Good afternoon, ladies and gentlemen, and welcome to the PTC Therapeutics Third Quarter 2018 Earnings 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. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Ms.
Emily Hill, Head of Investor Relations. Ma'am, you may begin.
Hello. Good afternoon, and thank you for joining us to discuss our 2018 third quarter 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 we start, let me remind slide on our simultaneous presentation, which contains from these forward looking statements as any and such risks can materially and adversely affect our business and results of operation. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly reports on Form 10 Q and annual report on Form Ten K filed with the Securities And Exchange Commission, as well as the company's other SEC filings, including our current report on Form 8 K filed on August 24, 2018.
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 our CEO, Stuart Peltz.
Thanks for joining us this afternoon Joining me on the call today are Marcio and Christine. Marcio will provide the commercial and clinical development updates. Christine will review our financials I'd like to ask you to turn now to the slides we have posted on our website to highlight some accomplishments in the third quarter. Let's start on slide 3. I'm going to spend time on today's call talking about our path to continue to build a leading fully integrated biotech company that has multiple platforms.
Our mission over the last 2 decades has been to be a scientifically innovative company that discovers, develops, and commercializes new therapeutics for patients suffering from rare disorders with Haima medical need. From this effort, we developed a strong BMD based business a potential best in class therapy in the development for SMA and 2 therapies in clinical development for patients suffering from rare cancers. At our Analyst Day earlier this year, we went into detail on our orphan oncology pipeline. Our development strategy is to generate early clinical data showing benefit to patients in these programs and then determine the best path that maximizes shareholder returns. I'm happy to report the most advanced programs PTC596 and PTC 299 have recently entered the clinic.
These efforts have built a strong commercial and scientific infrastructure with a solid revenue base. Over the next 3 to 5 years our strategy is to continue to build and grow our orphan disease franchise creating significant value for excited to be in such a unique position. We have a strong revenue base, strong talent and a diverse portfolio of small molecules and gene therapy candidates. This includes therapies and development as well as products in regulatory review or have been approved. We will remain we will maintain our focus on the rare disease space, focusing on monogenic disorders with high unmet medical needs.
Next on Slide 5. I'm pleased to report that we have already been executing on this strategy. With the acquisition of the gene therapy company Agilis, we have added 3 gene therapy programs, including one program with robust clinical results, that is expected to be submitted with regulatory authorities in which we'll be commercializing in Latin America. This is the first public call since the Agilis transaction. I couldn't be happier with the integration that puts PTC in the position to bring potential life transforming treatments to patients using our newest innovative platform, the CNS gene therapy platform.
I want to spend time reviewing this with you. Please turn to Slide 6. When we began our business development process, one of the principles was that as an ultra orphan rare disorders company, we needed to have gene therapy as one of our platforms to treat monogenic disorders. We were interested in certain approaches to gene therapy. Specifically, we wanted at first to focus on utilizing gene therapy targeting tissues with low turnover to ensure durability of effect.
We also considered that delivering gene therapy to a small contained region of the body as the advantage of being able to use microdoses to treat patients. Allowing manufacturing of lower amounts of the viral therapy. These considerations led us to the acquisition of Agilut with their CNS gene therapy platform. Our 3 lead gene therapy programs in CNS are for aromatic amino acid decarboxylase deficiency or AADC, Friedreich Ataxia or FA, and angelman syndrome or AS. What they all have in common in addition to being seen as disorders of higher medical need is that targeted delivery of the gene therapy can be employed.
Next on slide 7. The market opportunity for each of these gene therapies is exciting. Our estimate for the combined potential including approximately 5000 AADC deficiency patients, 25,000 FA patients and 70,000 patients suffering from Angelman Syndrome. We believe this is a valuable platform and we estimate that the combined addressable global market for these programs is One of the major benefits of this CNS therapy approach is the small quantity of material required. For instance, the direct injection of the AADC gene therapy into the brain utilizes a micro dose of viral vector of only approximately 2 times 10 to 11 viral particles.
