PTC Therapeutics' (PTCT) CEO Stuart Peltz on Q4 2017 Results - Earnings Call Transcript

PTC Therapeutics (NASDAQ:PTCT) Q4 2017 Earnings Conference Call March 6, 2018 4:30 PM ET

Executives

Emily Hill - Head of Investor Relations

Stuart Peltz - Chief Executive Officer

Marcio Souza - Chief Operating Officer

Christine Utter - Principal Financial Officer and Treasurer

Analysts

Derek Yuan - Credit Suisse

Joel Beatty - Citi

Eric Joseph - JP Morgan Chase

Tazeen Ahmad - Bank of America

Gena Wang - Barclays

Raju Prasad - William Blair

Brian Abrahams - RBC Capital Markets

Operator

Good day, ladies and gentlemen, and welcome to the PTC Therapeutics Fourth Quarter Financial Results Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. [Operator Instructions]

And I would now like to introduce your host for today’s conference, Miss. Emily Hill, Head of Investor Relations. Ma'am you may begin.

Emily Hill

Thanks. Hi, good afternoon, and thank you for joining us to discuss our 2017 fourth quarter and full-year corporate updates and financial results. Joining me on today's call is our CEO, Stuart Peltz, our Chief Operating Officer, Marcio Souza and our Principal Financial Officer Christine Utter.

Before I had the call over to Stuart, I would like to remind you that today we will be making forward-looking statements. These statements include all statements other than those of historical facts, including statements concerning financial guidance, our expectations with respect to the future commercial availability of and access to EMFLAZA and Translarna the timing and outcome of any future re-submission of an NDA for Translarna to the FDA, our future expectations regarding other clinical, regulatory and commercialization matters, including with respect to potential outcomes and anticipated timelines, anticipated timelines of our SMA collaboration with Roche, addressable per patient populations for Translarna and EMFLAZA, and the potential success of Translarna for the treatment of nmDMD and EMFLAZA for the treatment of DMD.

Actual results may differ materially from expressed or implied by forward-looking statements as a result of a variety of risks and uncertainties including those related to our commercialization of EMFLAZA and Translarna, including our ability to secure adequate pricing, coverage and reimbursement terms of third-party payers for our products in a timely manner, whether and to what extent third-party payers impose additional requirements before approving EMFLAZA prescription reimbursement, our ability to integrate EMFLAZA into our business and realize the anticipated benefits of the acquisition, changes in margin regulations, our ability to resolve the matter set forth in the denial of our appeal to the complete response letter we have received from the FDA in connection with our NDA for Translarna for the treatment of nmDMD, and those risks discussed under the heading forward-looking statements and risk factors in our Form 10-K for the year-ended 2017, which is available from the SEC and on our website.

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. We will disclose certain non-GAAP information during this call. Information regarding our use of GAAP and non-GAAP financial measures and a reconciliation of GAAP to non-GAAP is available in today's earnings release.

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

Stuart Peltz

Thanks, Emily. And thanks for joining us on this afternoon. Joining me on the call today are our Chief Operating Officer, Marcio Souza and our Principal Financial Officer Christine Utter. Marcio will provide the commercial and clinical development updates, which will drive our next phase and growth. Christine will end the call with a thorough review of our strong fourth quarter and full-year and our financial outlook.

2017 was a great year, we continue to grow our DMD very tight which included expanding Translarna use around the world. Furthermore as you know, we acquired EMFLAZA based on its differentiated efficacy profile and are providing access to patients in the United States.

As a global commercial stage rare disorder company with a growing pipeline we are pleased with the progress we are making to deliver innovative medicines and drive better outcomes for patients with rare disorders.

We are proud that 2018 is our 20th year in operation. Over the past two decades, we have worked to bring therapies to patients with rare disorders beginning with Duchenne Muscular Dystrophy. We discovered developing commercialized Translarna on our own. We have patients who have been on extension trials in the United States since our earliest clinical trial more than 10 years ago.

We have learned so much from working with these patients, including the importance of treating patients early and maintaining therapy and improving standards of care, because we know everything matters for Duchenne patients, we have been working diligently to bring Translarna to patients around the world, including the United States. We are pleased to have a path forward towards an accelerated approval so that U.S. patients like others around the world may have access to this important therapy.

Looking forward, we are well-positioned to continue to execute on our mission of discovering, developing and commercializing differentiated therapies for rare disorders. This includes continuing to build our research and development pipeline and to commercialize therapies so that patients have access to these important treatments.

Our commercial success with both Translarna and EMFLAZA is a reflection of our understanding of the unmet medical needs for DMD patients. We work diligently to ensure patients have access to therapies that make a difference to them.

