PTC Therapeutics Inc (PTCT) 2015 Q2 法說會逐字稿

Thank you for holding for PTC Second Quarter 2015 Conference Call. At this time, all participants are in a listen-only mode. Following the formal remarks, PTC management will open the lines for a question-and-answer period. Please be advised that the call is being taped at the Company's request and will be archived on the Company's website until August 13, which is two weeks from today.

PTC's current investor presentation slide deck is available at the same website location. At this time, I'd like to turn the call over to Emily Hill of PTC.

Thank you. Welcome to today's conference call to discuss second quarter 2015 earnings results, the commercial launch of Translarna and other corporate updates.

Before we start, let me remind you that today's call will include forward-looking statements based on current expectation. These include statements about our future expectations regarding clinical development, regulatory and commercialization timeline, the potential success of our product and product candidates, addressable patient populations and financial projections.

Actual results may differ materially from those indicated by these statements as a result of a variety of risks and uncertainties including those discussed under the heading special note regarding forward-looking statements and risk factors and our most recent Form 10-Q, which is available from the SEC or our web site.

Such statements represent our judgment as of today and PTC undertakes no obligation to publicly update any forward-looking statements except as required by law.

With that, let me pass the call over to Stuart.

Thanks, Emily and good afternoon. Thank you for being on the call. There's a lot to talk about today. I'll give you a quick overview of where we are and then go into the details. Let's start with Translarna.

After over 17 years of developing Translarna, which is now approved in Europe, it is exciting to be rapidly approaching the completion of our ACT DMD trial. This is the largest study of DMD ever conducted. We anticipate ACT DMD will have top line data available in the fourth quarter of this year. We look forward to a potential US approval and a commercial launch in the first half of 2016.

The commercial launch for Translarna for nonsense mutation DMD is going quite well. As of June 30, Translarna generated $11.2 million in product sales revenue year to date. There are now 106 commercial patients on therapy and we are shipping Translarna to 12 countries, including our first shipments to Brazil via Reimbursed Named Patient Program. We continue working closely with health authorities to bring Translarna to patients as quickly as possible.

Now let me turn to our efforts in cystic fibrosis. ACT CF our Phase III trial with Translarna is on track to complete enrollment by the end of this year. We are now preparing an application to add nonsense mutation CF to our label in Europe. This application will be based on results from our previous Phase III trial, including new analysis of our data, which will provide us with increased confidence in the positive benefits of Translarna for nonsense mutation CF patients. I'll provide more detail on this analysis in a few moments.

I'm also very excited about our SMA program, which is a collaboration with Roche and the SMA Foundation. As you may recall, proof of mechanism based on increased efficiency of SMN2 RNA splicing was demonstrated in both Phase I and Phase II studies. Dosing in the MOONFISH trial with temporarily put on hold in May, based on the preclinical eye finding seen in a long-term study in monkey. We've learned more about this finding.

Studies conducted so far combined with additional preclinical data expected in this fall could allow dosing of MOONFISH to resume in the first quarter of 2016. I'll address to this program later on today's call.

Let me take you through more details of what I just outlined. In terms of the commercial activities for Translarna in Duchenne muscular dystrophy, we are extremely proud to have launched the first approved treatment for nonsense mutation DMD to patients with this life-threatening disorder.

Translarna reads through nonsense mutation to produce full-length protein and therefore addresses the underlying cause of the disease. Translarna was approved by the European Medicine Agency for the treatment of nonsense mutation DMD in ambulatory patients aged five and older, last August and the commercial launch began at the end of last year.

Translarna's commercialization outside of the US is a staggered country-by-county reimbursement process. In Germany, we are very pleased to have received a G-BA rating of three out of a scale of six. This is important as it acknowledges Translarna as having convincing evidence of a clinically meaningful added benefit to patients. We are proud to receive this rating as it is another recognition of the importance of Translarna for nonsense mutation DMD patient.

We are also working through market access in the UK. The UK is in the process of putting in place a mechanism for budgeting ultra-orphan drug. As part of the process, NHS England has decided to include input from NICE resulting in a delay of the funding decision. We thank the patient groups and physicians for their ongoing support and we will continue working through this process to bring Translarna to DMD patients.

Translarna is now directly commercially available in four EU countries. We also have Translarna reimbursed in eight countries through reimbursed early access program in both Europe and Latin America. We are now shipping product to patients in Germany, Spain, France, Italy, Greece, Austria, Denmark and Norway. Outside of Europe, we are shipping product to patients in Turkey, Israel, Colombia and most recently Brazil.

