Sarepta Therapeutics Inc. (SRPT) CEO Discusses Regulatory Update Call (Transcript)

Jul.24.13 | About: Sarepta Therapeutics, (SRPT)

Sarepta Therapeutics Inc. (NASDAQ:SRPT)

Regulatory Update Call

July 24, 2013 08:00 ET

Executives

Erin Cox - Investor Relations

Chris Garabedian - President and Chief Executive Officer

Sandy Mahatme - Chief Financial Officer

Analysts

Brian Skorney - Robert Baird

Robyn Karnauskas - Deutsche Bank

Bill Tanner - Lazard Capital Markets

Ritu Baral - Canaccord

Chad Messer - Needham & Company

Lisa Bayko - JMP Securities

Tim Lugo - William Blair

Yaron Werber - Citi

Operator

Welcome to the Sarepta Therapeutics Regulatory Update Call. My name is Ivett, 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 Erin Cox. Erin Cox, you may begin.

Erin Cox - Investor Relations

Thank you, Ivett, and thank you for joining today’s call. Earlier today, we issued a press release providing the regulatory update for eteplirsen, our lead therapeutic drug for the treatment of Duchenne muscular dystrophy. The press release is available on the News and Events section of the Investor Relations portion of our website at www.sarepta.com. Joining me on the call today is Chris Garabedian, Sarepta’s President and Chief Executive Officer; and Sandy Mahatme, our Chief Financial 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, and the potential efficacy, safety, and clinical results from ongoing or future studies involving product candidate, the timing of an NDA submission for eteplirsen in the treatment of DMD; the potential filing and acceptance of an NDA for eteplirsen; the information necessary for the Agency to make regulatory determinations and our ability to provide such information; the potential regulatory approval of eteplirsen including under Subpart H Accelerated Approval; our ability to satisfy CMC-related requirements; our ability to manufacture candidates and provide the certain amounts of clinical and commercial supply; our ability to protect our intellectual property right, and our future financial performance including revenues, expenses, financing, and the sufficiency of cash reserves. These forward-looking statements, involves risks and uncertainties any of which are beyond Sarepta’s control. 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 official corporate documents filed with the Securities and Exchange Commission.

With that, let me turn the call over to Chris Garabedian, Sarepta’s President and CEO. Chris?

Chris Garabedian - President and Chief Executive Officer

Thank you, Erin. I am very pleased to provide you an update on our regulatory activities related to eteplirsen, our drug for the treatment of Duchenne muscular dystrophy, along with an update on additional activities related to our eteplirsen and DMD development programs.

Yesterday, we met with the FDA’s Division of Neurology Products as a follow-up to our End-of-Phase IIb Clinical Meeting that took place earlier this year. This meeting took place as a follow-up to the Agency’s review of the two summary documents that we provided them in May, one of which described dystrophin as a surrogate marker for the treatment of DMD, while the other provided a summary of all of our clinical outcomes from the trial.

I am excited to communicate that based on the feedback from the FDA in pre-meeting comments and in the meeting we plan to submit an NDA with data from the ongoing Phase IIb dataset in the first half of 2014. While the Agency would not provide any guarantee or assurance that an NDA submission would be acceptable for filing, they indicated that they are “open to considering an NDA based on this data for filing” and further indicated that they are not prepared to declare dystrophin as an acceptable surrogate marker prior to an NDA filing and stated that the question of “whether the production of a truncated, but potentially functional dystrophin is reasonably likely to predict clinical benefit will be a review issue.”

Furthermore, they requested additional information on the dystrophin methodology and potential verifications of the dystrophin quantification data that was provided to them in previous briefing and summary documents. We had a productive discussion in yesterday’s meeting on this and what specific information would be needed prior to an NDA submission, and we expect the details will be further clarified in meeting minutes and in further discussion with the FDA in the coming months. However, based on our discussion yesterday with the Agency, we are confident that any additional information that would need to be compiled and included in an NDA submission would still allow us to keep our timeline of submitting an application in the first half of next year. It is important to note that our discussions with the FDA and the feasibility of an NDA filing has centered largely on our clinical and preclinical datasets, and if the biochemical outcomes, clinical outcomes and safety database are sufficient for an NDA filing.

