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Sarepta Therapeutics Inc. (NASDAQ:SRPT)

Q4 2012 Earnings Call

March 07, 2013 8:00 am ET

Executives

Erin Cox – Investor Relations

Chris Garabedian – President and Chief Executive Officer

Sandy Mahatme – Senior Vice President, Chief Financial Officer

Analysts

William Tanner – Lazard Capital Markets

Christopher N. Marai – Wedbush Securities

Joseph P. Schwartz – Leerink Swann

Edward A. Tenthoff – Piper Jaffray & Co.

Liisa Bayko – JMP Securities

Kimberly Lee – Janney Capital Markets

Reni Benjamin – Burrill & Company

Operator

Welcome to the Sarepta Therapeutics Fourth Quarter and Full Year 2012 Earnings Call. My name is Sandra 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 Ms. Erin Cox. Ms. Cox, you may begin.

Erin Cox

Thank you, Sandra, and thank you for joining today’s call. Earlier today, we released our financial results for the fourth quarter and full year of 2012. The press release is available on our website at www.sareptatherapeutics.com and our 10-K will be filed on or before March 18. Joining me on the call today are Chris Garabedian, our President and Chief Executive Officer; 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 candidates, the potential and timing for regulatory review and approval of Sarepta's product candidates, the potential pricing and market opportunity for our product candidates, our ability to manufacture candidates, our ability to protect our intellectual property rights, future financial performance including revenues, expenses and financings, potential funding from the government and other sources, and collaboration and partnering opportunities.

These forward-looking statements involve risks and uncertainties, any of which are beyond Sarepta’s control. Any such risks could 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 Chief Executive Officer. Chris?

Chris Garabedian

Thank you, Erin. Good afternoon everyone and thank you for joining us. I am pleased to provide you with an update and overview of our activities and accomplishments in 2012 and since our last quarterly earnings call, along with our financial performance in the fourth quarter and for the full year of 2012.

2012 was a transformative year for Sarepta, where we achieved what many biotech companies inspire to do, which was to generate clinical data with our drug eteplirsen that demonstrates great promise in patients with a devastating and highly progressive disease Duchenne muscular dystrophy, and addresses the type of unmet medical need that have inspired many of us to choose a career in this industry. We are very encouraged by our eteplirsen dat asset and the promise that showed as a potential therapeutic for patients with DMD, who are amenable to an exon 51 skip.

We also believe that we have a road map for pursuing similar results and benefit in other DMD genotypes and have made three additional DMD drugs targeting exons 45, 53 and 50 into preclinical development. As we focus on 2013, we are committed to building out our capabilities to fully develop our broader DMD program, scale up manufacturing to meet the future commercial demand of these drugs, and continue to hire the staff required to carryout the execution of this program till product approval and commercialization.

In addition to these achievements in 2012 on our DMD program, we significantly fortified our financial position culminating in our $125 million follow-on secondary offering in December, which resulted in a cash on our balance sheet of $187 million at year end. These proceeds allow us to maintain eteplirsen on a critical path toward approval and to invest in larger scale production capability necessary to supply the drug for future clinical testing and eventual market approval of eteplirsen and the subsequent DMD drug.

Lastly, Sarepta also had a transformative 2012 as a result of some key corporate activities that included renaming and rebranding the company, recapitalizing our share structure and expanding our reach to new investors, increasing our institutional shareholder base from 18% at the end of the second quarter to 36% at the end of the third quarter to 66% at the end of the fourth quarter.

Additionally, we have completed the relocation of our headquarters to Cambridge, Massachusetts and have been recruiting high caliber senior level talent. We have added senior level positions over the last year that have included a new CFO, a new General Counsel, a new Head of Regulatory along with key positions to support commercial development, business development and clinical operation. I am confident that we have established a strong foundation from which we can execute on bringing potentially breakthrough treatments to patients with Duchenne muscular dystrophy and other disease areas with our differentiated technology.

This past December, we provided a further clinical update from our phase 2B extension study with eteplirsen and provided 6-minute walk test data to 62 week or 15 months that continue to show stability in this walking measure. This 62 week data presentation was also the first time that we provided a more thorough analysis of our 6-minute walk data by including various permutations based on the time points in which captured repeated 6-minute walk test measures. Specifically, we captured two six-minute walk test measures at base time and each time point in which biopsies was scheduled, which for weeks 12, 24, and 38.

Across four separate analysis of the 6-minute walk test that included maximum scores, minimum scores, lean scores and using only the first day, day-one measure the change from baseline in our modified intensive treatment analysis of those are valuable on ambulatory measures at week 24 and beyond range from less than 5% decline to 2% increase or essentially no signs of disease progression on the 6-minute walk test. Additionally, all analysis showed an improvement over the placebo delayed treatment cohort of 57 meter to 62 meter with signs of stabilization in the placebo cohort after distress signals confirmed by biopsies at 48 weeks and through week 62.

The phase 2B extension trial which is also known as Study 202 and is our long-term safety and efficacy study, we will be providing further clinical update from this study periodically including 74 week 6-minute walk test data as well as additional safety data that we expect to present in the first half of this year.

As we have previously stated, in the fourth quarter, we requested an end of phase 2 clinical meeting with the FDA to review the result from Study 201 and Study 202 as well as earlier clinical and non-clinical eteplirsen data and to discuss what is required to gain approval of the drug. This meeting has been scheduled and we’ll take place later this month.

We continue to see a favorable safety profile for eteplirsen, which we recognized as critically important for the chronic therapy that may be used throughout the course of the patient’s life. The 62 weeks of treatment, there were no serious adverse events and no clinically significant treatment-related adverse events. One patient had a transient elevation of urine protein on a urine dipstick test, however this elevation resolved within 24 hours resulted in no clinical symptoms and the patient continued to receive treatment. We had also observed the transient elevation of the urine protein on a urine dipstick test that resolved in 24 hours and a patient who received placebo during the first 24 weeks of Study 201.