Brazil is one of the largest markets in the world and it's worth noting the unique process they have for reimbursed early access. For patients with high unmet medical need physicians can request access for drugs for treatments they believe provide benefit to patients.

On a case-by-case basis, the Brazilian courts can authorize reimbursed access to these drugs. So far we are aware of about 18 patients who have gone through the individual approval process and are in various stages of gaining access to Translarna. We recently began shipping Translarna to the first of these patients through reimbursed early access.

As part of our commitment to patients, in the second quarter we also initiated the siblings program for brothers of patients involved in our DMD trial. For families with more than one child suffering from nonsense mutation DMD having only one child enrolled in our clinical trial with the access to Translarna can cause great threat. We worked to find a solution to ensure both siblings who were not eligible to participate in the trial can still have access. Because of this program brothers in both Europe and the US are now receiving Translarna.

As of July 28, we now have 106 DMD patients receiving Translarna in reimbursed program. This can be either through reimbursed early access or direct commercial sales. We will continue to provide patient numbers for the remainder of the 2015 fiscal year and will then assess what metrics to report to the investment community in 2016.

In addition to the 106 patients on commercially reimbursed Translarna, we currently have approximately 375 patients in our clinical trials and extension program. This was a total of approximately 500 DMD patients currently on therapy. As Translarna becomes commercially available we expect to transition a significant portion of these patients to commercial therapy.

We are also preparing for a US launch in the first half of 2016. As a reminder, we began submitting a rolling new drug application to the FDA for Translarna for the treatment of nonsense mutation DMD in December of last year. This has given the FDA an opportunity to review the majority of our materials ahead of our submission of the data from a confirmatory Phase III at ACT DMD trial. Top line results are expected in the fourth quarter of this year.

As you know Translarna is also rapidly advancing in nonsense mutation cystic fibrosis. Nonsense mutation CF is the most severe form of the disease for which there are currently no other treatments available or in development. ACT CF our second Phase III trial is on track for enrollment to complete by year-end. We anticipate results will be available in the second half of 2016.

We are in the process of finalizing an application to add CF to our Translarna label in Europe and are on track to submit this application to the EMA later this year.

In conjunction with our preparation for this submission we have been in discussions with experts and held numerous advisory board meetings. Natural history data indicate that while older patients tend to have a more gradual decline of pulmonary function, patients under 18 years of age experience more rapid rates of decline. In light of this data, PTC performed additional analysis. As a reminder, in our initial Phase III trial, our post-hoc analysis of non-TOBI patients overall showed an absolute change in FEV1 of 3.5% and a relative change of 5.7% plus a decrease in exacerbations of 41% versus placebo.

Our new analyses demonstrate that the subgroup of non-TOBI patients under 18 years of age experienced a robust treatment response including an improvement of FEV1 above baseline of 5.4% absolute benefit and an 8.4% relative benefit in FEV1 versus placebo. Importantly, the non-TOBI patients under 18 had a decrease in exacerbation of 60% versus placebo. We believe this analysis is an important new finding and plan to include it in our CF submission to the EMA.

As Translarna is already approved in Europe for DMD, the CHMP's initial review of the CF submission may be completed in as little as three months. This could mean a European launch of Translarna in nonsense mutation CF in the first half of 2016.

We are preparing for the potential that in the near term we could be simultaneously expanding Translarna's commercial access for DMD outside the US while launching for DMD in the US and launching for CF in Europe. We've continued to develop our global footprint to be ready for these commercialization opportunities. We now have a presence in over 30 countries across Europe, North America, South America and Asia-Pacific region. While this is quite exciting it's just the beginning.

There are many disorders with high unmet medical need where no existing treatment is available. The value for Translarna lies in its potential to benefit patients across the vast array of genetic disorders caused by a nonsense mutation. Our strategy is now to rapidly expand the clinical development of Translarna across multiple genetic disorders.

On average, 11% of every minute genetic disorder is caused by a nonsense mutation. There are now over 30 publications demonstrating Translarna's activity in many preclinical nonsense mutation disease models in different organ system. We are currently pursuing four initial indications in distinct areas, a neuromuscular disorder, DMD; pulmonary disease, CF; lysosomal storage disorder, MPS I and an eye disease aniridia.

