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Sarepta Therapeutics, Inc. (NASDAQ:SRPT)

Sarepta DMD Development Program Update Conference Call

May 13, 2014 11:00 AM ET

Executives

Jim Baker - Director of Corporate Communications

Chris Garabedian - President and CEO

Ed Kaye - Chief Medical Officer

Kara Boniface - Senior Manager of Community Relations

Analysts

Debra Miller - CureDuchenne

Christine McSherry - Duchenne Alliance

Valerie Cwik - Muscular Dystrophy Association

Ryan Fisher - Parent Project Muscular Dystrophy

Elizabeth Vroom - United Parent Projects Muscular Dystrophy

Alex Smith - Harrison's Fund

Diana Ribeiro - Action Duchenne

Alex Johnson - Joining Jack

Operator

Welcome to the Sarepta DMD Development Program Update Conference Call. My name is Vanessa and I'll be your operator for today's call. At this time, all participants are in a listen-only mode. Later we will conduct a question-and-answer session. Please note that this conference is being recorded. And now I will turn the call over to your host, Mr. Jim Baker. You may begin.

Jim Baker

Good morning. Welcome everyone to the Sarepta Therapeutics' exon-skipping program update for the Duchenne Muscular Dystrophy Community. My name is Jim Baker, I'm the Director of Corporate Communications at Sarepta. I am joined today with Chris Garabedian, our President and Chief Executive Officer; Ed Kaye, our Chief Medical Officer; and Kara [Boniface] our Senior Manager of Community Relations.

Chris Garabedian

So let me -- Jim you want me to….

Jim Baker

Yes.

Chris Garabedian

…take over the call? So thanks Jim. I also just wanted to highlight, we do have a new member of the team, Kara Boniface, who Jim introduced, is our dedicated person to the patient community. All of us are always listening to the patient community and we want to incorporate all the feedback we get into our overall DMD program and our communications strategies and making sure we are keeping a good pulse on the community. So, Kara will be reaching out to various members of the community to make sure that we hear your voice beyond calls like this in other ways that we interact with the community at various conferences. Kara, would you like to say hello.

Kara Boniface

Sure, thanks Chris, and good morning everyone. As Chris mentioned I am the Senior Manager of Community Relations here at Sarepta. Really excited to be here especially at such an important time for the community and I am looking forward working with many of you and getting your perspective and input on how we can move the conversation forward in the coming months.

Chris Garabedian

Great, thanks. And as you see on the webinar we have a forward looking statements. So we are going to be talking about our programs moving forward, and please refer to our SEC filings for risk factors associated with the company.

On the next slide, we highlighted our goals for today. So first we will provide an overview of the recent FDA guidance regarding eteplirsen and our follow on exons skipping therapies. Then we are going to review and Ed Kaye will provide detail around the critical next steps for both the eteplirsen and other follow on exon development candidates. We will describe our plans for regulatory filings and when we expect the various studies in our clinical program that we have announced to start. We will also review some additional resources we have for the community to get more information about participation in our clinical trials or genetic testing in the form of a collaboration that we announced last year with PPMD.

But then we are going to open it up to questions to many of the key DMD advocacy organizations in the U.S. and in the UK. So first I would like to start with the summary of the recent FDA feedback. So first and foremost we are thrilled that after a long year of discussions with the FDA and more recently around 5.5 to 6 months further interactions with the FDA as well as their involvement and getting further feedback from experts in the community and talking to many of you on the phone and other patient advocates. We have guidance that gives us a clear path forward for our DMD program both eteplirsen and some very encouraging signals on our follow-on exon program.

First and foremost, we announced based on the guidance we received from the FDA that we will be submitting a new drug application by the end of this year for eteplirsen in the hopes of gaining an accelerated approval in 2015. An accelerated approval of eteplirsen was something that the FDA discussed with us and they felt that with additional data as part of an NDA submission, they outlined two possible ways that an accelerated approval could be granted for eteplirsen. The first way was based on the dystrophin as a surrogate marker that could reasonably predict a clinical benefit, and the second way was on an intermediate clinical end point that could reasonably predict clinical benefit. And they highlighted the six-minute walk could be an endpoint that they use for that intermediate endpoint.

In terms of the additional data that they said would enhance acceptable NDA filing and a favorable review, I want to be very clear. While the FDA did not say that we could not submit an NDA on the existing data set, they did highlight that our chances of a acceptable filing and an approval of the drug would be increased or enhanced with additional data.

So what we've decided as a company is that we felt that we are still accumulating data from our ongoing Phase IIb study, both safety and efficacy and that we would have a lot more information to including in NDA by the end of this year. We also are exploring the feasibility of a fourth biopsy, so we could also see an opportunity to get additional dystrophin data to include in an NDA. In a moment, we'll outline what specific information we will have and when that will come for rolling into a NDA submission at the end of this year.

The second point in the FDA guidance was a clear understanding of what it would take if they were to approve eteplirsen under the accelerated approval format, what we would need to confirm the results under that accelerated approval. And they outlined two different ways that we could show either of which would be acceptable to confirm the eteplirsen accelerated approval to gain what we call a full or standard approval of eteplirsen.

The first way that they indicated we could get a confirmatory full approval of eteplirsen was through an open label historically controlled clinical study of eteplirsen. This would be a non-placebo controlled study. So every patient that is enrolled and randomized to the eteplirsen arm would get eteplirsen. And we would continue to follow those patients into the future and the FDA did not define specific endpoints and did not define specific time point in which we had to show a benefit different from natural history. But we would continue to follow these patients. And once there was a robust data set that we believed in discussions with the FDA would warrant a discussion around a confirmatory full approval, we would do it through this open label study.

The second way that they outlined we could confirm the results of a potential eteplirsen accelerated approval was through a placebo-controlled randomized study on a follow on exon-skipping drug. We discussed with them the interest that we have enrolling maybe more than one follow-on exon-skipping drug. And they understood that that was our objective and were supportive of including other exons in our broader program moving forward in this type of placebo-controlled study.

So, this is something that they indicated could also be used independently and mutually exclusively. In other words, we wouldn’t have to necessarily have benefit on both of those studies just one of those two studies to potentially confirm the Sarepta, the eteplirsen accelerated approval.

Lastly, the indication of using a confirmatory study based on follow-on exon-skipping drug was very encouraging to us and we believe provide some of that initial guidance of accelerating the development of the follow-on exon-skipping therapy. In that they encouraged us to move as rapidly as possible into a confirmatory study of these follow-on exons one or more and ultimately that means we have to get to a effective dose of 30 mg/kg per week as soon as possible and we will be working with the FDA to finalize the plans around the design of that study to make sure that we can start dosing at an effective dose as soon as possible so that it’s well powered on a clinical endpoint like six-minute walk.

On the next slide we outlined the key regulatory activities that I mentioned earlier. As I indicated we have emerging data coming out in the form of a 144 week data from our ongoing Phase II extension study. We will be exploring the possibility of a fourth biopsy later this year that could be enrolled in an NDA submission. We’ll have additional safety potentially from the initial patients enrolled in our ambulatory eteplirsen study.

