patients and patient advocates to ensure that we were fulfilling their needs to the fullest extent possible. It is for these…

Thank you, Doug. Good afternoon, everyone. Despite the headwinds facing our healthcare system due to the COVID-19 pandemic, I am pleased to report that our product revenue for the first quarter of 2020 totaled $100.4 million. Our experienced teams at Sarepta are actively working to navigate through the challenges of the COVID-19 pandemic and allow us to mitigate major treatment disruptions for patients taking EXONDYS 51 or VYONDYS 53. We will continue to navigate the environment, and are learning more each day on how to better serve our patients in this unprecedented time. We continue to work closely with our manufacturers, distributors, and specialty pharmacies, to provide an uninterrupted supply of our therapies. As a result, we've had no disruptions in supplying EXONDYS 51 or VYONDYS 53 to patience. Consistency of supply is key. Therefore, we will continue our efforts to ensure that EXONDYS 51 and VYONDYS 53 are supplied to patients throughout the COVID-19 pandemic. We have modified our commercial execution strategy in response to the strain to COVID-19 pandemic has placed on health care workers, hospitals, and distribution channels. Due to recent shutdown to restrictions at hospitals and clinics, our team is working closely with health care providers and specialty pharmacies, to transition patients to weekly home infusions. Fortunately, the vast majority of patients on EXONDYS 51 are already receiving home infusions. Patient safety remains our top priority. And since many of our patients are choosing not to delay or stop therapy, we have thoughtfully deployed measures to minimize the risk of COVID-19 for all our patients, and we'll continue to assess these efforts. We are working towards initiating patients on VYONDYS 53. However, this environment is challenging because physicians typically wants to monitor patients in the clinic for the first couple of infusions, and many patients are…

Thanks, Bo. Good afternoon, everyone. In the first quarter total revenues in line with expectations and following the close of the agreement with Roche, and the sale of the Priority Review Voucher that we received in conjunction with the approval of VYONDYS 53, we are in a strong financial position with significant capital to fund our pipeline and ramp up manufacturing while maintaining our overall timelines. In addition, we not have the ability to access Roche's significant expertise and greatly enhance our global opportunity for SRP-9001. Moving to the financials, this afternoon's press release provided details for the first quarter of 2020 on a non-GAAP basis as well as the GAAP basis. The press release is available on Sarepta website. Please refer to our press release for full reconciliation of GAAP to non-GAAP. Net product revenue for the first quarter of 2020 from our products EXONDYS 51 and VYONDYS 53 was $100.4 million, compared to $87 million for the same period of 2019. The increase primarily reflects higher demand for our products. In the quarter-ended March 31, 2020, we recognized $13.2 million of collaboration revenue, which relates to our collaboration agreement with Roche. In February 2020, we received an aggregate of approximately $1.2 billion in cash consideration from Roche consisting of an upfront payment and an equity investment in Sarepta. From an accounting perspective, $342.7 million is being recognized in revenue on a straight line basis over the performance period, which we estimate to be through the fourth quarter of 2023. This revenue has been excluded on a non-GAAP basis per Sarepta's policy. For the quarter, co-development under the Roche agreement totaled $16.4 million and are included as a reduction to R&D expenses. On a GAAP basis, we reported a net loss of $17.5 million and $76.6 million or $0.23…

Thank you, Sandy, and good afternoon. I would dive a little deeper into the top R&D related activities that Doug has highlighted with particular emphasis on the actions the team has taken to minimize and where possible eliminate the distractions and obstacles caused by COVID-19. First, our SRP-9001 microdystrophin program, we look forward to the imminent publication of the one year safety and functional data from the four clinical trial participants, who received microdystrophin in Study 101. As with any onetime therapy, we know you are interested in the durability of the functional response in these patients. As Doug mentioned, Study 102 is in very good shape. We have dosed all patients in part, which is the randomized double-blind placebo-controlled portion of the 102 Study. Notwithstanding some of the constraints arising from restrictions of patient visits to the sites, we have been able to continue monitoring patient safety as data quality. Some clinical evaluations would take place "Outside of the protocol defined window." These are not critical outcomes and we are already evaluating how to mitigate the impact of out of window assessments in our analysis and regulatory plans. We are also pleased to see that Nationwide Children's hospital is loosening COVID-19 restrictions and starting to resume clinical trial activities. And I should note that our second Study 102 site UCLA with Perry Shieh as investigator has not imposed restrictions. So, Study 102 is proceeding and we anticipate no delay in the readout of that study. As far as our Study 301 plans go, I am pleased to report that we have adapted rapidly to the COVID-19 related uncertainties of the next few months. We are maintaining close contact with all of our sites around the world. Investigators remain very excited about the program and want to start as soon…

Thank you, Dr. O'Neill. Let's open the lines now for questions.

