Sarepta Therapeutics Inc (SRPT) 2014 Q4 法說會逐字稿

Welcome to the fourth-quarter 2014 Sarepta Therapeutics, Inc. earnings conference call. My name is Ellen and I will 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. I will now turn the call over to Ian Estepan, Senior Director of Corporate Affairs. Mr. Estepan, you may begin.

Thank you, Ellen, and thank you all for joining today's call. Earlier today, we released our financial results for the fourth quarter and full year of 2014. The press release is available on our website at www.sarepta.com and our 10-K was filed earlier this morning.

Joining me on the call today are Chris Garabedian, Sarepta's Chief Executive Officer; Sandy Mahatme, Sarepta's Chief Financial Officer; and Ed Kaye, Sarepta's Chief Medical Officer.

I'd like to note that during this call, we will be making a number of statements that are forward-looking, including statements about our manufacturing capabilities and plans for eteplirsen and our follow-on, exon-skipping product candidates, expected initiation, enrollment, dosing and progress of our clinical trials, the potential market size for our DMD candidates, the potential applications of our research efforts to advance our PMO platform chemistry in various disease areas, our plans to -- in 2015 to advance our DMD programs and our promising early-development programs beyond DMD.

Sarepta's vision to develop multiple products for important indications using what we believe is the best-in-class chemistry, our planned timing of and efforts to satisfy FDA requests for additional data and analysis in connections with our planned midyear NDA submission for eteplirsen, the currently planned NDA content and the additional supplemental information and more complete data set that we expect to provide after the NDA submission.

The planned timing for obtaining FDA input, having meetings with the FDA and the topics that may be covered such as methods to assess dystrophin and muscle samples in requirements for an acceptable NDA filing. The additional planned biopsies in boys participating in our extension study and methods we plan to use to measure dystrophin.

Our plans to continue advancing and enhancing our understanding of exon skipping, the role of dystrophin and advancing dystrophin quantification and measurements, our potential manufacturing ramp beyond our current and planned clinical studies, the potential of eteplirsen as a lifelong treatment starting at the very young age, Sarepta's beliefs about eteplirsen's potential and the potential timeline for an accelerated approval and the timing of our plans to provide financial guidance.

These forward-looking statements involve risks and uncertainties, any of which are beyond Sarepta's control. Actual results could materially differ from these forward-looking statements, as any such risks can materially and adversely affect the business, results of operations and the trading price of Sarepta's common stock.

For a detailed description of risks and uncertainties we face, you are encouraged to review the Company's most recently filed annual and quarterly reports and other corporate documents filed with the Securities and Exchange Commission. With that, let me turn the call over to Chris Garabedian, Sarepta's Chief Executive Officer. Chris?

Thank you, Ian. Good morning, everyone, and thank you for joining us today for a financial and corporate update for the fourth quarter and full year of 2014. I will be providing an update on our lead candidate for Duchenne muscular dystrophy, eteplirsen, and our broader Duchenne muscular dystrophy program, including an update on the clinical and regulatory activities for eteplirsen and the latest on our follow-on, exon-skipping drugs for DMD.

Ed Kaye, our Chief Medical Officer, will provide a more thorough review of our recent clinical results and status of the current clinical programs, and Sandy Mahatme, our Chief Financial Officer, will provide an update on our financials for the 2014 year end. 2014 was a year in which we expanded our DMD pipeline and initiated several clinical programs to advance our PMO technology.

We made great strides over the past year in a number of areas. We worked closely and extensively with the FDA to determine a potential, accelerated approval, regulatory pathway for eteplirsen. We established a large scale of manufacturing of our PMO technology and these multiple batches of quality eteplirsen as well as drug product for our exon 53 and 45, exon-skipping product candidates for DMD.

And we expanded our clinical development programs for three drug candidates, with three new trials that began dosing patients in the last six months and two more trials that will begin dosing in the months ahead. Together, the successful development of these candidates would have the potential to address more than one quarter of the DMD population.

Furthermore, we advanced our research technology and identified multiple new applications for our proprietary PMO chemistry in the neuromuscular, rare disease and infectious disease areas. We look to build on this momentum in 2015 in advancing our DMD programs and the promising early-development programs beyond DMD.

In summary, this year, we will have six different DMD trials underway, dosing patients across a wide spectrum of the DMD population. While we cannot predict when we will have all of these studies fully enrolled, the target number of patients across all of these studies is more than 300 patients, with more than 200 expected to receive treatment across our three exon-skipping drugs.

Outside of DMD, we've announced some promising new research programs, including adult onset Pompe disease, Myostatin inhibition, and gram-negative bacterial infections among others, and continue to advance research programs in multiple areas that we have not yet disclosed. We are conducting research studies at our two research facilities in Corvallis, Oregon, and at our Headquarter location in Cambridge, Massachusetts, and have expanded our research team at both locations in the last six months to work with our current scientific-leadership team to advance our research platform.

We believe the favorable drug-like characteristics and the proof-of-concept, safety and efficacy data observed with our PMO chemistries and our DMD and antiviral programs can be applied to many other therapeutic areas in support of our vision of developing multiple products for important indications, utilizing what we believe is a best-in-class chemistry across the RNA-therapeutic landscape.

As excited as we are about our research platform and the progress of our clinical studies, our highest priorities are compiling and analyzing the various data requested by the FDA in the pre-NDA meeting minutes we announced last October, and meeting with the FDA in the second quarter to ensure our expectations are aligned with the FDA regarding our plans for an NDA submission and the requirements for an acceptable NDA filing.