Translarna truly is a pipeline within a product. We are setting our sights to deliver on our commitment to address rare and neglected disorders by pursuing a strategy for Translarna's pipeline expansion, which we are calling Ten by 20. By 2020, we plan to investigate at least 10 nonsense mutation indications in the clinic in order to maximize Translarna potential in both the product and the pipeline.

Let me now shift to the SMA program. SMA is a genetic neuromuscular disease caused by a missing or defective SMN1 gene, which results in reduced level of SMN protein. Insufficient level of SMN protein are responsible for the loss of motor neurons within the spinal cord leading to muscle atrophy and death in instance in toddlers in its most severe form. SMA is the leading genetic cause of death in infants. There are no marketed therapies for SMA.

RG7800 is an orally available small molecule that is being investigated for its ability to modify the splicing of the SMN2 transcript towards the production of full length mRNA. A tremendous amount of effort and resources have been put into this SMA program by all three collaboration partners.

Data from our Phase I study in healthy volunteers were presented at the annual meeting of the American Academy of Neurology in April. These results showed a dose dependent effect of RG7800 on SMN2 splicing demonstrating proof of mechanism.

After a single dose, there was approximately an 80% increase in full-length SMN to mRNA production. Based on the Phase I result, a Phase II multi-dose study MOONFISH was initiated last November in SMA patients. The primary objective of this trial is to investigate the safety and tolerability of RG7800 with pharmacokinetics and SMN biomarker as secondary measure.

Dosing of the first cohort of MOONFISH was successfully completed in April. RG7800 was well tolerated and preliminary review of the blinded data indicate substantial increases in SMN2 full length mRNA. These data are in line with the results from the healthy volunteer study and represents the second independent study showing proof of mechanism.

We announced on our last earnings call that the dosing of MOONFISH was temporarily suspended as we evaluate the non-clinical eye finding seen in monkeys after nine months of dosing at exposure levels above those dosed in the clinic. I want to remind you that the safety, tolerability and pharmacodynamic data observed with RG7800 in the clinic so far are encouraging and these pre-clinical findings in the eye have not been observed in humans. We have been working to understand this eye finding including performing additional preclinical studies. The results of these studies combined with the final study that we'll complete this fall could allow MOONFISH to resume dosing in the first quarter of 2016.

We are very excited about the SMA program. Previous and new publications have highlighted the importance of having SMN protein both in tissues within the CNS and peripherally. These results from these publications are significant as they emphasize the importance of a drug that can distribute both in the CNS and in the peripheral tissue. Our orally available small molecule have demonstrated broad tissue distribution in addition to crossing the blood brain barrier, which we anticipate would be advantageous in the treatment of patients with SMA.

Let me now turn to over cancer stem cell program targeting BMI1. BMI1 is up-regulated in the tumor stem cell population and it is an important component of the complex that allows cancer cells to become resistant to chemotherapy. As you may recall, our compound PTC596 reduced the levels of the BMI proteins in preclinical models. I'm very proud to have a fourth internally discovered program at PTC entering clinical development. PTC 596 entered into a Phase I study in the second quarter in advanced cancer patients with solid tumors. We are excited about this program and we'll keep you abreast of the progress as we move forward.

Furthermore, we have a number of interesting research programs that continue to progress. In addition to Translarna we have a nonsense suppression platform that is growing. We have follow-on program underway and are identifying a number of promising compounds to help maintain and extend our franchise in nonsense suppression of disorders.

With that let me turn it over to Shane. Shane?

As Stuart mentioned earlier, Translarna sales continue on a strong trajectory and we've now generated year-to-date June 30 sales of $11.2 million. In the second quarter, we recorded $6.2 million in Translarna net product sales representing approximately 69% sequential growth over the $3.7 million of normalized sales in the first quarter of this year, which excludes $1.4 million of deferred revenue booked in Q1 from 2014. As a reminder, in 2014 we had been recognizing revenue on a cash basis.

Total revenues for the second quarter of 2015 were approximately $6.8 million, compared to the prior period of $1.7 million. In addition to our commercial product sales we recorded $0.6 million in collaboration in grant revenues in the second quarter of 2015.

Research and development expenses in the second quarter were $28.2 million compared to $18.3 million for the same period in 2014. R&D expenses have increased year over year as a result of additional costs associated with our expanding clinical stage pipeline.