This is the total dose and is between 1000 to 10000 fold smaller compared to the systemic gene therapy dosing. This reduced dose requirement allows for scalable, modular manufacturing. Because delivery in the CNS is relatively contained and only small doses are used, there was a lower risk of immunogenicity. In fact, almost no immune response has been observed in the AATC gene therapy program. Lastly, another important point is that of the durability of the response, The CNS tissue had the lower rate of cell turnover, which is important because it allows the virus to be maintained and adds to the durability of effect of the gene therapy treatment.
In sum, the low dose required for targeted gene therapy combined with targeting slowly dividing cells is a strong competitive advantage of this platform. Turning to Slide 8. These gene therapy programs to treat the orphan neurological disorders fall into our area of expertise. We have over 20 years of experience discovering developing and commercializing therapies for rare disorders with high level of medical need. We understand the rare disorder market and have experience with country by country market access and pricing, driving genotyping efforts and patient finding.
This is enabled by our global commercial and medical infrastructure and is the basis for our success in commercializing rare disorder products. I'd now like to talk more in-depth on the 2 months advanced programs in our gene therapy pipeline. Let's turn to AADC deficiency first. Starting with Slide 9. AADC deficiency is a devastating disorder, which holds infant neurological and motor development, and similar to spinal muscular atrophy, the children are never able to achieve motor milestones such as holding their head up, sitting, or standing.
In its most severe form, this disorder results in childhood mortality between four and eight years of age. Following a single direct CNS gene therapy treatment, these patients have shown improvements in functional developmental milestones. Including having the ability to hold ahead position, to sit, to stand and even to walk. The results in clinical trials have shown increases in motor functions that were durable in the 5 year clinical trial follow-up. Now let's turn to Slide 10.
The AADC treatment is delivered via a single dose through direct direct delivery into the putanum using an established surgical technique. The AADC gene therapy program had substantial long term evidence of durable clinical benefit. The first patient was treated 8 years ago. Our regulatory package relies on data from 26 patients treated over the past 8 years. The data for this regulatory package as the longest term follow-up demonstrating durability of effect in the gene therapy space.
The improvements in these patients have been measured using multiple motor motor scales. Here on slide 11, you can see this. Observed clinical improvements are seen here in 2 clinical trials. The Peabody Development Motor Scale demonstrates clinical improvement in treated patients at the 1 5 year follow-up. As you can see, every patient experienced rapid and durable improvement in both fine and gross motor skills.
Regardless of their age when the treatment was initiated. This is compelling when said in context of the natural history where none of these motor milestones are achieved. Patients in these studies demonstrated remarkable improvement after gene therapy treatment, including head control, sitting, and standing. What's really remarkable about this gene therapy are the transformative changes that were observed in the treated AADC patients. I would like to share a video demonstrating robust improvements in motor development and cognitive ability in an AADC gene therapy treated patient.
On slide 12, I'd like to share one of the many videos we have of such a patient. What you will see here is a child suffering from AADC deficiency at two years old before initial treatment. You can see the child has limited motor function and is unable to lift his head or sit. At two years of age, he received a single treatment As you can see, after 1 year of follow-up, there is substantial change. You can see the child sitting upright independently and grasping the mirror.
After an additional year of follow-up at 4 years of age we see continued growth and fine motor function and cognitive improvement. The child is outstanding and interacting with a caregiver. We believe these results are impressive and you can We are working on Let me transition to future cataxia gene therapy program. This is the most advanced program in development for the underlying cause of FA. FA is a triplet repeat disease causing the loss of for tax and protein.
Again, the gene therapy will be directly targeting the appropriate region in the brain that is involved in Ataxia and will be utilizing microdosing. As you can see on slide 14, We're very encouraged by the preclinical data showing showing that in 2 large species, protein levels above the normal have been achieved. The robust animal data allows us to find an appropriate dose range to be used in patients. Let's move to Slide 15. We plan to file an IND for the F18 therapy program in 2019 and start dosing patients.
We believe this program will benefit from high patient advocacy group engagement. We already have a good relationship with FARA the leading FA patient advocacy group. Let's move to Slide 16. We are very excited about the path forward for these programs including the earliest stage program in Angelman Syndrome. We're very proud of our gene therapy pipeline, which we believe will drive both near and long term value creation for patients and shareholders.