We are now in the position of having two commercial products and we have built an effective global commercial operation. We seek to leverage our commercial platform by continuing to deliver new and differentiated therapies in rare disorders, which is in line with our mission and commitments to patients.

Our commercial execution has led us to a strong year-over-year revenue growth. In 2017 Duchenne franchise generated $174 million. Translarna reported revenue of approximately $145 million a 78% increase over the prior year. EMFLAZA reported revenue of approximately $29 million in 2017, having just launched in May. Our guidance for the Duchenne franchise for the full-year 2018 is between $260 million and $295 million.

As we announced on February 20, we received a response to our formal dispute resolution request for Translarna from the FDA's office of new drugs. While the office denied our appeal, they did recommend a possible path forward using the accelerate approval framework. The office of new drugs stated that they would allow a recondition of NDA containing the current data on effectiveness of ataluren with additional new data to be generated on dystrophin production.

While we demonstrated dystrophin production in the previous clinical trial in Duchenne patients using methodology available at that time, we will work with the FDA to design the study, which will utilize current validated methods to measure dystrophin. We are optimistic that this is a fusible path towards approval in the United States and we are working expeditiously to pursue it.

Before moving onto other updates I would like to take a moment to thank to the Duchenne Community for their continued support during the FDA process. We have heard from hundreds of patients and their caregivers, both families and physicians from across the world. Many wrote letters to the FDA and traveled to our Advisory Committee to speak about the positive impact Translarna had in their lives.

It is our goal ad intent to bring Translarna to the United States patients so that they have the same access and benefit experienced by [nonsense] (Ph) mutation Duchenne patient around the world. We want to make it clear that the U.S. clinical access programs will remain in place, while we are pursuing the path forward with the FDA and that the patients who are currently on Translarna will be able to remain in this program.

Let me know turn to our internal science research programs and pipeline. We are proud of these efforts and how they are progressing. Starting with our internally developed splicing platform the first oral small molecule as a treatment for its SMAs advancing in the clinic. The program is currently in pivotal studies in partnership with Roche and the SMA Foundation.

As we shared previously, the SUNFISH study in Type 2 and 3 SMA patients transitioned to pivotal stage in mid-October, triggering a $20 million milestone payment from Roche to PTC. The FIREFISH study is in Type 1 infants with SMA, based on the results of dose finding portion of the FIREFISH study, the appropriate dose for pivotal part of the study has been selected.

This phase will commenced in the coming weeks. Clinical data were presented on both the FIREFISH and SUNFISH studies in January at the International Scientific Congress on SMA including survival data from Type I infants.

In addition to SMA, our splicing platform have generated Huntington's and Familial Dysautonomia programs which are progressing and are in the medicinal chemical optimization stages. We also have a developing oncology pipeline which we look forward to highlighting at our upcoming Analyst Day on April 17th.

Let me now pass the call over to Marico, to update you on our clinical and commercial efforts. Marcio.

Marcio Souza

Our commercial success in 2017 reflect the value of the different stated DMD therapies we are bringing to patients. Our DMD franchise brings two out of the three approved DMD therapies to patients around awards.

EMFLAZA is approved in the U.S. for all DMD patients five and older and we are pleased with the recent published data on the long-term effects of EMFLAZA, which demonstrated the benefit of prednisone.

Translarna is available outside side of the U.S. for nonsense mutation DMD patients. The current published data for each of EMFLAZA and Translarna supports the mortar and respiratory benefits of these therapies. It's well documented that delaying times to loss of ambulation delays subsequent milestones.

Age of assisted ventilation in DMD patients is a predictor of age of death. We are proud of these DMD therapies and the benefits they bring to patients.

Let me now reflects on the commercial performance in 2017 beginning with EMFLAZA. We launched EMFLAZA in the U.S. in the middle of May, the reception of EMFLAZA by both patients and healthcare providers has been very strong.

Our launch term strategy has three phases. The first is to maintain patients who previously had access to EMFLAZA. The second is to convert patients on prednisone to EMFLAZA, which has been driven by the published efficacy data. The last phase is to penetrate into the approximately 50% of the patient population that is naïve to any corticosteroid treatment.

As they reflect on the progress of the launch the first phase has moved very quickly and we have now started to see a high degree of EMFLAZA script to renewals. Our 2018 guidance for EMFLAZA reflects our confidence that patients will continue to successfully renew prescription via their initial scripts. While these results are very encouraging, our work is far from over.

Based on our understanding of both our own internal generated results, independently published data, we believe that EMFLAZA should be the standard of care for all DMD patients. It’s encouraging to see that the most recent DMD treatment guidelines reflect and align with this deal.

As I mentioned previously, we continue to focus on switching prednisone treated patients based on the published data and DMD treatment guidelines, demonstrating relative benefits of EMFLAZA over prednisone. This data indicate that EMFLAZA delay the loss of major milestones by two to three years when compared to prednisone.