In the meantime, our regulatory team has been busy compiling the NDA and is ready to incorporate new safety and efficacy data as it comes in to meet our midyear target for an NDA submission. To highlight the key data sets that the FDA has requested as part of the NDA, we announced in mid-January, the 168-week clinical efficacy and safety data, and at the same time, indicated that we had already begun dosing the minimum range of 12 to 24 patients newly exposed to eteplirsen to fulfill the request of a minimum of three months of safety in these patients.

The compilation and the analysis of re-scored, dystrophin data is also on track, to be discussed with the FDA at a second-quarter meeting and included in an NDA submission. Lastly, we are still compiling and analyzing independent natural history data on the 6-minute walk test and MRI assessments from various institutions and expect to have analyses ready for inclusion in an NDA.

At a recent investment conference, we also announced progress in obtaining a fourth biopsy in patients from our ongoing extension trial Study 202 and we were pleased to share that we've already obtained biopsies from nine of the 12 boys in the study, with two more scheduled to receive biopsies next month for a total of 11. We are working with the FDA to ensure we gain their input on the various methods through which we will assess dystrophin from these muscle samples, as we believe these data will help us understand the levels of dystrophin production after almost 3.5 years of eteplirsen treatment.

We intend to measure dystrophin and our drug's activity through a variety of assays, including western blot, RT-PCR and immunohistochemistry. While the FDA did not require data from a fourth biopsy to be included in the NDA in its most recent guidance, we plan to include as part of the submission any data that has been fully analyzed and expect to supplement the NDA with a more complete data set after an NDA submission.

Similarly, while the FDA did not require the 192-week data from our Phase IIb study to be included in the NDA, we expect to share these data with the FDA in parallel or shortly after an NDA submission, to be considered as part of the review.

I want to highlight how grateful we are at Sarepta for the commitment of the boys in our studies and their families for enduring the requirements of this long-term study, with the extensive travel and clinical-outcome testing required to generate this important clinical information, and importantly, to undergo four surgical biopsies to advance our understanding of dystrophin production with eteplirsen treatment.

We hope to continue to enhance our understanding of exon skipping and the role of dystrophin while continuing to advance the field of dystrophin measurements and quantification. The cause of Duchenne is an inability of these boys' genes to produce the dystrophin protein. Our drug is designed to produce a functional form of the dystrophin protein and we think it is important to understand the degree and extent that we are able to do this in muscle after several years of treating with eteplirsen.

We would not be able to achieve this without the brave and heroic efforts of the boys in our studies and their supportive families as we hope this understanding will support an NDA submission for eteplirsen and potentially help establish a surrogate marker for follow-on, exon-skipping drugs for DMD. Lastly, I'd like to convey that we currently have enough quality drug supply to dose all patients in our current and upcoming clinical studies across our three, exon-skipping drugs for DMD.

Our manufacturing ramp beyond the clinical studies planned will be dependent on the timing of our NDA submission and in the anticipation of a potential approval of eteplirsen in the US. If we are successful in achieving an accelerated approval of eteplirsen, we expect to prepare enough drug supply to manage any commercial demand for eteplirsen at the time of the product launch. With that, I'd like to turn the call over to Ed Kaye, our Chief Medical Officer, to provide an update on our clinical activities.

Thanks, Chris. I'd also like to express our gratitude to all of the families who have made sacrifices to participate in our various clinical studies and appreciate their willingness to contribute to our understanding of our exon-skipping products and advancing the science of Duchenne muscular dystrophy. To begin our clinical update on our DMD program, I would like to provide a brief summary of our recent 168-week data, which we announced earlier this year.

The topline data we released from our ongoing Phase II extension study, Study 202, included a summary of 6-minute walk test results, pulmonary function outcomes and the safety profile for eteplirsen through 168 weeks. The ten boys in our modified, intensive treatment analysis which included all those patients who could perform the 6-minute walk test remained inambulant through 168 weeks. However, all patients did show a decline in distance walked on this measure since the week 144 timepoint.

The continuous eteplirsen cohort showed a benefit of 65 meters which is statistically significant through week 168 on the 6-minute walk test compared to the placebo/delayed treatment. We are encouraged that we've seen a sustained benefit of the eteplirsen treatment cohort over the placebo/delayed eteplirsen cohort, going back to the week 36 timepoint.

We believe these data are encouraging, given the average age of these patients and our selection criteria, which excluded boys with relatively high 6-minute walk test baselines. Since we are also excluding boys who were younger than seven years of age, our boys started at an average of age of more than nine years and today, we have half of the boys who are in their teens with an average age of 12.5 years.

It's important to note that the boys in this study were expressly chosen to participate through our inclusion/exclusion criteria because they were anticipated to decline on the 6-minute walk test over a 24- to 48-week period based on their age and also their baseline 6-minute walk test distance. To emphasize this point in our modified intent-to-treat analysis, it has taken over three years for the eteplirsen-treated arm to lose about the same amount of distance that the placebo/delayed group lost in the first 36 weeks of the study.

It is notable that a significant difference can still be seen 2.5 years later despite the small sample size in the initial stabilization and subsequent rate of decline has been similar across both cohorts now that both have received eteplirsen for more than 2.5 years.

Our pulmonary function test, which include data from the two non-ambulant boys in our study continued to show stability across the entire cohort, specifically pulmonary function has remained stable over three years across this 12-patient cohort as measured by percent predicted, maximum inspiratory pressure, MIP, and maximum expiratory pressure, MEP.

The absolute maximum pressures showed increases over this nearly three-year timeframe. The increases of MIP and MEP and the stability of MIP and MEP percent predicted were generally consistent across the cohort, including the two non-ambulant twins who have now been stable for more than two years in a non-ambulant state. Our clinical observations in lung function are supported by our preclinical studies which demonstrated high levels of protein expression in the diaphragm.