All of that will be rolled into an NDA submission that we are targeting for the end of this year. The FDA also showed good flexibility of accepting data that we may receive after an NDA filing, but still in time for the NDA review period or a potential advisory committee, public advisory committee meeting.

They did indicate that that would be likely. We would expect a public advisory committee to take place sometime in the first half of next year. And then again, assuming the NDA is accepted for filing and we have a favorable review, the potential for an approval decision would come we believe six months after the filing or some time in this summer or late summer of next year assuming we will get a priority review designation.

So that outlines the FDA regulatory path. I'd also mention that we will be seeking scientific advice on the eteplirsen dataset we have and the feasibility of submitting a MAA application under similar accelerated approval or exceptional circumstance, conditional approval guidelines that the EMA has. We will be seeking that scientific advice by the end of this year and we'll have a better understanding of what it will take to get eteplirsen approved in Europe.

On the next slide, we just highlight more specifically the details around the FDA approval process. As I mentioned, we would expect to submit an NDA by the end of this year. Once an NDA is submitted, we would find out within 30 days if it’s granted a priority review. Again we have fast track designations, this is a disease where there is no currently approved FDA approved drugs for the treatment although cardiac steroids are used as a standard of care and so we believe this would qualify for priority review. We would find that out within 30 days after an NDA submission.

Within 60 days of an NDA submission the FDA would make a decision whether or not the NDA was acceptable for filing that is when the NDA would be officially filed by the FDA, 60 days after our NDA submission. Shortly after that 60 days the FDA issues what is describes as a day 74 letter or approximately 14 days after the filing.

In that Day 74 letter, it will typically provide the intension to have an advisory committee meeting of independent experts to review and comment on the strength of the NDA filing. At that point the FDA would be moving towards reviewing the other details taking the advisory committee panel’s advisement in consideration and make an approval decisions again in a priority review such situation would be six months after the filing or eight months after the NDA submission. If we did not get a priority review a standard review is typically 10 months from the date of filing.

With that I would like to give a brief summary of all of the studies that we have planned to be initiated this year. We are going to continue to follow patients in our ongoing study 202 Phase IIb expansion study. We will be initiating dosing in the third quarter, by the end of the third quarter of our historically controlled confirmatory ambulatory study of eteplirsen. This is the study that we have been preparing and discussing with the FDA and we are in further along in protocol development and preparing for initiation of that study.

The other two studies that we announced on the call a few weeks ago were two additional studies that are for safety and exploratory markers and those would be in patients who are younger than would be included in the ambulatory population. These would be patients in the 4 year to 6 year old range. And then we also will be initiating study in the more advanced DMD population, who have more limited walking ability than would qualify for our ambulatory study that would be less than 300 meters or in a non ambulatory or wheel chair dependent state.

We expect those studies to be initiated later this year with dosing to start in the fourth quarter of this year.

We also hope to initiate the first follow on study, we have a study plan in Europe with our exon 53 drug candidate this is being supported by an EU grant and we've already been in discussions with the investigators on that study and we expect that study to start dosing later this year.

And then we hope to start initiating enrollment in our follow on placebo controlled study which we announced we would be including exon’s 45 and exon’s 53 in that study which would be powered for a six minute walk end point would require biopsy pre and post and would be an important study to confirm the benefit of eteplirsen across this technology and other genotypes.

We also announced our intention to begin designs on a national history study, because we want a cohort of all of the amendable genotypes that might qualify for studies moving forward with our DMD program. So we've announced up to eight DMD drugs in various stages of screening or research or pre-clinical development and when we have open INDs on these follow-on exons, we would hope to include those in our placebo-controlled kind of master protocol of our follow-on exons and we want to get as many patients as we can prior to those studies beginning and we can start following those patients of all genotypes in the natural history study. We don't have the specific details of that at this point, but look for more details for that later this year.

With that, I would like to turn the call over to Ed Kaye, who will go over the details of getting a study up and running and started prior to dosing. And why we can't just start dosing patients tomorrow in these area of studies, there is a lot of details and work that goes in into planning and preparation for these studies and he is got his team working very specifically on getting the study started as quickly as possible. So with that I'll turn it over to Ed Kaye, our Chief Medical Officer.

Ed Kaye

Thank you, Chris. And good morning everyone who has called in today. Obviously everyone would like a clinical trial to start tomorrow, but I just want to walk you through what is involve and what are some of the processes that have to occur before we can initiate our clinical study, and especially as we’re expanding into new exons.

The first thing that has to be done is to develop a protocol. This is really the blueprint for the study in which all of the inclusion and exclusion criteria what tests are going to be done and what order, how long it’s going to be done and all of the planning it really starts with the protocol. Then obviously the most important thing of course is really to identify investigators who understand clinical research and who want to participate and have patients. Then we go about and contract with a clinical research organization to that help us conduct a study, because this is a large undertaking in a very large geographic area and we use people that can initiate the sites and that could make sure that the study and the protocol has been followed. We obviously have to have approval from the FDA for the protocol. We submitted to them have final approval. Then at each site we have to have the institutional review board approve the protocol and usually there are variations on the inform consent that have to occur.

Then we go about training the investigators and the clinical site staff to make sure that everyone understands what has to be done and what are the procedures because we want to make sure that it’s done in every site in every location at the same way so that the data is really of a very good quality. And then of course we have to have enough drug and it has to be released and label to be able to get to all the sites. So, all of this work has been done. We have gone a long way. We are completing the final touches on our Study 301 protocol, inform consents; all of that has been in the pipeline. Obviously what we are looking at is making sure that we are going to be ready to screen patients and to have everything up and ready.

If we look at what really -- what is involved in the clinical trial typically for the patients and the families, the first thing that the families will do is really to contact the clinical site. And we will have the all the sites that will be posted on clinicaltrials.gov and also on our informational website Let’s Skip Ahead once they become available. Then families can reach out directly to the site to obtain more information. Before we can do anything, we need to have an inform consent. Patients need to understand what’s involved in the study, what are risks and the potential benefits and also they have to be informed and that they obviously can withdraw from the study without any penalty at any time.

And so the families will talk with the clinical investigator, have that informed discussion and so they can go ahead. And then we move to a screening visit and that’s when the investigator really determines whether or not a patient is eligible. You have to do the screening test to make sure you qualify for the study. Then if all of the eligibility criteria are met, the patient can then start the participation in the study. And then once in the study, we will have of course study assessments; we will be doing that at regional centers throughout the country; and then the patients to make it easier for the weekly infusions, may receive their infusions at a local infusion site which of course has to go through the approval process.

This is really -- the next slide really is a summary of what are eteplirsen studies; what are we going to be doing to really understand this drug better. So the first one is Chris mentioned is our open label, the historically controlled confirmatory study. So the -- what we determine for the eligibility criteria, they will be boys between 7 and 16 years of age, they all have to walk a minimum distance and of course they have to have the appropriate genetic mutation that would be a amenable to exon 51 skipping. And this is in our treated group.

In addition, we will be filing boys with the same eligibility criteria that are not amenable to exon 51 skipping and we will be using that as our controlled group since we -- so we can understand what the population is doing. And this will give us very useful information for all of the various different deletions that are available.