Overall, there has been no study discontinuation with trials or hospitalization and all patients continue to receive treatment. This safety profile is incredibly important as we prepare to speak to the FDA about the risk-benefit trade-off of an accelerated approval pathway. In a disease where there are no approved therapy and we are dealing with a rapidly progressive disease were no intervention typically leads to irreversible decline in function and ultimately death. We believe the safety profile combined with the robust and statistically significant biochemical and clinical benefit warrants consideration for accelerated approval.

We recognized that the DMD community play the key role in representing the unmet medical need in the patient population, and we continue to be deeply grateful to the DMD community for their positive feedback, support and efficacy. We understand the community's desire to gain access to eteplirsen as soon as possible and I want to say it again that we hear you and we're working expeditiously to ensure that we can get eteplirsen since the patients that may benefit as quickly as we can.

As we stated consistently, as a drug developer, we have to ensure that we adhere to the standards set forth by the FDA to determine the appropriate path towards approval. We have great respect for the role of the FDA in protecting the public health and we also recognize the steps they have taken to expedite the development and approval of treatments for rare and serious disease, for which there are no other therapy. The accelerated approval pathway is an important mechanism the FDA as viewed to facilitate earlier approval of drugs to treat serious diseases on the basis of surrogate or clinical end points that can be measured earlier in drug development followed by confirmatory trials to verify the anticipated clinical benefit.

During our end of Phase b clinical meeting this month, we will discuss the design and endpoints of a confirmatory pivotal study that will support full approval of eteplirsen. Additionally, we will discuss the feasibility of filing for accelerated approval based on the current data set.

I would like to summarize the full eteplirsen data set that we have summarized in our FDA briefing document. There has been 38 patients exposed to eteplirsen across four studies including Study 201 and 202 of the placebo controlled 24 weeks study and our long-term efficacy of safety extension study. Of those 38 patients, 36 have received pre and post-treatment biopsies to measure dystrophin levels in their muscle tissue and we have observed dystrophin increases in 28 of those 36. And in every patient, there are 20 out of 20 that received a weekly dose of at least 10mg/kg of eteplirsen.

In both our placebo-controlled Study 201 and our Open-Label Extension Study 202, we met our primary end-point of an increase in dystrophin-positive fiber at 24 weeks and 48 weeks respectively and achieved an average of 47% dystrophin-positive fibers or essentially half of all muscle fibers measured, and levels that range from 30% to 60% across all patients at 38 weeks across the five genotypes, including two who are in a non-ambulant state when the dystrophin was measured in their muscle biopsy.

There were no significant treatment related adverse events and the drug has been tolerated in patients receiving doses as high as 50mg/kg for a duration of 62 weeks. Later this year, we will have patients who have received at least two years of drug exposures at doses as high as 50mg/kg per week. If we were to pursue a 30mg/kg dose for approval, this would translate to over 30 patient-years of drug exposure at the 30mg/kg dose level. We believe that favorable safety profile is critical when considering an accelerated approval of a drug for Duchenne through the morbidity and sequelae associated with the disease are rapidly progressive and irreversible.

Lastly, we have a strong statistically significant difference on a clinical endpoint that has been acceptable to the FDA for approval of other rare diseases. While this benefit on 6-minute walk is based on a small number of patients, the size of the treatment effect and the general consistency across the ambulatory patients that were valuable beyond 24 weeks, suggest that the dystrophin we are producing in the muscles would reasonably predict that the 6-minute walk benefit and the stability we’ve seen in these patients over 62 weeks is reproducible in confirmatory studies.

Once we’ve met with the FDA, receive their feedback, and understand their perspective, we will evaluate next steps for eteplirsen and make a decision on whether or not we will file for accelerated approval. We will communicate next steps for the eteplirsen program as soon as we have sufficient information and are confident in our plan.

It is also important to note that we expect to have additional dialog with the agency in the second quarter of this year, which will inform the eteplirsen registration program as it relates to the manufacturing or CNC section of an NDA. As we have previously stated, we continue to plan for the initiation of the confirmatory study in the latter part of 2013 with dosing to begin in the first quarter of 2014.

Our scale-up manufacturing plants have begun in earnest and we have began producing drug supply at a larger scale or what we’ve described as mid-scale production batches for our confirmatory clinical trial with eteplirsen and development of our follow-on DMD drug. We are still on track for having stability data for submission to the FDA in time for drug release in the first quarter of 2013 to begin dosing our confirmatory study.

We have also started planning for even larger scale production to satisfy the potential commercial demand of eteplirsen and to prepare for the subsequent demand that we may need for any follow-on DND drug. And we are prepared to begin those efforts in earnest as seriously have a better understanding of the regulatory pathway based on our FDA discussions.

While we will be producing our morpholino at a larger scale for the first time, we have a lot of expertise and know-how related to this chemistry, and we’ve been producing the drug for clinical trials, or I should say producing the chemistry and morpholino for clinical trials for more than a decade. And we’ve been producing drug supply for our eteplirsen study for several years, with good stability and purity profiles and good compatibility batch-to-batch. While there are always list and scale up, we believe this synthetic chemistry has favorable qualities for scaling up based on the drug properties we’ve seen to date and are confident in our ability to develop the same drug product at a larger scale.

Now, with regard to our earlier stage DMD pipeline, we announced last quarter in November a new collaboration to develop an exon-skipping drug targeting exon 53, which will be our fourth product candidate for the treatment of DMD. The collaboration with the Professor Francesco Muntoni, a University College of London scientist, as well as a Dubowitz Neuromuscular Center, the Institute of Child Health and other scientists from the EU and U.S.

The collaboration is supported by an EU Health Innovation research grant made available through the European Commission. The agreement includes IND-enabling activities and the initiation of clinical proof of concept studies in Europe for a drug candidate targeting exon 53. We also continue to make good progress on two additional DMD drug candidates targeting exon 45 and exon 50. We expect to hold IND meetings with the FDA on at least two additional exon by the end of 2013.

I am also pleased to report that we have now selected lead sequences in all three of our follow-on DMD drug, and we will be preparing them for preclinical studies to begin later this year. These products will now be referred to as SRP 4045, SRP 4050 and SRP 4053, the last two letters corresponding to the target exon that is being [step].