SG&A expenses were $17.2 million for the second quarter of 2015, which compares to $88.7 million in the same period last year. SG&A expenses have increased [year-over-year] as a result of the growth we are experiencing associated with our commercial activities in support of the launch of Translarna across Europe and other regions.

Our organization is growing across many roles both for the ex-US launch activities as well as in preparation for a potential US launch in the first half of next year. We reported a net loss of approximately $38.4 million for the second quarter of 2015 compared to approximately $25.1 million for the same period of 2014.

Additionally, we finished the quarter with $255 million in cash and marketable securities on our balance sheet and no debt. We currently have $34.2 million shares issued and outstanding, which includes $0.4 million shares in restricted stock grants.

Joining us for our Q&A is our Chief Commercial Officer, Mark Rothera. Operator, can we please take the first question?

Thank you. (Operator Instructions) Anupam Rama, JP Morgan.

Just wondering -- just two quick ones, if you could talk to a little bit about the sequential patient adds either in the commercial sales countries or the reimbursed access countries as well and if there is any difference there? And then if you could give us a sense of how mapping in Europe is going to for nonsense mutation DMD patients to the specific centers of excellence, so if you can give us an update there?

Yes, thanks for the call, Anupam. Maybe I'll have -- Mark, why don't you take this?

Okay. Thanks for the question. So clearly we're very happy with the way the launch is progressing. As we saw we delivered $11.2 million in sales year to date. And as you said, a 69% growth Q2 over Q1 from a revenue perspective. As we are going through the launch process, I think you quite rightly outlined that what we're doing is we're overlaying sort of sequential launches from countries and early access countries all at slightly different rates of uptake and system.

So it can be a little bit lumpy, it's not a linear add, but what's really great is that we now have 12 countries, up and running. And as Stu said, we have a footprint now that gets us over to 30 countries around the world. And just to illustrate that lumpiness, just in the last two days since we declared 106, we have already another four patients that have gone on to drug. So that brings us to a total of 110. So, it's a very dynamic situation.

You also mentioned patient identification. This remains a very high priority for us as an organization. This is a very rare disease. We are of course the first to launch a drug in this area and we've been focusing on mapping patients to centers in Europe. So, for example, in the big five EU, we're around 40% of the expected prevalence now mapped. And we continue to create awareness around the need for genotyping and extending our presence in some more centers, if you like, some of smaller centers where the DMD patients are. So we continue to grow the number of maps and identify patients in Europe day to day.

Tazeen Ahmad, Bank of America.

The first one, Stu, when do you think doctors will be in a position to talk about the efficacy that they're seeing with Translarna in the commercial setting? I know that their view is that because it's a safe drug everybody will try to prescribe it to their nonsense mutation patients. But based on what you know about the drug and the natural history of the disease, how long do you think it would take to really tease out what kind of effects its having?

Thanks for the question. Obviously, I think we talk to patients throughout the period and so I think there has been anecdotal discussion about the efficacy. So, I think we feel pretty good. We've heard a lot of indications of what they're doing and so I think there is -- so I think we feel pretty good about is. Also, I think that goes along with the fact that there is high compliance also, I think which is also indicative and helpful that gives you a pretty idea that people are staying within the trial as well. So it's been very strong in the early stages and I think this is really quite telling.

And then I think while we here considerable amount of anecdotal information, I think the other thing that we have set up in place especially for commercial sale is the registry which over time will collect data. And really the purpose there is, well, we have demonstrated that Translarna changes the course of the disorder, we'd like to get long-term data over time and I think the best way to do this is through registry. So I think we feel -- I feel pretty bullish about, I feel really good and this along with the registries would be very helpful.

And are there any other details that you can share about the SMA program? Thanks for the update. What gives Roche the confidence that they can restart the trial or enrolling the trial again in 2016?

That's an important, so SMA, so as you remember I think there a couple of important points here. Right, this is an orally available drug that distributes quite well throughout the body, so it goes into all tissues, and we showed that both in animal models, both the periphery as well as in CNS, we've been able to see substantial SMA changes. And then in the Phase I as well as in the Phase II we saw striking changes. What's really important is we know that the drug effects we have in activities. So that's really important, and that we didn't see any alteration in the clinical. This was really a preclinical finding and what was really important was, as we said we put this on hold while we understood the preclinical find.

We obviously had to -- we learned a lot about, obviously the importance of the monitorability and so I think that was one thing that gave us confidence that there is a strong path forward. I think that was the key point in there.