However, there are other sections that go into an NDA including Chemistry, Manufacturing and Controls or CMC section. And we will be meeting with the FDA to further discuss the NDA requirements as it relates to CMC activities and will play a role in the FDA’s ultimate decision whether or not to file. Although we will need to gain clarity from the FDA, we believe we can meet the anticipated CMC requirements in time for a submission in the first half of 2014.

With respect to our manufacturing scale up efforts, I am pleased to report that we successfully manufacture the test batch that would be described as a reduction to practice batch that is a scale between small scale and mid-scale production where we can learn about any operational problems that might occur with our process at a larger scale and allows us to deconstruct the steps of the process and make any tweaks that might be required. I am very pleased to report that our reduction to practice batch provided products comparable to that currently in the field with operational yields similar to those observed with our small scale process. This gives us confidence as we proceed with our mid-scale production runs that we are on track to generate the drug supply needed to initiate our confirmatory study in the first quarter of next year.

Furthermore, we have made significant progress with our various contract manufacturers within our supply chain and have a clear idea of our timeline as it relates to drug supply in the event of a commercial approval in 2014. While there are no guarantees, if we use the yield assumption from our reduction to practice run and do not encounter problems with our mid-scale production runs and eventual large scale production runs. Based on the 30 milligram per kilogram per week approved dose of eteplirsen, we can have drug supply for more than half to all of the potential market demand for eteplirsen in the U.S. by the fourth quarter of 2014. Of course, even if we are able to increase product supply, it is not a guarantee that we will receive FDA approval or that other factors won’t influence our ability to make drug available to patients such as distribution access and reimbursement.

We continue to have dialogue with the FDA around a potential confirmatory study design and we’ll continue to finalize the protocol for this study in the coming months for initiation of dosing in the first quarter of next year. We know that the six minute walk test will be a primary end point in the study and therefore we will be enrolling an ambulatory patient population. We are planning on enrolling approximately 60 patients on the eteplirsen treatment arm. We also expect to include a similar number of patients in an untreated control arm that would include patients that are amenable to a skip of exon’s 45, 53, 50 and 44. We have not determined if a placebo arm will be required and we will be having subsequent discussion with the FDA related to finalizing a confirmatory study design.

One of the key advantages of including patients in a control arm that are amenable to other exon skipping drugs is that we can plan to rollover these patients on the study drug for their amenable exons as soon as we have an open IND and have drug available for dosing which could come as early as the one year follow-up is completed for some or all of these amenable genotypes. With respect to our follow-on exon skipping drugs that are in preclinical development, we have had pre-IND meeting for an exon-45 skipping drug and have initiated preclinical animal testing with that compound. We have a pre-IND meeting planned for an exon-53 skipping candidate later this year and plan to start preclinical animal testing later this year.

We have identified a lead sequence for exon-50 and are conducting lead sequence selection for exon-44 and we’ll be planning to speak to the FDA about the incremental requirements for an IND filing for these compounds later this year. We are still on target to submit an IND for at least one of these drugs by mid-2014 and two or more by the end of 2014. As we previously reported, we continue to follow patients on eteplirsen treatment in our Phase IIb extension study. And we’ve recently reported six minute walk test data through week 84 with demonstrated stability in the 6-minute walk test in all patients in our Modified Intent-to-Treat analysis. We will be presenting an updated 96-week dataset at the World Muscle Society Meeting to take place in Pacific Grove, California in October of this year.

Let me end my prepared comments with my appreciation for the collaboration and involvement that we have experienced on this program from the FDA and how they continue to help with our DMD program by providing clear feedback and direction in their communication. As I stated before, we are very pleased with the level of responsiveness and engagement from the Division of Neurology Products and from the leadership in feeder, as we work with them to determine the most expeditious path forward toward the product approval.

I would also like to acknowledge the significant effort that we have witnessed from the parents of DMD boys and other advocates within the DMD community who have been very active in engaging the FDA directly to highlight the urgency of getting effective treatments to the patients who need them. We continue to be impressed with the DMD community’s understanding of drug development, the role of the FDA, and the importance of highlighting the risk benefit trade-off when considering approval of new therapies for diseases devastating, irreversible, and fatal as Duchenne, and we share their sense of urgency in our efforts to make eteplirsen available for the patients who can benefit.