Now, I’ll provide a brief update on our active government-sponsored infectious disease programs for the treatment of the life-threatening hemorrhagic fever virus of Marburg, and our influenza drug candidate, AVI-7100. Our current drug candidate from Marburg the AVI-7288 has shown excellent efficacy with administered intravenously at 15 mg/kg in multiple non-human primate studies. We reported unprecedented data in the delayed time to treat setting last year where we showed 100% survival with a 14-day course of treatment after 40 days, despite initiating treatment 48 hours after infection, and 83% survival when initiating treatment 96 hours after infection.

On March 4, we announced new data from a non-human primate study that showed comparable efficacy but with intramuscular delivery, these results to reinforce the strong efficacy of AVI-7288 while showing that the drug can be delivered via convenient IM injection, an alternative delivery method that has the potential to greatly enhance the practical utility of this drug in a mass casualty situation.

In addition, these data demonstrates the versatility of our platform as it provides proof of concept with a new generation of morpholino. In this case, our PMOplus or positively charged morpholinos in a new effective method of drug delivery. We also completed a PK study with our Marburg drug in non-human primate that reinforce the efficacy results we’ve seen from previous studies, but when compared to our human PK exposure level suggested that a lower dose in human may result in the efficacious exposure levels that we observe in non-human primate at higher doses.

These data tell us that exposure to AVI-7288 and our morpholino PMOplus drug chemistry does not scale on a strictly mg/kg basis and provide support that a therapeutic window in human at lower doses may be efficacious allowing for a potentially greater margin of safety. This will be important as we proceed with our multiple ascending dose or MAD study in healthy volunteers in the first half of this year. We expect to complete dosing of all cohorts in our Marburg MAD study by year end with final results ready for communication in early 2014.

All together, these findings provide significant proof of concept for the antiviral activity of another morpholino chemistry and could serve as a model for activity in other serious infectious diseases and potentially other therapeutic areas beyond infectious disease. I am also incredibly pleased that we announced that we were able to revive our influenza program by entering into a Clinical Trial Agreement with the National Institute of Allergy and Infectious Diseases part of the NIH to conduct a Phase I study with AVI-7100. This drug candidate has a novel mechanism of action and potentially broad-spectrum activity against influenza viruses, including Tamiflu-resistant virus strains.

The agreement establishes a former between NIAID and Sarepta to allow NIAID researchers to proceed with a Phase I, double-blind, placebo-controlled, dose-escalation study to assess the safety, tolerability and pharmacokinetics of single and multiple doses of IV formulation of AVI-7100 in healthy volunteers.

While the development of AVI-7100 was initially supported by the Department of Defense, we are very pleased that another agency NIAID has also seen the potential of this drug with the goal that is focused on the civilian population. This is important as we believe our drug platform is inevitable to potential pandemic applications like flu and other infectious diseases that continue to generate news reports due to breakouts or more leasehold or resistance strains like dengue, tuberculosis and retinal virus to name a few.

Beyond our current clinical programs and you continue to identify new applications for our technology platform and our more advanced to more fully chemistry. We are working with several academic researches that are expert in a variety of disease areas and are receiving a tremendous amount of interest in the properties of morpholinos based on the success we've had with the programs that I have described in Duchenne and Marburg specifically.

While we are not ready to disclose which programs are being prioritized for our pipeline, we are focused on areas in other rare and neuromuscular diseases, other infectious disease areas including antibacterial applications and other disease areas beyond rare and infectious disease.

As we develop solid preclinical proof-of-concept data for a particular disease, we will make a determination of whether to pursue a particular program internally to bring other drugs into our proprietary pipeline or whether we would identify the right industry partner to pursue a particular disease area.

As I've described, we have a lot ahead of us at Sarepta in 2013. And we have provided a range of guidance that allow us for preparing the company for success. Our operating loss is expected to be in the range of $85 million to $115 million and this includes a scenario in which we would pursue an accelerated approval filing.

Importantly, the large majority of increased expenses in 2013 over 2012 is related to our manufacturing scale up. These large increase is driven by two factors. Firstly in collaboration with contract manufacturers, we are manufacturing all of the drugs that will be required for eteplirsen's clinical program along with the drug supply that is needed to conduct a preclinical program across exon 35, 53 and 50 to support studies that will be conducted through 2013.

Secondly, the ramp up to large scale manufacturing, we’ll establish a capacity that will create significant value in the coming years as this large-scale production capability will be used to supply drug to meet the market demand upon commercialization and will be adapted and expanded to supply drug for other exon targets in the U.S., Europe and elsewhere.

Another way to look at this investment is that every vial we produce of eteplirsen will be used for confirmatory clinical trials that will create more value for the broader DMD program or result in a commercial sale, which will generate future revenues for the company and provide a path toward profitability. While our investment in manufacturing will increase significantly this year, we have maintained a lean efficient organization while attracting a stronger talent base with our recent success and the move of our headquarters to Cambridge, Massachusetts.

We have a lot of important events ahead for the company and for the remainder of the year, and we have built the right team to execute on all the activities required for success. We look forward to providing you with progress update in future quarterly calls and in another investment and medical conferences throughout the year.

That concludes my corporate update, and I would like to turn the call over to Sandy Mahatme, our Chief Financial Officer to give you a financial update for the fourth quarter and full year 2012.

Sandy Mahatme

Thanks, Chris. In the fourth quarter of 2012, we reported an operating loss of $10.4 million compared with an operating loss of $9 million in the fourth quarter of 2011. The incremental loss is a result of $6.3 million decrease in government contract revenues offset by $4.9 million decrease in operating expenses.

Revenue for the fourth quarter of 2012 was $7.3 million, down from $13.6 million in the fourth quarter of 2011. The $6.3 million decrease was due to the August 2012 stop-work-order and subsequent termination of the Ebola portion of the Ebola Marburg U.S. government contract due to a lack of available U.S. government funding. The Ebola termination did not impact the Marburg portion of the contract. Revenues from the Marburg portion of the contract also decreased due to the timing of activities throughout the normal progression of the contract. These decreases were partially offset by revenue from the intramuscular administration contract with the U.S. government for the Marburg virus that started in August 2012.