Thank you. [Operator Instructions] Our first question comes from Salveen Richter with Goldman Sachs. Your line is now open.

Good afternoon, and thanks for taking my question. So with regard to limb-girdle, when you present this high dose dataset in the second quarter, could you just comment post dose selection what the options are going forward with regard to trial designs for the registrational study?

Sure, thanks for that question, Salveen. So, broadly speaking, we're working with the agency on those questions and the development pathway even as we speak. So, as we quote earlier, the good news is that notwithstanding the COVID-19-related issues, all of the kids have been dosed, all of the kids have been biopsied. We will provide an update both on biomarker data, expression data, and safety data this quarter, and then shortly thereafter we'll make a dose selection. That will inform -- limb-girdle 2E will inform the rest of the sarcoglycan dosing as well. And then over the course of the rest of this year we're doing two things. The one thing we're doing is building manufacturing supply. You may have heard during my opening remarks that we actually are already in a GMP run for limb-girdle 2E, which I would just linger on for a second and give kudos to our technical operations group for being able to get to that point even during these very disruptive times. And then with respect to the development pathway, we're in an ongoing dialogue with the agency on that, we'll update toward the end of this year. Our broad view is that we need to find a development and regulatory pathway that takes into account severity of this disease so that it is executable, a pathway that is fast and efficient, and one that considers the fact that with respect to this particular gene therapy the gene that is being inserted in these children and the protein that's being expressed is the native protein, the absence of which is causing the degeneration and ultimately the demise of patients who have limb-girdle 2E, which one might argue should create a very efficient pathway to an approval, but I can't give you the specifics of that yet. We're in the midst of discussions with the agency over the course of this year. By early next year we should have two things complete. We should have our process development complete as we do, GMP material ready, and a good understanding with the CBER and FDA on the development pathway for limb-girdle 2E, and then the development pathway for the rest of the limb-girdles. And we'll come back and we'll talk about all of that next year. Our goal certainly is to start a pivotal trial in 2021 with respect to limb-girdle 2E.

That's helpful. Thanks, Doug.

Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is now open.

Hey, thanks very much for taking my question. On microdystrophin regulatory path, I'm curious your latest thoughts as to what you'd aim to bring to regulators for Study 3 to potentially support approval. I guess I'm wondering if that may change -- if there may be any changes given what you might be able to collect or what FDA might require given the pandemic and the later start? And then I guess along those lines, have you had any specific feedback from FDA on this out-of-window data collections of Study 102, and if at all you think that might impact your ability to use it as registration enabling without full functional data from the commercial scale material in Study 3? Thanks.

Yes, thanks for the questions. Let me start with the second part of the question first, and then go to the first. So on the second part of the question, we have documented the few out-of-window functional visits as the FDA's guidance has suggested. So the good news for all of us dealing with this pandemic is that the FDA is being very forward-thinking and thoughtful about addressing the disruption associated with COVID-19 in ways that ensure that we don't find ourselves with studies that are significantly delayed as a result of COVID-19. So there's already guidance on that, and we're documenting any delayed visits in accordance with that. The second thing I should note is that there have not been a significant number of delays. That even independent of that documentation process to ensure that we don't have any technical problems. As we look carefully at the study there is no reason to believe there's an affect on the powering of the study, or on the readout, or on the viability of the study, or on the timing of the study. So I just want to be very clear, in an abundance of transparency there have been a few instances of patients with out-of-window functional visits in light of the fact that there was a period of time, which is coming to an end now, at Nationwide, where Nationwide Children's Hospital was limiting some of those in-clinic visits, that's disappearing, but that will not, from our analysis, have any impact on the viability of the study or the integrity of the study or the readout or the timing, or the probability of success of the study. So I think we're in really good shape with respect to Study 102 right now. And honestly I say this, and I'm giving…

Thanks very much, Doug.

Thank you.

Thank you. Our next question comes from Tazeen Ahmad with Bank of America. Your line is now open.

Hi, good afternoon, guys. Thanks for taking my questions. I'm sorry if this question was already asked, but Doug, can you clarify for me, for Study 102, how often are the patients actually being monitored for the functional visits, and specifically I just wanted to get a sense for the biopsies that were scheduled to be taken for the patients in Study 2, do they have to be taken per protocol at a certain point of time after they were dosed or is there any flexibility in when the biopsies can be taken?