In summary, we are very encouraged by the FDA feedback and the Sarepta organization will be working hard in preparing for the NDA submission to take place in the first half of 2014. We will have continued dialog with the FDA over the next six months to ensure that all of the information that comprised the sections of our NDA submission will be satisfactory for their filing decision. Of course, the FDA has provided no guarantees or assurances that an FDA submission will be accepted for filings, but we are encouraged that they are “opened to considering an NDA based on these data for filing to clarify these data referred to be eteplirsen data we provided them in briefing and summary documents. And we intend to work with the FDA to submit an NDA that addresses all of their requests.

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

Question-and-Answer Session

Operator

Thank you. We will now begin the question-and-answer session. (Operator Instructions) Our first question comes from Brian Skorney from Robert Baird. Please go ahead.

Brian Skorney - Robert Baird

Hey, good morning guys. Congrats on the update from the FDA. It sounds like it was a very productive meeting. I think people are really going to be focused on kind of how the agency really framed up to the comments around whether or not they would declare dystrophin as an acceptable surrogate endpoint, and what exactly if they were to accept the NDA and potentially approve it. What sort of approval we would be looking at? What sort of endpoints they are primarily focused on? So, I mean, I guess my question is in your dialog I mean, would this be an accelerated approval and think there has been some speculation given the clinical data and some temples comments at the PPMD meeting around whether or not dystrophin would be acceptable could potentially actually just be a full approval based on the clinical data? I guess any sort of color you could give on whether the FDA is primarily looking at dystrophin as the endpoint in the study and would approve on dystrophin with the clinical data supportive of that or the focus is really on the clinical data with dystrophin as support to the 6-minute walk?

Chris Garabedian

Yes, Brian, thanks for that question. So, a lot of our discussion with the FDA has centered around dystrophin, because we believe that dystrophin is a viable surrogate marker for the treatment of Duchenne. And while it is important for eteplirsen, we believe it is as important if not more important to the broader DMD program as we bring forth follow on exon-skipping targets for Duchenne and eventually would pursue a class approval, so that every Duchenne boy that could benefit from our technology with exon-skipping could have drug available to them. So, we are committed to establishing dystrophin as a surrogate and we understand that the FDA needs to be thorough before they declare a new surrogate marker for a disease is acceptable. And so we have focused a lot of our attention in really understanding what is it required and they have been very clear that the data to-date as I stated in the press release and in my comments, they cannot make a decision prior to an NDA submission and filing, but it would be a review issue. And so we are prepared for that. And we believe we can bring the level of information needed to establish dystrophin as the surrogate. However, we also are aware and understand the flexibility that the FDA has at their discretion to apply product approvals outside of accelerated approval. They have granted full approvals to many drugs on limited datasets on uncontrolled studies, on single trials, and this has been well-documented, outlined most notably in a white paper put out by the National Organization of Rare Disease authored by Frank Sasinowski. It really shows the flexibility that the FDA has in granting full approval.

So, the other thing that the FDA communicated to us is that an NDA is an NDA. We don’t submit an NDA under accelerated approval. We submit an NDA and the FDA has at their discretion how they interpret the dataset and what type of approval they will consider given that dataset. So, we understand the FDA has a lot of flexibility. We are committed to establishing dystrophin as the surrogate marker. We will work with the FDA to determine the best way to achieve that, but we are focused on submitting an NDA in the first half of 2014. We have a very rich clinical outcomes dataset, we believe based on the 6-minute walk benefit now through week 84, and we continue to follow these patients. And based on the safety profile and given the risk benefit in Duchenne. So, we are just very pleased with all of the data and what that could mean for a potential approval, but it’s too early to speculate how the FDA may consider our NDA submission and if they file what type of approval they might consider.

Brian Skorney - Robert Baird

Thanks Chris. That’s helpful.

Operator

Our next question comes from Robyn Karnauskas with Deutsche Bank. Please go ahead.

Robyn Karnauskas - Deutsche Bank

Hi, guys. Congratulations and thanks for taking my question. I guess two quick questions. I said, first of all, how much of the commentary in the press release is standard commentary from the FDA about how there is no guarantee that the filing will be accepted? And in your opinion at the meeting, do you feel like there is anything that maybe skeptical that they wouldn’t even accept the filing? And then second from the financial point of view, I know you have an ATM, you are raising money that way, do you have enough money to support the manufacturing that you are going to do to aggressively support half the market to all the market in the United States? And maybe you can give us some color on how many patients that really – how confident you are now and how many patients that would really translate to?