Lastly, I'd like to highlight the safety profile of eteplirsen. Through 168 weeks, we've continued to exhibit a notable level of tolerability with no clinically significant treatment-related, serious adverse events, treatment-related hospitalizations or treatment discontinuation. In the past 24 weeks, there have been no incidents of transient proteinuria.

More notably, the rate of proteinuria across the study has occurred at a lower rate than the placebo background rate in the first 24 weeks of the study. Given that eteplirsen has the potential to be a lifelong treatment to be initiated in many patients at the time of diagnosis at a very young age, we believe the safety profile will be important to health care providers and families when choosing a potential DMD therapy.

In summary, the 168-week data represents the longest continuous dosing trial of any exon-skipping therapy to date and has generated a robust body of evidence of treating boys in both the ambulant and non-ambulant state. We continue to be encouraged by the 6-minute walk test data seen to date and the ongoing ambulation and pulmonary function of the boys.

The focus for the clinical-development team here at Sarepta for the first half of this year is on the successful execution of the confirmatory and other clinical trials. Last year, we initiated our Study 301, PROMOVI, which is our confirmatory study of eteplirsen in patients seven to 16 years of age we can walk at least 300 meters on the 6-minute walk test distance.

This study is proceeding on schedule in regard to site initiations and enrollment. The projected time for full enrollment is the end of 2015. The study of PROMOVI non-ambulant DMD boys up to 21 years of age, Study 4658-204, has been initiated and enrollment is progressing on schedule, with the completion of enrollment anticipated by midyear.

Study 4658-203 is our study which includes younger DMD patients, ages four, five and six years of age. The study incorporates MRI studies and includes a non-exon 51 [eminimal] untreated control arm. This study is expected to commence enrollment in the second quarter of 2015. Other studies evaluated in our follow-on, exon drugs are well into development.

Study 4053-101, conducted entirely in Europe, has been initiated and the Part 1 dose saturation phase is currently enrolling, with full enrollment of both phases of the study on track to be completed by the end of 2015. Our remaining confirmatory trials, Study 804, is progressing nicely towards study initiation.

This study is a double-blind, randomized, placebo-controlled study, which incorporates an innovative study design in that it includes patients amenable to either exon-45 skipping or exon-53 skipping. The minimum number of patients enrolled for each drug will be approximately 30 patients each, with the two-to-one randomization of patients to either drug or placebo arms and a target enrollment of at least 90 boys in total.

The Study 4045-804 will be initiated in the US by midyear, with the EU enrollment beginning in the late 2015, early 2016. With that, I'd like to return the call back over to Chris.

Thank you, Ed. Ed's clinical update really highlights Sarepta's dramatic transformation over the past couple of quarters. Less than a year ago, we did not have the quality drug supply to begin treating patients outside of Study 202, as we had focused much of 2013 and early 2014 in establishing a larger scale of production, improving our manufacturing processes and generating quality drug product.

In this short time period, we have released sufficient quality drug supply for robust clinical program that will be generating data over the course of the next couple of years, and obtained additional feedback on FDA expectations for an acceptable NDA submission that we continue to work towards.

We believe we have a potentially best-in-class, disease-modifying drug candidate with a strong biochemical data set, good clinical outcomes and a strong safety profile in late stage clinical development with the opportunity of an NDA filing later this year for a potential accelerated approval in 2016. I'm very proud of our team's execution and we are well positioned for the future. Now, I'd like to turn the call over to Sandy Mahatme, our Chief Financial Officer for an update on the financials for the 2014 year end.

Thanks, Chris. Good morning, everyone. This morning's press release provided details for the fourth quarter and full year of 2014 in both an adjusted or non-GAAP basis as well as a GAAP basis. The press release is available on the SEC and Company websites.

The non-GAAP results we will discuss on this call provide a more accurate picture of our ongoing operations and impact of operations on our cash balance and they exclude the impact from the valuation of our outstanding warrants and stock compensation expenses.

I would like to point out that all warrants have been exercised or have expired as of the end of the third quarter of 2014. Please refer to our press release for a full reconciliation of GAAP to non-GAAP. In the fourth quarter of 2014, we reported an adjusted or non-GAAP net loss of $38.6 million, or $0.94 per share, compared to non-GAAP net loss of $29.1 million, or $0.77 per share in the fourth quarter of 2013.

The incremental net loss is primarily the result of increased operating expenses as a result of corporate growth as well as a decrease in revenues from our government contracts. Revenue for the fourth quarter of 2014 decreased from the $2.6 million of revenue for the fourth quarter of 2013, primarily due to the July 2014 expiration of the Marburg portion of the Ebola/Marburg US government contract.

Adjusted research and development expenses were $28.4 million for the fourth quarter of 2014 compared to $23.6 million in the fourth quarter of 2013, an increase of $4.8 million. Adjusted general and administrative expenses were $10.5 million for the fourth quarter of 2014 compared to $8.2 million in the fourth quarter of 2013, an increase of $2.3 million.

For the full-year 2014, we reported an adjusted or non-GAAP net loss of $112.7 million, or $2.81 per share, compared to a non-GAAP net loss of $78.1 million, or $2.31 per share for the prior year. The incremental net loss was primarily the result of a $4.5 million decrease in contract revenue and a $30.6 million [increase] in operating expenses.

Revenue for the full-year 2014 was $9.8 million, down from $14.2 million in the prior year, primarily due to the July 2014 expiration of the Marburg portion of Ebola/Marburg US government contract. Adjusted research and development expenses were $86 million for the full-year 2014 compared to $68.6 million for the prior, which is an increase of $17.4 million.