I'll now pass the call to Marcio to review our growing DMD franchise and the products for which we in license in Latin America commercial rights. This important new collaboration with Akcea leverages our strong commercial infrastructure and brings us 2 new substantial commercial opportunities. I will also ask Mauricio to update you on the advances that we've made in our niche oncology programs. Hey, thanks, Stu.
As part of these strategies to just outline, we also looked for in licensed opportunities that would leverage our strong existing commercial infrastructure. In the third quarter, we were pleased to announce an important agreement with Akcea, which allowed us to commercialize 2 rare disease drugs in Latin America, TEGSEDI and Waylivra. TEGSEDI has been approved for the treatment of patients with ATTR with polyneuropathy in the U. S, Europe and Canada. The polyneuropathic form of hATTR occurs more frequently individuals of Portuguese ancestry.
Because Latin America and in particular, Brazil contains a large portion of such patients, the region is of strategic importance for TEGSEDI. Based on March research data we conducted, we have learned that TEGSEDI is highly regarded by physicians in Latin America for its clinical profile. In fact, the predicted allocation of market share by the physicians shows a predominant use of BEGSEDI over competitive products. We believe an additional contributing factor for this competitive advantage is that the subcutaneous delivery method is preferred in Brazil, which as a country lacks sufficient infrastructure for infusion center across its extensive geography. We estimated about 6000 eligible patients in Latin America for TEGSEDI.
Genetics of ATTR diagnosed in general patient mapping are key next steps to enable successful launch. And we're well underway with such activities. On the regulatory front, we intend to file our marked authorization with ANVISA in the first half positioned us as a partner of choice for Akcea. This infrastructure is based off the success of our growing DMD business, with both Translarna outside of the U. S.
And Emflaza in the U. S. Our GMD franchise was strengthened in the first half of this year on several fronts. DMA approved a label expansion for Translarna in nonsense mutation DMD for patients aged 2 to 5. Because DMZSdegenerative disease treating patients early, allows for better preservation of muscle function.
Importantly, this label expansion allows patient encounters that recognize DMA approval to gain access to therapy at a younger age. We have recently submitted for label expansion for non ambulatory patients. DMA has validated our application and we are working now going through the regulatory process. While most clinical programs focus on ambulatory patients, there is an equal infusion unmet needs to treat non ambulatory patients with TMZ. Our DMD franchise also includes Emflaza, for all U S CMD patients over age five.
We are working hard to establish Emflaza as the standard of care in the United States. As we stated last quarter, there are a number of levers to pull to effectively establish Emflaza as a standard of care. When such factor we discussed was the bridging program to allow for access to therapy before reimbursement, This was an importance too in our early commercialization efforts to bring patients on board. For a subset of patients, however, the breach program is load reimbursement timelines. In September, this program was discontinued.
And patients from breach are now being transitioned to commercial products. We are seeing the early impact of this change since the end facts support our efforts to establish its standard of care. We remain focused on maximizing the value of Emflaza. And part of the equation is to have the right structure in place. Based on our experience over the 1st year we've been able to adjust and redeploy our field force.
We have recently decided to expand the field team both on the medical and commercial side of the business to increase our coverage to the accounts, especially the ones outside of the main centers. In the third quarter, our revenues for the DMD franchise totaled approximately $53,000,000. This includes $22,600,000 for Emflaza and $30,400,000 for Translarna. Since the close of the third quarter, we have received a sizable order of Translarna from Latin America. Which is in the process of being finalized.
Based on this visibility, we are maintaining our 2018 Translarna guidance of $170,000,000 to $185,000,000 for the full year. For Emflaza based on our visibility of individual patient use, in order dispensing dynamics, we are narrowing the range of our guidance to $90,000,000 to $95,000,000 and therefore, we are adjusting our DMD franchise guidance for the full year 2018 to $260,000,000 to $280,000,000. We're also reiterating our guidance of 15 percent composite growth for Translarna through 2022. I want to express my enthusiasm for our gene therapy platforms. Ahead of our BLA filing for ADC next year.