We will require the boys to be on a stable corticosteroid dose. And the endpoints of course would be the primarily the six-minute walk test and then dystrophin. Sites will be located all of United States, and the timeline is in the third quarter. The two new studies that Chris had mentioned and with discussions with the FDA is they are very interested in looking at boys that are at a younger age group and then what we have previously studied and what we plan to study in our pivotal study, and these are boys who are four to six years of age and they also have to have a deletion that is amenable to exon 51 skipping.

So as Chris mentioned, this is really a safety study; we will be looking at biopsies and dystrophin, looking at other measures specifically things like North Star, but again this is not a power study, this is small really to look at the safety in this population.

The other important group that we are very interested in because there are so many boys that fall into this category and those are boys that are 20 years or less who are unable to walk a minimum distance or a non-ambulatory. And again the main criteria would be that they have to have a deletion that would be amenable to exon 51 skipping. We will not require a biopsy for this study. And it really is primarily a safety measurement. We'll get things like pulmonary function. And this of course would be -- both of these studies would be in the United States and our plan is to start them up in the fourth quarter of this year.

And moving on to some of the other studies in follow on exon studies, we have two new clinical trial that are planned to begin end of this year or early 2015, one of which is in open label study of 4053 which is our exon 53 skipping drug. This is actually as Chris mentioned has been in development for some time with our investigators in Europe and it's going to be primarily in the United Kingdom, in France and in Italy and this is part of European Commission FP7 grant. It's going to be boys 6 years to 15 years of age, who also have to walk a minimum distance. They will have a deletion that would be amenable to exon 53 skipping and then they would be also on a stable corticosteroid regimen.

Six-minute walk test will be the primary clinical end point and dystrophin will be our pharmacologic endpoint. Obviously, we will be collecting safety and this is well on its way to be started in the third quarter. We have been planning this for a number of months with our colleagues in Europe. And this is right on track for starting in the third quarter.

The other study is we've heard about of course is a new study, so this development will be for exon 45 skipping and 53 skipping. This is a test to be confirmed by the FDA, we have to be in agreement with what the protocol will look like. And so at this point is that it would be boys again primarily from 7 to 16 years of age similar to what was done in the 51 study, it also has to be able to have a minimum walking distance, be on a stable steroid dose and then they would be amendable to exon 53 or 45 skipping. Similar to our confirmatory exon 51 study with eteplirsen, it's a six-minute walk test and dystrophin. And this would be then in North America and in Europe and as I mentioned at the end of this year or the beginning of next year.

So just to ramp up, this year is really to look at multiple studies and really trying to enroll these patients as soon as possible by the end of this year beginning in next year. And it really gives us an opportunity to look at a broad population to the DMD patients to participate.

We will be including and I know a lot of people have been asking about this, but patients previously treated with drisapersen may be eligible to participate. The only request for previous drisapersen-treated patients will be that they have to be off of the drug for six months for a washout period.

Also we will not allow them to be concurrent clinical studies of investigational drugs, which is fairly standard of course. And then we were looking really for the opportunity for patients with multiple genotypes to participate. And all of the clinical site selection it’s currently underway and we will be trying to get this information out as soon as it is determined. The way you can find out information is really to sign up on the Let’s Skip Ahead. And then we can then know where patients are located. This also may help identify sites to make sure that we can make it as easy as possible for patients to participate as far as the geographic location.

So Chris, I am going to turn this back over to you.

Chris Garabedian

Great. All right, thanks Ed. Yes, I just want to underscore what Ed just described. In all of the studies that we have outlined and then as I mentioned earlier the intention to begin the designs around a natural history study and we talked about an untreated cohort in the eteplirsen ambulatory study. This was not a requirement of the FDA, but we felt that we could show a benefit at an earlier time point, let’s say 48 weeks before the FDA maybe comfortable with a benefit versus historical controls. And so we’ve designed that ambulatory study to include a untreated cohort.

So when we think about not just the exon 51 amenable population in all of the eteplirsen studies, of which we’ve been as inclusive as we could be to get meaningful information for the regulators. And so not only would you likely have a chance of qualifying for the eteplirsen study, almost any other genotype would qualify for either an untreated cohort in that eteplirsen study we’re looking to have a similar match type of cohort for the younger population study. We indicated the follow-on exon studies that are moving forward. And so those who are amenable to exon 53 or exon 45 could potentially qualify for a treatment study.

And then we are continuing to move our follow-on exons beyond those three that we’re studying treatment studies with to get open INDs and to potentially include them in this kind of master placebo-controlled study.

So we are opening up the interest for participation in our studies to a wide variety of genotypes and a wide spectrum of disease. And so the best way we can identify and determine which of the studies any patient may qualify for is to contact us through our Skip Ahead website and keep on top of when we identify sites and investigators and you see those that maybe at your institution or an institution close by then you can start inquire about how to get in these various studies. But if we can get your information we can do a better job of identifying the potential studies that you may qualify for. And at the time that we have open INDs on drug candidates beyond exon 51, eteplirsen exon 45 and exon 53, we would be looking for those who are in are untreated cohorts or are natural history study as the first pool of candidates to identify for our treatment studies.

So I just want to emphasize that this program that we have announced is very inclusive and spend the spectrum across the Duchenne disease spectrum and really allows for a lot of different genotypes to participate in various components of our trials.

So if you look at this slide currently that shows our existing DMD pipeline, we have identified eight exon-skipping drugs that are in various stages of lead optimization or preclinical development. And we’re not planning to stop there. We have collaboration ongoing with Steve Wilton and we are doing a lot of work internally to determine lead sequences for all the exon deletion genotypes including even the rarest mutations. We are also looking at the feasibility of applying this technology to other non exon deletion population, this could include duplications, it could include double skips that are required, it could include infringe stop code on non-sense mutations. But we need to start with the exon deletion program we have outlined here, but we hope to figure out our strategy where this technology can be applied and how we can potentially apply this technology to all of the DMD patients that could benefit from our unique chemistry and our exon skipping technology.

And this just highlights how fragmented the market is. You can see exon 51 skipping addresses the largest number of genotypes in terms of prevalence and you can see exon 45 and 53 combined have about the same number of patients or slightly more than the exon 51 amendable populations. But once you go beyond that, you really start to see it tail off after exon 44, 52 and 50 you see really 2% or less of the population who would benefit from any single exon skipping drug. And this really requires the unique development strategy. And what we would say is that we are encouraged of the early signals from the FDA about how they view or follow on exon candidates and how they are looking at this technology and expecting it to behave similarly.

Of course we have to prove it. We have to collect that data. We already have preclinical data that shows a very similar safety and pharmacology character as our exon 51 drug. We need to show that we're safe in humans, we need to show that dystrophin can be produced and we need to show similar clinical outcomes and benefit in these follow on exons. And we hope as we get exon 44 and exon 50 and exon 52 and exon 55 and exon 8 with open INDs that we would add those as amendments to the protocol we describe for 45 and 53 to include those patients in our randomized placebo controlled. We don't have details of when that maybe at this point, but that is our intention and will continue to move forward to get those other exon skipping drugs potentially available through the clinical trial we describe.