Research and development expenses were $12.8 million for the fourth quarter of 2012, compared to $18.7 million in the fourth quarter of 2011, a decrease of $5.9 million. The decrease was primarily attributable to termination of the Ebola portion of the government contract and reduced spending on the Marburg portion of the government contract due to the timing of activities. This decrease was partially offset by increased spending related to the intramuscular administration contract.

General and administrative expenses in the fourth quarter of 2012 were $4.9 million, compared to $3.9 million in the fourth quarter of 2011, an increase of $1 million. The increase was the result of additional personnel costs associated with key positions hired in the second quarter of 2012.

Now I would like to turn to an overview of the full-year results. For the full year 2012, the operating loss was $29.7 million, compared to an operating loss of $35.9 million for the prior year. The $6.2 million improvement was the result of the $14.5 million decrease in research and development expenses and a $1.4 million decrease in general and administrative expenses, they were partially offset by a $9.7 million decrease in revenue from government contracts.

Revenue, revenue for the full year 2012 decreased about $37.3 million from $47 million in 2011 primarily due to the Ebola stop-work-order, and the completion of the H1N1/influenza contract with the U.S. government in June 2011.

Our research and development expenses were $52.4 million for 2012, compared to $66.9 million for the prior year, a $14.5 million decrease. The decrease was primarily due to reduced costs related to the Ebola portion of the Ebola Marburg government contract, the completion of the H1N1 contract in 2011 and a reduction in our overall non-DMD proprietary research.

General and administrative expenses for 2012 were $14.6 million, compared to $16 million for 2011, which is a decrease of $1.4 million. The decrease was primarily due to reduced professional service costs and severance costs compared to the prior year.

The net loss for the fourth quarter of 2012 was $62.1 million, or $2.36 per share, compared to a net loss for the fourth quarter of 2011 of $1.4 million, or $0.06 per share. The net loss for the full year 2012 was $121.3 million, or $5.14 per share, compared to a net loss in 2011 of $2.3 million, or $0.11 per share. The increase in the net loss for both the fourth quarter and the year was primarily due to the change in valuation of outstanding warrants to purchase common stock.

In addition to prior equity financings, we issued warrants that are classified as current liabilities and are adjusted to fair value on a quarterly basis with the change in fair value being included in net loss. The amount that has included in net loss is a non-cash item and we’re not required to expend any cash to settle the warrant liability.

The warrant liability is primarily affected by changes in our stock price during each financial reporting period which causes the warrant liability to fluctuate as the market price of our stock fluctuates. In the fourth quarter of 2012, the increase in our stock price resulted in the warrant valuation increasing which resulted in other expense of $51.8 million.

In the fourth quarter of 2011, the decrease in our stock price resulted in other income of $7.4 million. For the full year 2012, the change in the warrant valuation resulted in other expense of $91.9 million while in 2011, the decrease in the warrant valuation resulted in other income of $33 million.

We ended the year with cash and cash equivalents of $187.7 million, an increase of $147.8 million from the prior year. This increase was primarily due to a $118.1 million from a public stock offering in December $36.2 million from our ATM facility, $20.6 million from the exercise of warrants and $3.8 million from stock option exercises. These sources of funds were partially offset by $29.7 million of cash used for operations during the year.

Now turning to 2013 guidance, we anticipate that revenue will be in the $18 million to $24 million range and that loss from operations will be in the $85 million to $115 million range. This guidance is based on the assumption that we will continue to receive funding from current government contracts for Marburg. If we do not receive this funding, our guidance will change. Additionally, as Chris indicated, our operating loss guidance is largely based on continuing development and scale up of manufacturing for eteplirsen and a follow-on DMD drugs.

With that, I would like to turn the call back over to Chris.

Chris Garabedian

Thank you, Sandy. Operator, we can open up the call for questions.

Question-and-Answer Session

Operator

Thank you. (Operator Instructions) And the first question is from Bill Tanner from Lazard Capital Markets. Please go ahead.

William Tanner – Lazard Capital Markets

Thanks for taking the question. Thanks Chris for the update. Just couple of questions on the upcoming conversation with the FDA, I think earlier this year you said the FDA really hadn’t seen much other than the press releases and obviously now you’ve submitted a briefing document, I'm curious as to whether there have been any conversations with the FDA in the ensuing period or you really waiting for the official meeting and then I had a follow-up on that please.

Chris Garabedian

So we don't comment on what they take place in terms of conversations that we may have with a agency meeting up to formal meeting. So basically, I think we're going to communicate after we have the formal meeting and after we haven’t understanding the conclusions of that meeting will be any comments that we make will be following that.

William Tanner – Lazard Capital Markets

Okay. Because you haven't read letter bolded in your press release, it sounds like you are expecting a definitive path forward after the meeting with the FDA. So appreciating it happened, could you help us understand a little bit may be as to what the expectation should be and maybe that timeline that it's going to be a definite thumbs up or thumbs down in terms of applying for accelerated or still more back and forth just maybe help us understand the timeline along which you will be able to communicate and how definitively you might be able to do that.

Chris Garabedian

Sure. So we said pretty consistently that this meeting that will take place later this month will allow us to determine on if and accelerated approval filing is feasible. Okay, so we're going to take the results of that meeting and the discussion and dialogue and the meeting minutes that we will get from that and make a decision as a company of whether or not to pursue an accelerated approval filing. The timing of that will be dictated more from our discussions around CMC issues, and we expect that meeting to take place in the second quarter of this year.

Again that will be based on how much stability data did they need at that time of filing. We have a lot of data on the batch records of scale that we've been producing at (inaudible) over the last several years. That may be sufficient for filing that mainly to be supplemented within a mid-scale batch record and eventually large scale batch record. So until we really have a good understanding, the flexibility that the FDA may have around our CMC section of an accelerated approval NDA that would dictate the timing.

