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Sarepta Therapeutics (NASDAQ:SRPT)

36-Week Clinical Results Call

July 24, 2012 8:00 AM ET

Executives

Erin Cox – Manager, IR

Chris Garabedian – President and CEO

Analysts

Charles Duncan – JMP Securities

Bill Tanner – Lazard Capital Markets

Ted Tenthoff – Piper Jaffray

Mike King – Rodman and Renshaw

Chris Marai – Wedbush

Ritu Baral – Canaccord

Operator

Good day ladies and gentlemen and welcome to the Sarepta Therapeutics Inc. 36 week clinical results conference call. My name is Laura and I will be your operator for today. At this time, all participants are in a listen-only mode. Later we will conduct a question-and answer session. (Operator Instructions). I would now like to turn the conference over to your host for today, Erin Cox, Manager of Investor Relations. Please proceed.

Erin Cox

Thank you, Laura and thank you for joining today's call. Earlier today we issued a press release detailing 36 week results of a 6-minute walk test in our Phase IIb DMD study. The press release and the slide we will be presenting today are available on the event section of the investor relations portion of our website at ww.sareptatherapeutics.com.

Joining me on the call today is Chris Garabedian, Sarepta's President and Chief Executive Officer. I would like to note that during this call we will make a number of statements that are forward looking including statements about the development and clinical status of Sarepta's product candidates including an eteplirsen and the potential efficacy and clinical results. These forward looking statements involve risk and uncertainties many of which are beyond Sarepta's control.

Any of such risk could materially and adversely affect our business, results of operation and trading price of Sarepta's common stock. For a detailed description of risks and uncertainties we faces, you are encouraged to review the company's filings with the Securities and Exchange Commission.

With that said, let me turn the call over to Chris Garabedian, Sarepta's President and Chief Executive Officer. Chris?

Chris Garabedian

Thank you Erin and I am very pleased to share some important news today about our drug for the treatment of the Duchenne muscular dystrophy eteplirsen and I will be sharing new data from our Phase IIb extension study that strongly supports the potential for this drug that slows the progression of this devastating genetic disease.

I regret that Ed Kaye, our Chief Medical Officer is not available to join the call this morning as he's presenting at a conference of clinical development leaders and could not be here with me today. This is also the company's first conference call Sarepta Therapeutics and I can't think of a better opportunity to kick off a new era for the company and our platform technology than with the announcement of a significant clinical benefit, a first for the company for its serious life threatening disease and based on our innovative RNA based morpholino technology.

Before I discuss the clinical results of our Phase IIb extension study that we released this morning, I'd like to express my appreciation for all of those that have been patient and persistent and their belief in this application of our technology as there are many who have been waiting for this sign of hope including the DMD patients themselves, their parents and family members and the broader community of researchers, healthcare providers and advocates in the DMD community.

Furthermore I'd like to thank Sarepta's employees and collaborators who have worked hard in giving this program the best chance to succeed and lastly, I'd like to thank those investors who have been steadfast in their belief and support of the company during some challenging times of uncertainties.

I will now go over the details of the data on our primary clinical outcome measure, the 6-minute walk test, but I would like to provide some context and remind you that we had previously reported that eteplirsen resulted in the production of significant levels of novel dystrophin after 24 weeks of treatment. Specifically we observed an average of 22.5% dystrophin positive fibers as a percentage of normal after 24 weeks at a dose of 30 mg/kg of eteplirsen weekly. This key biochemical marker is the essential protein that is lacking in patients with Duchenne muscular dystrophy and it was our primary endpoint in our placebo controlled 24 week Phase IIb study, study 201.

We met this primary end point with a high degree of statistical significance with a p-value of 0.002. however, we did not observe significant level of dystrophin at the 12 week time point and produced an average of less than 1% dystrophin fiber in patients who received 50 mg/kg of eteplirsen underscoring the meaning levels of dystrophin are not present in muscle biopsies until beyond 12 weeks of treatment. This information suggested that there may be a delay of up to 12 weeks or beyond in our ability to show significant treatment effects on the primary clinical outcome measure that distance and meters walked in a timed 6-walk test and that we might need to follow patients beyond 24 weeks to prove the treatment effect on walking ability.