So, I'm going to turn this over actually to Louise Rodino-Klapac to respond to both of those questions.

Sure. Thanks, Doug. There is a certain visit window for the biopsies but as Doug mentioned, in terms of flexibility, any out of window just needs to be documented as per the FDA guidance. So, as we look at it, there's no particular delays or misses within the protocols that will be meaningful to the outcome of the study.

Okay, and did you know what percent of patients were a little bit delayed in getting the biopsies?

No, I'm sorry. We're distant, for those who may wonder why there was an enormous delay, we're distant from one another, and I actually insisted that I direct the questions, so, apologies for that, Louise. So, Louise, I'm sorry, could you answer the question?

No, there was just -- I don't know the exact number of visits that were delayed, but it's due.

Okay.

Very small, very small number.

Okay. And then as we think about limb-girdle to follow-up for the pivotal study that you're going to start next year for the 2E subgroup. Can you just remind us of how big of a population that is relative to the rest of all GMP?

Well, it's very rare. This is an ultra rare population. I don't think we've gone out and given the exact numbers as one of the things we've said, if you look at the entire epidemiology and population of all of the patients that we're looking at, we're talking about a group of patients that are about 70% of the size of Duchenne Muscular Dystrophy, but the limb-girdle 2E is a very rare form of limb-girdle and very severe form of limb-girdle. So we haven't nailed that, we haven't nailed the size of the trial down but obviously with that in mind, when you consider the rarity of the disease, and you consider that this is really, this is kind of the perfect sweet spot opportunity for a gene therapy. This is a monogenic disease, well-characterized, well-understood. It is the lack of a structural protein, it is a single structural protein that is causing all of the damage and degeneration and loss of life that comes with 2E and the gene therapy that we have created and that Louise has created, we'll introduce a gene that codes for the actual native protein, the lack of which has gone through. So again, I don't have an answer yet on the exact development pathway. We're working on that actively with the agency over the course of 2020, but it is certainly our goal to have a very, have a development pathway, regulatory pathway that that has the speed, and leanness that one would imagine, with the disease of this rarity, well characterized monogenic and with, if we can get very high expressions and we're already there with our current dose that return to these patients, the very protein, the lack of which is causing their disease.

Okay, thank you.

Just a reminder everyone, one question, we have really full queue. The line is going to be silenced after you ask one question, thanks.

Thank you. Our next question comes from Debjit Chattopadhyay with H.C. Wainwright. Your line is now open.

Hey, good afternoon guys, and thank you for taking the questions. So given that you're at the 20 mg per kg dose with SRP-5051, what should be the 12-week dystrophin expression that would excite you to advance the 45 and 53 programs rapidly?

Yes, thank you very much for that, Debjit. Look what I can say broadly about this is that, first of all, 12 weeks is a very early period of timing we're looking for dystrophin. So I wouldn't commit in advance that we will even be looking for dystrophin at the 12 weeks, what we will be looking at is Exon skipping and what you will find within and of course through reminds us I'm sure everyone knows this, but the Exon skipping is the very activity that results in the truncated form of the RNA that in turn creates the protein that is the slightly truncated but otherwise fully functional dystrophin that we're trying to achieve, and what we know, at least in animals, we know two things, we know number one, there is an obvious direct correlation between amount of Exon skipping as you would well imagine and amount of dystrophin production. So looking at Exon skipping is a perfect, a brilliant marker for what kind of dystrophin we might find over time. I'll give you an example with respect to Golodirsen, we had made some fairly bold statements about what we probably would see with Golodirsen versus Eteplirsen and that was all because of what we had seen early days and the relative Exon skipping that came from Golodirsen versus Eteplirsen. So I think Exon skipping is a great marker, and what we're going to be looking for, of course, that would get us excited is the relative amount of Exon skipping you might see from PMO at 12-weeks, versus the amount of Exon skipping that we will see with the PPMO at the doses that we're talking about right now. We don't have it yet. We'll see it in the second-half, and we'll all come together, and we'll have data on tissue exposure and Exon skipping and safety and the like and dosing levels, but I can at least tell you that in animal models, we were we would have been getting excited at doses significantly below the doses that were now dosing through. And I think at the inception of the single-ascending dose, and then the multi-ascending dose study, when we started this, our animal models or mouse modeling and then our non-human primate models got us to a point that where we would be very happy with six mgs but we get increasingly happy up to about 12 mgs per kg, which is what we envisioned would be the ceiling and how high we can get and certainly with respect to this peptide conjugated PMO, more is better with respect to dosing if we can get the higher dose safely, and the fact that we're at 20 mgs per kg right now, it makes us very, very pleased, I will say. And while it hasn't affected as a delay in the program as we have to continue dosing, I don't think it's a delay that any rational person is going to complain about.