With that, I'm going to turn it over to Jim Baker, who will discuss in more detail some of the resources we have for the patient community before we open it up to Q&A.

Jim Baker

Thanks Chris. I just want to take a moment to describe our Let's Skip Ahead resource center. And that's available at skipahead.com and includes a number of resources and information on exon skipping, genetic testing and clinical trials. We've an exon mapping tool on this site that can help make the connection between an exon deletion mutation and an exon skip and some more description over that link.

In addition, you can visit there the Let's Skip Ahead website and signup for updates and as we have new information, we'll send out emails and we will post information on the website. Also again, we are thrilled to have Kara Boniface on as well and as you reach out to Let's Skip Ahead to our email or phone line, she would be helping to get back to you with the information you are looking for.

We're also really thrilled to partner with rather support a program that's administered by PPMD called Duchenne and this program offers genetic testing and no costs to eligible patients in the U.S., we are unable to access genetic testing to the barrier such as costs for a lack of insurance coverage. And in order to learn more about eligibility, you can contact Duchenne Connect and here you see the e-mail address and phone number for the Duchenne Connect coordinator. Again this is a great program administered by PPMD and Duchenne Connect that we are proud to support.

And with that, I'll turn that back over to Chris.

Chris Garabedian

Great. Okay. Look, we just wanted to mention that this effort that we've embarked upon and trying to get very clear guidance from the FDA and to advance our broader DMD program and our eteplirsen program specifically was with a lot of help along the way. We are very appreciative of all of the energy efforts in every form that have taken place to help us move these programs forward. Many organizations were involved in the early development of eteplirsen and our platform technology. And then that group has increased significantly over the last year in our involvement with other investigational sites, our interactions with regulators around the globe and importantly the many patients organization who have made their voice heard. And there are many who have helped along the way and there are many organizations whole have made it an emphasize to make sure that the regulators are doing everything they can to understand this disease, to understand the urgency and to understand that a flexible regulatory pathway is required for this type of disease for this type of technology.

And so we just want to highlight and say thanks to everybody that’s involved. There are more beyond on this slide but we wanted to highlight these who have played a more integral part of the development of this eteplirsen compound and our follow-on exon-skipping drugs and also importantly that this is a collaboration that is required for us all to be successful; collaborating with regulators, collaborating with researchers and clinicians around the globe and collaborating with the patient efficacy communities and patients and parents themselves who may not be strongly affiliated with any one organization, but are just there trying to do the best they can for their family and for their child with Duchenne.

So with that we also wanted to acknowledge the specific investigators sites who’ve been involved in the eteplirsen Phase IIb study group as well as the exon 53 study skipping and the collaborators. These are the folks who’ve been involved in generating our current datasets with eteplirsen but also those who are preparing to expand our technology into exon 53. And then of course we expect many more sites to be involved in our program moving forward and as we identify those sites we’ll be communicating that through our skipahead website and through other means to identify how patients can reach out to various investigator sites moving forward.

So with that we also want to mention, we’re going to open up the Q&A, but we also want to highlight there are other ways to contact the company. You can send an email to skipahead@sarepta.com with any questions, comments clarifications of any communications that have come out of the company. We also have a phone, toll free phone number that you could call and as I mentioned at the beginning of the call we have dedicated resource now to Community Relations. We will continue to invest in how we can do a better job of communicating to patients, parents families of DMD patients and the broader community at large.

So with that, operator we’d like to -- I would like to turn it over to Jim Baker who moderate the Q&A.

Question-and-Answer Session

Jim Baker

Operator we would like to start the Q&A with Debra Miller from CureDuchenne.

Debra Miller - CureDuchenne

Hello, hi can you hear me?

Jim Baker

Yes Debra we can hear you fine.

Debra Miller - CureDuchenne

Great, hi. Well first of all Jim thank you so much for your work on this on the webinar and to everybody at Sarepta for trying to get these drugs to our kids as soon as possible, much appreciate at. Should I go ahead and ask both of my questions right now?

Chris Garabedian

You can ask one at a time, Debra.

Debra Miller - CureDuchenne

Okay. So my first question is regarding biopsy and I am just curious to know if all the trial participants have agreed to the first biopsy? And do you feel comfortable with your conversations with the FDA that there is actually an agreement on the dystrophin analysis and are you reasonable sure that the FDA will accept your new biopsy data as it surrogates?

Chris Garabedian

Yes. So Debra I will answer the main part of your question and I will have Ed describe what stage we are at in understanding the feasibility of the fourth biopsy. So the FDA was very clear in their guidance that dystrophin could be one of the pathways that they use to approve eteplirsen under the accelerated approval pathway and they highlighted that the existing dystrophin data set could be enough to gain that accelerated approval with dystrophin as a surrogate. But they indicated that they wanted to collaborate with the company which we are to do a more detailed review of the methodologies that were used to generate the data set. They had the data set, we provided them all of the information that they have been reviewing but what they have not done is gone and really walked through specifically how the analysis was done.

With the pathology lab at Nationwide Children’s in Columbus, meeting the pediatric neurologists overseeing the analysis, right; all of the reviewers and the technicians understanding how well controlled the dystrophin analysis actually was, how we made sure all of the settings were consistent, how it was done under very controlled circumstances in a very dark room that you need to identify exactly what is a dystrophin positive fiber et cetera, the complete algorithm that were used to identify the dystrophin intensity et cetera. And so that’s what the collaboration with the FDA will do is allow them to understand the great level of detail, the high quality and the controlled manner and blinded reviews that were conducted across this analysis.

Now they also indicated that it may be helpful to get additional data. They understand that we may not be able to get every patient to agree and participate. We would like to get that fourth biopsy. We are encouraging this to the site. We hope the parents of the boys in the study will agree to it, because we think that will add even more so to the robustness of our dystrophin data set and even enhance what we believe is already a very strong dystrophin data set. Of which might have more credibility with the FDA after this more detailed review.

So, there is no guarantees, there is no promise that the FDA has made, but they were very clear that it is one of the ways they can apply the accelerated approval pathway. Ed, and the team have been working with the site to figure out the feasibility. We don't have guidance at this point. But Ed, do you want to comment on the fourth biopsy?

Ed Kaye

Sure Chris. I think Debra, it's important obviously we would not do the biopsy until we are certainly integrated with the FDA. There is lot of work that has been going on to make sure that they understand what's going on. And so before we would ever subject these boys to a biopsy, we'd make sure that the data would be very useful. And we do believe that showing continued expression is something that could add to our package, we would include it into the NDA. And obviously, we're working with Jerry Mendell's site, developing the protocol, making sure that we can get this. Obviously, we also have to have IRP approval and then certainly the families have to consent.

So, we're looking at this very intensively; we think this could be very important; and there is a lot of aspects. But I think this is a priority for us.