So along with the preclinical work that's ongoing as well as some data that's expected, I think that in itself would allow us to have the potential to start in the first quarter of next year. And maybe the next point I think would be -- the other thing I also want to make, but this program has been -- is incredibly important obviously to us and Roche as well as the SMA (inaudible) community as a whole. And so this has been a very strong program and so were overall very excited about RG7800 moving forward. It was obviously a large amount of chemical optimization. We've always had a strong program to have additional molecules to move forward and that's always something that we have in the background as well. So I think what gives us a lot of confidence is that we have a strong program with RG7800 as well as additional other compounds.

Okay. And then maybe one last question, maybe this is for Shane. Do you have any idea of when you'd receive the input from NICE in order to be able to launch in the UK?

Yes, maybe we will give a little bit of color here. So just to give everyone a little background, the NHS England has delayed the overall process and therefore they've asked for a specialized review. So maybe I'll have Mark if you want to give a little more detail on the overall process and where we are at.

Sure. So across the context is the 12 countries have already made the decision to reimburse Translarna, including eight in Europe, including big countries like Germany, and France, and Italy and Spain, and as you know NHS England has been putting in place a new mechanism to evaluate the funding of highly specialized and orphan drugs over the last six months.

And we had expected the NHS England was going to make an independent decision on the funding in June. However, we learnt in late June that they decided to wait for NICE's inputs, the National Institute of Clinical Excellence, and often the NHS does rely on NICE recommendations to determine funding decisions. So we're expecting NICE will produce a draft guidance on Translarna in October with a final decision in February. So we're now highly engaged in the NICE process and will continue to work to help the patients to get access to this treatment as quickly as we can.

Geoff Meacham, Barclays.

Stuart, why don't you talk a little bit about the additional indications for Translarna, the 10 indications? Have you guys looked into this from the standpoint of being able to do a trial with a number of different indications, assuming that they're smaller disease markets, for things like using surrogate endpoints or biomarkers or do you feel like one by one you have to tackle them as you did with DMD and CF and down the road MPS and aniridia?

Thanks, Geoff. That's really a good question. So what we've done thus far, as you said is CF and DMD, we've done independently and obviously, if you think about (inaudible) new chemical entity and DMD was a new indication and so a new therapeutic area with a new mechanism of action. So we started out one by one and we are, as we said after CF and DMD is aniridia and MPS and then we're look at a number of others. But I think you actually have a very good point. And if you think about some metabolic cycle diseases where various mutations can lead in the sense -- in the same cycle and that you may look at certain metabolic diseases and be able to in a sense, in specifically small numbers, put them together and use in the sense of similar output. And so you have a very good point that that's one of the things that we're considering. You can do that with some of the lysosomal storage disorders as well as well as some of the eye diseases.

So I think in some ways we're looking at doing some one by one, some we're doing thinking about it exactly the way you placed it. And then others, we may do some physician investigator trials as well on on some of those. So, I think we're going to take a multi-prong approach to this.

And the way I think about this is as we've got the first European approval on the precipice of completing this trial and then having -- in Translarna in a sense we're changing from right early on you're usually quite protective of the molecule. Now we're in this position now to really try and expand this to bring it to as many patients as possible so it creates value for them and also our investors.

So I think that we're really at the right time to really get this going right now and that's what we're going to be pretty aggressive about.

Then just a follow-up on an earlier question, just on commercial. In some of the countries that you've launched that for the longest period, is there any trends with regard to time to get reimbursement for that process to complete? I'm just curious how you guys can optimize that even further?

So thank you for that question. What tends to happen is that you have really trends according to each different country system so that in a country where the reimbursement is a relatively efficient process things go very quickly. There are some countries where it's case by case. We've mentioned Brazil which is third or fourth largest market in the world when it comes to treatments of this nature. Those are case by case applications from physicians and patients that have to be adjudicated in the court case by case. And so that can take some time although we are very pleased to have learned just recently that already the courts approved 18 cases in Brazil and we've already initiated shipments to the first of those patients. Again, it's not really so much in one country specifically those variations, but you see variations between different countries.

Heather Behanna, Wedbush.

Firstly I just had a question on the cystic fibrosis data, the new data. I was wondering if you could just give us some color on how large the subgroup is of patients under 18 who were not on TOBI. And if we might see those data at NACFC or at another conference coming up soon?