I'm excited to report that we now have evidence that this thesis seems to hold true. In our Phase IIb extension study of eteplirsen and DMD study 202, we achieved a statistically significant clinical benefit of 69.4 meters on the 6-minute walk test, which translates to a significant delay of disease progression on this measure of ambulation. This benefit was seen in patients who received 50 mg/kg of eteplirsen after 36 weeks of treatment compared to a placebo cohort who received only 12 weeks of eteplirsen treatment or in effect were delayed treatment of eteplirsen for 24 weeks. I will refer to this cohort as the placebo/delayed treatment cohort.

Of the four placebo/delayed treatment patients, two have received 50 mg/kg for 12 weeks and two have received 30 mg/kg for 12 weeks. Based on the previous 12 week biopsy data from patients treated with 50 mg/kg of eteplirsen, we do not believe any of the placebo/delayed have been taking eteplirsen long enough to have produced meaningful levels of dystrophin to be experiencing a treatment effect.

If you look at the slide that's on the webcast, in our intent to treat population, using the predefined statistical analysis that was written in the statistical analysis plan for study 201, the placebo/delayed treatment cohort declined in average of 78.0 meters from their baseline 6-minute walk test distance or a decline of approximately 20% from their base line score of 395 meters. This compared to a decline of only 8.7 meters in the eteplirsen 50 mg/kg weekly cohort or a decline of approximately 2% from their baseline score of 396 meters. This difference resulted in a statistically significant benefit with a p-value of 0.019. Furthermore a statistically significant benefit was also seen at the earlier time point of 32 weeks. Through 32 weeks there was a 59.8 meter benefit with eteplirsen based on an average decline in the placebo delayed treatment cohort of 62.5 meters while the eteplirsen 50 mg cohort declined only 2.7 meters or in average of less than 1% from their base line value.

This resulted in a p-value of 0.045. The magnitude of this benefit is unprecedented for a disease modifying drug in DMD and is a greater effect than has been seen in other drugs that have been approved with 6-minute walk test data as an endpoint, most of which have demonstrated a benefit of 30 to 40 meters. There was no significant difference between the placebos delayed cohort and the eteplirsen 30 mg/kg weekly cohort. The 30 mg/kg cohort requires further explanation as there were two boys that were randomized to the 30 mg/kg cohort that showed signs of rapid progression shortly after enrollment in the study. While the two boys qualified for this study based on the 6-minute walk test baseline value, they had the two lowest base line scores in the study, they were both below 250 meters by week four and each were 100 to 200 meters below all of the other patients in the study by week 12, a time point that we now know is too soon to see meaningful levels of dystrophin and likely too soon to expect a treatment effect on slowing or reversing of feet (ph) declines on this ambulatory measure.

Both of these boys could not complete the 6-minute walk test by the 24 week time point and have now progressed to a non-ambulatory state. However, we continue to follow these patients because both patients demonstrated novel dystrophin production in muscle biopsies at week 24. They had no drug related adverse events and are continuing to reverse eteplirsen treatment allowing important information to be captured about the safety of eteplirsen and the potential impact of the drug in non-ambulatory patients such as effects on upper extremity function, pulmonary function and cardiac function.

We completed additional analysis in the modified intensive treat population that excluded the two non-ambulant boys who exhibited early and rapid progression on ambulatory measures. In this modified intensive treat analysis, we combined both of the eteplirsen treated arms for a total of six eteplirsen treated patients and performed analysis on relevant sub groups compared to similar placebo treatment subgroups. It is important to note that every placebo delayed treatment patient saw a decline on the 6-minute walk test distance of more than 55 meters by week 36 while none of the six eteplirsen treated patients in this modified intensive treat declined by this amount and four of this six declined by less than 30 meters or saw an increase in their scores from base line.

Furthermore, all of the placebo patients had a reduction of more than 15% from their baseline 6-minute walk test while none of the eteplirsen treated patients in this analysis declined by the degree and four of the six ranged from a decline of less than 10% to an increase of more than 14% of their baseline 6-minute walk test.