Under a full approval NDA if we decided not to pursue and accelerated approval we don't believe that the manufacturing becomes a gaining mechanism and we are comfortable that at the time that we would file the confirmatory study result that we would have a full CMC section prepared at that time.

So again the decision of whether we file under – under a short approval will be made following this upcoming meeting and timing of that would be made after we have a better understanding of the CMC discussion.

William Tanner – Lazard Capital Markets

Got it. And just one last question, I don't believe we’ve same data since the 62-weeks. So I guess the presumption is any data that have been collected since then are consistent with what you would publicly disclose previously.

Chris Garabedian

Well, we are not commenting on any follow-up, but yes it’s fair to assume that either we haven’t evaluated that data or it’s consistent with what it’s been previously. And obviously if we have the data and it was different then that would be something we would disclose more immediately. But we have been saying all along that we expect to have a clinical update in the first half of this year and that continues to be the guidance.

William Tanner – Lazard Capital Markets

Okay. Thanks very much.

Operator

Thank you. And the next question is from Chris Marai from Wedbush Securities. Please go ahead.

Christopher N. Marai – Wedbush Securities

Hi, good morning guys. Congrats on a great year. I was wondering if you could discuss expectations around the 74 week data, I think Bill was alluding to the fact that you may have this data on hand currently. So I was wondering what would constitutes favorable results in your eyes. Since we are going to see data in all 10 days all the 48 weeks on dosing, one might expect that it’s a deterioration in the benefit cost all the way especially if you compare it to placebo control. Could you guide us to what you are thinking about might be out positive or very positive data in that data set?

Chris Garabedian

So, Chris, again, we are very encouraged that the 52 weeks we show the stability from base line as well as the stability in the growth from the 36 week time point before we expect to get this is going to be present through 48 and now 52 weeks. We hold stability or the slow progression maintained right, we don’t know how long that could be maintained or if there would be maintained in definitely.

We do know that it is the small sample size that effort-dependent test where there maybe variability, and importantly we have a move to only taking a 6-minute walk test measure one in any subsequent time point unlike what we did at baseline 24, 48 weeks where we took two measures where we had dystrophin and 6-minute walk test. We understand a more consistent measure of 6-minute walk into why it was our primary endpoint, it’s why the statistical analysis plan that we focused on was on 48 week.

So while we look forward to presenting a follow-on data. The expectation optimistically would be to maintain the stability on these walking tests moving forward. So right now, we are focused on the upcoming FDA meeting and making strongly case that we can with the data set that has been provided for them in the recent documents.

Christopher N. Marai – Wedbush Securities

Great. And then is it safe to assume this data has been provided to the FDA just judging by timing you likely have it, and then in terms of presentation where we see data on individual patients.

Chris Garabedian

Yeah. So, we’re not sharing what and what hasn’t been including the recent document. I sufficed to say the primary analysis is going to be a greatest interest because that like any drug study, you proposed what you expect an outcome to be and then the data used to support that thesis and that thesis will describe at 48 weeks based on the dystrophin and supportively on the 6-minute walk test.

We got to know there are future presentations. Again at this time, we (inaudible) not any thoughts or opinions about what we would provide beyond, what we provided historically and the 62 week presentation is an example of what we would expect to present minimally on subsequent time points. Again, this is a small study and sharing patient by patient data is not something that we believe is the responsible thing to do. Possibly overtime, that we could consider sharing that, but at this time we are keeping it to the way we’ve been describing this data previously. Interestingly, Pharma came out with a position saying, it will be responsible for sponsors to put out individual patient data from studies. We think this is even more of the case in a small sample like this where many of these patients are known in the community. They speak openly about being in studies and so it’s a different level of knowledge of patients that we wouldn’t typically see in a larger sample size.

But again, we’re sticking to our guidance, we’ll providing a periodic update on the clinical outcome measure 6-minute walk and we expect to have (inaudible) full data in the first half of this year.

Christopher N. Marai – Wedbush Securities

Okay great. And just one real quick follow-up, do you have another endpoint data at that 74 time point, or just an experiment walk test?

Chris Garabedian

Yeah we’re not providing any guidance at this time, Chris.

Christopher N. Marai – Wedbush Securities

Okay, thanks very much.

Operator

Thank you. And the next question is from Joseph Schwartz from Leerink. Please go ahead.

Joseph P. Schwartz – Leerink Swann

Good morning. Thank you. I was wondering if you could give us some insight into how you are thinking about the optimal time for you to put product upon stability longer-term stability testing from your, from whatever commercial manufacturing scale supply you are assembling now?

Chris Garabedian

Yeah. Well Joe this is a common practice that we will do production and we take drug product from those ones and put it on stability as though a matter of course. And so, and then we’ll be testing on that at various time points that we will generate data that we can submit to the regulatory bodies. So that is standard practice and that’s what we intended to do for any lots, whether that be mid-scale or large-scale, moving forward. So the comments earlier was centered around...

Chris Garabedian

The willingness of the FDA in terms of the amount of (inaudible) stability, that that would be required for registration of package. Is that the question you asked?

Joseph P. Schwartz – Leerink Swann

Yeah, it does seems to me anyway that it would, the stability data is a real rate limiting step for you to access to the market in a practical sense so that’s why I was curious about your thinking about when you will be able to determine to match how much is required and how are you are assembling the their commercial, the way with all turning effect fact that will now. Can you talk a little bit about the progress that you made organizing the means to supply sufficient quantities of commercial product?

Sandy Mahatme

Yeah I would love you so listen to the comments at the beginning of the conference. They describe, the quarter we are going to be meeting with the FDA to talk about our manufacturing point moving forward. And how we potentially supply the commercial demand in the event that we would pursue an accelerated approval filing. That discussion will be important, the FDA has been flexible in the past around these types of issues depending on the drug, the data that is being generated to date, which is being treated.