Thank you. Our next question comes from Alethia Young with Cantor Fitzgerald. Your line is now open.

Hi, this is Emma on for Alethia. Can you give us any color on what the actual processing requirements look like for a patient to transition to home infusion, just what the percentage of patients are currently on home infusion for VYONDYS and EXONDYS and what those trends might look like next quarter?

Sure, I'm going to turn this over to Bob before I turn it over just to remind everyone with respect to EXONDYS, as it stands today, the vast majority of patients are on home infusion and well with respect to a launching product line VYONDYS, we will see a greater percentage of patients that start in hospital, it will over time be the same case that the vast majority of VYONDYS patients will become home infusion as well. Of course, Bo can talk to you about the things that we're doing today to accelerate that process. Bo, with that?

Yes. Thanks, Doug. And to Doug's point, the majority of our patients are already at home infusion, but for the patients that are being dosed in the hospital, it's really just an authorization like a reauthorization process with payers. So it's just more of a paperwork process of transferring the authorization from in hospital infusion to home infusion. So, there is a couple weeks delay for those patients that do need to transition but we do expect this to ease over the next couple months.

One other thing, I would say on this topic is this, there's a lot of process involved both in the launch of VYONDYS and EXONDYS. And one of the things you might have heard in my opening remarks was about the fact that we're watching very carefully how payers are going to react in the middle of this crisis to ensure that payers don't themselves tend to take advantage of the disruption that's occurring with COVID-19 in ways that might profit them to the detriment of children. In fairness, I should note that payers are based on everything we're seeing right now doing exactly the opposite that in fact, I think that very laudably payers have been looking for ways to reduce some of the obstacles that might be imposed as a result of COVID-19 to ensure that kids could stay on therapy. I'll give you just one example. With respect to State Medicaid, I'm informed every single state, all 50 state Medicaid have been have requested and have been granted by CMS waivers that allow them in turn to waive prior authorization requirements and to extend kids on therapy without the need to go through the prior authorization process. I don't want to suggest that that means that they're not going to impose prior authorizations. They likely still will, but certainly that is a significant step in the direction of ensuring that COVID-19 doesn't get in the way of kids who have access to therapy, and I really do think they deserve kudos for that.

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

Thank you for taking my questions. I have one regarding limb-girdle beta. So, there was an abstract 503 on cohort one data at the ASGCT, PDF abstract, but somehow the final Web site doesn't have this abstract anymore. Just want to double check that there will be no data at the ASGCT from limb-girdle, and also given good safety so far we see from microdystrophin program, limb-girdle program has the same factor and the promoter, is it fair to say higher dose safety should be largely in line with microdystrophin program.

Well, on the latter part, I'm going to say that we're going to comment on that when we release the data and we'll have that data released this quarter. So, you won't have to wait very long to get an update on limb-girdle about the expression and safety. But your point's well taken. Just so we're clear and it's actually, you're exactly right, which is - this is the same promoter. This is the same vector and what we're currently calling this is a prior dose or high dose on limb-girdle is the same dosing level that the kids with Duchenne Muscular Dystrophy ever received, both in 101 and 102, and together that is significant number of patients that have that dose. With that, I'm going to turn it over to, Louise, who might comment on ASGCT and limb-girdle, but maybe give an overview of what kind of abstracts or posters we might have at ASGCT?

Sure, yes. In terms of the clinical data, it will be -- we will release it later this quarter. So we will add ASGCT there are two preclinical abstracts that will be presented as poster for limb-girdle, and that will be focused on long-term expression data and then also expression in later stages of disease. This is all preclinical, and then of course we'll have our symposium, where we'll outline the background on the development of our constructs, and also talk about the microdystrophin data -- nine months data.

Thank you. Our next question comes from Ritu Baral with Cowen. Your line is now open.

Hey, guys, this is [Sushant] [Ph] on for Ritu. A question on Study 102, I'm wondering what some of the assessments being outside of the window, have you had to revisit the statistical analysis plan and what adjustments are about to be made? Thanks.

Yes, thanks for asking the question. We've looked at it carefully and there is no adjustments necessary. We don't have a concern on the statistical analysis plan. In broad strokes you're going to have this concern on powering. We don't think there's any impact from the modest number of out of window functional visits to calm any concern regarding integrity, and certainly as we've said before, it won't have any effect on timing. Dr. O'Neil, if there is anything I've missed in that, feel free to add to that, or correct me if I misstated anyhow.