Adjusted general and administrative expenses were $37.2 million for the full-year 2014 compared to $24.0 million for the prior year, which is an increase of $13.2 million. The balance of our cash, cash equivalents and investments was $211.1 million, as of December 31, 2014, compared to $264.9 million as of December 31, 2013, and a decrease of $53.8 million.

The decrease was primarily driven by the use of cash to fund our ongoing operations, offset by the net proceeds we received from the exercise of warrants and stock options as well as the Company's public offering in April of 2014. We are anticipating providing guidance on our non-GAAP operating loss for 2015 during our Q1 earnings call. With that, I'd like to turn the call back over to Chris.

Thanks, Sandy. Operator, we can open the call to questions.

(Operator Instructions)

Steve Byrne with Bank of America.

Just following up on your last comment, there, Sandy, about -- you said you'd provide guidance after the first quarter. Can you comment qualitatively about R&D expense? You have $30 million in the fourth quarter with the new trials enrolling. Roughly, where do you think that run rate could be during the 2015 period?

Steve, thanks for the question. We will be in a better position in early May once we have -- or had our discussions with the FDA. Right now, it would be a bit premature.

But having said that, with our clinical trials enrolling, we expect that expense should ramp up. In addition to that, the R&D expenses also include manufacturing expenses so both those expenses are in that line item so we will see an increase. But at this point, it would be a little early to guide on the expense there.

Okay. And then question for Ed. As you look at these natural history databases, do you think that you'll be also able to look at pulmonary function in those comparisons in addition to percent ambulation in 6-minute walk metrics?

Steve, that's a good question. Certainly, we're looking -- we're doing analysis for the 6-minute walk test and we're also looking at the feasibility of pulmonary function and trying to make that comparison, too. So, we are working on that, but we haven't determined what the feasibility will be.

Okay. Thank you.

Jeremiah Shepard with Credit Suisse.

In terms of the 192-week readout from the 202 study, how might we think about the trajectory going forward? Are there any patients at risk for losing in relation between the last readout and the next readout?

Jeremiah, this is Chris. We -- as we've mentioned, we're not guiding on any new disclosures. We're focused on bringing all of our data to the FDA and focused on working with them to get an acceptable NDA filing. The 192-week data, as you know, we will have around midyear and we can share that with the FDA.

In terms of expectations, I think we consider this data set already a success in having maintained ambulation over more than three years in these 10 boys that we've been following on the 6-minute walk test. So, we know that they've experienced declines.

We know this is not a cure, especially in the advanced age and more progressed disease that these boys had at baseline. So, again, we don't know when or who or how many will lose ambulation. But, we stated, going back to two data points ago, that we had a couple boys below 300 meters and that those would be projected to decline and that we indicated that 168-weeks, we believed it was a finding if those two boys were still on their feet.

So, we, again, would not be surprised if we see continued declines if the majority of boys maintain ambulation. We think that is a positive finding of clinical outcomes. But, we're not guiding on expectations around that. This is a progressive disease. We -- as we've always done, reported on these every 24 week updates. Ed?

I think that's exactly right. Obviously, what we started to see at the beginning of week 144 is that there is a decline and obviously, we expect that, that will continue. But, I think it's really the rate of decline that we're seeing the difference and that's what we're really commenting on, that we're seeing a slow rate of decline but we don't expect to stop the disease.

Okay, and in terms of the NDA filing, you're still saying mid-this year. But is there any expectations for when you might be able to provide some more clarity?

Like, for example, would you need to wait from the meeting minutes before you actually update the Street? Or do you actually think you might have some guidance from the FDA following the meeting in Q2?

Jeremiah, it's hard to predict this, right? Over the last couple of years, we've had a variety of different interactions with the FDA. Some that are very clear, definitive conclusion. Some that we can report on based on the pre-meeting comments and meeting itself.

Some that we've had to wait for the meeting minutes to provide that clarity. Again, we've always tried to be very transparent about our communications with the FDA.

So, once we have something more definitive to guide the Street on, we will do so. But, it's hard to predict when, how, what that looks like in terms of the reconfirming and more specificity around the NDA filing.

But right now, we, as a Company, are committed to a midyear NDA filing. But we also need to go to the FDA with some of these new data sets, discuss that with them and to make sure we are in alignment of what is going into the NDA and enable a successful filing. That's all we can tell you at this point.

Just the last question. In terms of that meeting you're going to have in Q2, do you expect to have all the data the FDA requested last October and the meeting minutes that you received last October?

We won't have everything fully compiled and analyzed but the substantive parts of those data set requests, we believe we would have. So, we think the important elements that we believe the FDA is going to want to focus on will be part of that meeting.

Great. Thanks for taking the questions.

Chris Marai with Oppenheimer.

Congrats on the quarter. I wanted to just touch base again on the additional information requested by the FDA and really, could you comment on what's the most consuming or complicated part there? Is that the biopsies?

And then just to recap, with respect to those biopsies, the new biopsies, that is, are you analyzing those differently from the first set in the Phase II trial? Thanks.

Chris, there's two answers to that. I think compiling and analyzing data that is not our own is probably the area that is requiring the most work. So, this is the natural history data. Collecting and analyzing data that's not ours and from various institutions.

So, we are in the process of that. That's something that is very time intensive, right? We know our own data sets very well. We know how they come in. We know how to structure the analytics around that. But, we're dealing with multiple and disparate data sets from different institutions that requires a lot of work to compile.

As it relates to the fourth biopsy, again, as we described, this was not a requirement of the FDA. But, we believe that it enhances the understanding of this drug and its effect in the muscle within these boys. So, we want to work with the FDA to ensure that we are doing it to their satisfaction.