Reaching naïve patients is yet another critical step in our long-term strategy. It is known that in the U.S. about half of the DMD patients are still not currently treated with any corticosteroid treatment. This is a result of historical view of the benefits risk profile of these agents that predates the current DMD treatment guidelines and our launch efforts.

In addition to this standard of care guidelines the publication in The Lancet and the CINRG Natural History Study which shows EMFLAZA specifically delayed loss of formulation and improve lung function when compared to untreated DMD patients.

Our goal is to get all eligible patients on EMFLAZA. We have been actively engaging with physicians, payers and patients discussing the benefits of EMFLAZA as a critical component of DMD treatment. We are excited with the current progress of EMFLAZA and proud of the fact that more patients than ever are receiving this best-in class therapy. I’m also pleased to confirm that the out of pocket costs for those patients will remain close to zero.

Now switching gears to Translarna as Stuart said, we remain committed to bringing Translarna to U.S. patients and at the same time we continue to expand the adoption globally. We are pleased the FDA has recommended a possible path forward towards accelerated approval as a result of our successful launch of EMFLAZA in the U.S. our commercial team knows the pediatric neurology landscape well, which will facilitate a potential launch.

Outside of the U.S. we first launches Translarna in 2014. In January of this year, we guided to a 15% CAGAR through year-end of 2022. We are excited about Translarna’s growth outlook. The main driver is the continued update of Translarna used in the regions where we are operating. In western Europe, Latin America, and most recently in the Middle East and central and eastern Europe.

Growth will be more of a consequence of our focus on this areas rather than further geographic expansion. There is a significant opportunity for growth in this region especially because of the younger population and a high birth rates.

We are also seeing continuous growth in the more established regions, including the EU5 where we have been present for more than four years. It's not uncommon in ultra-orphan disorders to continue to identify patients once a drug is available. Patients and physicians have expressed the benefit of treatment from Translarna and compliance has remained very high with over 90%.

Let me now provide a short update on the development problems for DMD. As we have said before, we appreciate the perspective of the DMD community on the importance of treating patients as early as possible to preserve muscle function. We have plan to conduct a pediatric study for EMFLAZA as requested by the FDA. This study upon completion would provide us an additional six months off market exclusivity.

Additionally, we have completed a PK study of Translarna in children aged two to five, data from this study was the basis of our submission for label expansion to DMA, which is currently under review. Both of these efforts aligned well with the intent of DMD guidelines to begin treatment at the time of diagnosis.

Our long-term Translarna study 041 has started enrolling patients in the third quarter of 2017. As a reminder the conduct of this study is a specific obligation of our EMA approval and the FDA has stated it could serve as a confirmatory study in connection with an accelerated approval. We are confident that we are well equipped to drive value with both its strong commercial and clinical capability and our continuous focus on transforming lives of patients with rare disorders.

I will now hand the call back to Stu. Stu.

Stuart Peltz

Thanks, Marcio. I would like to share more detail on data recently generated in our SMA programs. Most of you are familiar with the program, which is based on our small molecule splicing platform.

This technology has been used to discover potential new therapies for Spinal Muscular Atrophy or SMA a rear genetic neuromuscular disorder that generally manifests early in life and is the leading genetic cause of death in infants and toddlers.

We have a robust program in collaboration with Roche and the SMA Foundation around oral SMN2 splicing modifiers. We believe that an oral systemic therapy provides a competitive advantage because it of the broad tissue distribution and ease of administration.

Earlier clinical data have shown that RG7916 drives SMN2 splicing towards a complete restoration of full length SMN2 messenger RNA.

As we have discussed before, there are two registrational studies ongoing. In October 2017, SUNFISH entered the pivotal stage and is currently enrolling. The second registration directed trial FIREFISH is an open-label two parts study in SMA Type 1 infants.

Based on the results from the dose finding portion we have recently selected the dose for the pivotal part of the study, which is expected to transition to pivotal stage in the coming weeks. The primary end point is ability of the ability of infants to sit unsupported as assessed by the Bayley Gross Motor Scale.

The SMA program also has an open-label trial known as JEWELFISH. JEWELFISH allows SMA patients from other studies of SMN2 splicing targeting therapies to gain access to RG7916. Results from all three trials were recently presented in January at the International Scientific Congress on SMA in Kraków.

A presentation reviewing the ongoing dose-finding Part 1 of FIREFISH in the Type 1 SMA infants highlighted survival data, as well as safety and interim clinical data. No patients had discontinued due to its adverse events. Early interim clinical data reported no patient lost the ability to swallow and no patient has required tracheostomy or reached permanent ventilation.