Chris Garabedian

Thanks, Robyn. So, regarding your first question about the comments that I provided in the press release in my comments, my verbal comment, so the process with these FDA meetings, it is fairly standard and that is the sponsor poses questions and have topics of interest for a meeting, they request a meeting, submit a briefing document that the division and agency reviews. And then they will typically provide what are described as pre-meeting comments. Pre-meeting comments are provided very proximate to the actual meeting, sometimes hours before, sometimes a day before, but it’s really intended to use as a discussion point and it provides some level of clarity of the FDA’s position as you go into the meeting and have a fuller discussions of those topics and questions. Generally, those pre-meeting comments are without the benefit of an exchange with the sponsor. So, sometimes, they can be more conservative or boiler plate or standard language as you’re describing. And again we announced what we did this morning because we were encouraged enough by those pre-meeting comments and what ensued in the meeting yesterday to be confident that we could submit an NDA that has a reasonable likelihood, no guarantee of acceptance from filing by the agency.

And we will continue to work with the agency over the coming months to ensure that or increase the probability that it would be accepted for filing. But that’s all I’m prepared to say now. I would not say and would not want to characterize our communications with the FDA as some other subtext of likely filing or unlikely filing. Again, we are encouraged by our dialogue with them. We are preparing to submit an NDA because we believe it has a good likelihood that the FDA will accept it for filing. They told us what I have stated in the press release which is there open to considering an NDA filing based on the data we shared to them to-date. But again we were not expecting them nor have I seen them provide any guarantees or assurances prior to any NDA submission that I don’t believe there is any precedent for that for them to make that kind of decoration before a sponsor has actually submitted an NDA application. But again we are encouraged by the communication and the clarity, a feedback and direction that we are getting from the FDA and are confident based on that to prepare for NDA submission.

Regarding the product supply, again a lot of the guidance we provided earlier this year that we intended to spend for 2013 was with the expectation of accelerated approval or preparing for NDA submission, a potential commercial launch earlier and so that included some of the startup efforts for large scale manufacturing, which we would need obviously to provide for the full commercial demand. That is proceeding nicely. Again we don’t feel cash constrained, the last cash balance that we communicated was in conjunction with the ATM announcement, but we had a $165 million on the balance sheet. And so again we are going to – we have the ATM in place for up to $125 million and so we are very comfortable with our cash position and our options moving forward. But at this time we are not going to comment on if how when and how much, but again we have enough cash to continue to proceed and to generate a lot of products supply that would be used for confirmatory study and potential commercial launch. But we haven’t guided nor are we prepared to guide on exactly what that investment is going to be to satisfy the full commercial demand for eteplirsen.

But again the efforts that we have on manufacturing are proceeding nicely and the contract manufacturers we are using and the expected supply that we would able to have right now, we are feeling very encouraged and confident. In terms of the number of patients that is guiding our view. If you look at the general consensus around epidemiology and incidence and prevalence of DMD, we estimate there are between 1,800 and 2,000 patients that would be amendable to eteplirsen, amendable to an exon-51 skipping drug.

So, when I say half to all of those patients by the end of 2014, this takes into account those numbers of patients, but also what we would expect in terms of uptake in the marketplace. We have used the very aggressive uptake that was witnessed by Kalydeco for cystic fibrosis, another genetic-based target in which a drug was available and these are estimates I don’t have the exact figures. But I believe they were able to achieve upwards of 80% or more of the amendable patient population in the first year after commercial approval. And again we’re talking at the U.S. market specifically. So, with that type of the adoption curve even with kind of warehousing a patient that would be just waiting for product supply that’s where we’re getting those figures and the confidence that we could satisfy half to full market demand. And again this is without even the consideration of the potential of another product that might be competing for those patients. So, this is assuming no competition and if there was competition obviously then we would even be more comfortable in satisfying the commercial demand. But at this point that’s all we are comfortable guiding based on what I have just described and what’s in the comment.

Robyn Karnauskas - Deutsche Bank

And just to make sure I understand what you’re seeing clearly is this just because of the delay in the filing is originally I know that you would be capacity constraint and is this due to just intermediate scale or are you also seeing full scale on line by the end. And the question I asked initially on the ATM have you drawn down anything from the ATM so far?

