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Sarepta Therapeutics, Inc. (NASDAQ:SRPT)

UBS Global Healthcare Conference

May 13, 2014 8:30 AM ET

Executives

Christopher Garabedian - President and CEO

Analysts

Natalia Medina - UBS

Natalia Medina - UBS

Good afternoon and thank you for coming to the 2014 UBS Global Healthcare Conference. My name is Natalia Medina and I am happy to be your host for this session. Our next presenter will be Christopher Garabedian, President and CEO of Sarepta Therapeutics. A breakout session in 20D East will be immediately following this presentation. Thank you.

Christopher Garabedian

Thanks Natalia and thanks for UBS for inviting us to present here. So today I would like to be an update on what Sarepta Therapeutics is working on particularly in the DMD, the Duchenne muscular dystrophy space. I will be making some forward-looking statements, so please refer to our SEC documents for guidance on risk factors associated with the Company.

So, recently in April we announced the outcome of a number of months in dealing with FDA on providing guidance to our Duchenne muscular dystrophy program, and this was the combination of a 5.5 month to 6 month process, in which we had four meetings, from November through March and they issued a guidance letter in April, that really provided us clarity on the path forward and what it would take to get approval of eteplirsen under an accelerated approval pathway, but also what we would need in terms of a confirmatory trial or evidence to get full approval of eteplirsen.

So there is three main areas of that feedback. The first was outlining two distinct pathways in which they could apply accelerated approval to eteplirsen without the need for confirmatory clinical or dystrophin dataset, the data from a new trial. The two areas they outlined of the potential ways they could apply the accelerated approval pathway was they indicated it could be approved using dystrophin as a surrogate marker that would reasonably predict clinical benefit. So let me talk a little bit about that for a minute.

They indicated that they would like to collaborate with the Company which we were already doing on doing a detailed review of our dystrophin methodology and this involves going to the site in which the dystrophin was collected, stained for, evaluated and quantified. They indicated that upon that more detailed review the existing dystrophin dataset could be used as the basis for accelerated approval. They also indicated that it may be helpful if we got a fourth biopsy and we also believe that that could bolster what we believe is an already strong dystrophin dataset. So that’s the first way that they outlined that eteplirsen could be approved under the accelerated approval pathway.

The second area that they outlined was what is described in the accelerated approval guidelines and was reinforced with the FDASIA legislation in 2012, which is on an intermediate clinical endpoint, and they specifically identified that it could be approved on the six minute walk test data from our ongoing 201/202 study. We will be bolstering that dataset with 144 week data later this year that would go into an NDA submission by the end of this year.

So based on this guidance from the FDA that indicated that an NDA should be filable with additional safety and efficacy data, we have indicated we’ll be submitting an NDA application by the end of this year. The timeline as it relates to that is, if it is accepted for filing that would be 60 days after submission of the NDA. Then if we got priority review, which would typically be granted 30 days after a submission, that would be six months from the date of filing to drive a PDUFA date on whether the drug was approved or not. So that would put us to of the summer of next year or for example if we submitted an NDA in mid-December, that would put the PDUFA date into a mid-August timeframe next year.

The second area of guidance they provided was what they would need to see in terms of confirmatory evidence, should they approve eteplirsen under the accelerated approval pathway. They actually outlined two distinct ways that we could confirm on accelerated approval of eteplirsen. The first was through an open-label historically controlled clinical study of eteplirsen. So this would be a non-placebo-controlled study. Open-label we would enroll ambulatory patients of a certain age range, we have announced 7 to 16 years of age. We will do a primary analysis on those who have baseline six minute walks between 300 meters and 450 meters. But we would still allow patients who are healthier than that to still qualify for this study and get drug.

For those that can’t walk 300 meters, we are planning a companion study in the more advanced population and also those who are non-ambulant, where we would be capturing safety data in that population and we expect to enroll upwards of 20 boys in that study. The ambulatory study we’re aiming for 60 to 80 patients. We also announced that we would be doing a younger patient study, these are boys who would be between ages of four and six years of age regardless of the ambulatory status, but we would be collecting dystrophin data in those patients.

The second way that they indicated we could confirm a accelerated approval of eteplirsen was on another follow on exon study, this one they would require would be placebo-controlled and could be on any one follow-on exon. We indicated to them that we might want to boost the power and the speed of enrollment of a well-powered study to include more than one exon target. So we’re planning a kind of a master protocol that would enroll both 45 and exon 53 minable patients that could also be amended to include other exon skipping drugs as we got open INDs and had those available for study drug.

What the FDA further stated was that they want us to do both of these studies, but only one of them would be required to confirm evidence of an accelerated approval of eteplirsen. Further they said that while they want us to pursue both of them, their only specific requirement was to have both of them enrolling at the time they approved eteplirsen under the accelerated approval pathway. We think this really underscored their understanding of this technology and how they could apply learning from eteplirsen to the follow-on exon and likewise more burden approved on exon-skipping dystrophin production, safety and clinical outcomes from follow-on exons to bolster and support their understanding and strength of the eteplirsen dataset.