Posted on the SUNFISH and JEWELFISH studies, also supported safety and tolerability of RG7916 at all doses. Preclinical data were also presented demonstrated that RG7916 increased its SMN protein levels in brain, muscle and blood. These increases were proportional and correlated. These data demonstrate the relevance of SMAs protein levels increases in the blood as the projector of SMN upregulation in the target organs such as the brain and muscle.

The SMA program is not only progressing towards an oral and systemic treatment for SMA patients. It also validates that our Splicing Platform Technology can identify selective compound that modulate pre-mRNA splicing. We are now applying our expertise to other challenging diseases with high unmet medical needs, and have internal preclinical programs.

We are pursuing additional programs targeting pre-mRNA and the splicing including Huntington's disease and Familial Dysautonomia. We will share more about these wholly-owned exciting splicing programs as well as highlighting our R&D pipeline at an upcoming Analyst Day, on April 17th.

I would like to turn the call now over to Christine Utter, our principal financial officer. Christine.

Christine Utter

Thanks, Stu. Earlier today we issued a press release summarizing the details of our financial results for the fourth quarter and full-year 2017 and I refer you to that release for full detail. I will start with a few comments on our financial performance and our guidance for 2018.

Starting with our top-line results we reported strong performance across our DMDs franchise. As Stu mentioned, our results for 2017 were impressive with reported total net product revenue of $174 million.

We have provided guidance for the DMD franchise in 2018 of $260 million to $295 million. Translarna net product sales were $145.2 million for the full-year, representing 78% growth in both expansion into new territory and increased penetrations in existing geographies.

EMFLAZA net product sales reflects success of their launch with reported revenue of $28.8 million for the full-year 2017 having just launched in May. Total revenues for the fourth quarter of 2017 were $78 million partially influence by a one-time $20 million milestone as prior to the SMA collaboration and a large Translarna order from Latin America. This compares to $25.2 million in the fourth quarter of 2016.

For the full-year of 2017 total revenues were $194.4 million compared to $82.7 million in 2016. The change in total revenue was a result of the expanded commercial launch of Translarna, the successful U.S. EMFLAZA launch and a $20 million milestone payment achieved from Roche.

For the full-year 2017 non-GAAP R&D expenses were $102 million excluding $15.5 million in non-cash stock based compensation expense compared to $100 million for 2016 excluding $16.8 million in non-cash stock based compensation expense and $0.8 million in a one-time restructuring expense.

For the full-year of 2017, non-GAAP SG&A expenses were $106.2 million excluding $15.1 million in non-cash stock based compensation expense compared to $77.3 million for 2016 excluding $18.2 million in non-cash stock-based compensation expense and $1.6 million in one-time restructuring expense.

For the full-year 2017, net interest expense was $12.1 million compared to net interest expense of $8.3 million in 2016. This increase in net interest expense for 2017 is primarily a result of an increased related to the $40 million secured loan facility which we closed during the second quarter of 2017 partially offset by interest income from investments.

Net loss for the full-year of 2017 was $79 million compared to $142.1 million for the same period in 2016. This decline in net loss reflects our growing revenue base as we continue to leverage our successful international corporate infrastructure. Cash, cash equivalents and marketable securities totaled to approximately $191.2 million at December 31, 2017 compared to $231.7 million at year-end 2016.

I will now hand the call over to the Operator to start our question-and-answer session. Operator.

Question-and-Answer Session

Operator

[Operator Instructions] Our first question comes from the line of Alethia Young with Credit Suisse. Your line is now open.

Derek Yuan

Hey, thanks for taking my question, this is Derek Yuan for Alethia. So congrats on the progress. I guess I wanted to just first know further about ataluren FDA situations, so basically can you provide more color on what level of dystrophin data do you think that FDA has paragraphed that they want to see your new NDA filing. And also could you just remind us what did you see in your earlier study of the dystrophin expression. Thank you.

Stuart Peltz

Thanks for your question. Yes, so I will start by reminding you that we previously demonstrated the dystrophin production after 2018 treatment in nonsense mutation Duchenne patients where we saw 61% of the patients demonstrating dystrophin that was statistically significant. And that we used obviously for proof-of-concept that going to do clinical trials.

So in terms of what the results from the appeal, obviously while we were disappointed that the patients don't get it tomorrow, we are pleased that there is a clear path forward now and that based on the decision at the appeal that the results from the clinical trials and we think that's important as well, along with the dystrophin production would be sufficient for accelerated approval.

And in our discussions with the FDA it was really any dystrophin that’s statistically significant above the untreated controls. So we are now in the discussions with the FDA to talk about with them both the trial, the dystrophin trial as well as the methodologies that we would utilize to look at dystrophin. So that’s where we are at right now and overtime when we complete our discussions, we will describe to you what the next steps are.

Operator

And our next question comes from the line of Joel Beatty with Citi. Your line is now open.