Chris Garabedian

Yeah. We’re not going comment on the ATM and if and whether we’ve drawn down on the ATM. Regarding the large scale, mid-scale. Yes, this would assume that we have large scale production online by the end of 2014. And regarding any limitations beyond that point, it’s really time dependent and not resource or technical challenge dependent. There is always risks in scale up when you’re doing it for the first time, so refer to our SEC filings for the risk factor associated with manufacturing. But generally speaking, this just takes time, we have sub-units that go into API production. API production takes time then we need to at least get some initial stability on those vials and those validation and quality control before drug release. So, this is just more time dependent then resource or technical challenge dependent in terms of getting more product supply ready for the market.

Robyn Karnauskas - Deutsche Bank

Great, thank you so much.

Chris Garabedian

Alright.

Operator

Our next question comes from Bill Tanner from Lazard Capital Markets. Please go ahead.

Bill Tanner - Lazard Capital Markets

Thanks for taking the questions. Chris a couple for you, as I remember at the end of the – when you had end of Phase II meeting, it seem that there were some questions that the FDA had about functionality of the dystrophin those being produced. And I think you made comments at that point in time that they wanted to know is it going to the right places in the cells, forming complex with be appropriate molecule. So, based on your prepared remarks it sounds like there are perhaps still some lingering questions. I guess I’m wondering what data were actually provided to the FDA over the course of last few months and what is still needed and is it something that you’re going able to demonstrate or convince the FDA that it is functional based on biochemical assay versus actually having to show that there is a clinical benefit and I have a follow-up please?

Chris Garabedian

Yeah. So, Bill the – first I would just make a general comment. This is an evolving process, right. If I would look back to our earlier discussions with the division and with the agency regarding dystrophin, I think both the company had not done the full review and assessment from the literature and full understanding of everything that was at our disposal to make the strongest argument. And therefore I think the FDA didn’t have at their disposal by everything they needed to become experts in dystrophin. We have seen this evolve what we believe in a very positive manner in terms of an increased understanding by the division in the agency dystrophin, the different assays that are used, the different ways to quantify it our arguments for why we believe is a functional dystrophin, our arguments for why the immunofluorescence analysis is very meaningful in terms of conferring a lot of information about the localization of the dystrophin, the intensity how it restores other glycoproteins that make up the dystroglycan complex. So, again, we feel that this has evolved in a positive direction and we understand that the FDA would always love more understanding, more clarity. This is the big decision for them. We understand that establishing a new surrogate for a disease for the first time. And so we are working with them. We will be continuing to work with them over the coming months to determine what additional information is needed to increase their knowledge and understanding of dystrophin as a surrogate. So, this is just an ever evolving process, and we will continue to provide the more data. We do believe that the clinical outcomes also color the thinking around our dystrophin analysis.

And that as we continue to follow these patients and they continue to perform well in terms of stabilization on 6-minute walk, it becomes harder and harder to dispute the treatment effect that our technology is having and the technology is expressly designed to create dystrophin. And so these links should be made clear and clear as the clinical outcomes continue for us as we provided currently through week 84. So, again, the FDA does not typically provide answers a priority before there is an NDA submission. Making a decision on filing is not going to be made until there is an NDA that’s been submitted. If they decide to file a decision on approval, it’s not going to be until they do their full review. This is not unique to Sarepta or eteplirsen or DMD. This is standard practice by the FDA. And we are doing everything we can to be transparent on the process and what we are providing them and the dialog that we are having with them, but again we never expected the FDA to provide any guarantees or assurances on filing, on approval, on how they might consider approving this drug. And again that’s all were prepared to guide at this point.

Bill Tanner - Lazard Capital Markets

Sure. It makes sense. And then just one last question and there was something in your press release about the FDA wanting to better understand the methodology and verification of dystrophin quantification, I understand that obviously in the field there is really no uniform or consensus opinion as to how it should be measured? Is this something that’s in your viewpoint would be a little bit more on the more trivial side of providing the evidence of the FDA or convincing them as to the fidelity of your measurements or how it’s being actually measured? I guess nothing is planned trivial, but…

Chris Garabedian

Yes, I would. So, I don’t think I would characterize anything as trivial when we are dealing with FDA request. Obviously, there is a reason for anything that they will request and ask for, but I would say, it’s supportive information that they are seeking. And again, this is a discussion and a negotiation and they have shown a lot of flexibility and willingness to understand how we have approached dystrophin our arguments around the different ways to assess it via the various assays, the different ways to determine quantification of the dystrophin. And again, we believe all of the information are seeking and potential requests are manageable and can be provided as part of an NDA filing. And we will be hammering out the details. Please understand the meeting took place yesterday, approximately 12 hours ago or a little bit more than that. So, I think we are trying to be transparent. We had enough information to feel confident that we would be prepared to submit an NDA in the first half of 2014, but obviously we don’t even have the meeting minutes from yesterday’s meeting and there will be continued dialog and exchange about what additional information would they like to see us include in an NDA submission. So, again stay tuned as we have more clarity and get more information about that we will try to be transparent about that to the market.