No corrections necessary. I told Doug we have looked and these out-of-window assessments are not absolutely critical and have no impact on our statistical analysis plan.

So, we remain on time.

Thank you. Our next question comes from Joseph Schwartz with SVB Leerink. Your line is now open.

Thanks very much. So, based on the age of the patients that you've enrolled in Study 102, how do you expect their North Star scores to change over the duration of part A? And how is the study powered to detect a difference between the two arms? There is a copious literature suggesting that North Star can increase during this age range. So I'm just trying to think about what kind of an increase 9001 will have to produce in order to succeed?

Let me give you the broad stroke. I'll give you a broad stroke answer on that. Some of the nuance I'm probably going to avoid simply for confidentiality, competitive reasons. I can do the broadest stroke. The broadest stroke is the following. I suspect that no one has better patient level data on Duchenne Muscular Dystrophy. It's epidemiology. It's of course then Sarepta. Obviously the leaders in Duchenne Muscular Dystrophy would've been close to the patient community and the data for eons. We have not only all of the literature, we have our own data, patient level data we have access to synergy data, we have access to all of the data from BioMarin that they had back in the day that we negotiated, and so, we're well-informed to build this, the study that we built to your point in a nuanced way, what you see across four to seven year olds in broad strokes is that there is the possibility for a couple point potential linear -- not linearized, I apologize, non-linearized a couple points increase potentially between the four and five year range, but you will see them coming over the top and actually declining, starting to significantly decline in the six and seven-year-old range. As you know, these kids are four to seven. All of that nuance understanding of the course of this disease that has been used for inform the protocol that we've used, and beyond just that, we of course have the benefit of the first four patients that we've had. We've had about some of that data as well, but we've used some of the data that we have gleaned from the first four patients to help us consider the powering of this study. I will note by the way, I don't know if we've talked about this, but the one-year publication on the first four kids, that cohort will be published very soon imminently, and it was all that went into this, and just to make the broad stroke point, the powering of this study was over 90% when we got to 40 patients. So we feel confident about the protocol, about the powering, and certainly about the progress, the Study 102.

Thank you. Our next question comes from Christopher Marai with Nomura. Your line is now open.

Hey, good afternoon. I'm just thinking about the path forward for limb-griddle muscular dystrophy with regulators and the potential for using expression data. I was wondering, just how much expression data it might need to see there and if the FDA has any concerns or if you have any concerns about also I suppose, just the sarcoglycan complex being sort of reformed by re-expressing the protein and making sure that's intact and if you are prepared to provide any localization data in that regard, if it's required. And then just real quick with PPMO, I mean, how much data will really satisfy you guys with respect to safety at any given dose call it 20 mgs per kg. What kind of timeframe are we looking at before, we can get confident that you could move forward and say 20 or 50? Thank you.

Okay. So, as it relates to limb-girdle, we're still working on the development and regulatory pathway itself as you've anticipated. We certainly think that this should be a very lean approach, and frankly, in a perfect world, we think that this would be a perfect opportunity to be approved on a biomarker of expression. You raise a really interesting point about what about the reconstitution of the dystrophin associated protein complex and the fact that we think that is a very important element to looking at this. And that's another important biomarker. Is there, when you upregulate as an example, beta-sarcoglycan, do you see that dystrophin associate protein complex itself also begins to upregulate so that other proteins in that complex would start to come together and be express where they would be missing before because the DAPC is not coming together. That is important. And that regardless of whether the FDA of its face would demand it, we do think that's something important that we should show and be able to prove. And the good news is by the way, we have seen that repeatedly that one of the things that should get someone very excited about this is that it's -- that this is the native gene, the native protein already at our previous dose, very strong expression, properly localized to the right place. And to your good point, associated with the upregulation of the other proteins that make up the dystrophin-associated protein complex, this is one example. You see a very strong correlate between upregulation of beta-sarcoglycan and alpha-sarcoglycan, which these kids have a gene that's to properly code for alpha-sarcoglycan, but you don't see this significant amount because in the absence of beta-sarcoglycan there is DAPC. So, I think all of the facts and circumstances around that are going to come into play when we think about the development plan, what we think we should be able to avoid would be a lengthy trial that would require for instance, a placebo control trial and the like, and we're still working with the agency. We still have a lot of discussions to go with the agency to land on the right answer. There are -- what if there are a lot of places to land between an accelerated approval on a biomarker, which would of course be our -- the answer we think is great. And on the other hand, a full blown placebo-controlled trial, but we'll come back early next year and provide an update to everyone.