If you look at the slide now on the webcast, we showed here that we conducted a subgroup analysis by age base line 6-minute walk test and genotype across the modified intent to treat population and there was a benefit across every subgroup in favor of the eteplirsen treated patients that ranged from 36 meters to 82.5 meters. Among the subgroups greater benefit were seen in the younger patients and in patients with higher baseline scores on the 6-minute walk test as both of these subgroups had more pronounced treatment benefit which resulted in a high level of statistical significance with p-value of 0.004 and 0.0001 respectively.

Lastly, we looked at response by genotype and there was no evidence that a treatment effect may vary by genotype. There were five genotypes that were amenable to an exon 51 skip represented in the study and the most common was the 4950 (ph) deletion where five patients were represented; three placebo and two treated. In this population we saw a 68.5 meter benefit in this genotype cohort within approximately one meter or 0.9 average increase through 36 weeks in the eteplirsen patients and a 67.6 meter average decline in the placebo/delayed treated the patients.

Lastly we also completed a full review of the safety profile through week 36 thirty and this includes the eteplirsen treated patients after 36 weeks including the two non-ambulant boys and the four placebo patients after 12 weeks of eteplirsen treatment and no treatment related adverse events have occurred with eteplirsen, no serious adverse events have occurred in the study and no patients have discontinued therapy and furthermore there have been no safety related laboratory abnormalities observed in any patients.

In summary, we now have demonstrated in three key elements that we believe is required of a successful disease modifying drug for the treatment of Duchenne muscular dystrophy. First we have demonstrated as previously reported, a statistically significant increase in novel dystrophin at 24 weeks with an average of more than 20% dystrophin positive muscle fibers as a percentage of normal and we will be capturing a third biopsy at the 48 week time point and expect to have a more robust dystrophin dataset to share in early October.

Secondly eteplirsen has been well tolerated and we have seen a favorable safety profile through week 36 on important characteristic for a disease that will likely require lifelong treatment.

And thirdly and finally, we have demonstrated an unprecedented and statistically significant benefit with eteplirsen on a standard measure of ambulation and progression of disease in Duchenne muscular dystrophy, the 6-minute walk test with the benefit of 69 meters after just 36 weeks.

If you look at the slide now on the webcast, I want to highlight that this treatment benefit is quite significant when you compare eteplirsen to other drugs that have used the 6-minute walk test as a primary clinical outcome measure. The most advanced disease modifying drug in development for DMD Ataluren, demonstrated a 30 meter benefit after 48 weeks of therapy.

Additionally, there were three drug approvals for other rare diseases that had a 6-minute walk benefit that ranged from 28 to 30 meters over different time periods. For example Myozyme, a drug that received approval for Pompe disease, another neuromuscular disease had a 28 eight meter benefit over 78 week time frame. And Elaprase, a drug that received approval for MPS2 or hunter syndrome had a 30 meter benefit over 52weeks.

Lastly in October we will have additional data through 48 weeks including additional safety data, additional 6-minute walk test data and additional muscle biopsy results for dystrophin. We plan to prepare that data set for a FDA meeting around the end of the year to determine the design of a confirmatory study and discuss the fastest path toward regulatory approval. We at Sarepta Therapeutics are simply thrilled by these results and believe we have a drug that represents a major advance to treat the underlying cause of Duchenne muscular dystrophy and we are committed to the further development of this drug and will carry a sense of urgency in the pursuit of regulatory approval to make it available to patients to who may benefit.

Operator that concludes my prepared remarks and we can open up the call to questions

Question-and-Answer Session

Operator

(Operator Instructions) And your first question comes from the line of Charles Duncan, JMP Securities. Please proceed.

Charles Duncan – JMP Securities

First of all thanks for taking my question. Secondly, really congregations on very nice result periods. It's great to see for these patients. My first question is, you had talked about the timeline to 48 week datas, let me make sure I understood some of the discussions or the points that you made with regard to patients. All patients continued and you are going to see 48 week data in October?