Yes, I think we're looking to present and I think part of this is -- actually if you go back and think through our understanding the natural history, and I think there's been a lot of work in CF and really trying to understand this better and from our learnings from the DMD and how important that is to look at particular groups of which you'd expect to see larger differences. And certainly the patients who are under 18, well, they have higher FEV 1, they tend to see greater declines and so you might see better effect of that and that was what we've been talking with some of the key experts. And so we did that and the good news is that the groups were well balanced. So that was a stratification factor going to less than 18. So that's what's made it actually a well balanced, so the groups are well balanced and those about -- in that group about 25 patients or so per group.

So we feel pretty good about this data that it is actually helping, giving a stronger view of seeing an improvement and it's actually an improvement above baseline. So we'll be presenting that at a conference in the near future.

And then I also just had a question on the SMA program. You've been alluding to a study that will be reading out in the fall. Can you give us any color if that's something that you're working on monitoring, how potential toxicity arises or if you could give us any color on whether or not it's reversible or any other information?

Yes, sure. So, yes we've been doing -- obviously the importance as we said about monitorability and then also as part of usually preclinical studies there is a recovery portion that you can monitor. So we just wanted to complete the recovery portion of that. So that's what we will be doing.

Christopher Marai, Oppenheimer.

Thanks for taking the questions. Just another update I guess on cystic fibrosis. Thanks for the new data but I was wondering if you could also comment on the rate of enrollment in that trial. And when do you think that will be complete and perhaps why it might be slower than I guess was originally anticipated and if it is holding up the cystic fibrosis conditional approval filing for Translarna in the EU?

No. Yes, thanks for the question. I think that's a good question. We are actually -- we are happy with the CF enrollment. I think what we have been saying that it will be completed by the end of the year, and as such that contract and that's what we are doing. We are now preparing the filing so that we will get that in. So I think we feel pretty good about this. So I think yes -- no I think all cylinders are firing pretty well here and we are excited to be doing this.

Okay then with respect to the exclusion of tobramycin, is that causing any issues by your estimation?

So just to remind everyone tobramycin compound had a launch activity and so we are not really finding this to be a real issue. The physicians can move patients to other inhaled antibiotics and so we haven't' really found this to be a problem. And so -- and I think that is reflected by just that we are pretty well on track in terms of what we thought enrollment would be.

The only thing that needs to be if anyone was on inhaled tobramycin there needed to be a wash-out period prior to the trial but beyond that I don't think we've really seen any real issue.

Okay, great. And then I am wondering if you could just comment perhaps on what you are seeing from the expansion trial for Translarna and DMD. I know you are running central for Phase II as well as of course new enrollment in the expansion study from the Phase III. And also with respect to that are you aware of this six minute walk with that extension study enrollment and does that give you further confidence in the readout for the Phase III trial? Thanks.

Yes. So the extension trial is ongoing both in the current trial as well as the extension trial have been going on for the previous trials as well. Now there was a data where we stopped the trial and then restarted. And in the case of the US obviously we were just doing safety. So we are gathering those data over time. We are very encouraged that the majority of virtually all the Translarna patients have stayed on therapy and we have patients sum up to four year and have been very well tolerated. So we are in the process of collecting or have collecting all the safety and efficacy. There is not a lot of data there yet to actually present but at an appropriate time we would plan to, so once we have the complete data set. So that program is ongoing.

Ritu Baral, Cowen & Company.

The first question is on how you're going to release the DMD data in Q4 as you've guided, obviously all the primary endpoint six-minute walk data, but do you anticipate having some of the other key secondary end points at the time of top line data release? And if so, would do you consider with those most important secondary endpoints, whether it be North Star or some of the function test including rise from the floor. Any thoughts on that right now?

Yes, no, thanks for the point cycle question. I think yes as we said we plan to release the data sometime in the fourth quarter of this year. I think our goal will be to certainly tell you about the primary top line data. The most important of those data are those -- what must be key secondaries at the time of function test as well. And then those (inaudible) are more tertiary endpoint. So clearly the six-minute walk test and depending on how quickly you release the data, how much we will know but I think we are planning to as soon as we get the data. We are excited about this and once we complete that analysis we will put a report out there for you.

Got it. And I get back to the SMA update that you gave us. You mentioned additional preclinical studies that you guys were going to start. Can you tell us a little bit more about those and what physiology those focus on?