So, this is where it's hard to predict how all of those discussions and all the different ways we're going to measure dystrophin are going to play out in the sequence of -- as we compile those data. But, again, if we can improve the way we capture those data to the satisfaction of the FDA, that's going to be the priority. That's all we're ready to say, at this point, until we have more information to share regarding the fourth biopsy.

Okay. That's helpful. And then you noted that if you have better guidance on accelerated approval, you're prepared to produce additional product. But it sounds like you're currently not there yet in terms of manufacturing.

What's holding you back from this level of production? Is it just not technically feasible? Is the cost too high or are you just unsure of the chance for approval at this time point? Thank you.

Thanks, Chris. Of course, we don't have a guarantee of approval, all right? We'd be in a different situation in terms of ramping up commercial scale. What we have been focused on over the last couple of years is producing the subunits that go into the API production, okay?

So, we have the sufficient subunits to prepare for a commercial launch. This reduces the time frame from converting those subunits into a final product or API. So, as we get traction and as our assessment of the probability of success increase, we're going to pull the trigger to start preparing for that commercial scale.

But, to do that prematurely, and have drug product that is sitting on the shelf, it's costly. It's inefficient for the Company to do that.

So, I think we will be prepared if we need that drug supply, but we're not going to put additional resources behind it. We want to conserve as much capital as we can on the balance sheet until we know we need that drug supply.

Okay. Great. And then slightly soft ball question, here, how's progress coming in the EU? And then just could you comment on the Rest of World expectations and if potentially accelerated approval were to occur in the US, would you to be expecting to access Rest of World market? Thanks.

Chris, so -- thanks, Chris. So, Europe, we already gave an update earlier this year that we did have an early meeting. It was a nonbinding guidance meeting where they indicated that the current data set that we have today is unlikely to be sufficient for a conditional approval. However, it was a very productive collegial meeting.

They encouraged us to go back and talk to them as more data emerges, whether it's from our existing study or the new studies that are ongoing. So, we expect to continue that dialogue with the EMA. At this point, we have not indicated that we would be filing an EMA on the current data set.

So, we will continue to provide updates with that progress. If we were to obtain approval in the US by the FDA, we would look at those territories that could reference an approval in the US for potential commercial approval in those territories.

Again, it's premature to speculate on that but that's something we thought about. We plan for the possibility of that but our focus right now is working with the FDA on the chance to get this drug approved in the US and then we'll be ready to address where else we could go beyond that.

Got it. Thank you.

Simos Simeonidis with RBC Capital Markets.

Thanks for taking the questions. This is David in for Simos. I have a question. In addition to safety data, are you planning to collect any upper limb or pulmonary data from study on non-ambulatory boys?

Yes, you mean in the Study 204, the non-ambulatory? Yes. We would be collecting efficacy endpoints, some new tests, looking that are exploratory performance, upper limbs tests, et cetera. And we will be doing detailed pulmonary function on these boys.

I see. All right. Great. Thanks.

Debjit Chattopadhyay, Roth Capital Partners.

Chris, I was just wondering. I mean, has the rescoring of the dystrophin been completed and do you see any showstoppers with that data set?

Yes, Debjit, we've said on multiple times now, we're not going to be discussing any of the compilation and analysis status or updates. We are doing all of the data that the FDA requested and when we have that compiled, we'll bring that to the FDA and we will discuss it with them. Until then, we're not going to comment on any data analysis or compilation of that in the interim.

Fair enough. In terms of the enrollment of the PROMOVI study. In that tracking as far as expectations, can you update us on the number of patients in the two arms? Are you also taking biopsies from the control arm? Is that an issue in terms of enrolling patients there?

Yes, so Debjit, I'll just say we indicated we will not be providing updates on specific enrollment numbers for patients. Again, we've highlighted that we started dosing in two of the eteplirsen studies, our exon 53 study in Europe. Again, we've also indicated that we hope to have a potential data readout end of 2016.

That would enable -- that would require a full enrollment. We're closing out the 301 study by the end of 2015. So, that's all the guidance we're giving at this point. Ed, do you want to take the other questions?

Yes, and I think in regards to the questions, as far as the biopsies, recall that for the PROMOVI study, it is a non-exon-51 amenable group so we are not requiring biopsies for this group.

We are obviously doing the biopsies, two biopsies for the treated cohort. So, obviously what we've tried to do is to make this study as easy as possible for the non-treatment control group, just so that it is not too burdensome.

One last question on the eteplirsen and SRP in the US. Could you update us on what the progress is or what we do should expect going down now for 2015 and 2016?

You're referring to the interference that was in play in -- on the exon 51 eteplirsen and exon 53? Look, there is no particular updates to provide at this point.

We expect the first phase of the proceedings to play out towards the latter half of this year. And, until then, we have filed our arguments and it will play out accordingly over the next year. So, at this point, we would have nothing further to update on the interference.

Thank you so much, Chris.

Joseph Schwartz with Leerink Partners.

I was wondering. I guess I don't understand why another meeting with the FDA is required. So, can you talk about the areas that you feel you need to get more clarity on? I guess I don't understand why you just don't perform the work that the FDA requested in October and file in mid-2015. Thanks.

Thanks, Joe. I think it's a fair question. However, if you recall in our October guidance, they asked us to come back to them and we believe that is because they asked for additional data and they wanted to allow a discussion of any new data that would go into the NDA.

We want to make sure that the division and the reviewers have what they need to consider the potential approval of this drug. We want to make sure that NDA is complete enough for them to do an adequate review of the drug.

So, it's in our best interest to make sure there's alignment there. And, if there's any questions or clarifications that are needed in any of the additional data that we've compiled, whether that be the 168-week data, whether that be some of the new safety data, whether that be the natural history analysis, whether that be the rescore of the dystrophin-positive fiber, we want have an opportunity to discuss that with them.