Chris Garabedian

Yes, that's right Charles. So all patients continue to take the drug. We are collecting biopsy data at 48 weeks. So this 48 week dystrophin data in eight of the patients that were the original treated cohorts and will have 24 week biopsy data in the placebo/delayed treatment patients. We will be preparing the full dataset including the clinical outcome and the safety measures together with the dystrophin data and all of that data will ready to be shared and released in October. Importantly one of the premier muscle meetings of the year as world muscle society that takes place in the second week in October and we are planning to submit a late breaker abstract with these data the deadline is in august and we do expect that these will be excepted and will be presented at world muscle society meeting in the second of October.

Charles Duncan – JMP Securities

Chris in terms of next steps, I'm just kind of wondering, post-October likely, what they might be. First of all, do you think that you go to the agency and talk to them about pivotal study design and also you made a few interesting observation regarding younger patients and then higher baseline. You think you can incorporate that those observations into some stratification criteria for the conduct of that next study.

Chris Garabedian

Charles I think we want the benefit of evaluating the 48 week data before we draw any hard conclusions about the right design, potential stratification what the right endpoints and inclusion criteria are for a confirmatory study. So all along we had planned on preparing the 48 week data set in a briefing document requesting end of Phase IIb meeting with the FDA and we will have that discussion with them. So we intend to talk about what is that confirmatory study needs to look like. One of the conclusions that we drew from the subgroup analysis is that it looks like if you can start treatment earlier, whether it be in a younger patient or a healthier patient, it may be beneficial, that's the signal based on analysis we have. It did not suggest that there was no benefit in the older patients or the more progressive patients. We did see a very nice treatment benefit. It just simply was greater in the younger patients and the higher baseline 6-minute walk score. So again, we'll continue to evaluate that as the dataset emerges in 48 weeks and will take all that information in to the FDA with the right design for a confirmatory study.

Charles Duncan – JMP Securities

And then final question is it seems like this is a pretty capital efficient program. Do you think that you can carry it over the goal line, the goal line being approvability without a partner or do you intend to seek a partner and in what region if any different one.

Chris Garabedian

Well Charles, I've always said that we are putting all options on the table. I have to evaluate the return on investment and the economics that are related to raising capital to take this forward on our own, versus what a partner might bring to the table in terms of economics of the deal. That is always a calculation that I'm willing to consider in terms of what's best for the program, what's best for investors and ultimately what's best to get this product in the market to win the faster we can get this product to patients is ultimately the best path for a shareholder return for doing the right thing for this program. So we will evaluate all the options on a continuous basis and again, we're very encouraged by this data that this is a drug that can gain approval and will do everything to pursue that.

Operator

And your next question comes from the line of Bill Tanner, Lazard Capital Markets. Please proceed.

Bill Tanner – Lazard Capital Markets

What in terms of looking at the biopsy and the amount dystrophin actually product, what's the correlation or is there a correlation between what was observed with that as compared with a 6-minute walk test results.

Chris Garabedian

So let me share what kind of we know and what the hypothesis is. So because we had staggered biopsies in the 24 week stays of the study and we had the high-dose biopsy to 12 weeks where it was not long enough to see the dystrophin then the cohort that we're seeing, this large benefit in the intent to treat population, we do not have dystrophin to correlate to that outcome. We will have dystrophin at 48 weeks, we'll capture that and we expect that we're going to see a good levels of dystrophin in the 50 mg/kg at 48 weeks. So it's very hard to do a correlative analysis on dystrophin. Furthermore, the four boys who were on 30 mg/kg who we did feed dystrophin at high meaningful levels that included the two boys who rapidly progressed long before we saw dystrophin or would've expected this to be dystrophin in their muscles. So again, that the correlative analysis is hard with a small sample size and data that we have today. I think we can draw better conclusions when we have the 48 week dystrophin data. But the hypothesis is that the 50 mg/kg cohort is producing dystrophin, that if we had been able to capture serial biopsies, that we would have seen high levels of dystrophin in the 50 mg cohort at 24 weeks and we'll have to wait for the 48 week data to find that out.