So what are we going to be collecting to go into a NDA submission? So as we mentioned the FDA was very clear that the more data we collect and make part of this submission assuming that it’s consistent and favorable with the existing dataset, the stronger right our ability to get an acceptable filing and ultimately a favorable review would be. However they’re not saying we can’t submit an NDA at anytime that we see fit, we’ve made the choice that we’ll have a stronger NDA submission and a stronger dataset to bring to an advisory panel if we wait for the end of the year to submit that.

And the reason we believe that is that we would hopefully have the fourth biopsy data at the time of that NDA submission, we’re still looking at the feasibility of that, we will know in the coming weeks how many patients that if we have at least half or more we believe that it’s worth pursuing that fourth biopsy. We’ll have a 144 week data from our ongoing Phase IIb study and that would come in the second half of this year and could be rolled into an NDA submission by year-end. And then we would likely start dosing the ambulatory study with eteplirsen by the end of the third quarter which means we would have some early exposure data in new patients with eteplirsen that could be again included in an NDA submission by year-end.

They also showed a lot of flexibility in accepting supplemental data if we submitted an NDA by the end of this year, during the review process and we would hope to have that considered at an FDA advisory panel. And so we’re expecting to have a 168 week data to be supplemented during the NDA review process and we also hope to have exposure data in not only longer duration of the ambulatory patients but in the younger population would begin dosing by year-end and in the non-ambulatory or advanced population. And if we had safety data for those patients that could be submitted after an NDA submission we would do that as well.

Here is the schema outlining of the NDA submission and the process to filing advisory committee and an FDA approval decision. And on the lower part of the schema you see the data when we would potentially have it available to start preparing for submission to the NDA.

I’d also like to add that we’re planning to talk to the EMA about the pathway for approval of eteplirsen. And we hope to have our first meeting with them to discuss what it would take to get eteplirsen approved in Europe by the end of this year. We will be beginning our next follow-on exon, exon 53 dosing in Europe in the fall of this year and in terms of the other follow-on studies that you see here outlining all the studies that we have planned for the remainder of this year. We expect to start enrolling patients in a placebo-controlled study of exons 45 and 53 by the end of this year the U.S. that could be expanded to be a global study but we expect the initial enrollment to take place in U.S. sites.

So here you can see we have five studies planned in addition to our ongoing eteplirsen study which will be the sixth study we have enrolling or dosing at various stages across our DMD platform and that we’re also planning a natural history study where we can start to enroll patients and start capturing natural history data even beyond the exons listed here so that we have a ready patient population as new follow-on exons become available through open INDs and through drug supply we can start considering enrolling them in this master placebo-controlled protocol.

So we have got a lot ahead of us at Sarepta over the next year and so we have been really focused on strengthening our balance sheet. We raised approximately 100 million recently to add to our cash balance of about 233 million at the end of the first quarter. We have been building out a strong management team. We have moved into a new space in Cambridge, that’s about 45,000 square-foot of administrative offices as well as 15,000 square-foot included in that of lab space. And we still have our Corvallis, Oregon facility that has research small-scale manufacturing and some of our analytical R&D and quality control.

This is our senior management team here which all come from companies who have driven success in the biotech and pharmaceutical space and are used to commercializing drugs going through the regulatory and development process and understand how to build a profitable global biotech enterprise. In previous meetings I have described in detail the Duchenne muscular dystrophy program, it’s a devastating disease where it affects mostly boys who lose the ability to walk usually in pre-teen years, start to lose the pulmonary function in their teen years, and often passed away in their early to mid 20s. The disease is marked by their inability to produce the essential protein dystrophin because of the outer frame mutations in the dystrophin gene that render them unable to affect read-through of the dystrophin gene in production of the protein.

Our drug works by targeting the bad actor in the dystrophin gene, in the case of the boys in our lead program study, it’s exon 51, so by silencing exon 51 or hybridizing it out of the reading frame as you can see depicted in this cartoon here we are able to restore translation and we have shown in every patient in our study that we are able to produce dystrophin protein in their muscles. This was our Phase IIB study design in which it drove the datasets that we have shared with the FDA over the last year, and that we have been discussing with them to form the basis of an accelerated approval. We learned in this study as our primary endpoint was dystrophin production, that there was a delay in dystrophin treatment.

The 50 milligram per kilogram per week dose was no different than placebo on our primary endpoint after 12 weeks of dosing, but after 24 weeks both in the crossover placebo patients as well as the original treatment cohorts we see robust levels of dystrophin in the muscle tissue. And after 48 weeks of treatment we see continued increases in dystrophin production. As you can see an example of immunofluorescent images that show what a pretreatment biopsy looks like versus the accumulation of dystrophin between 12, 24 and 48 weeks and what a normal healthy muscle tissue looks like. Now we don’t expect that we’re producing normal healthy individuals, we’re producing a internally truncated dystrophin, that’s a kin to a Becker dystrophin or what is known as Becker muscular dystrophy, is a much milder, oftentimes milder phenotype and is not as characterized with the rapid progressive decline that requires boys to be in a wheelchair at a young age.