Joel Beatty

HI thanks. First question is on Translarna sales ex-U.S. in the past we saw some lumpiness with Q2 of 2017 being particularly higher and then coming down in Q3 and now it's back up again in Q4. Could you characterize whether this increase from Q3 to Q4 is the same lumpiness that we saw in Q2 or have sales kind of flattened out?

Stuart Peltz

Sure. Hey Marcio do want to?

Marcio Souza

Sure and hey Joel and thanks for the question. In Q4 we saw a growth, we continues to see growth across all the regions in number of patients any revenue. So what you described is exactly how this business grows right throughout the year. We do have a little bit a variability, a little bit lumpiness as we described in the past and that influenced the quarter-to-quarter.

What we do look in the way we forecast every year is likely look into the total number of patients in the year is our expectation in terms of net patient exit and that’s how we create our guidance and that we just communicated to all of you.

So it’s going to be, we expect that to continue to be a little bit of lumpiness throughout not only 2018, but beyond as well. But at the end of the day our commitments for all the patients who stay on drug and to continue to grow in every region is really what we are aiming for. Did that answer?

Joel Beatty

Okay, yes, yes got it and one other question, EMFLAZA sales in the U.S. you have talked about three stages of growth. One being patients previously on EMFLAZA, another being on patients on prednisone and the third on naïve just steroids. Could you discuss the size of those opportunities, how many patients are available in each of those three buckets?

Marcio Souza

Sure absolutely, so our estimates is that there is around 10,000 or so in the United States that would be eligible for EMFLAZA, what we have right now as we are being - the last time we gave patients number was two quarters ago 1,500 patients at that point in time and we continue to see obviously patients grow on that regards. The split of patients on the remaining, so all patients in the U.S. as I mentioned on the remarks, about half of them are naïve.

So we see that's and there might be naive in this strict senses of naive or they might have used steroid a long time ago and for many years not have exposed to that, so they don’t have recent and current exposure to any type of corticosteroid. So that's obviously a pretty big size and then for the other half, it's about half of those as well between 20% and 30% or so that would be on prednisone.

So we still have a way to grow in terms of penetrating that to segments, we think we did a really good job, the teams here are very proud of the work of the team on really getting all this patients on drug, they come from all three segments or the ones to give the false impression that is only coming from one segment for the patients we have right now, but there is the majority of them we really focus on patient with prior experience to deflazacort, EMFLAZA. So going very well so far and we want to continue to benefit all three of them.

Stuart Peltz

Maybe from a big message point of view, especially with what recently come out with the lancet that Duchenne Muscular Dystrophy guideline with a specifically called out that patient should be on deflazacort or EMFLAZA and also with the recent publication from the CINRG Natural History really differentiating the EMFLAZA from prednisone.

I think that makes it really our goal is that because of the differentiation that we believe that all patient should be on in EMFLAZA that gives us further information to discuss with physicians and patients why we transition them onto EMFLAZA.

Joel Beatty

Great. Thank you.

Christine Utter

You are welcome.

Operator

Our next question comes from the line of Anupam Rama with JPMorgan. Your line is now open.

Eric Joseph

Hey guys its Eric on for Anupam, thanks for taking The questions, just a couple form us. I guess first on Translarna and sort of the existing commercial footprint that you have. You kind of know the exact talent group to come from deeper penetration of the current geographical footprint, just wondering if you would sort of characterize for us a bit more kind of where do you see reaching the greater growth opportunities maybe EU versus other geographies currently and sort of what the kind of hurdles are to deeper penetration, broadening access are and then I have a follow-up.

Stuart Peltz

Sure go ahead Marcio.

Marcio Souza

Sure. So they are little bit different on the region we have like when we look into long-term, but just to walk you through a little bit so we do expect all the regions to continue to grow and I think that's very importance, because sometimes we see this concept that the EU5 because we have been there for a longer time is well penetrated, there is not a lot of growth, we will still see a substantial amount of growth throughout the years to come up from Eastern and Central Europe.

It's mostly driven by two factors there. So one is we continue to see patients growth like we are very happy with all the work that our medical teams, that our marketing teams are doing on patient identification, on patient-finding throughout the world, but especially on challenging geographies that are more penetrated. So in the short-term there still a lot of growth that comes from that.

As we move more to the long-term then we are seeing the geographic expansion that we did last year in the last two years I would say, bringing even bigger role to get through our long-time guidance like Latin America, it’s a young population very large countries, still a lot of patients to be found.

And most recently as I mentioned in the remarks as well, we have Central and Eastern Europe and the Middle East where the penetration is very small, the patient-finding activities has just have started. And we are really trying to unify time to diagnose, age of diagnose to drive this patient growth across the years and so far we have been extremely happy with the results we are getting.