Debra Miller - CureDuchenne

Okay, great. Thank you. My next question is on -- you touched on the rare mutations and I wanted to ask a question specifically on duplication mutation. CureDuchenne has been working with Kevin Flanigan at Nationwide Children's on the duplication mutations and he seeming to make some progress there. And you mentioned working with Steve Wilton. Will you also be working with the work that Dr. Flanigan is doing at Nationwide regarding the duplication mutation?

Chris Garabedian

Yes, let me make a general comment on -- again, I mentioned at the beginning of the call about our interest in seeing how our technology can be applied as broadly as possible so that every DMD patient that can benefit from our technology that we will do everything we can to work with the regulators to have a pathway. And that includes duplication; it includes even those beyond the single exon deletion skips. Ed would you like to elaborate all the researchers that we do collaborate with including Kevin?

Ed Kaye

Yes. So Debra, obviously we are collaborating with Kevin and have been working with him for his duplication. But as Chris mentioned, we're probably working with at least a dozen different investigators throughout the world to try to see how well the exon skipping technology can work. So we have a number of collaborations, we have a whole team and Art Krieg and his group are working with a number of investigator so that we know exactly what this RNA platform technology can do. So it's really a very broad effort that we've taken quite seriously and not only in DMD, but we're looking at potentially expanding into other indications.

Debra Miller - CureDuchenne

Okay, thank you very much. And thank you again for all your words.

Jim Baker

Thanks Debra. Operator, we’d like to now open the line for Christine McSherry from Duchenne Alliance.

Christine McSherry - Duchenne Alliance

Hey Jim, can you hear me?

Jim Baker

Yes, we can hear you.

Christine McSherry - Duchenne Alliance

Okay, great. First of all, I want to thank Sarepta for everything that they’ve been doing, have done certainly very aggressive in Duchenne field and as a community, we’re enormously grateful for that. And my questions are more about some of the non-ambulatory studies that you're talking about. Wondering if you can provide detail on the study endpoints that will be included in the younger patients study and in the non-ambulatory study? It's my first question and also, will biopsies be required in the older patients?

Chris Garabedian

Ed, would you like to address that?

Ed Kaye

Yes, that’s fine. Good morning, Christine. As Chris has mentioned Christine, the study is really not powered for an endpoint. So, we try to make these more of the safety study. So, looking at the older population, we will -- first of all, we will not require a muscle biopsy, the reason being is that because of the atrophy we wanted to make sure that we didn’t biopsies boys and potentially couldn’t get a good muscle sample. So because of that we will not be biopsying them. And we will be looking at safety endpoints, we’ll be looking at pulmonary function, we’ll look at some upper extremity but we try to make it more of an exposure study to make sure that we understand the safety. In the younger boys, again very similar, it’s going to be primarily a safety and non-powered study. We’ll be looking at things like the North Star and more exploratory endpoints. But again because we don’t have really any experience to understand what we might expect to see, it really is an exploratory endpoint. The younger boys, we are interested to make sure that we can see dystrophin and that the pharmacokinetics is very similar.

So, we’ll be looking at these studies. They will be let’s say a simpler study than what we’re doing for the confirmatory 301 study.

Christine McSherry - Duchenne Alliance

Great, thank you. And then just beyond eteplirsen, do you plan to conduct additional studies on the follow-on exon-skipping candidates in the non-ambulatory population? So for instance, the two other studies that you outlined that will be coming up probably in early 2015, will you be enrolling non-ambulatory patients in that as well?

Chris Garabedian

Yes. So, Christine, right now, we don’t have details around our broader program and what other patients would be included. I think what I would say is that we have focused from the very beginning on dystrophin as an important marker in this disease and what we want to do is to show that our technology is producing dystrophin that’s leading to good clinical outcomes. And we believe if we do that in the various populations that we study in which we collect biopsies that we can make a good compelling argument that regardless of stage of disease, we are restoring dystrophin across various genotypes and across multiple follow on exon skipping drug candidates and that the regulators will look at that and realize that the technology is working the way it’s supposed to work and that essentially using clinical outcome data from those that we can better understand the measurements like six-minute walk or even some of the exploratory markers in younger patients that the regulators would understand that we should not be denying a more advanced population or non-ambulant from getting access to a dystrophin producing drug.

So we have to wait to determine what level of evidence do the regulators need to see to be able to provide us an approval whether that’s an accelerate approval or a full approval to be able to gain a broad label so that all of the patients can benefit from our technologies, not just those that are ambulant or are young or are non-ambulant but all of them as long as we’re showing were safe, were producing dystrophin in every patient that we dosed the drug into and that for those that we better understand the clinical outcomes and natural history who are those are benefiting. And so at this point, we need to talk to the regulators about what else is required in the follow on exons to be able to gain the accelerated approvals of exon 45, 53 and the others and what would eventually lead to our hope of a potential class approval. And then we would collect whatever safety, whatever clinical outcomes we would need post marketing in all the non-ambulant or any other populations across disease spectrum.

Christine McSherry - Duchenne Alliance

Great, that helped so much. Thank you, Chris.

Chris Garabedian

Okay.

Jim Baker

Operator, can we please open the line for Valerie Cwik from the Muscular Dystrophy Association.

Valerie Cwik - Muscular Dystrophy Association

Good morning. And I would like to have my thanks to Ed and Chris and the team of Sarepta for providing all this great information directly to patients and [analysts] in neuromuscular community today.

I have got a couple of questions that have come from our families across the country; you’ve address a lot of the questions we have received, but I would like to follow-up on the study in the young man who have more advance disease or are no longer walking. I might have missed it and I don’t remember if you mentioned whether or not that study requires those young men be on steroids. And as part of that question based on what you know about eteplirsen, do you expect to see a benefit on [lymph-stained] pulmonary function or other functions with eteplirsen in this older rate population?

Ed Kaye

Yes, hi Valerie. These are really excellent questions and obviously this is new information as far as the study and the study design. Literally when we got the letter from the FDA requesting some of the studies, my team started working on developing the protocol. So we have a lot of work yet to be done and we have further discussions with the FDA. Our plan is to start with at the end of this year.

What I can tell you is that we are not as I mentioned we are not planning to do muscle biopsies on this population. We will now require a stable dose of steroids, because obviously some of these boys are no longer on steroids. And I think your question about what do we expect; we will be doing exploratory endpoints looking at obviously things like pulmonary function to follow cardiac function. We can look at some of the exploratory endpoints in the upper extremities.

And obviously we won't know what to expect. Our hope is that we will stabilize the remaining muscle that is there overtime. And that's what we will -- is really the purpose of the study is to try to understand what we can expect to see. Do we stabilize pulmonary function similar to what we've seen in the younger age group, can we have an effect on preventing further the decline in the upper extremities. And those are the kind of pieces of information that hopefully we’ll learn as we perform this study.

Valerie Cwik - Muscular Dystrophy Association

Great. And then as you well know families are anxious to participate in all of the upcoming trials and you very nicely laid out what it takes to plan and conduct a study. Can you be a little bit more specific about when details might be available regarding trial sites on specific inclusion criteria things like that? I know you are planning to launch late in the year, but if you can be a little bit more specific about that? And then just one sort of housekeeping issue; are you planning to post this webinar on your sites so families who weren't able to listen live can go back and listen to it later?