As we said we were -- this was an eye finding and we wanted to just understand some ongoing studies to understand more about metabolism, the normal things that one would do. And then looking at making sure -- obviously looking at how do you monitor and things like that was important. So that's sort of thing that we would be doing so that we can then go and say yes we understand the safety issues and potential safety issues that could be, how to monitor it and what it looks like after recovery. And so those are things that are ongoing right now. So I think at the end of the day I think we as part of development program we feel we are learning about this and this data will be all put together in the fall so that or completed so that we then based on this data we have this could allow MOONFISH to restart in the fourth quarter 2016 -- first quarter, sorry, first quarter.

Are the new studies just in monkeys or are they across multiple species?

So right now -- this is the recovery obviously was the monkey portion. Other than that just as constrains of partnership, the precise details I am not able to disclose right now.

Got it. Back to the new CF analysis that you presented. Was that something that was asked for by the EMA or something that PTC thought was important? I am just trying to get to if there are may be implications for any potential label in the EU?

No. This is something that we were thinking about as well as, when you think about stratification factors and the understanding of the natural history that really there's been -- considering the amount of work that has been done in CF and natural history that people are looking at more carefully. It looks like really that there is this where the rate of decline occurs more rapidly in the younger patients and then in terms of pulmonary function you see a plateauing after a certain age in terms of -- or slowing of the rate of law. And so that -- so it's really that sort of analysis and talking with key opinion leaders, experts in the field that based on this really important and learning that we said, went back and looked at this to take a good look at it, it really was to be able to see the 8.4% relative increase which really above baseline and the 60% reduction in the exacerbation in this group helped really give and really excited the experts in the field and gave us confidence, continued confidence of the data. So this is going to be part of our submission.

So it was more a PTC and KOL driven analysis?

Yes.

Okay. And last question really quickly. Are you still on track for MPS1 biomarker data by the end of the year?

I think so. What we have been saying is that we've announced that the trial is ongoing and that we are going to have some data. Our plan really is to have some data by the end of the year.

Simos Simeonidis, RBC Capital Markets.

Thanks for taking the question. This one is for Shane. Shane, just to make sure we are comparing apples to apples, in terms of net revenues for Translarna the $6.2 million for this quarter, should be compared to the $3.7 million for Q1, meaning there's no deferred revenue including the $6.2 million.

Yes, that's right, Simos. If you recall in 2014 we were recording revenue on a cash receipt basis where we booked actually I think about $0.7 million of revenue in 2014 and had deferred receipt that had not receipt cash payment into 2015. That was then recognized in the first quarter when we had enough of a track record of end receipt that we felt comfortable changing our accounting to record revenue on shipment and change of ownership and therefore the first quarter we recorded $5.1 million of Translarna product sales which was comprised as you point out of $3.7 million of really Q1 demand plus the recognition of the $1.4 million from the 2014.

Okay, great. And then as you are going into other countries and geographies, in terms of price per patient, should we still be thinking of the $300,000 per patient per year number?

Yes. I think we are very still very consistent in terms of our own internal thinking about how we think about the price per patient per year still being $300,000.

Perfect, last one. This is probably for Mark. Mark, if you can help me understand maybe the progression of the launch. In the three iterations of the numbers of patients you have given, tell me if this is being an unfair comparison what I am going to say, the first number I saw was 42 patients roughly for the first two months of the year, it was February 21. Then had another 40 for the next two months for the year by April 30. And now for the next two months it was down to 24 patients.

Is it that it is going to be kind of lumpy as you get maybe just one more country for example instead of three to four countries quarter to quarter versus this being a slowdown in the number of patients you are getting on.

Yes. I think that this is in the very early stages of launch. What you are seeing is that lumpiness due to the fact that you get boluses of patients for example coming on as you get say a major market that opens up and you get a bolus and then -- so what you are doing is you are sort of overlaying this very different markets with different situations. So it's not going to be a steady state growth scenario yet. It is going to take us a while before we have a large enough massive countries and we have long enough trajectory of sales to start getting some more predictable pace of patient add.

But as I say I think the thing that is very encouraging is that we are getting great feedbacks from the markets where we've already launched. We are already in 12 countries now and because our footprint has grown to now 30, we expect to see more countries come on stream and to increase numbers of patient accrual in existing countries.

And then actually to Mark's point really, if you think about it like we had the cut-off date like July 28 but in the last couple of days we just got four patients. So it goes and it's just unpredictable when they come up. So I mean just shows you from 106 to 110 in two days. So I think at the end of the day we are pretty happy about how it is progressing.