I think if there was something to change in that and the FDA felt that they had enough and no meeting was required, you know, that might change it. But right now, they've requested a meeting dating back to our October guidance and we plan to fulfill their request.

Okay. Thanks for taking my question.

Ritu Baral with Cowen.

I just wanted to follow up on something that came up in an answer to Chris' question on Europe. What was the EMA most focused on when they basically decided that the data set wouldn't be adequate for them especially, in regards to trial design or dystrophin. Given they have, actually, approved Translarna before the US did, what are the key takeaways we should be taking from all of this?

This is Ed. That's a fair question. There really weren't any major concerns that were raised. It was really was coming down to this small data set and the fact that it was only on 12 patients and obviously, translation has a much larger data set in addition to their ongoing Phase III studies, so it really came down to the numbers of patients. That was where their concern was.

Was there any discussion about their perspective on dystrophin?

No. We really didn't have that discussion. Obviously, they were interested in our data set but they didn't really comment on the specificity of dystrophin as a biomarker.

Ritu, I would just add that we did share with them our current clinical program. We discussed with them the eteplirsen confirmatory study. There was a good exchange, a good opportunity to explain the trial design, the untreated cohort, our expectations and overall, we all left with the feeling that it was a really good exchange, that there was a good knowledge base in the reviewers that we spoke with. We were encouraged by it.

Again, we think that even if some of the ongoing data that were collected for the FDA may provide us another opportunity to go back to the EMA even before additional data is compiled from Study 301, let's say. So, again, we left encouraged. It's just that this moment, there's not much we can do with the current data set.

Got it. Thanks for taking the questions.

Robyn Karnauskas with Deutsche Bank.

This is Evan on for Robyn. Thank you for taking my question. Just a quick one in regards to the MRI data. Have you had issues getting access to this?

Has the FDA -- have they been -- had to intervene to get it from the independent parties? When you describe some of the important elements that the FDA would want, what are those? Thank you.

MRI data, I just want to clarify -- this -- while it was a recommendation of the FDA, they understood the limitation of capturing all the data we might want to see from the independent centers. So, we are getting as much data as we can. Again, it's unclear at this point what a treatment effect of an exon skipping drug will result in on MRI.

I think we've watched, like everybody else, the understanding of the disease progression on various MRI markers like stat fraction as an example, but we still don't understand what a treatment effect of exon skipping will have in interpreting MRI data. So, it's hard to speculate, at this point, what are those markers and endpoints that might show a signal or are going to have the most impact. Ed?

I also want to emphasize that the sites have been incredibly generous with their time in sharing data and helping us. So, we really have not had any problems with getting the data. I think what Chris has mentioned, it's really -- we're trying to understand what is the treatment effect on the MRI because this hasn't been done before.

Also, recall, we only have three patients with baseline, so it makes it challenging and this is, I think, an area that is certainly very interesting. It's very exploratory and we are following up in our Study 203 in the younger population, to really understand how to use the MRIs. So right now, honestly, we don't have enough information to really know what to expect.

Okay. Then my other question was, Chris, I believe you've described important elements of your package that the FDA might want at this upcoming meeting. What are those versus the things that are less important?

Well, so, the three areas, again, it's hard to know exactly what each member of the division is going to be focused on and looking for. But what we believe are going to be the important elements to discuss with them are the 168-week data, the dystrophin rescore, and the natural history analysis on 6-minute walk because it's the area that puts our 6-minute walk data into the appropriate context. So, those are the three areas that are going to largely be our focus for the second quarter discussion with the FDA prior to an NDA submission.

Again, the fourth biopsy, we will be preparing that. We would not have that likely in time for that FDA meeting and so we think that would only add to the data set. We think those three elements I just described would be sufficient to make sure there's alignment on what would go into the NDA, especially given they did not require the fourth biopsy data to be in the NDA.

Excellent. Thank you so much for taking my questions.

Heather Behanna with Wedbush Securities.

Just a quick question on the control arm for the confirmatory study for exon 51. If you could just talk about boys that are enrolled better in amenable to exon 45 and 53 and if they get moved on to the placebo-controlled study for those drugs on to a treatment arm, will you have to enroll more boys? Or how would that work, logistically?

That's a good question, Heather. I think obviously, we would not prohibit anyone from going into a treatment study from really, which was a non-treatment control arm. So, we are anticipating that.

And recall based on the timing, we will have some valuable data and we know that even as little as nine months of data can be very beneficial. So, we'll allow those patients to rollover.

There's certainly going to be a delay in Europe. That won't start until towards the end of the year.

So I think we should be able to get an adequate data set. And remember we are including many deletions and based on the natural history, the expectations is that if your age and baseline 6-minute walk test distance -- most of these deletions behave in a fairly similar fashion. So, we're fairly optimistic that we should have enough data to be able to make a comparison.

Heather, remember we use a mixed model repeated measures analysis. So, those data points, if we have four months or six months or eight months, as Ed suggests, can still be used in predicting the decline of that untreated cohort.

If they do end up enrolling in a placebo, it's possible we could get those measurements in that placebo arm. Again, we don't even know how many it will be from the 4553 in that untreated cohort. So, we'll ensure that the statistical analysis will be sound regardless of any of those scenarios.

Great. Thanks. And then just a quick question on manufacturing. If you do get the green light and do file the NDA, will it require another CMC meeting with FDA? Or, are you all set on that front and know how you need to execute?

Well, obviously, there is a quality section, CMC section in the NDA and so that's going to provide all the latest information that we believe they would need to provide an approval, including approval of our manufacturing in commercial drug product. So, that would be the expectation.