Bill Tanner - Lazard Capital Markets

Okay. Thanks Chris.

Chris Garabedian

Thanks.

Operator

Our next question comes from Ritu Baral from Canaccord. Please go ahead.

Ritu Baral - Canaccord

Hi, guys. Thanks for taking the question. How does the ambiguity around FDA’s view of dystrophin and Subpart H impact the confirmatory trial design? You had mentioned that the trial be focused on 6-minute walk, but how could it impacted otherwise? And can the FDA require a confirmatory trial outside of the Subpart H path?

Chris Garabedian

So, I am just trying to understand the question, Ritu. So, I think the confirmatory study we are planning to move forward, because we believe it’s important to have supportive data on both the dystrophin and 6-minute walk to complement our Phase IIb 12 patient study and the previous experience with the eteplirsen from the dose ranging and previous UK studies. Obviously, the discussion around a confirmatory study is in the backdrop of our pursuits of an NDA submission. Obviously, that was made clear to the agency and division in yesterday’s meeting based on their pre-meeting comments and the dialog and discussion that ensued yesterday. So, obviously any discussion around the confirmatory study has had that as the possibility. And from yesterday’s meeting in this point on will be with the backdrop of an NDA submission obviously without any guarantee that the product will be approved, but is coloring obviously that the dialog and discussion around the issues with the confirmatory study and whether or not a placebo arm is feasible and what it would mean if the product were to gain an approval of while the study was underway. So, those are part of the dialog in discussion. So, your question around could a confirmatory study be required outside of accelerated approval, I think what you are asking is that if the agency decided to approve our drug under a full approval outside of the context of dystrophin as a surrogate under Subpart H, could they still require a confirmatory study?

Ritu Baral - Canaccord

Yes.

Chris Garabedian

My understanding is that a full approval would not require a confirmatory study, but we are proceeding with that confirmatory study, because we believe it’s important for not only eteplirsen conformation, but for the broader DMD program as we established the utility of exon-skipping and how it may inform the rare exons and the follow-on exons, where we may not be able to power a clinical study, because of the finding patients for such a study. So, again, we have always said it’s an important study for us regardless of the demands from the FDA, but again, we are having dialog with the FDA with the presumption that we Sarepta will pursue this confirmatory study even in the event that we get a full approval with the eteplirsen in 2014.

Ritu Baral - Canaccord

Got it. And any clarify as far as when we might know about or required placebo arm for this trial.

Chris Garabedian

I think we would hope to hammer that out in the next several months, but obviously we want to have a final protocol at some point in the fourth quarter. So, we can submit the IRBs and be ready for the dosing and the screening and the dosing to start in the first quarter of next year. So, again, over the next several months, we hope to probably cover, but once we do, Ritu, I’ll be communicating that once we have something more definitive.

Ritu Baral - Canaccord

Got it. And very quick follow-up, which is actually a follow-up to Bill’s question on the methodologies for quantification, verification, what at least are the sort of current controversies and focus points in the DMD landscape around these issues, is it sort of sensitivity of assays or quantification antibodies, what are the current focus points in the community?

Chris Garabedian

Gosh, I’d say it depends on your ask and I think there is a lot of different opinions when you are entering into kind of a new area by new, I mean that what is the best and most validated method, which has not been clear and doesn’t have full consensus. And again, we have argued that the path we have chosen is the right one. And again, we believe we have made a compelling case for this. And that the FDA is at least seemingly understands our point of view on this. But I’d say in terms of verification, it is that the quantification and the values that are derived from these analyses and including our analyses is meaningful. And that it is something that can be interpreted as something that is reasonably predicting clinical benefit, I mean that’s what we are pursuing as a surrogate marker that dystrophin and the levels we are showing and the way we have captured it would reasonably predict clinical benefit. And so I think the more robust, our clinical outcomes, the more that we can look at the dystrophin analysis through the more favorable ends that this is correlated and should be validated. So, I think it’s mainly on quantification and understanding how it’s been quantified and what the meaningfulness of that quantification is. I’d say generally speaking, that’s where I think the field would like more clarity.