Okay, great, sounds good. Congratulations on all the progress.

Thank you.

Thank you.

Robyn Karnauskas, Deutsche Bank.

Hey guys this is Ale on for Robyn. Thanks for taking our questions. So in terms of DMD what kind of penetration levels look like in some of the countries that have been reimbursing the longest such as Germany? And then also what are your thoughts on the DMD panel in the fall and the way to PTC and with your enrolling submission do you think you will be at the panel?

Mark, why don't you do the first part?

So well Ale sharing with you overall patient numbers on retrospective basis we are actually not going into details on a country by country basis. So I am not in a position to share with you specifics of our market share in a country. But I think you can see from the overall numbers how we are like growing and how that supporting patients in more and more countries.

And then in terms of your question on the potential panel, I think right now I think what's been reported is that there is planning to be an advisory committee in the November time frame of from the neurology panel so it is not obviously interesting to think that there will be one. Obviously we could welcome the opportunity to participate in the DMD panel and there is pioneers in the space. We've obviously been very deeply invested into development of therapies for DMD patients.

We have had numerous conversations with the FDA and I think they have even been able to -- they told us that we could tell everyone that this is really of their highest priority and that we could tell that to everybody. And so what we are doing is working closely with them in terms of what's the fastest route to get and allowing the patients as quickly as possible and as we go through this process we will keep you posted on how we agree and what's the best way to move forward in this.

(Operator Instructions) Debjit Chattopadhyay, Roth Capital Partners.

Just wondering on the CF data, is it fair to assume that a bulk of the benefit is being driven by the younger patients and how does that reflect on the ongoing ACT CF study in terms of enrollment? Are you specifically enrolling an X amount younger patients or it's too late to change enrollment criteria?

Good question. So I think what we've done is to -- that there was -- if you think about it that is the less than 18 years old there was about a 8.3% improvement above compared to placebo and then the less than 18 there was about a 4.3% relative improvement to placebo. So you see a bigger effect. And I think obviously the criteria for entry into the trial is basically similar to -- the current trial is similar to what was previous and so we expect to have a fair number of patients that will be less than 18 years of age and that what we will do obviously is within the plan is also makes this an important stratification and part of an analysis. As well as looking at the overall we will look at this group as well. But I think at the end of the day we expect to see a statistics with significant improvement in pulmonary function reduction that's the basis that would be just larger in this particular group. So we feel pretty good about it.

And since Translarna is largely a weight based drug, I'm just trying to understand what the average age of the patients are on the commercial drug right now. Just to get a sense of what the physicians are thinking, are they putting the younger patients on the drug first or they are putting the older patients?

Thanks for that. That's a good question I think right now our -- what we have on label is five years and greater that are ambulatory, so they are predominantly putting in patients that are five years and older. So the spread of that is as long as they are capable of being ambulatory, so we get a spread of that.

You'd mentioned 106 patients and then four more recently added. And there was a 18-patient number from Brazil. Just wondering, does that 106 include the 18 patients or Brazil shipment was just one or two patients and it's really not indicated in the 106 or 110 number as yet?

Yes. I think what I was giving you as an example was the 18 that we know that the courts have approved but we've only just initiated in the first one or two patients. So there is a lot of works still to do to ensure that we are supplying those other patients that the courts has approved.

Great. One last question on the SMA program, so when you expect to restart it, would you think you're going with the highest dose which was I believe the 90 milligrams or do you think you would need to go with a lower dose to avoid eye toxicity, if any? And in terms of impact on the SMN2 copy number with the lower dose versus the higher dose? Thank you so much for the questions.

Yes, thanks for the question. Yes, so as we move forward on and make the decision to move forward and initiate dose we'll probably give more color to that at that point. So right now we are not disclosing much more than that. Thanks for the question.

I'm not showing any further questions at this time. I would now like to turn the call back to Stuart Peltz for any closing remarks.

Yes. I want to thank you all for joining the call this afternoon. In closing, we are really very pleased with the progress that we're making to drive the growth in 2015 and beyond. We're quite encouraged by the early results of our Translarna launch and product sales revenues that we've generated. And we're excited about our growth prospects both in DMD and CF and look forward to advancing the solid pipeline we have built that we hope will bring value to patients with rare and neglected disorders.

So, thank you for the time -- taking time to be here this afternoon.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude today's program. You may all disconnect. Everyone have a great day.