Eric Joseph

Got it that’s helpful. And maybe just a quick one on SMA if I could. Pivotal portions of both SUNFISH and FIRESISH underway or getting underway near-term. Just wondering if you could give us a sense the anticipated enrollments curves in either study, and also to what extent regulators are sort of interested in tissue related SMN expression outside of the peripheral blood at all. Thank you.

Stuart Peltz

Sure. As you know the SUNFISH has been in pivotal studies and FIRESISH just picked the dose and therefore we will be studying that in the coming weeks. We anticipate these to go pretty well, It’s our global study and we are getting patients into these studies not only in countries where other drugs unavailable, but also even where there are approved products for them, we are still seeing patients choosing to enter into these studies as well.

So we anticipate rapid recruitment over time in these studies, so we feel pretty good that these will be completed relatively quickly. And so obviously while this won’t be the first-in-class, we do think there is a real opportunity for us to be the best-in-class, because when you think about it this is a easy drug to take it orally bioavailable, throughout the body including not only in the CNS, but also into other tissues that are affected - in organs that are affected such as the liver, the muscles, the bone. So we think there is a substantial advantage to that. And I think we have heard other key opinion leaders actually talk about that as well. So we think that’s a truly important advantage.

Marcio Souza

So just to answer your question specifically about the need for regulators and the distribution the tissue or the expression of the tissue right. So of course Stu just said, that is a oral bioavailable drug, so we expect to distribute throughout. We just showed some preclinical work, really showing the distribution of this drug in terms of like the compartments and really get into all the target tissues and there is no expectation right now that that would be a required or even a desire to see on a drug like RG7916 to have that kind of influence.

Stuart Peltz

But one thing we just see which was clearly also an advantage was we were able to look at complete restoration. In preclinical models we saw a complete restoration of the SMN to RNA to SMN RNA that produces the protein and that level we saw one-to-one, but seen what was in the blood and what was in the brain and we not only saw that in the animal model, but also similar sort of levels that we see in all other rodents and other non-human primate study as well.

So we are confident that it actually distributes quite well and so that looking at the changes that you see in blood, we feel pretty confident there will be - that is what you will see within the brain so we are excited about that as well.

Eric Joseph

Got it. Thanks so much for taking the questions guys.

Stuart Peltz

Thank you.

Marcio Souza

You are welcome.

Operator

Thank you. And our next question comes from the line of Tazeen Ahmad with Bank of America. Your line is now open.

Tazeen Ahmad

Hi Stu, thanks for taking my question. Maybe another one on SMA I'm sorry if you have talked about this earlier and I might have missed it, but in terms as the criteria for patients that are allowed to enter the SMA trial. What other therapies are they allowed to be on concurrently and also how do you in the grand scheme of things envision your drugs being used, is this the amount of therapy, is this just add-on, kind of walk us through how you think the market opportunity for this could develop?

Stuart Peltz

Yes, sure. I think that’s a good. I think from concurrently obviously in the pivotal studies we really want to make sure that we are looking at the benefits of a drug on their own, so there won't be other therapies. In the long run and this is a question we get all the time in terms of other therapies. I think obviously we want what is best for the patient, but what we have seen thus far is that the transcript itself for the RNA that [indiscernible] we have seen complete restoration of that RNA to the messenger RNA.

So from a splicing point of view, we think that whatever can be made or whatever can be made into SMN RNA will be done so. So we don’t know if there will be necessarily a need for other compounds that actually it effects the splicing of efficiencies of it only time will tell.

We currently do have a trial JEWELFISH that is ongoing that allows patients to have available RG7916 who would like to take it, who have been on previously other therapy as well so we are making that available. And then obviously when you think about what a patient may need that could be concurrent forward is something that improves muscle mass or function might be useful as well. So certain of those that increase muscle mass or improve muscle function certainly could probably be helpful in combination with it in the long run.

Tazeen Ahmad

Okay, so how big of a pivotal program do you think one would need for this?

Stuart Peltz

So for the FIREFISH study it's 40, in this case it's an open label study, just to remind you FIREFISH has for Type 1 infants that are diagnosed within the first three months, there would be 40 babies, 40 infants that would be enrolled in the trial and we need to see we think we need about five to be able to assist to be able to see.

In the case of SUNFISH it's about a 168 patients this is a placebo-controlled study that two to one in terms of the placebo to treat the patients. So that’s a well 90% powered study to be able to see the benefits there as well.

Tazeen Ahmad

Okay thanks for that and then how long do you think it would take to enroll? Because those are not small studies.

Stuart Peltz

As I said one is 40, one is 168. We think that they will actually rapidly enroll. And I don’t think we have disclosed our timelines yet.