Ritu Baral - Canaccord

Great, thanks for taking the questions.

Operator

Our next question comes from Chad Messer from Needham & Company. Please go ahead.

Chad Messer - Needham & Company

Hi, thanks for taking my question and congratulations on what that sounds like was a productive conversation with the FDA. If I remember back from the last meeting in March, one thing you talked about when you are describing some of those conversations was the FDA allowing sort of early safety data from this next study that’s going to start in 1Q to sort of bolster or supplement the safety package of your submission? Can you just describe a little bit more that you have gotten any more clarify on exactly how that would work getting safety data out of an ongoing study?

Chris Garabedian

Yes. Chad, the guidance that we provided previously is still our guidance based on the FDA feedback and communication, and that is that the safety was we believe clearly addressed in the previous minutes in our previous communication. And I’ll just repeat what they communicated to us previously and this has not changed. It is that if the FDA filed the NDA, in other words, after we submit an NDA and after the FDA files that NDA, it could be supplemented I refer you back to our press release, where we give the actual quote, but it could be supplemented with the early experience from our confirmatory study. So, as we start dosing in the first quarter you can envision that if we submitted an NDA in the first half of 2014, we would have patients who are exposed to eteplirsen at a dose that we would be seeking a registration approval, and we could submit any of that safety data to the agency to help them make their determination of approval of the drug. Again, that was our previous guidance and that remains the case today.

Chad Messer - Needham & Company

Okay, thank you.

Chris Garabedian

Thanks Chad.

Operator

Our next question comes from Lisa Bayko from JMP Securities. Please go ahead.

Lisa Bayko - JMP Securities

Hi, thanks for taking the question. Congratulations on the news, certainly very exciting. As one point of flexibility the FDA has dosed, I mean might they go with a dose other than 30 mgs and what doses will you be considering for the Phase III?

Chris Garabedian

Yes, we believe that our dataset to-date strongly supports 30 mg/kg as the appropriate dose. We continue to follow boys at a dose of 50 mg/kg because we believe it is good supportive safety data for potential dose escalation if physicians aren’t seeing a clinical response eventually but ultimately the biochemical data and the dystrophin analysis suggest that 30 mg/kg is as good as 50 mg/kg in fact numerically it was better at 48 weeks and clinically now that we have followed these patients both that were early treatment and on the placebo is suggestive that the stabilization we are seeing is as good in the 30 mg/kg group as the 50 mg/kg and that includes the placebo crossover 30 mg versus 50 mg. So again we feel strongly that there is strong evidence that 30 mg/kg is as good as higher dose and we wouldn’t want to unnecessarily expose these boys, pediatric population to a higher dose that is necessary.

Obviously the pursuit of that dose would be what we choose for our confirmatory study and in terms of approval on the data package that we would submit as part of an NDA that would be a review issue obviously and our arguments would be stated in the NDA and the FDA was just as they have at their discussion how they might consider approval of the drug under accelerated approval or a full approval scenario they could have commentary on the dose that would be approved. But again our case would be made for 30 mg/kg and again that’s how we can provide in terms of guidance at this point.

Operator

Our next question comes from Tim Lugo from William Blair. Please go ahead.

Tim Lugo - William Blair

Thanks for taking the question and congratulations on this productive meeting. Did the agency give you any feedback on how comfortable they are with the current state of available natural history data in these patients and is that perhaps the reason for an inclusion of a control arm in the confirmatory study?

Chris Garabedian

Yes, so Tim that’s a great question and it was part of our dialog yesterday as it related to our confirmatory study and I would suggest describe it as we will continue to have discussions with the division in the agency around our confirmatory design. But we did highlight the fact that there are recent publications and an increased understanding of natural history and we are probably sitting at a time point where there is more published natural history on Duchenne than we’ve ever seen in terms of robustness of populations, in terms of subset analysis, in terms of really understanding the course of this disease particularly as it relates to 6-minute walk test and they expect to decline by age, there is more emerging data on genotype and really showing conformity across many of the common genotypes that there is more homogeneity across these genotypes than heterogeneity.