Chris Garabedian

Yes. So Valerie we are planning to the post the webinar for listening later by any families who couldn't participate on the call live. Yes, regarding the timing, we don't give specific detailed guidance because we’d rather get the details worked out and then communicate them once we have them. But we are working quickly. We've given highlights of when we would expect those studies to start enrolling and dosing patients.

So you can imagine that over the coming months as those detail start to come into focus, we'll share the appropriate details as we get them and as we know them to be factual. We don't like to make too many forward-looking statements and then find out that for reasons whether it's FDA or other reasons, we're making adjustments.

So that's why we don't like to anticipate exactly when we'll have the details, but we do like to be transparent and quick in our communication. Ed, would you like to comment?

Ed Kaye

Yes. So obviously, Valerie, we're going to have details on the 301 study relatively soon. We have to wait for final approval from the FDA submitting the protocol and making sure that we're not -- we don't have to make any changes. And as soon as we get that data, certainly inclusion exclusion criteria, we’ll publish that, we’ll publish on the site.

We're still looking at sites; we're doing all of the site assessments looking at our ability to perform some of the exploratory endpoints. So as soon as we're done with that and as soon as we get sign up, we will do that certainly for 301. The other study, other two studies will take a little bit longer, because we have a lot of work to kind of formalize the protocol and get by and submit it really to the FDA.

So we'll try to make it available on certainly Let’s Skip Ahead and then also we will file on clinicaltrials.gov as soon as it’s formalized. And obviously, as soon as we know and we have confirmed it, we will publish it and let it known to the overall community.

Valerie Cwik - Muscular Dystrophy Association

Great, thank you.

Jim Baker

Operator, can we please move on to Ryan Fisher from Parent Project Muscular Dystrophy?

Ryan Fisher - Parent Project Muscular Dystrophy

Hi. Can you hear me?

Chris Garabedian

Yes. Hi Ryan.

Ryan Fisher - Parent Project Muscular Dystrophy

Hi. I just want to reiterate that the community is really thrilled about your progress to-date and certainly about the flexibility that’s coming out of the FDA. You really give the tremendous help and we really appreciate all you and your teams do.

My first question is regarding drisapersen. Will all former drisapersen boys who wish to switch trials included and will there be an age limit?

Ed Kaye

So, what we’re -- obviously the boys have to be off of drisapersen for a minimum of 24 weeks or six months. And certainly they would be eligible just like anyone else, but they would have to meet all of the other eligibility criteria for the studies that we’re including. So yes, so really the only the difference is they’re off of drisapersen for six months, but then they would have to meet all or whatever other studies that we have that are available they certainly could participate.

Chris Garabedian

Yes. Let me just add on that. So, to be very clear, we are opening -- if they qualify on all of the other criteria for any of our studies with eteplirsen as long as they have that 24 week washout, they would qualify and be able to participate in our studies. So we’re not making any special requirements or restrictions on age or other criteria for former drisapersen-exposed patients or drisapersen trial participants. We know many were on a placebo arm and never were able to be dosed with drisapersen. So they’re welcome as well. And we do know that Prosensa also has programs in other follow-on exons, natural history studies et cetera.

So again, each family has to determine what is best for them, but we would not be excluding anybody because of participation. Now having said that, if a patient has washed out for 24 weeks but re-doses the clock starts again, so we would have to make sure anybody who has been exposed or would be exposed more recently or later this year would still have to go off the drug, wait 24 additional weeks before they would then qualify for one of our studies.

Ryan Fisher - Parent Project Muscular Dystrophy

Okay. Thank you so much. My other question was about the confirmatory testing sites which you really did answer with Valerie, but do you have any idea of the number of sites that you will have for confirmatory study?

Ed Kaye

Yes. So Ryan this time we are looking at an overall participation rate of about 35 sites, some of the sites will be regional centers that will collect the efficacy data. So we will have a limited number of efficacy sites where patients will go for their things like the six-minute walk test. But then to make it more convenient, we will have more infusion sites that will be located throughout the country.

And again we don’t have the exact number because we are looking at the patients where they are geographically were also wanting to make sure that we don’t have any redundancy. And we’ll be doing that really over the next few months and should have that completed over the next several months.

Ryan Fisher - Parent Project Muscular Dystrophy

Wonderful. Thank you so much.

Jim Baker

Operator, can we please move on to Elizabeth Vroom from United Parent Project Muscular Dystrophy.

Elizabeth Vroom - United Parent Projects Muscular Dystrophy

Hello, this is Vroom from (inaudible) I am asking questions on behalf of the United Parent Projects. Thank you so much that I can ask questions on behalf of parents outside the U.S. and UK. And my first question in fact is Sarepta announced seven trails to be in the work before the end of the year, this year, but how realistic this is new trials will start (inaudible) also given everything at just explained and all the time needed to set up a trail because the patient to enroll patient to identify patients and so on. So and also how should these trails will indeed be executed as given the fact the Phase III trial that was announced for early 2014 at several patients meetings include the meeting in November 2013 this trial did not start yet.

So basically no trial delayed or will it never happen and connected to that will patients who participate in these new trials or drug studies have any guarantee that they will be provided an extension after duration of the trial?

Chris Garabedian

Yes. Elizabeth I would like to answer your second question first and then I will have Ed comment on the resources we have to do all this. So regarding the timing of the what was then described as the eteplirsen confirmatory study in ambulatory patients, you are right we had indicated early 2014 for almost all of 2013 that was our guidance including up to the action Duchenne meeting, but that was prior to receiving the November communication from the FDA.

You have to remember throughout that whole year, we were gearing up to start dosing in the first quarter of 2014 and then when the FDA provided us feedback in November, they had some serious questions about our path forward, our clinical trial design and these were new issues that were raised around our trial and what we would need to do moving forward.

At that moment, we announced that we could no longer meet that timeline and we have to work with the FDA. That was almost six months between that November communication and April in which we got the clarity in the guidance letter to be able to predict, when we could start the next study. So, there has been no delay on our side except for the change in the regulatory guidance that came out in November. But we have been preparing for this time, where we would have this clear guidance. And Ed can describe our preparedness in more detail.

Ed Kaye

Sure. A little bit, I think Chris really mentioned what some of the external delays that occurred. But just want to reiterate that, even though we have been having, we didn't have clear guidance from the FDA, the group here at Sarepta has really been working very hard and preparing for the confirmatory study. So, we had already contracted with our CRO, we had contacted sites, even though we did have a final protocol, in fact we have written two separate protocols, one for two different types of studies, just to be ready for this day.

And now we will be submitting those protocols back to the FDA. So a lot of work has gone on behind the scenes and we're very confident that for our confirmatory study that will be really on course.

The other thing and I think as you know the study in Europe for exon 53 has really been starting since last year and we've been working with our collaborators certainly in the UK, in Paris and in Italy; we have numerous meetings and that’s again for Q3 of this year and that’s well on its way and we’re continuing with that project.

Obviously for the two studies that were just requested by the FDA, these are new. But we plan to utilize some of the existing sites that are already up -- will be up and running for Study 301 and also using the same CRO. So hopefully, we can expedite that by using some of the sites even though it will be two new protocols and have to be approved by the FDA, they are a little bit simpler and a little bit easier.