Thank you. Our next question --

Nope, before we go on, I've been promised that even though there were two questions; I will turn this over to Dr. O'Neill to answer the question on the PPMO.

So today we are actually happy with the safety profile that we're seeing, and with the numbers in our ascending cohorts, ascending cohorts, and the ascending dose, we believe that we have sufficient numbers. I think we are able to judge safety by looking both at the clinical outcomes, but actually are obviously able to monitor the target talks that were identified not to the top. So, we believe with those numbers we can comfy make decisions. Obviously looking forward, safety is always a matter of numbers, but these numbers are I -- we believe adequate for making that initial dose selection.

Thanks.

Thank you. Our next question comes from Joel Beatty with Citi. Your line is now open.

This is Shawn Egan calling in for Joel. Thank you for taking my questions. On the PPMO congratulations on the 20 mg per kg dosing, maybe you can just count on or talk a little bit about any preclinical data or work you've done on microdystrophin gene therapy plus the PPMO combo and what you've seen there.

So I think at this point all we'll say is that it's an area of keen interest to us, and we are doing a preclinical work on those on two different concepts. One concept is the value of three treatments with a PMO or PPMO in advance of a gene therapy to enhance the competent the value of this therapies into enhance expression. And as relates to that, I can't lean over and talk about literature that already exists. Dr. White is an example has some literature where he in the mouse model pretreated with a -- I believe it was a peptide conjugated PMO, and then dose with gene therapy and he found enhanced expression. That's one area and we're looking at that area. The second one of course is a very significant one, which is to explore the benefit of a commutated value of a PPMO on the one hand, and gene therapy and the other, and you can envision a world in which you would get a synergistic value between a really significant expression from the gene therapy construct, like our SRP-9001, coupled with robust expression of a truncated district then that you would get from a PPMO. We're doing a bunch of work on that. We're not ready to discuss it in any detail, but it is certainly something that we need to continue to work on in advance of the launch of our gene therapy program. Assuming that we're successful in clinical development as well as in advance of the success of our PPMO program as well, I think, people in their models that we're working assumption that gene therapy will entirely cannibalize the RNA platform, and while I can understand why some people look at the exciting aspects of our gene therapy and imagine that, I think it's probably early to it to believe that's the case and we have some tantalizing research that might say there is a value to these two therapies together.

Thank you. Our next question comes from Matthew Harrison with Morgan Stanley. Your line is open.

Thank you. This is Max Skor on for Matthew Harrison. Sorry if I missed this, but can you confirm that all microdystrophin release essays have been built, but do you still need to be validated, and are these In Vitro potency assets? Thank you.

Yes, great question. So yes, I can confirm that all of the assays are belts. I can confirm it up 24 assays. All of them are either validated or qualified. Some assays need to be qualified. What assays need to be validated, I mean there are two that are in the later stages of that validation. I can also tell you that it's not the potency assay, but all of the really crucial bespoke assays are either validated or qualified. The last two that are in the last stages are really that are very routine. These are very sort of nearly off the shelf routine assay, so all of the really significant ones have already been validated.

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

Thanks for taking the question. Just want to follow-up quickly in your comment earlier on looking for exon-skipping at 12 weeks, but not necessarily dystrophin, after you started getting exon-skip dystrophin, or in the case of gene therapy, after you start expressing microdystrophin mRNA, how quickly would you expect to start seeing meaningful dystrophin levels and then how does this continue to trend over time? How long does it take for example to reach steady state?

So, I'll give you the broad stroke, and then Dr. O'Neill, if you have additional color on it. I mean, first of all, we got it -- we definitely have to take RNA and microdystrophin gene therapy and put them in two different buckets. They're very different. With respect to microdystrophin, we know the answer is three months, so what we've seen as you know with respect to SRP-9001 in our first four kids, we took biopsies after three months and those kids had 90% and higher dystrophin expression, so clearly we get a really fast onset for the gene therapy. For RNA, it is a slower process and it occurs over time, probably for a host of reasons, but it occurs over time in fact we saw a significant difference over a long course, a period of time with both EXONDYS and with respect to VYONDYS and then we saw I think the one between one year and four years there was a significant difference in the amount of dystrophin and that may be in part because with this chronic therapy. The cryotherapy keeps increasing the benefit over the long-term. One of the reasons, frankly, during this difficult COVID crisis that we're so focused on ensuring the kids don't skip dosing because skipping a dosing, isn't simply missing a dose. They may be missing the cumulative benefit that you're getting from being on therapy over a long period of time, but with that said, I'll turn to, Dr. O'Neill, maybe provide some more color.