Again, the process that we've been using would be the same process we use for the commercial scale. So, we've had good reproducibility, multiple batches now. So, we're very confident that we have a quality drug product that would meet the specifications and we believe that upon approval, those specs would be established in the NDA and we'd be given approval for commercial sale.

Great. Thanks for taking the questions.

Brian Klein with Stifel.

Just one quick question. Do you plan to publicly present or report on the biopsy data prior to your NDA filing?

Again, we're not guiding on that at this point. I think the first priority is to bring any data that we believe gives the FDA confidence or understanding of our data set fully to enable the NDA.

It's hard to predict at this point the timing of all of the fourth biopsy data. And, how concordant that will be with the timing of the NDA submission. So, we'll have to determine what we have, where the discussions are with the FDA. And again, what we've said is that prior to any disclosure of data, we would want to make sure that there was alignment with the FDA that was appropriate to disclose new data if we were in the midst of discussions with the FDA around an NDA or the midst of an NDA submission and filing.

Okay. Is it fair to assume that at some point you plan to present pr report on that data? Even if it's not prior to an NDA, but that at some point, you would want to make that data public?

Yes. Of course. We've always been focused on communicating our data set and being transparent. I think this is a delicate time, in that we want to focus our energy on getting an acceptable NDA and working collaboratively with the FDA to do that in the most expeditious manner. So, of course, if we had data that we wanted to disclose, we would bring that to the FDA, discuss that and make sure that they were comfortable with our communication around any new data.

Great. Thank you.

Brian Skorney with Robert W. Baird.

This is Morgan on for Brian. I just had a quick question regarding the second quarter meeting. Just trying to get a little more color on the timing.

So Sandy mentioned that we would be able to get an update on the R&D spend on the first quarter call following the FDA meeting. Does that mean that we'd be able to potentially get an update there, too? I'm assuming that the meeting would possibly be in April. Is that right to think about?

Well, you know, it -- I think what we want to do is provide an update to the best that we can on the next earnings call, okay? It's hard to predict what information we would have at that point and at that moment.

We don't know if we're going to have the meeting by then or any communication at that point by then or any substantive feedback at that point. But, as we do, we give updates along the way. If we have more information to provide and more clarity on guidance for rest of year spend, we'll do so.

But look, if you look back last year, right, we had a couple revisions to guidance because of kind of changing landscape of our efforts and timing of things, and prospects for NDA and the timing of that NDA. We're in a similar situation now.

We don't want to over commit, over promise. But at the same time, we're trying to be very purposeful and transparent of our intent to have the information we need at some point in the second quarter. But at this point, we don't have clarity or are not providing any guidance or speculation about guidance around that FDA communication.

Okay. Great. Thanks.

Adam Walsh with Canaccord Genuity.

Just to follow-up on that one. So, Sandy had mentioned that the guidance for R&D, there was something about having more visibility in early May about, I believe, the FDA meeting. I just am curious.

Is the FDA meeting actually something you have on the calendar already? Or is this something that you are going to plan to ask for?

So it's not on the calendar, as we sit here today. We expect it to happen in the second quarter. If we are also stating that we anticipate a mid-year NDA, we obviously wouldn't cut that too close to the timing. So, you can expect that, that would have us enough time to at least process the final modules of the NDA with that FDA feedback and guidance.

So, again, that's the most clarity we can provide at this point and that's why we said second quarter. I think what Sandy was trying to convey, was that on our next earnings call, whatever new information can help us understand and elucidate our spend for the rest of the year, we'll provide that. We may not have all that we want and need at that point, but we'll try to share as much as we know at that point.

Thanks. That's helpful. And then just one follow-up. I know it's a very sensitive time around the FDA meeting and the upcoming filing. There was a question asked earlier around the fourth biopsy release.

Of all the things that the FDA has asked you for, the MRI, natural history, additional safety data, the rescoring of the dystrophin and so forth, are there any of those that you can tell us whether or not you'll be releasing information on? Or is what you said about the fourth biopsy, having to meet with FDA and get clarity and get comfortable with whether or not it would appropriate to disclose, does that apply to all of the things that the FDA has asked for? Thanks.

Yes. Thanks. It does apply to all the things the FDA has asked for. The reason, again, just backing up to the April guidance we provided last year, where the FDA outlined two pathways for accelerated approval. One based on an intermediate clinical endpoint such as the 6-minute walk and the other based on dystrophin as a surrogate that would reasonably be likely to predict clinical benefit.

All of these data sets may support any one of those pathways or either of those pathways. We think that the totality of the data is the most important thing. How does all of this fit together from the context of this disease and our drug effect.

So, looking at any one particular piece of data in a vacuum, probably won't tell the whole picture and that's why we're focused on compiling everything. That we can, discussing the most important elements with the FDA and then determining what's appropriate and potential disclosures prior to, let's say, an NDA briefing book would be, I'd say, to the latest that this would be out there. Again, that's why we are not providing any guidance of any of the data disclosures until we really sit down with FDA.

Great. Thank you.

Yaron Werber with Citi.

This is Kumar Venkatesaran on for Yaron. Thanks for taking my questions. For the fourth biopsy, which muscle are you guys taking this biopsy from and how is this different from the earlier biopsies? Also, when do you plan to start the polio trials in the US?

Sure. It will be from the deltoid muscle, which was the last muscle group that we obtained and we are also -- obviously we'll be using controls for this. Again, the whole focus is, I think what we've tried to do with the fourth biopsy, we had a long-standing, lengthy conversation with the FDA to make sure that they're comfortable with the whole processing the muscle and with the outcome measures.

We want to make sure that this precious tissue that the boys have donated, that it's used for the best, make sure the FDA gets the answers that they want. So I think we're certainly making progress on that and this is proceeding as planned.