And then certainly with our follow-on exons, with our experience with exon 53 in Europe, that gives us some advantages and we’ll be having discussions with the regulatory authorities trying to expedite these other approvals. And that certainly is end of this year or beginning of next year. So, there is a lot of work to be done. We have a very large team here that we put in place to try to get it done. And obviously, we are using all of our resources of the people in the U.S. and now in Europe to try to get this done. So I think we’ve done a lot, we know -- we appreciate it’s a lot of work, but I think we’re well on the way.

Elizabeth Vroom - United Parent Projects Muscular Dystrophy

All right. But it still means that there can be unexpected delays like now because of FDA or whatever, that was more or less my question, if you -- how sure it is that the timeline as you discussed. But I understand that you still will have with FDA your discussions which might change plans?

Ed Kaye

Well, one thing I will say is that the FDA has made this a priority and they have told us that they want this up and running very quickly. So I think because of their sense of urgency, I’m hoping that this will keep on time. Obviously, there is always unexpected delays that could occur and we never know until the study starts, but we will do our best.

Chris Garabedian

Yes. But just to be clear Elizabeth, as it relates to eteplirsen, we’re not waiting for additional guidance or additional guidance meetings with FDA. We have a clear guidance from them on the eteplirsen program moving forward. We will obviously be submitting protocols to the FDA as a standard before we move forward with those programs to give them a chance to comment if they have any. But we don’t anticipate at this point any further delays or any surprises from any regulatory discussions because we believe the guidance we’ve gotten has been pretty clear from the April communication.

Elizabeth Vroom - United Parent Projects Muscular Dystrophy

Okay. Thank you so much. And then you only didn’t answer the question about extension trials, if these trials the new trials, if you have plans for extension trials after the period of the trial you announce this over?

Chris Garabedian

Yes. Let me mention, Ed our philosophy related to that. Look, we believe our technology is producing benefit in these patients. And as long as that continues to hold up in our trials, we know that this is a therapy that would be required for life in a DMD patient. And so, it is our intention to continue dosing patients following them. Even after a drug approval, we would hope to continue to follow some of these patients with collecting some safety updates and clinical updates. So our plan would be that once a patient is initiated that we would continue that treatment indefinitely as long as the program continued to move forward and we were continuing to move forward to our commercial approvals in those specific territories.

Elizabeth Vroom - United Parent Projects Muscular Dystrophy

Okay, that’s great. And then the last question, shorter, you mentioned your plan to speak to the EMA. Do you think the EMA will accept result from a trial where the boys have stopped walking or taking out of these statistic analyses? And if you put them back in the statistic, how do these data relate to the similar trial Prosensa did in a limited group of boys and included the boys that or kept the boys in the that stopped walking, kept them in the statistics; do you have any idea on that?

Chris Garabedian

Yes. Well obviously Elizabeth, the reason we are talking to the EMA is to really understand their position on the existing data set. So we don’t have that answer; we don’t know how they will respond to it. But again we are hopeful based on the FDA’s understanding of the disease how to interpret our data set in the context of Duchenne. And often EMA can sometimes be more progressive in their thinking than the FDA, not always, but. So that encourages us that if the FDA seems to be comfortable with a potential path forward with eteplirsen on the existing and emerging data set that EMA may feel the same way. So we’ll know, again we’ll have the initial perspective on that by the end of this year.

As it relates to excluding the two boys that went non-ambulant and any contrast to the Prosensa early study, I really do think that’s apples and oranges. Our study although was small was started as a placebo controlled study with a prospectively defined endpoint of dystrophin. We did that randomized blinded, that analysis was done on a blinded basis, we had pre and post treatment biopsies on every patient and we shared that on every patient.

In the Prosensa study, they didn’t even have a pretreatment biopsy on the majority of those patients. And they did a six months biopsy similar to what we did and they never shared that information. They did not select the population that would have expected to decline when they started that dose escalation. We expressly wanted boys who would decline on six-minute walk. And so it really is an apples and oranges. And ours was much more controlled and we were much more specific about the endpoints and what we would be looking for.

So, but we understand; we haven’t talked to the EMA yet, we need to get their feedback and their perspective but we think the data is compelling enough now out to over two years to at least have that conversation with the regulators.

Elizabeth Vroom - United Parent Projects Muscular Dystrophy

Okay, thank you for your answer.

Chris Garabedian

Great.

Jim Baker

Operator, can we please open the lines of Diana Ribeiro from Action Duchenne; Alex Johnson from Joining Jack; and Alex Smith from Harrison's Fund.

Alex Smith - Harrison's Fund

Hi there. Can you just hear me?

Jim Baker

Yes.

Alex Smith - Harrison's Fund

Thanks very much for having us on, really glad to have the invitation. Like you said we got Diana, Action Duchenne, Alex from Joining Jack and myself from Harrison’s Fund, UK members of the (inaudible).

We all applaud on your work to-date and we’re excited about possibilities for the future and incredibly came to make forward as fast as fast we possibly can in UK and Europe. So we have all been [updated] with questions from the community about implications -- about the implications eteplirsen could have here in the UK and Europe as well as many questions about your follow on exon programs and plans.

Obviously we can’t ask all our questions received today, but following the questions that many are asking and we would definitely appreciate your response to the one submitted, we can’t ask in this forum to able to share with our communities as well. And first question was have you started talking to persons about a placebo license deal with eteplirsen or are you likely to challenge the patent, is there a timeline for this? And if a deal could be done, what are your timelines for ramping up production of the drug to have enough to be able to market outside of the U.S?

Chris Garabedian

Thanks Alex for that question. So, first I'd like to say that obviously we are interested in finding a way to make eteplirsen available in Europe and the UK. So that is something that is important to us. We believe our technology is best in class. We believe that the safety profile, the dystrophin data, the clinical outcomes we've seen to-date would benefit patients in Europe and the UK. And we do want to find out how to make that possible.

However first, we need to determine what is it going to take for the regulators to approve eteplirsen? So that's something we can do prior to resolving any patent dispute or negotiating any type of cross license. And we think that is the most important activity that we can focus on over the next year.

So for example, if Prosensa gave us a free license tomorrow of the patent that is potentially blocking us on eteplirsen in Europe and the UK; we would still be doing the same thing to try to figure out what it would take to get eteplirsen approved in Europe.

So, I think from that vantage point, we do think that after we talk to regulators and we potentially understand if another trial would be required in Europe and the UK or if they would consider an approval on the existing dataset and emerging dataset then we would want to look into the possibility of could we accelerate a ruling on the patent opposition that is underway based on the November 2011 European patent outcome. And so, that's one thing that we would explore once we know what it would take to get eteplirsen approved in Europe.

The other alternative is what you've described, which is to negotiate a cross license of that patent in Europe and the UK. And again, we would like to understand what are the requirements before we sit down and negotiate on reasonable terms what that cross license would look like. But make no mistake, all of our activities and our intention to discuss with regulators is also understand exactly what it will take to get eteplirsen approved in Europe and the UK and how quickly can we make that happen. And then we think there are several strategies that we can employee to figure out how to get around or overcome any barriers as it relates to patent and freedom to operate.