So we highlighted this and just to speak to some we had the – one of the best natural history studies with longitudinal data going out to two years out of the Italy group Elena Mazzone and Eugenio Mercuri, we have Craig McDonald who has presented recently on new analysis on 6-minute walk that is waiting publication. We know that there is a natural history article by Nathalie Goemans that’s in press and the combined collective of these three international natural history experts and with the robustness of the database is that they are mining to understand the natural history, we believe we are in a very strong position to understand what’s expected in terms of natural history. Now we’re going beyond saying that we will compare our treatment arm to natural history. We believe that we should have this control group that’s not amenable to 51, which is appropriate since we don’t have drug available for those patients, and we believe shaping similar inclusion criteria will met a very similar decline as if we had a placebo group. But again this is an ongoing dialogue with the FDA. I think there is more data emerging, there is an increased appreciation of the understanding of natural history by the agency but we just have not finalized those discussions and we hope to in the next several months.

Operator

Our next question comes from Yaron Werber from Citi. Please go ahead.

Yaron Werber - Citi

Okay, great. Thanks so much for taking my question I appreciate it. So, Chris just a question for you on I mean that there is no question dystrophin is obviously central and very relevant, right. There is no question the biology is very clear, the question as you mentioned it really has to do about the predictability of the reasonably likely to forecast the clinical benefit, what are the levels and does it co-relate between the level of dystrophin correction and then actual clinical benefit. Can you maybe just address to us kind of what’s – so what’s the thought from FDA is your Phase I/II data in the 12 patients, is that going to be enough to kind of get them comfortable about the predictability of it. Is this something that they need to get comfortable with sort of a priority before approving you or is that something that can be done sort of part of the confirmatory study? What I am really trying to understand is that’s really the discussion right, because your data on the Phase I/II had a modified ITT. The overall study wasn’t very robust and patient wise and the number of patients at the dose were very small, we are talking four to six patients per dose at the 30 or 50, that’s my question kind of is that enough to really answer the question also in terms of safety?

Chris Garabedian

Yeah, so first I mean the safety issue I think I addressed in the previous question and we have been very clear on the FDA feedback on safety, so but your question around dystrophin and the robustness of that, again this is – the dialogue as it relates to accepting dystrophin as a surrogate under the Subpart H Accelerated Approval. Again separately the clinical outcomes I think we have highlighted even the FDA themselves have been out there talking about that if not about the size of the studies, but it’s about the treatment effect and even about temple and 0250 recent comments that they were noted earlier in the call by one of the analyst. At PPMD I was really talking about clinical outcomes that are robust in a small study can form the basis of a full approval, okay. So, I think we need to separate the distinction of the clinical outcomes we are seeing and how the FDA may interpret that versus the evidence of dystrophin and that correlation and the definition of likely to predict.

So, I think we believe that our dystrophin analysis is robust and is consistent across genotypes. We see it independent of the dose and we see it correlating with the range that we have seen 30% to 60% dystrophin positive fibers at the 48 week time point that this is leading to stabilization in all of our valuable ambulatory patients now out through week 84 from the previous time point. So, this will only be added to in terms of data as we continue to follow these patients through ’96 and beyond. But, yeah I mean I think that is ultimately what the FDA has to consider is what is the level of evidence and proof that they need to accept dystrophin as a surrogate given the small sample size and given the data set that we produced to-date and that’s how we are going to be working with them on what additional information can we compile and put into a NDA submission that gives him that you increased level of confidence or the level of confidence where they can potentially evaluate it as a true surrogate. It’s hard to say because this is an evolving process, Yaron, and we’ve guided what we know to-date, but I’m sure will get more clarity on that over the coming months.

Operator

Thank you. I’ll now turn the call back to Chris for closing remarks.

Chris Garabedian - President and Chief Executive Officer

Okay, thank you, operator and thanks for the analyst questions and for those who are listening in. Again we are very excited about our interactions with the FDA and are confident enough in those discussions to announce our pursuit of a submission of an NDA in 2014. Our teams are going to be working very diligently to compile those components of an NDA and we look forward to continue dialogue with the FDA around our confirmatory study and look forward to further updates from the company as we get them on our confirmatory study on our pursuit of this NDA submission and any other developments associated with our DMD program. So, thank you all for tuning in and look forward to the next call. Thanks.

Operator

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

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