So, Vincent thanks for your question. The half-life of wild type, your full-length dystrophin is in the order of weeks, this we know, and as Doug has said the -- not surprisingly, the time to transcribe as high fidelity and translate the high fidelity dystrophin, which is such a large gene, actually, is it measurable in many hours. I think, so those are important biological questions then from the point of view of looking at 12-week data. The key decision will be driven by the relative potencies of PPMO to PMO. And what we really -- the robust data set that we have at that timeframe, really forces us for crisis to compare exon-skipping, which I think is actually a very valuable way of making the decision about going forward as selecting doses, and as Doug has said, as you can expect from what I just said about the half-life of dystrophin, and the synthetic timelines for the dystrophin one would expect to see ongoing accumulation over many weeks and months. So that's the reason why we're actually focusing on the exon-skipping at 12 weeks, but also, we are measuring tissue levels off the PPMO, and we'll be able to compare that with PMO as well, so that really enables us to really test multiple types of the hypothesis.

Understand this about -- let's talk a moment about what we know about our RNA technology to PMO generally, so we -- thinking about our PMO that make it so clever, is that number one is precise, then we know we get the PMO to the right place, it induces excellent skipping, it transforms messenger RNA, it puts it back in for making dystrophin. We know that. We know it's safe, right? The PMO, we can dose at very high level and that's a very significant safety window, and there with it's therapeutic window. Then, the one limitation and it is a significant limitation of our PMOs, is that as a neutrally charged molecules, I think it entered the cell well and as a result of that. A lot of the PMO that is infused, it doesn't get into the cells until it is utilized, it's urinated out, so the goal of all of this -- the unlocking of RNA technology and the potential profound improvement of the RNA technology comes from something that is, it is simple to discuss, frustratingly simple and difficult to execute, which is, can you find a delivery vehicle that can safely get the PMO in the cells in much greater exposure? That's the question in animal models, the PPMO does that very mechanically, it's a positively charged peptide, it interacts with the negatively charged elements on the outside of the cell, it creates warbling and uses vesicle to get into the cell in great abundance, an order of magnitude greater than you would see with a PMO. And so, that's the biggest issue for us right now. Can we get to strong therapeutic doses, what we envision to be therapeutic doses of the PPMO without inducing your safety signal, and if we can, I think mechanically, we're going to be very excited about the potential of the PPMO. And in that regard, we need to see this data and we'll have a data readout in the second-half of 2020. The exciting thing about where we're right now is that we're 20 mgs per kg when we envisioned at least some time ago that our ceiling was going to be about 12 mgs per kg.

Thank you. Our next question comes from Anupam Rama with JPMorgan. Your line is now open.

Hi, all, this is [Sacks on the call tonight] [Ph] for Anupam. Hope you're all well, and thanks for taking our question. I think in the prepared remarks, Doug, you mentioned that you do not yet have clarity to provide updated guidance for EXONDYS, but maybe from a high level, what were the levers for growth from $31 million in 2019, and maybe how are you thinking about the push and pull levers for the guidance to consider with the ongoing COVID-19 pandemic? Thanks so much.

Yes, look, I'll give you the broad strokes. So our growth with respect to EXONDYS doesn't relate to price. Let's make sure we're clear about that. So there is only one lever and it's patients on therapy, staying on therapy, and we're finding more patients and more patients coming on therapy. That is it because as hopefully people know, and I think I've said in other forums many times, we launched EXONDYS in 2016, we have taken no price increases over that period of time and we don't envision taking a price increase. Our goal is to grow through serving this community and having more kids benefit from our therapies, and as an example with respect to VYONDYS, we priced it at parity with EXONDYS, obviously take a price increase there. So we look forward, that's the level and the risk to revenue is modest for the second-half of the year certainly with respect to EXONDYS because with respect to EXONDYS, the great majority of kids are already in home infusions. And while there are a number of different elements that could be disruptive over the course of 2020, that's significant disruption in kids that don't have the ability at the peak of this crisis to get into a hospital to get it in fusion if you're in hospital, and the good news is most of the kids are not. So when I talk about EXONDYS in particular, we're talking about it. Basically, everything we see today, and as I said, I'm not giving updated guidance, because we're in the middle of something and we don't have sufficient clarity to give guidance that we feel confident about other than to say what we're seeing right now would be a modest and short-term in that. We'll see a little more significant delay and impact on VYONDYS for the simple reason that we're in launch phase with VYONDYS that a more significant number of patients will start in the hospital although we're working to try to reduce that number, but even with respect to that, we think that's going to be modest, and we think that's going to be a short lived issue. So, broadly speaking, I think we're in good shape. We're serving the patient community, we're trying our very best and I think we're so far succeeding and keeping them safe. And any impact on revenue ought to be really quite modest and quite short lived, but with that, Bo, am I missed anything?