Bill Tanner – Lazard Capital Markets

Okay and then as it relates what you think you need to see functional improvement. I think actually with (inaudible) Myozyme, there is a respiratory component to their approval as well or actually what they measured. But just as it relates to DMD, would it be do you think just a fact of an improvement in walking distance or ambulation would be adequate for it to gain approval? Was there another component of a clinical response as you think the agency might want to see in addition to improvement in walking?

Chris Garabedian

Again, each disease is different and so we have to be careful with apples comparison if you will. The disease progression of Duchenne, generally when the boys are in an ambulatory state, you don't see us comprised pulmonary function. And so again, they are relatively healthy and stable and then you see the really the decline start when they after they lose ambulation. So and we typically take longer to show that benefit on pulmonary function. But we are capturing pulmonary function measures, cardiac function measures that was not intended to be a clinical efficacy endpoint but we will look at that and capture that. There is no suggestion to date that the regulators would be looking for something beyond 6-mintue walk. Again, PTC had paid the lot of the way with Ataluren, another disease modifying drug as DMD and what their registration program looked like. Prosensa, a competitor in the exon skipping space, is in a pivotal study with the 6-minute walk test as a primary endpoint.

So we believe this is the right endpoint and again the robustness of the effect size, we are very encouraged by it.

Bill Tanner – Lazard Capital Markets

And then maybe just a last question. Can you remind us of what has been observed thus far in the biopsies with respect to cell infiltration? I'm just curious if one would anticipate that obviously this growth in production in these kids, whether it would be viewed as a foreign protein and a priority, whether there would be some anticipation that treatment over a longer period of time might induce kind of an immune response?

Chris Garabedian

Yes, we've looked at this in all of the studies we've done and looking at the muscle biopsies and looking for any anti-dystrophin, antibodies that would be produced and we're not seeing any type of adverse immune response, immunogenicity related to this production of dystrophin, including in-patients who had zero dystrophin at baseline because these boys start with zero to up to 5%. So some of them are producing kind of a skipping dystrophin and others don’t to that degree.

So again we're very encouraged. We'll continue to look at that at the 48 week timeframe. We did see some signals in an earlier study on a reduction of T-Cell Infiltrate, an inflammatory response in the muscle biopsy. We were encouraged by the data to date in terms of, we saw no increase in information. We look forward to the 48 week data, where again we should have a tighter co-relation of is the restoration of dystrophin across these 12 boys resulting in a reduction of T-cell.

These analysis can take longer so we're focusing first on the dystrophin and it's not clear when we would have the T-cell data after the October timeframe but we will be looking at that and prioritizing that as one of the secondary biochemical markers.

Operator

And your next question comes from the line of Ted Tenthoff, Piper Jaffray. Please proceed.

Ted Tenthoff – Piper Jaffray

I'd like to share my sincere congratulations on this result. It's really exciting to see this sort of boys. Without getting into too much detail explain if you would or (inaudible) what the statistical, is there a statistical hit to take by excluding those two boys or how, how does the statistic work around that, such that this A, the delayed treatment, placebo group can still be statistically or can still be measured for significant and also how excluding those two boys impacts the analysis?

Chris Garabedian

Yes, Ted, thanks. Let me try to answer that. I'm not our statistical expert and we can have a follow up call, explain in more detail but the short answer, I'll do my best, yes, there is a statistical hit that you would take when you have kind of the outliers like we saw in the intent to treat population. The analysis that we led the press release with was the predefined. We identified for the 24 week analysis in our statistical analysis plan a specific statistical methodology that increasingly seems to be preferred by the FDA. They are moving towards this mix model, repeated measure test where it's not just the time point at baseline and the time point that you are at in follow up but it takes into account all of the repeated measures and basically uses that to predict the slope and ultimately where the patients would expect to end up based on those average multiple measure score.

When you have outliers that would violate a normal distribution it has two impacts. One, you take a statistical hit but it also adds to the interaction across the cohorts. So this is why we see a different number when we apply our intent to treat population that includes the two boys. When we take those two boys out it follows the more normal distribution and this would be applied without this rank sum test that would be required when it doesn’t fall on normal distribution.

Ultimately the statistics are not as strong but we did hit statistical significance despite that but the numerical values are slightly greater. When we applied the modified intent to treat which is outlined in the press release you will see that we had a higher P value but the treatment effect was reduced slightly from 69 meters to 66 meters. But that can explain not being a status issue.