We enrolled a generally older population and a more advanced population than is typical of ambulatory studies. They were over nine years of age on average. Their baseline six minute walk across the total population was about 370 which is consistent with other natural history studies and other clinical studies that have been done in Duchenne. And this is our data out to 120 weeks that we communicated earlier this year. And we showed that the early treatment group has maintained stability on the six minute walk test. And this is very encouraging because you just don’t see this in Duchenne muscular dystrophy over this timeframe.

But more importantly the placebo patients were declining, all of them more than 15% from their baselines and then stabilized after we showed demonstration of dystrophin in their muscle biopsies. This was a mean score that we did. The previous one was the primary endpoint and the maximum score of 2 measures that were taken at baseline and at various time points along the way. And this is what the natural history consistently looks like in Duchenne muscular dystrophy. These are multiple natural history studies over 48 weeks or up to 2 years, and you can see all of them decline. These are greater than seven-year-old boys.

And again, there’s a range, there’s variability but generally between 40 and up to 100 meter decline in a year, and you generally see 100 to 120 meter decline over two years. This is our dataset overlaid on the abundance of natural history data. Of course this is not a direct comparison trial, but just shows you that the slope of the curve on progressive disease is different than what you see across these natural history studies. And this is the same data taken from the last time point before dystrophin was demonstrated in their muscle biopsies and you see no difference between the treatment group and the placebo cross over. This was the modified intent to treat there were two boys who lost ambulation early on in the study at 24 weeks the first time point that we showed dystrophin in these twins muscle biopsies they were no longer able to do the six minute walk test.

And these were the individual patients who were -- remain ambulant and you can see that all of them have generally stabilized two exceptions that declined between 10% and 15% from weeks 36 to week 120, but again this is even slower decline than what we would be expected from the natural history and notably one of those boys the one who declined the most was the boy who was essentially stable from week 36 on until he broke his foot he had a distal tib-fib fracture and usually this is a mark of loss of ambulation and wheelchair dependence for the rest of their lives. He was able to recover and he has done two six minute walk tests since but he did see a decline from before we broke his foot.

And then we have other clinical data on pulmonary function that again the most next to six minute walk the most well characterized endpoint in Duchenne and the most validated in terms of use for FDA approvals of neuromuscular conditions and we think a very important marker. These are all of the results through 120 weeks for the total cord this includes the twins so this is in intent to treat from the beginning of the study. And we saw increases on MIP, maximum inspiratory pressure, increases on maximum expiratory pressure, increases on forced vital capacity volume. We saw a slight decline in forced vital capacity percent predicted, this is age and height adjusted. But we would typically expect declines of more than 10%, or about 10% or more, a year. And again, this is after 2.5 years of follow-up.

We even percent predicted we saw stabilization and numerical increases in MIP and MEP. This is what the natural history looks like from age seven onward. We see declines on MIP and MEP percent predicted in multiple natural history studies, and yet, our boys, and this is consistent across the cohort, show the stability over more than two years. Our safety profile continues to look very favorable with no different than placebo in the first 24 weeks, but it continued to see a favorable safety profile with no treatment related clinically significant adverse events through this timeframe.

And again we’ve had treatment-related AEs where transient proteinurias in a handful of patients. And we believe that this safety profile is driven by our unique backbone chemistry that is we believe very differentiated from the two methyl chemistry that is also in the clinic for Duchenne muscular dystrophy with a competitive agent.

These are our follow-on exons. As I’ve described, exon 45 and 53 will be ready for IND submissions later this year for ready for enrollment in our follow-on placebo-controlled trial by the end of this year. We have other exon-skipping drugs in the pipeline at various stages of discovery preclinical and lead optimization. Exons 50, 44, 52, 55 and 8, we might consider including these drugs in our follow-on treatment study as they become available through open INDs and drug supply.

And this is a sense of just those eight exons that I’ve described comprised almost half of the overall DMD population. Our goal is to make sure that our technologies apply to every boy who can benefit from exon-skipping and our technology and it will require flexibility from regulators because as you can see once you get beyond the top few you have 2%, or sometimes less than 1%, or less than 0.5%, prevalent in these very rare mutations.

As I’ve described earlier, we’ve got a lot of activities this year, a lot of milestones as we move toward an NDA submission towards the end of this year. And obviously an advisory panel would ensue in the first half of next year if we have an acceptable NDA filing for a PDUFA date that would come in the summer time.

And we continue to advance our platform. We believe our chemistry, the morpholino chemistry, which we’ve been filing and have issued patents on a lot of modifications to the PML platform and we think this is really best-in-class chemistry in the RNA space and we’ve hired Art Krieg, our Chief Scientific Officer, to continue to advance this technology beyond Duchenne muscular dystrophy into other genetic targets. And we still have our infectious disease portfolio, two programs which are being supported by the U.S. government, a DoD program that’s supporting our Marburg hemorrhagic fever virus program and an NIH support for an influenza pandemic H1N1 program.

As I mentioned, we have a strong balance sheet. We raised another almost $100 million recently net that added to the more than 200 million we had at the end of the first quarter. And we have good volume in trading at about 38 million outstanding shares as we sit here today. Thank you very much.

Question-and-Answer Session

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