And so we think this is a scenario that would allow them and encourage them to be flexible about, the amount of stability data needed, so it is not a rate limiting example, or not as much as of a rate limiting step. Keep in mind that we expect that if the drug-related available that demand will be very strong particularly if we had limited supply and that this is not drug, that’s going to be sitting on the shelf for months, that alone would hope six months to a year or more.

But again we think the properties of this drug are such that we would expect similar stability and, similar purity profile and essentially the same substance in vials regardless of small-scale, mid-scale or large-scale batch production record. So obviously we want to have some data to support that. But I think that will be something that will be encouraging to allow for supplemental data to come to talk. But again we will have more information after a CMC discussion with the FDA that we intend to have in the second quarter.

Joseph P. Schwartz – Leerink Swann

Great. Thank you.

Operator

Thank you. And the next question is from Ted Tenthoff from Piper Jaffray. Please go ahead.

Edward A. Tenthoff – Piper Jaffray & Co.

Great. Thank you very much for taking the question and my congrats too on really a transformational year. I appreciate to the clarity on the timing of the meeting. Couple of questions, so firstly, with respect to the other exon-skipping drugs, how you are going to be advancing into the clinic. Can you give us an update there in terms of what are some of the additional steps that need to be done prior to IND filing, again an issue of the manufacturing that’s holding that up there. Is it a matter of preclinical tox works, are you still in the process of coming up with sequence, where are you in the process along with those. And then I have kind of a house keeping question if I may as well.

Chris Garabedian

So Ted, in my prepared comments I discussed that we provided guidance that includes manufacturing for our follow-on exon. So we are prepared to provide the drug required to keep those on a critical path and through the preclinical studies. We also mentioned – I mentioned that we have identified lead sequences on these follow-on exons for exon 50, exon 45 and exon 53.

We also mentioned that we will have at least two pre-IND meetings on these follow-on DMD exon target. And those pre-IND meetings will provide further clarity of what our growing assumptions are and what would be required for clinical testing. Obviously we have a lot of good information from our discussions around eteplirsen and what was required. We also had our formal PPMO discussions around what would be require preclinical.

So we have a lot of information going into the assumption. We think now with a very robust eteplirsen database, there may be more flexibility than we realize, but we have to have that discussion with the FDA first in the pre-IND meetings to determine that. But we are assuming at this point that we would need to do the full preclinical package, but there may be situations, for example the rodent work that’s already been done with the surrogate exon-skip, exon 23 and the DMD mouse model, we would not likely to have to be repeated.

The question is, do we need to have another nine month primate study or will a shorter term primate study at suffice, may be they will need to require an additional primate study. So there is a lot of questions we want to clarify in a potential pre-IND meeting, but sufficed to say we feel we are on track with these follow-on exon. As we indicated, we expect to had at least one IND filed by mid-2014, which will be ready for clinical testing by 2013 and the more of those we can have ready by that time point the better and we will have to see if that’s feasible.

Edward A. Tenthoff – Piper Jaffray & Co.

Great. Excellent. And then a follow-up question on the warrants, obviously there is a lot exercised last year and you are not filing the K for may be a couple of days still. What is the outstanding warrant situation and where roughly are those exercise prices?

Chris Garabedian

So I let Sandy share what is remaining from our previously reported warrant.

Sandy Mahatme

As of the year end, we had about 3.5 million warrants outstanding and the average price is approximately…

Edward A. Tenthoff – Piper Jaffray & Co.

Sorry, broke up there. Average price of…

Sandy Mahatme

So the average price was approximately $9 and we had about 3.5 million warrants outstanding.

Edward A. Tenthoff – Piper Jaffray & Co.

Excellent. Thank you very much.

Sandy Mahatme

Those have an expiry of 2014, Ted.

Edward A. Tenthoff – Piper Jaffray & Co.

Okay, great. Thank you.

Operator

Thank you. And the next question is from Liisa Bayko from JMP Securities. Please go ahead.

Liisa Bayko – JMP Securities

Hi, thanks for taking my question. First question is on breakthrough status, is that anything you are considering and it seems like at least the feedback from FDA to the parent meeting that was recently held, indicated that consistent with our thinking that this was really the ideal candidate for breakthrough status. How might that help your prospects that accelerated approval?

Chris Garabedian

Yeah, obviously we’ve been following the communication on breakthrough and we announced awards of breakthrough and again, the language on the breakthrough designation do seem to support that eteplirsen would be qualified based on early clinical signal from a early stagy study. The awards today have been all with products that have a quite robust clinical datasets, the pharmacyclics and the Vertex compound is what I'm referring to.

We know there have been several that have been declining on breakthrough and it's not clear what criteria would lead the agency to decline a product and whether something beyond whether it stated such as manufacturing et cetera are part of that decision criteria. We again are meeting with the FDA later this month and this is something that we have prepared ourselves for. If we decided to pursue a breakthrough designation filing, I've communicated previously that we would make that determination in the first half of this year, and again I think that could accelerate that strategy would be our direct communications with the FDA. So again stay tuned we're not changing our guidance with respect to that we will have our strategy determine in the first half of this year and stay tuned.

Liisa Bayko – JMP Securities

Okay, great. I understand there is really two clinical meetings toward the determination of accelerated approval or not. The first part of the clinical, can you talk from that meeting what you are looking for from FDA to feel like an accelerated approval of the appropriate path based in that clinical?

Chris Garabedian

We’ve shared this thinking previously, there are two objectives primarily of the meeting is to gain feedback on a confirmatory study design that we are intending to start dosing in early 2014. And then secondly, to access the feasibility that our current 38 patient data base and 12 patient phase 2B study would satisfy the requirement to at least consider a package for review under an accelerated approval pathway. There is a few things that make up that determination, one is the safety database, second is dystrophin and the robustness of our dystrophin analysis as a surrogate marker.

And then the third is, does that dystrophin surrogate marker reasonably predict the clinical benefit and is the supported data and the 6-minute walk test result are something that they feel is the signal that needed to support that the dystrophin production would reasonably predicted this clinical benefit we're seeing. And so obviously these are very nuance conversation, but we hope that will get a fairly straightforward in ambiguous response, so that we can make a good determination as the company. That's probably the most color I can provide you at this time.