No, Doug, you covered everything. Thank you.

Thank you. Our next question comes from Tim Lugo with William Blair. Your line is now open.

Thanks for taking the question. For the commercial supply trial, the ongoing issues around COVID impact, how you think about that Study size, maybe adding additional sites than you originally anticipated or additional geographies where you may enroll patients or even just the overall powering of that Study?

Thanks for the question. Now the Study remains on pace and on track as originally envisioned, both the size of this study, the fact that it's a multi-country multi-institute, the fact that it's placebo-controlled, et cetera. So the design hasn't changed on that study. I have said that the one logistical risk in the start of that study is that you've got to get studies up and running, you've got to get -- in a perfect world you have in-person site initiation visits from our clinical operations team and the like. We want to make sure everyone is properly trained so that we have consistency across all of the sites all around the world. So there's a lot to do. And so, we envision that there will be a modest delay in the initiation of that trial just to make sure that we're being thoughtful and cautious about that the COVID-19 as we're starting. That means there'll be a modest delay. I say modest because we still have every intention of starting Study 301 in the second-half of this year. So we're talking delays measured in a couple of months, not measured in significant amounts of time, but beyond that I think things are proceeding, and we haven't made any significant changes to the approach that we're taking.

Thank you. Our next question comes from Liisa Bayko with JMP Securities. Your line is now open. Liisa, if your line is muted, please unmute.

Oh, sorry. Thanks for taking the questions, and congratulations on the strong quarter. Just wanted to know if you could give us a little bit more detail and color from the quarter itself in terms of how many patients actually started on VYONDYS just so we can better understand the dynamics there. And then also any changes in gross-to-net or any of those kind of details that we should be thinking about given patients' insurance and maybe kind of levels of unemployment there might. What's the right way to think about some of those dynamics? Thank you.

Sure. I will turn this question over to Bo, although I think some of the nuance we're probably not at liberty to disclose.

Yes, Liisa, obviously we're not going to give -- in regarding to patient numbers for EXONDYS, and we won't with VYONDYS, but I will tell us even though VYONDYS is obviously smaller than EXONDYS from a population standpoint, we were very pleased with the progress that we were making with payers and coverage, we were much further ahead than we were with EXONDYS. We have 148 million lives that are covered either restricted policy or two labels, so we were very pleased with that, and the launch was going to our expectations. So it's just the small hiccup of the pandemic that put the little things and pushes into, but we were overall very, very happy.

Thank you. I am not showing any further questions at this time. I would now like to turn the call back over to Doug Ingram for closing remarks.

All right, thank you. I'll be brief. Thank you all very much for joining us for our earnings call. And hopefully you've seen here that like so many other companies, and frankly individuals, not just in the United States, but around the world, this pandemic has caused enormous numbers of challenges and obstacles for the Sarepta team by -- as I've said before, I'll say it again because it bears repeating, I am unbelievably proud of the Sarepta team for the ability to stay on mission. 90% of this team transitioned to working from home, and yet we did that on the Friday, we got up on Monday, I have taken a careful look at every metric you can see, and not only externally, when you see the way we're tracking against our milestones, but through all of the metrics you'll see that this organization remains as productive as it was on the Friday before we all went to working from home. So there is a lot of learning in this, probably not just for Sarepta, but for all of us about the ability to be efficient even in a virtual manner. We are mission oriented as an organization. We have never taken our eye off the need to bring a better life to these kids. And even through this difficult and distracting period of time, even in a period of time when our workers themselves have to worry about their own loved ones and about themselves, they have not lost sight of the fact that Sarepta is on mission. We're going to continue to execute across 2020, and we're going to be excited to give you additional updates across the year. We can give you better clarity on sales in our second quarter earnings call. We have a number of significant milestones across the rest of this year. I think the rest of this year into 2021 is going to be an enormously consequential period of time, not only for Sarepta, but for the patients that we serve. So, thank you all very much. Everyone please stay safe, wash your hands, and let's get this crisis behind us.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.