Let me just add. So, one of the areas that we're particularly interested in on the fourth biopsy is getting a good Western Blots with the appropriate antibody DISC-1 which has been the standard antibody. As we've discussed previously, of the original Western blots were done with a less sensitive antibody that's not typically used, DISC-1 of 6, it is used for immunofluorescence, not typically used for Western blots.

And so that's why we are looking to get untreated control data so we can compare those Westerns with untreated patients of Westerns, since we don't have those baselines. Kumar, I'm sorry, you had a second question. What was the second question?

Just the 405 Study, what are the plans for that in the US?

That's going to be rolled into what we described as our Study 804. This was the master protocol where we're doing a placebo-controlled study with both exon 45 and 53.

As Ed described, we already have a studied dosing, exon 53, in Europe. But in the US, we expect 53 and 45 to be enrolled in that Study 804.

Okay. Great. Thank you so much.

Steve Brozak with WBB Securities.

Just one quick question. You made a really good point in terms of inclusion/exclusion criterion. But the question rolls around what do you expect to happen from biological functional standpoints when the therapy is commercially available for boys that are, obviously, younger, with better 6-minute walk times.

How do you think FDA is going to interpret that? Because obviously, they've got to look at the whole picture and I would want to get your thoughts on what do you think they will be looking at as far as that?

Steve, one of the reasons that we have rolled out three new eteplirsen studies was to show the safety of this drug in the broadest population possible from young patients, as young as 4 years of age to an advanced population as old as 21 years of age across these three studies. We are actually doing biopsies and will have a change from baseline on dystrophin in the younger patient population.

So, I think our intent to get as much information across a broad swath of the DMD population will give the FDA what they need to enable the broadest label possible. Now, in terms of clinicians, what we expect and what we've heard feedback on is -- and we agree, that of course, the earlier you can initiate treatment, the better the potential outcomes might be over the long term. While they still have good muscle preserved, they are not an advanced stage of the disease, that the earlier you start with preserved muscle to restore dystrophin, that you might really change the course and trajectory of this disease in a pretty profound way.

What we did in the clinical trial, to show a treatment effect in a small population, the only way that we could do that in a small population over a relatively short period of time is to really look for those patients that were on a decline, right? That we expect it to decline so that a treatment effect should show a separation, as we showed.

So I think that is where I think it would be wrong to assume that the benefit that would be conferred in this Phase IIb study is the best we could hope for. I think we would expect that the outcomes could be much more favorable if you start much earlier in the disease progression and then over the long term. Ed, do you want to comment?

I think that was the reason why the FDA was so interested in having this study of broad population. Because that are clearly aware that there would be a demand in the younger and in the older boys and to have some understanding of the safety and the potential outcomes.

Obviously, until we do the studies, we will not know if we have a better outcome in the younger boys. We hypothesized that, that's the case because they have more muscle and they are in a healthier position. But, that's why we are doing the study and we'll know that in the not too distant future.

Great. Thank you, gentleman.

The final question from Tim Lugo with William Blair.

This is (inaudible) Raj on for Tim. Just two quick ones. Given your remarks on EMA meeting, potentially a larger sample size, what are the plans for re-engaging them with the revised data set that's being submitted to the FDA? And then when can we expect an update on the non-DMD pipeline and are there still plans for potential partnering opportunities? Thanks.

As I mentioned earlier, I think as we compile these new data for the FDA, first priority is to discuss it with the FDA. The strengths and utility of that data will help guide us to win the right time to reengage EMA.

Look, we've got people who are engaging with European opinion leaders. We have the study in Europe. We expect the Study 804 to ultimately rollout to European sites.

So, we are very in touch with the European DMD clinician and advocacy community. So, as we generate these new data, we want to make sure that we find the appropriate time to reengage them for potential conditional approval. Until we get through that step of compiling this data, I think we're not going to guide on when and the prospects for that next meeting to be.

In terms of the other research pipeline, again, it's highlighted in the prepared remarks that we have two research facilities. We're continuing to do experiments. We've made a tremendous amount of progress with our chemistry and new applications over the last year to 18 months and we've highlighted some of those more promising programs.

We've got a lot more that we've not disclosed. This year, we're going to be focusing on continuing to advance the most promising programs to identify lead candidates that we can start potential preclinical development. Until we know what those most promising programs are and the timelines for that, that will come in future disclosures.

Again, we think we have a very promising technology platform that has a best-in-class chemistry in the RNA therapeutics space, that has a lot of potential utility across a variety of therapeutic areas. And we're absolutely open and to engage partners to advance this technology across a number of therapeutic areas. Of course, a lot of partners want something more definitive, further along, clearly differentiated from any pipeline in those particular disease areas.

I think the more we accumulate and the more we show that we have a technology that really is differentiated, and again, we think we've done that to a degree in antivirals and even in our DMD program. You know, we expect that to enable partnerships down the road. So, again, we're continuing to be open to partnerships across pharma and biotech on our technology.

Thanks, guys. Congrats on the progress.

We have come to the end of our question-and-answer session. I'd like to turn the call back to Chris Garabedian for closing remarks.

Thank you, operator. Again, just want to highlight that we've achieved a tremendous amount of progress in executing across our clinical program. We're moving very rapidly towards fulfilling the FDA requirements and are excited about meeting with them in the second quarter to enable an NDA submission by midyear. This does remain our number one priority.

We do know that and are acutely aware of the urgency of the Duchenne patients and families and are working tirelessly to meet the FDA's guidance for that successful NDA. We appreciate the many families, patient advocacy groups and healthcare providers for their support and continued efforts throughout this process and appreciate all of you for your interest in Sarepta and thank you very much.

Thank you, ladies and gentlemen. This concludes today's conference. Thank you for participating. You may now disconnect.