Liisa Bayko – JMP Securities

That's very helpful. Thanks. And then once you do decide, yes, we’re going for an accelerated approval or not, so let’s go with it. We go ahead with this approach. Once you make that decision how much time do you think it will take you get the application and how prepared are you?

Chris Garabedian

Liisa, as I mentioned, the first meeting is the one later this month will help us determine the feasibility of whether or not we will file under accelerated approval. The timing of such an NDA will be determined by our CMC discussions with the FDA and not really have in the second quarter.

Liisa Bayko – JMP Securities

Right, so then once you pass that market you say, okay we check the box on group CMC and clinical and we're going to proceed forward, let's go under that scenario and how prepared do you actually submit the filing another words would that be a two months process, six-month process from guidance on how long it would have to take?

Chris Garabedian

So I mean you can look to many in this three comparable, I think that could range from three to six months, it’s a huge endeavor, obviously, but further the delay of filing because of any CMC issues would mean that we can be working on all of those sections over that time period before we even submit or ready to submit. We could end up with a rolling NDA submission where we had to submit sections that already prior to. And it’s hard to provide guidance, but if we had all of the data that we needed in hand, then I think you could see something more rapid. But I’d say three to six months is reasonable to assume based on comparable across the industry.

Liisa Bayko – JMP Securities

Okay great. And then one final question. I know we’ve got the NDA meeting earmarked as the next important meeting for the DMD community. Could you let us know if that’s place we should look for your next clinical update of the Phase IIB open label data?

Chris Garabedian

Yeah, we haven’t determined what venue and how we will disseminate that data. So again there are many smaller meetings across the globe that occur, there’s many of our collaborators present at these various meetings. So again we’re not providing any guidance of where that venue would be at this point. And again it could also still be communicated in the press release, but always communicated that we expect a update sometime in the first half of this year.

Liisa Bayko – JMP Securities

Thanks a lot.

Chris Garabedian

Thanks.

Operator

Thank you. And the next question is from Kim Lee from Janney Capital. Please go ahead.

Kimberly Lee – Janney Capital Markets

Good morning. Quick question here. How much stability data do you have right now or may be how much would you have by the end the year when you plan to start your confirmatory trial?

Chris Garabedian

Yeah, we have stated that we would have three months stability to submit to the FDA for drug release for clinical trials, and again based on our experience in those that we talk to, that should be sufficient for drug release for clinical studies that would be supplemented with further stability data as we get it, so that we would have for the dosing to being in the first quarter of next year.

Kimberly Lee – Janney Capital Markets

Okay. So does that mean you have not started the stability testing yet, or would have any data by your CMC meeting with the FDA?

Chris Garabedian

We’re not providing specific guidance on that at this point Kim, I did mention in my prepared remarks that we have begun production at this mid-scale, but we’re not providing any guidance on when we might have stability. And again the CMC meeting that calendar at this time, so I [don’t] hope we could say that we would have, but again this briefing documents for the FDA meeting that have to go in what would we have at that time. Again we don’t believe that that’s going to be a critical component of understanding the flexibility with the FDA may have moving forward.

Kimberly Lee – Janney Capital Markets

Okay, great. And then one last question here. How much safety based on what other companies similar to you have done in the past, how much safety data do you think you will need for a potential approval?

Chris Garabedian

Well, are you talking accelerated approval or full approval?

Kimberly Lee – Janney Capital Markets

Accelerated.

Chris Garabedian

Yeah well, again I in my prepared remarks, I communicated the robustness we believe our safety database is. And that we would have more than two years exposure, as though we as this fall, it’s only as August that we could compile by the fall. That translates if we would pursue a 30mg/kg dose to our more than 30 patient-years of exposure at that dose level. Again you can look at comparable drugs that have even received full approval with databases of safety, we’ve got many patient-year exposures at the time of approval. So again we don’t believe full approval safety data base would be problematic if we would have pursue what we’ve been describing as the 60 to 80 patient treated study in a confirmatory study.

Again the FDA is important in this dialogue and we're going to having a lot of upcoming meetings with the FDA that will determine what shapes our view of what's going to be required.

Kimberly Lee – Janney Capital Markets

Great, thanks.

Operator

Thank you. And the next question is a follow-up question from Bill Tanner from Lazard Capital Markets. Please go ahead.

William Tanner – Lazard Capital Markets

Thanks for the follow-up. Chris I apologize if you have touched upon this. But, can you just remind us the preclinical safety work that's been done and do you comment on the adequacy of that and what kinds flexibility the FDA may have?

Chris Garabedian

The preclinical safety is very strong and robust and consistent with the safety profile we're seeing in the clinic. So we have completed our long term animal tox, the nine months primates the six months now that juvenile grow these studies and those – that data has been at the FDA for while now the study report have been finalized. And again we think it's a further kind of an explanation point of the safety profile of the drug.

The FDA was particularly concerned with kidney toxicities and wanted to have a full analysis of specific kidney markers will be constructive this long-term study. We have not seen the kidney toxicities again we've reported that both in our short-term studies and our long-term studies these have been in poster form at various scientific meetings that Pete Sazani, our Head of Pre-clinical has been also launch.

So again our safety profile supports the – we're not seeing the dopamine toxicities up to 320 mg/kg in primate. We studied up to 900 mg/kg we studied up to primate. We are very confident with our safety profile, and we believe it will enhance the view of our safety profile, but I think at the end of the day the FDA is going to be most concerned with our clinical safety data base.

William Tanner – Lazard Capital Markets

And Chris, is the FDA is concerned about the kidney toxicity is that a priority concerned about eteplirsen or is that a reflection I guess concerned about our competing compound do you know?

Chris Garabedian

It may be partly due to kidney toxicities we’re commonly seeing for RNA therapeutics, but I think it's more for the reason that we are clear to the kidney. We know from other conjugated morpholino, but it is the dopamine toxicity as we found with our oligonucleotide-peptide that has been reported in the literature. And so I think it was more driven on the morpholino conjugate and the fact that we're clear to get kidney – using pretty high dosage as well, we believe is more of the reason not necessarily related to other chemistry.