Ted Tenthoff – Piper Jaffray

One quick follow up on that. The two boys if I recall correctly from AAN, who fell out of this range and who declined rapidly were both in the 30 mg per tick cohort, correct?

Chris Garabedian

That's right.

Ted Tenthoff – Piper Jaffray

So, and again, I can follow up offline with a follow up question. One last one.

When it comes to the date of release in October will that be a press release as well and where do you anticipate releasing this, this full data set to the medical community.

Chris Garabedian

Yes, so Ted, again as a public biotech, when we have material information that we guided on, we would likely put topline results in a press release but you may not have been on the line but I mentioned earlier that we are going to be at World Muscle Society in the second week of October and we are to be submitting a late breaker abstract, the deadline is in August. To present this we do expect we would be accepted and we would have a full presentation at that meeting in the second week of October.

Operator

And your next question comes from the line of Mike King Rodman and Renshaw. Please proceed.

Mike King – Rodman and Renshaw

Let me add to the congratulations to your results and your continued efforts. A couple of questions that, a little bit of, forgive me because I'm not intimately familiar with the study design but Chris, can you just talk about whether the age cut at 9.5 years, is that prospectively defined or was that just where you saw it kind of divide into a coequal cohorts?

Chris Garabedian

Yes, we had small numbers right. So we didn't really have the luxury to predefine the subgroups. So these are post talk and what we simply did is to try to have some level of power and meaningfulness, is we had six treated patients in the modified intent to treat and two placebo and it just happened to breakout nicely that half the patients, three treated and two placebo were below 9.5 at baseline and three treated and two placebo were above. So it worked out nicely but that was the post talk division.

Mike King – Rodman and Renshaw

And the results or lack thereof, to the two boys at 30 that progressed rapidly begs the question about how you guys feel about those and when we saw each other a few days ago, I think you guys are of the mind that duration is more important than dose but can you talk about how you feel about dose? Do you feel like 50 is right? Could 30 potentially be right or could you potentially move higher than 50 in order to drive even additional dystrophin production.

Chris Garabedian

Yes, Mike, I think this is a case where we continue to gather more information. This is new information than what we had at 24 weeks. We will have more information at 48 weeks, particularly as it relates to dose response and dystrophin production. We will be looking closely at that and will continue to see how the 30 mg per kid cohort of the two patients who are ambulant for example, what their dystrophin levels look like vis-à-vis the 50 milligrams dystrophin levels at 48 weeks. We will see how the placebo patients, now that they've been on a drug, they will have been on drug 24 weeks, do they start to show signs of slower progression or stabilization of the disease because now they're reducing dystrophin hopefully in the 24 weeks.

So it's too soon I think to make hard conclusions around the dose. I am encouraged by the 50 mg where I don't believe that we need to look at higher doses and I think the question is, there is a longer duration at 30 mgs, I'll get you there. And again if we think long-term about treatment of this disease and we start thinking about boys who would be treated earlier when they're healthier, it may be that 30 mgs is sufficient if you can start early and start producing dystrophin before they have a chance to really show significant signs of progression on ambulation. So hopefully that answers. I don’t have the definitive answer now but we're very encouraged by the 50 mg cohort.

Mike King – Rodman and Renshaw

Yes, what we can do is informed speculation here. So think that does answer as far as you can, you're able to. And then also kind of ties back to your second slide with the sickness (inaudible) test curves where the curves are overlapping at 12 weeks, until 12 weeks and then they splay in a pretty pronounced way. Do you think that that's characteristic of this particular patient population or is this sort of generalizable to BMD?