Tazeen Ahmad

Okay. I only asked because they would potentially be competing with other therapies that are approved and if you want to just look at patients that are not on another therapies you know what would be the pitch for the parents of these children for their children in the study.

Stuart Peltz

Well I think that’s a good point, I think the pitch is if you go back and look at the preclinical data is was really quite astounding. We would argue that if you look at what we was been published and talked about within the preclinical studies, they was certainly the most exciting data set that was performed and the fact that is orally bioavailable that it distributes well throughout the body and it can be consistently taken has a lot of advantages to it. We do know that it pulls some muscle as well as nerve as well as effecting other organs and so we think there is a real lot of advantage for an oral drug that can be consistently taken.

Tazeen Ahmad

Okay. And then if I could ask a question about DMD. Going back I know you discussed dystrophin earlier in the call, but in the past especially with your most recent pivotal study, it seemed that you were pretty adamant that measuring dystrophin may not be the right way to determine the efficacy of Translarna. So I guess why do you think now might be a good time to go about collecting this additional information, because I think FDA in the past might have suggested it to you and correct me if I’m wrong why do you think that collecting the information now would be the best route forward.

Stuart Peltz

So a couple of points there, one is that actually, we are a long time in agreement with the FDA or in discussions with the FDA where it didn’t necessarily predict clinical benefit and therefore it was proof-of-concept study. And since we had done study [indiscernible] and demonstrated dystrophin we went into preclinical efficacy.

And even to this day I think it’s very clear that the dystrophin levels don’t now even correlate with efficacy. However the FDA has come around to the notion that any dystrophin is important can predict benefit and that what they said is that - and I think this is important that was and we made this point that they gave us a path in the appeal process that any dystrophin that statistically significant above the controlled treatment along with the current clinical data that we have today would be suitable for accelerate approval.

So while in the past we were doing clinical benefit studies that this is now path that is availed to us where we think is the most expeditious path to bring Translarna to the U.S. patients. And so we are confident that - we believe that we will be able to show this into very rapidly as we can to bring it to patients and we think this therefore is the best path for us to move forward on - we have agreement with the FDA, we are going to be moving forward with that.

Tazeen Ahmad

Okay. And so last question for me is when should we expect the next update on the DMD path in the U.S.?

Stuart Peltz

So I think where we are right now is we are working to discuss with them the methodology and get agreement on what will move forward on and we think that's probably a three to six months process and so we will update you that on that as we understand it.

Tazeen Ahmad

Okay. Thanks Stu.

Stuart Peltz

Thank you.

Operator

Our next question comes from the line of Gena Wang with Barclays. Your line is now open.

Gena Wang

Thank you for taking my questions. The first one is for SMA just wondering when will we have a update from both FIREFISH and SUNFISH in terms of the clinical measurement such as a chopping trend for Type 1 patient and also milestone achievement?

Stuart Peltz

Yes thanks for that. As we said what we have did is we were conducting - let me just remind you that we are talking about was first the dose-finding or the two parts study the first part with a dose-finding study that have been transitioned in here the pivotal portion of it. So you will obviously we have multiple doses of that so therefore its easier and clearer to see what the survival data looks like.

As the data matures I think we will have an opportunity to talk about the mortar milestones as they read out throughout the year at some point that we will be doing this, but right now we have now transition to the pivotal studies and we have continued to be obtaining additional data throughout the year so we would be able to report that it's appropriate time.

Gena Wang

Okay, and also Stu you mentioned that I think that FIREFISH pivotal trail you mentioned that four or five babies, if they can sit would that be consider approvable as you see four to five babies that can sit out of those 40 patients?

Stuart Peltz

Yes, so we said by just simply looking at power calculation that you will see five babies out of 40 would statistically significant.

Gena Wang

And that will be comparing to the Natural History right?

Stuart Peltz

We would anticipate that to be case. Since they are actually on their own Type 1 babies are capable of sitting and you don’t see that would be pretty awesome.

Gena Wang

Okay, and just one last quick questions do you also mention that the dystrophin level for the U.S. ball marker data so you come on that dystrophin level to compare to untreated patients just wondering was that the feedback from the FDA. We know that in the past I think FDA comment on comparing to the base line rather than untreated patients and just wanted to get more color?

Stuart Peltz

That will be part of the final agreement, yet so that's we have said untreated or baseline that's yet to be defined, but I think there is some precedence be using a controls versus peers control so certainly obviously it would be faster to be able to look at dystrophin levels and compare it to untreated blended controls if possible, but that’s yet to be determined in the discussion with the FDA.

Gena Wang

Okay, thank you very much.

Stuart Peltz

Okay. Thank you.

Operator

And our next question comes from the line of Raju Prasad with William Blair. Your line is now open.