William Tanner – Lazard Capital Markets

Got it. Thank you.

Operator

Thank you. And the next question is from Reni Benjamin from Burrill & Company. Please go ahead.

Reni Benjamin – Burrill & Company

Hi, thanks for taking the question. Congratulations on the progress. Chris, can you give us may be a status update on the patent around the world, when we may a see an appeal let’s say in Europe. And I guess related to that, is there European or rest of world strategy based on discussions with the FDA as they come out that you guys are formulate?

Chris Garabedian

So Reni, regarding the patent positions, obviously we have competence of matter on eteplirsen in the U.S. and Europe. We have licensed to the well tend patent that covers all of the exon targets that are of interest to us with variety of sequence and reason to work within. We reported frequently on our patent opposition that went to hearing in November 2011 in which we invalidated nine of the 11 specific claims on target that comprised approximately top of 11 exon, but we've lost on two of those, exon 46 was one of those. And again commercially not as critical because exon 44 can treat many of those exon 45 dilution patients, but we could not and then claims around exon 51.

So we've been waiting for the summary of that patent opposition hearing and has not been posted, which unfortunately is what start to clock on a potential appeal. So at this time, we are still waiting that decision, but again we believe that we have good arguments on an appeal, and we don't state our specific of strategy. There's no other pending opposition or litigation and again we stated frequently here comfortable with our freedom to operate in the U.S. and Europe outside of the 2 exon targets in Europe that I mentioned.

Regarding the rest of world strategy, we’ve really been focused on gaining U.S. approval initially. We are planning to speak with the EMA about our data set and particularly also around development strategy for a follow-on exon and that will inform up for a European strategy. We are aware of other countries around the globe that use the FDA and/or the EMA has referenced where we might be able to use data to file in those other countries, but at this time first thing is first we're focused on the U.S. to the FDA.

Reni Benjamin – Burrill & Company

Perfect. Thank you.

Operator

Thank you. And the next question is a follow-up question from Chris Marai from Wedbush Securities. Please go ahead.

Christopher N. Marai – Wedbush Securities

Hi Chris, thanks for taking a follow-up. Just a real quick question here you mentioned that you’re producing that what you guys described as mid-scale manufacturing. Could you guide us to what you thoughts are on and what mid-scale constitutes, 5X you did for the last trial or 10X or 100X how should we go about thinking about that mid-scale manufacturing? Thanks.

Chris Garabedian

Sure. I think importantly the way to think about it is that, it’s a capability that we are developing. So while we can talk about what’s one mid-scale batch produce from the drug product obviously that’s going to driven by the yield that we will be producing on a consistent base, which we need to determine those yields and we have some ideas from the small batch yields of what that would do at scale.

So I think it’s important to look at it as a capability that can be reproduce, that can be expanded within one CMO or expanded to other CMO, which becomes a simple issue of buying the equation in and having the space to expand that capacity. But we’ve stated previously that is about five to six fold greater than our small batch of production that we’ve been doing on a consistent basis. And put that in the context that has been the scale that has been producing all of our drug products beyond just to even the eteplirsen 12-patient study.

We’ve had that capability in house for a while and we’ve been using it with external CMOs was as well, but that’s been providing a drug for only eteplirsen or other exon targets for preclinical development as well, as well as our other programs, including our infectious disease program across what was Marburg, the Ebola flu, all of our previous drug programs that had been conducted using it in a different morpholino chemistry.

So again it is important to say we are scaling up because the volume of drug that we expect was on a need for follow-on studies for commercial demand is going to be much greater than we’ve needed historically. And again we’ve said that large-scale would be five to six greater than mid-scale. And there may be a daily talk about super large-scale. So again it’s suffice to say, we are focused on this on getting manufacturing scaled up the right way so that in the future it does not become a rate limiting step for further programs.

Christopher N. Marai – Wedbush Securities

Great, thank you, that’s very helpful.

Chris Garabedian

Okay.

Operator

Thank you.

Chris Garabedian

Operator we just have time for one more question.

Operator

Thank you. And the last question will be from Joseph Schwartz from Leerink. Please go ahead.

Joseph P. Schwartz – Leerink Swann

Great, thanks so much for fitting me in again. I want to ask sort of the flip side of what I and others had asked regarding the manufacturing. And that is, how are you thinking about the likewise that rationing might be required for this drug. I know it might be difficult to answer with any precision at this stage before meeting with the FDA. But then by those things [helping] how do you think that they might be thinking about the need to ration, and then how will that process work of selecting patients?

Chris Garabedian

Yeah Joe it is premature to talk about that, because we have a lot of discussions ahead of us with the FDA. We do know that the FDA has shown precedence and flexibility in situations where there’s a high unmet medical need like duchenne, where the difference of a year or 18 months or two years could be significant for patients. So the idea that it many be better to get drug out there sooner even if we don’t have enough supply to fulfill the full commercial demand.

So we need to discuss that possibility with the FDA, we don’t want to guide or comment. Obviously that’s always a difficult decision process and that would be something that we would in collaboration with the FDA. I think they have used a lottery system for previous, what you are describing as rationing. This week we had dialogue, this a spectrum of disease, right. And we know that it’s very progressive, so it’s really hard to determine how that selection process would go. But all we would be committed to is to try to make it, as reasonable and fair as we possibly can. But again we have to have that discussion with the FDA before we could provide any type of guidance on that.

Joseph P. Schwartz – Leerink Swann

Great, thank you.

Chris Garabedian

Okay.

Operator

This concludes the question-and-answer portion of today’s call. I will now turn the call over to Mr. Chris Garabedian for closing remarks.

Chris Garabedian

Just I would say thanks everybody for listening in to this year-end and quarterly call update. We appreciate the interest, appreciate the questions, we got a lot ahead of us and we look forward to communicating more progress updates throughout the year.

So thanks for your interest.

Operator

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

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