Chris Garabedian

It's a good question Mike. When we design this study and we shape the inclusion criteria we did it with an eye toward trying to enroll patients that we would expect would be on a decline. I think what we were surprised by with how stable both groups were frankly, through 12 weeks because now we know even the treated group didn't have enough dystrophin at that early time point. So it's hard to predict that it may be somewhat of a placebo effect where they were just enrolled in a study and maintaining and stabilizing and ultimately the disease catches up to you and that's kind of what we saw starting after week 12 and really starting to progress beyond that. We've talked to experts in the field about natural history and the 6 Minute Walk Test. For example Craig McDonald [ph] has written several papers about the natural history and the 6 Minute Walk Test specifically and this confirms very much with what we would expect in a patient population, in the inclusion criteria of above seven years of age, with the baseline 6 Minute Walk scores that we used as an entry criteria, it fits very nicely with what we would have expected a placebo cohort to look like.

Mike King – Rodman and Renshaw

And then one final question. Just one clinical supply, if you're gearing up for registration studies in '13 will you have enough drug product to be able to satisfy the demand for the trial.

Chris Garabedian

Yes, well we have been working with contractor manufacturers already. Obviously we are continuing to produce drugs to supply this current study in the extension phase. So we have our suppliers who know how to produce this drug and a situation like this we have to figure out how many patients do we need in a confirmatory study and what is that going to take, what is that going to cost. So that's all going to be evaluated but again we'll have a more definitive read on that when we meet with the FDA and at that point we're in parallel planning for making sure we have the right drug supply for what we expect a confirmatory study to look like.

And of course we're thinking about how do we prepare for commercial scale? This is something if we end up having discussions with the FDA where we can see some path to accelerated approval we have to start thinking about drug supply even beyond the confirmatory study. So that’s something we are putting a lot of attention to internally and probably feel we're in a good position from where we stood today.

Operator

And your next question comes from the line of Chris Marai from Wedbush. Please proceed?

Chris Marai – Wedbush

Congratulations on what looks like really great data. So most of my questions have been answered but you can help me understand the design of a registrational trial, maybe including sort of a range of numbers, patients that you may include and for the cohort groupings or types of patients that you might include and then just following that, given this data, it would be reasonable to assume that there is a good chance for us to, for your follow content on treating exon 45 and exon 51, could you elaborate maybe at this time where they are in the clinic and a timeline that you may expect for those to progress further?

Chris Garabedian

Yes, Chris, I was challenged with the 24 week data set and I really started to think hard about a pivotal study and what would be needed but the recent data set at 36 weeks is encouraging in that I think it may need an easier path to designing a confirmatory study because of the treatment effect we're seeing. So I'd imagine that we would see a way similar study design, similar inclusion but this would probably be over a year of therapy, but again we need to talk to the FDA and, and what they believe is important to show in a confirmatory study.

I know there's a lot of sensitivity around placebo controlled studies. I know even the FDA feels that if you prove a drug effect in a placebo controlled study in a rare disease like this, what is the burden required for future placebo controlled studies? We're assuming we do need to do a year-long study, placebo controlled study, and we look at other rare disease areas and commonly the traditional approval can be gained by a 60 patient study and so we think that's manageable whether that is a 40 treated versus 20 placebo or a 45 treated versus 15 placebo. We have to determine that but that is for discussion with the FDA and everything that would share at this point is just speculative until we are able to look at the 48 week data, design the right type of study, figure out the right powering and then having that discussion with the FDA.

Regarding the other exons, again this is the proof of concept clinically that we were waiting for to give us the encouragement that these follow on exons can be reproduced to produce similar results. We have two collaborations ongoing on exon 45 and exon 50 and we are negotiating for a grant on exon 53, a next most prevalent exon beyond exon 51 in (inaudible) and so this is what we like about this program, is that once we have a definitive read in this lead program (inaudible) we think that the community will embrace accelerating the development pathway and potential approval of follow-on exons and it's a nice investment thesis as well, where you can reproduce something with the same technology, the same manufacturing process. We're seeing similar PK always have safety PK with our Mark Baleno [ph] backbone chemistry. So we're very excited to pursue these other exon skipping drugs as well.

Operator

And your next question comes from the line of Ritu Baral from Canaccord. Please proceed.

Ritu Baral – Canaccord

Congratulations as well from me. Can you guys just address how important you think genotype plays into overall response to the drug and is there anything unusual about the genotype in the two boys that were rapid decliners?