Alex Smith - Harrison's Fund

Fantastic. The second part of that question is just around to ramp up production to have enough go-to-market outside of U.S.?

Chris Garabedian

Yes, that's a great question. Yes, so for that we are in the process of preparing for commercial scale if we were to able to receive an accelerated approval in 2015. Now we would not be ready on that day of let's say eteplirsen approval in 2015 to supply the demands across Europe and in other territories around the globe.

However, once we achieve that large scale capability and we have a process for large scale production, that’s something that can be reproduced and expanded within our current contract manufacturers or even bringing on new contract manufacturers. The lead time generally is about a year or sometimes more to convert a new facility to be up and running on a new scale and a new process that they would be doing for the first time.

And so we believe that we will have an understanding of when we would need to have that drug supply, what the regulators would be looking for and asking to figure out what the gating decision is of when we pull the trigger to expand that large scale production to be able to satisfy the demand in those other territories.

Alex Smith - Harrison's Fund

Okay, great. Thanks a lot guys.

Chris Garabedian

Thank you, Alex.

Diana Ribeiro - Action Duchenne

It’s Diana from Action Duchenne. And I guess we want to thanks on behalf of the UK and from all our families and members of Action Duchenne. And me following on from Alex’s question and there are lot of families who are quite anxious about access the clinical trials. The question really is can patients in the UK participate in the U.S. trials and what would be required and what would they need to move to the U.S. for example?

Chris Garabedian

Ed?

Ed Kaye

Yes, hi Diana. I think obviously this is something that is important. But I think one of the challenges we have is, this really is a very complicated trial. So, we have two biopsies which require patients at baseline and then at one other time point later in the study we have every three month studies at the regional center for their efficacy endpoint, we have weekly infusions. And really right now we don’t have the capability to be able to transport patients and families for this kind of intensive study in the U.S.

Obviously we are, as Chris had mentioned, we are very interested in trying to understand what would be required in the EU to get these studies up and running and eventually to get approval. So right now I would say that it’s not a practical possibility.

Diana Ribeiro - Action Duchenne

Okay. I appreciate it. it would it be really good to perhaps do some follow-up after webinar in terms of, mainly towards the end of this year and once you have done the NDA filing in terms of what your plans are and with your dialog with the EMA and your strategy for Europe moving forward?

Chris Garabedian

Diana just let me add though, Ed described earlier on the call that the exon 45 and 53 placebo-controlled study, we will be looking into making this a global study as well. And if we are able to expand that study globally as we mentioned as new exon-skipping drugs came online and we were able to get those approved for dosing in patients, we could see expanding it to the other exon targets like exon 50, exon 44; the other ones we mentioned 52, 55 and 8 initially.

And so again I think we are providing an opportunity for those in the Europe and the UK to participate in some of our trials. As it relates to eteplirsen we do need to talk to the EMA first and then decide what our strategy is for clinical trial requirements and how to get the drug accessible in those territories.

Diana Ribeiro - Action Duchenne

Okay, fantastic, thank you.

Alex Johnson - Joining Jack

Hey, it’s Alex Johnson from Joining Jack. Can you hear me?

Chris Garabedian

Yes, Alex.

Jim Baker

Yes.

Alex Johnson - Joining Jack

Hi. Thank you Chris, Jim and Ed for hosting this afternoon’s webinar. If you are planning on treating all patients, you are potentially amenable to exon skipping, how long do you estimate that it will take to get all exons into clinical trial and then approved by regulators and what can we do at the communities to try and help to accelerate this process?

Chris Garabedian

Yes. Alex that’s a great question, but it’s a difficult question to answer. And this is because there really aren’t guidelines that exist for this type of technology. And what we are trying to achieve which I described earlier is how do you get drugs approved that are so low in prevalence that it’s infeasible to conduct a clinical trial that’s well powered and producing meaningful clinical data.

So, what we have outlined previously publically is a strategy that we don’t have buy-in yet, but we will want to talk to regulators in both the U.S. and Europe and elsewhere, and we will need the communities’ support of this is that -- if we are able to show similar safety and pharmacokinetics at a similar dose of 30 mg/kg per week across several or a handful of drugs, so let me just paint a picture. If we do this exon 45 and 53 study and even if we are able to include a couple other drugs to get dystrophin and safety and combine the clinical outcomes together with these other exon targets, we could bring the FDA and the EMA with evidence that these drugs behave similarly that they have a similar safety profile that they produce dystrophin at a similar level based on the exon skipping efficiency that we see in vitro of the lead sequence.

What we would hope to achieve is what we described as a class approval. That would be, they would grant us the ability to make the drugs available and I'm talking about the not just the first three or four or five, but the next 25 drugs available for all of the boys who would benefit all of the rare mutations on -- and we would of course meet any obligations the regulators would have of following these patients for safety, maybe they would say try to get a couple of patients to prove that dystrophin is being produced, maybe they would want us to follow a small number of patients over the long term for clinical outcomes. But we don't think that there is a feasible path to enroll all of the rare exons into meaningful or well powered clinical studies. And so, we don't have clear guidance of what that would look like, but we think if dystrophin is accepted as a surrogate marker, that is the first step in applying this class approval. Because then we can show that the exon skipping that we're achieving with the first three, four, five drugs is producing the same levels of dystrophin of a similar range and it's safe than we think that there is a pathway.

So, it's very hard to predict exactly when all of those drugs or if all of those rare drugs would be approved. But we at Sarepta are committed to talking to the regulators and trying to find the path forward that would allow that. And we will keep the community informed of our efforts and our success and if we can benefit from the community help in highlighting the importance of these rare exons then we will definitely reach out and then break that. We’re getting a little bit of a feedback from a couple of lines, but Alex did that answer your question?

Alex Johnson - Joining Jack

Yes, it did. Thank you. And we really appreciate the commitment from this time how as (inaudible).

Ed Kaye

Great.

Chris Garabedian

Thank you, Alex.

Jim Baker

Thank you, operator. That concludes the question-and-answer period. I just like to mention that we received a few emails during the course of today's presentation, but there were some -- that some may have experienced some technical issues. The full recording will be posted on Sarepta's corporate website for those who may have missed portion of the call. Chris?

Chris Garabedian

Okay. Well Jim, thanks a lot. Again, we are trying to communicate to the DMD community and the patients when we have important updates. We think this was one of those cases where we had a lot of information that we communicated over the several weeks. And we wanted an opportunity to talk to you directly as the patients and families of DMD patients and the patient [advocacy].

We appreciate all of those who represented the DMD patient community who came up with the questions on this call. We appreciate all your efforts to represent, all of those families out there around the globe who are interested in therapies, interested in our technology. And we appreciate your interest in Sarepta and our activities. And we look forward to continuing that dialog and continuing to communicate [peace] through various means moving forward.

Ed Kaye

Thank you very much.

Operator

And thank you ladies and gentlemen. This concludes today’s conference. Thank you for participating. You may now disconnect.

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