Raju Prasad

Thanks for taking the question. Just one on the five year 15% CAGAR guidance. What percentage of that did you say current patients at are on therapy that are just gaining weight getting bigger versus new patients stats? And does that number also include the expectation you will get the label update for the two to four year patients in DNA?

Marcio Souza

So the three components that you just mentioned right, so the organic growth for patients, we are currently adding new patients obviously these patients are going to be getting older and heavier so that [indiscernible] well in the expansion. I would say proportionally the biggest part of this continues to be from patient growth to adding new patients constantly that's the biggest driver of the market.

We are very happy that the compliance and the dropout rate are very, very are low for dropout in the compliance is very high, so maintain patient is all something - we don’t see only obviously from the financial standpoint, but even happier we are that these patients are still alive and thriving. So that's quite important for us.

And as they continue they gain around three or so kilograms per year that’s the historical cohorts for Duchenne if you look into our clinical trials and our commercial experience so that consumes as well. But that's not a significant part of the growth. In terms of two to five or the younger than five, shall I say that include as well in the later part of the guidance. The average age of diagnosed globally is still higher than five.

In some countries it’s a little bit lower than five and other countries its higher, but it is still around five the average so not a lot in the next four years for example five years is going to be driven by that segment so much. Although we are working very hard to reduce the age of five years and hopefully these patients are going to have even a better and longer life if we can get them to be diagnosed when they show symptoms that is around two years of age.

Raju Prasad

Great. And then could you provide any general commentary on study 041 enrollment trends and is that something that you might try and take a little cut of data and submit it to the FDA as well it’s just effectiveness there that you have already submitted that will be going into your kind of additional data for accelerated approval?

Stuart Peltz

Yes. Obviously Study 41 is the global study, that’s 36 month trial where the first 18 months are placebo-controlled, so the consequence of this being a placebo-controlled which sort of precluded you from really bringing in any other data too much earlier, but on the other hand.

I think what is important is with the FDA in our discussions with them it was pretty clear that what would be needed for accelerate approval would be the clinical data that we currently have as and the dystrophin data and that the Study 041 would serve as confirmatory trial of the accelerated approval process. And so I think that's the way we would set it up that way and I think we would just go with that I think that's would make sense.

Raju Prasad

Great and just maybe one last. Anything anecdotal you can say about patients have enrolled in JWELFISH why they are coming off present therapies and would you enroll anybody that has been on a gene therapy trial and JEWELFISH?

Stuart Peltz

You know, we are not really discussing details of that. Well I would love to, I don’t think we are into position to really talked about that right now.

Raju Prasad

Okay, great. Thanks for the question.

Stuart Peltz

Thank you.

Operator

And our final question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is now open.

Unidentified Analyst

Hi everyone, this is [Rick] (Ph) on for Brian thanks for taking our question. So we had a question about the progress for the pediatric EMFLAZA study, we are wondering if you could just give us latest updates on the study, the FDA discussions around it and then furthermore, could you maybe discuss how important the pediatric indication is for your projecting for the EMFLAZA.

Stuart Peltz

Go ahead Marc.

Marcio Souza

Sure, I will be happy to address that. So let me start by your last point there, so our projections for EMFLAZA do not includes the pediatric trial right now, we only gave guidance to 2018 for EMFLAZA. If in the future we move towards that I'm going to make sure to clarify whether or not it includes.

We received a written request from the FDA, we consider extremely important that no data was ever generated on the use of steroids in patients younger than five. So it's not only strategically for us that is important, but what we have been hearing from the patients groups from the key opinion leaders is that this is an important study for them to really understands about this patient and the influence the care guidelines the updated care guidelines that was just publishing the Lancet suggest that patient should immediately be included and treated with steroid so any information clinically PK that can be given to them like a very positive feedback.

Having said that we are just working on the final details with the FDA, we intense you conduct the trial as we mentioned on the remarks and as soon as we have more clarity on that and timelines and so on we are going to be updating all of you.

Unidentified Analyst

Great. Thank you.

Marcio Souza

Thank you.

Operator

Thank you. And this does concludes today's Q&A session and I would like to return the call to Mr. Stuart Peltz for any closing remarks.

Stuart Peltz

Yes. Well thank you again for being on the call. We are looking forward to a really productive 2018 as we continue to execute on the commercial front with our Duchenne Muscular Dystrophy franchise. For the United States patients we are going to work to finalize the dystrophin study design with the FDA and look forward to conducting that study as expeditiously as possible.

On the SMA front, our SMA program will continue to have data that and we will be talking about that as the relevant medical meetings this year, we look forward to updating you on these fronts and the other exciting developments in our pipeline at our Analyst Day on April 17th go and mark that into your calendar and thanks for joining us today.

Operator

Ladies and gentlemen, thank you for participating in today’s conference. This concludes the program, and you may all disconnect. Everyone have a great day.