Chris Garabedian

Yes, Ritu, that's a good question. So that's why what we wanted to look at genotype and why we highlighted in the press release and in the script. So we had five genotypes represented that are amenable to an exon 51 skip. The two boys, we did look at their genotype and we had another patient who received treatment, who was a responder in the study with the same genotype. So we are encouraged by that and we believe that the other factors that were leading to the two boys' decline are more evident, that we've been working with Craig McDonald [ph] on, is to better characterize it. He has the model that looks at 50% predicted value and again, the two boys that were below 250 meter four weeks, they were significantly lower in 12 weeks and there is enough data to project their decline without looking at genotype but we were encouraged that there was a good data treatment effect in the same genotype of these boys.

We looked at 49, 50 because we had a large enough sample and also because the placebo group was randomized to have three patients with the same genotypes. So we wanted to make sure that people didn't believe that 49 50 was the reason for this progression and we had two patients with 49, 50 who treatment and that's why we highlighted that. It was consistent with the treatment across the population and we a demonstrated treatment effect, that this was not an artifact of genotype. Interestingly in our previous UK study, 40 – 50 came up because it seemed to be one of those genotypes where we saw better dystrophin responses. But again against there is, there uh, treatment. It's not weighing. The treatment effect overall, it's are consistent with the overall population and again when we look at the other genotypes we don’t have large numbers but there's nothing to suggest that there's anything different in terms of treatment effect by dystrophin.

Ritu Baral – Canaccord

And going back to what you had previously mentioned about the increased sort of dystrophin production with younger age and I get Lutts Progressive Disease, what's the biology behind a better response there? Do you think that it's a different sort of quality of dystrophin where the dystrophin sort of arranged in the complex, any sort of explanation behind that?

Chris Garabedian

This is something that has been seen with other progressive diseases that the earlier you can treat before you see a clear sign of progression, the better. This is always a challenge for doing clinical studies because if you treat too healthy of a population you need larger numbers and longer duration of follow up. So it's always hard to thread that needle of getting progressed enough population to show a treatment effect but that's not too far progressed where like the two boys showed where you don’t have enough time to show a treatment effect.

So again we're not surprised by that. I think what it tells us, is that when you are treating a healthier younger boy there may be a better chance to assess the slope in the course of the disease progression. We can still have an impact in older and, and, and more progressed disease and we even believe in a non-ambulatory setting like these two boys. They continue to take the drug and we believe that we might see some stabilization of other measures that would typically be progressing in a non-ambulant state. So again, it's a continuum. I don’t think we're trying to say anything hard and fast, who would be candidates for treatment but it does suggest that it's not good to wait to treat, that if you can treat earlier and healthier, that may be better for the course of the disease and so again it's just a signal that we would want to confirm with further data and additional studies.

Ritu Baral – Canaccord

Got it. And do you expect that dystrophin expression and total dystrophin levels will go up further when you do your week 48 biopsy versus what we see in your week 12?

Chris Garabedian

We don’t know the answer but we're looking with anticipation on answering that question. We know in animal models we can see levels beyond what we saw in 24 weeks and so we believe there may be a plateau, once you have a healthier muscle, the muscle tissue is leaky, it's harder to get the drug in the muscle cells but again that's theoretical and we really won't know until we see if there is a plateau, where that plateau occurs and whether we see levels in the 20% to 30% range or do we see something beyond that? We're excited to look at the 48 week data to answer that question.

Ritu Baral – Canaccord

And next question, can you remind us again about the, I guess percentage of population with this particular exon skip versus some of the other more common variations of the MD as well?

Chris Garabedian

Yes, so this is the drug that treats the most prevalent set of mutations that can be treated with a single exon skipping drug. It represents 15% of the exon skipping amenable population which is 85% of the DMV. Effectively that's 13% of total DMV would be candidates for this treatment. That translates in the U.S. for example to about 2,000 patients that would be amenable to an exon 51 skip.

Operator, I think that includes our time for questions and again I just wanted to tell everybody we're very excited by this. We appreciate the interest in eteplirsen and Sarepta Therapeutics and thank you very much.

Operator

Thank you for your participation in today's conference. This concludes our presentation. You may now disconnect. Have a great day.

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