These efforts include patient identification, mainly in cerebral palsy and epilepsy centers, where AADC patients are up misdiagnosed. We have preliminarily identified a large group of patients with cerebral palsy with normal MR 5. At this stage, we believe there are in between 100,000 to 150,000 patients from these centers with normal MRI, who should be screened for ADC. We are in the late stage of establishing partnerships to responder the use of a sensitive and low cost blood test, which can be used to screen those patients for ADC deficiency. Because patient finding and identification has such a strategic value and impact for all current and future indications we're working on, we have decided to We are happy with the progress we've seen so far in patient densification and we plan to share more details early next year.
Our research supports the prevalence previously reported, and we estimate 5000 patients worldwide with about 1200 patients in the United States living with AADC deficiency. Let me now transition to another important milestone achieved this quarter in our oncology portfolio. At Analyst Day, we shared our goal to file an IND for PTC 299 in AML and have it cleared with the FDA before the end of the year. I'm pleased to report that we not only achieved this, but you also have the site open and have the first patient screen in this trial. We expect to continue to advance 299 in the AML indication during 2019.
Our second oncology candidates, PTC-five ninety six, has progressed as well, and the DIPG trial is open for enrollments. And we expect the 2nd trial in Sarcomas to be opened before the end of the year. We look forward to sharing more of these programs as they progress. I'll now turn the call back to Stuart. Stuart?
Thanks, Marcio. Most of you are familiar with our spinal muscular atrophy program, which is in pivotal studies. The SMA program reflects the scientific innovation of which PTC is founded. The idea of a small molecule selectively altering splicing was foreign only a few years ago. This technology has now been on use to discover potential new therapies for SMA.
A rare genetic neuromuscular disorder that generally manifests early in life and is the leading genetic cause of death and infants as toddlers. We have a robust program in collaboration with Roche and the SMA Foundation around oral SMA 2 splice feet modifiers. We believe that an oral systemic therapy provides a competitive advantage because of its broad tissue distribution systemic SMN protein increases and ease of administration. Earlier clinical data has shown that Risdiplamp drives SNN2 splicing towards the complete restoration of full length SMN2 messenger RNA. This program is currently in pivotal stages with 2 registrational studies.
Firefish for type 1 infants and SUNfish for Type 2 and 3 patients. Data from the dose finding arms of firefish and SUNfish were recently presented in the world Society Congress. An important aspect of the World Muscle Society Congress presentations was the first clinical data presented from the type 23 patients. The SUNFISH study reported a median 3 point improvement in motor function measurement at 12 months of treatment. The pivotal portion of SUNFISH is fully enrolled and powered to detect a 3 point difference in motor function measurement at 12 months.
There is a potential to file an NDA for this program as early as next year. 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 compounds that modulate pre mRNA splicing. We are now applying our expertise These include programs in Huntington's disease and familial dysautonomia. I'd now like to turn the call over to Christina our Principal Financial Officer.
Christine?
Thanks, Stu. Earlier today, we issued a press release summarizing the details of our financial results for the third quarter of 2018, and I refer you to that release for full details. I'll start with a few comments on our financial performance and our guidance for 2018. Starting with our top line results, we reported $53,000,000 in combined revenue across our DMD franchise for the third quarter of 2018 compared $41,800,000 in third quarter were $30,400,000 for the third quarter of 2018. This compares to $32,000,000 in the same period last year As Marcio mentioned, we recently received a large order from Latin America.
This visibility allows us to reiterate our full year Translarna guidance. Our Translarna guidance of $170,000,000 to $185,000,000 contemplates uneven ordering patterns and reflects the total patient demand our 15 percent CAGR for Translarna through 2022. For Emflaza, we reported net product revenues of 22.6 $1,000,000 in third quarter of 2018, an increase from $9,800,000 reported in the third quarter of 2017. We adjusted the range on our Emflaza guidance for 20.18 to $90,000,000 to $95,000,000 from the 18 DMD franchise revenue guidance to $260,000,000 to $280,000,000 from 2.60 $900,000 for the third quarter of 2018, excluding $4,400,000 in non cash stock based compensation expense. Compared to $26,400,000 for the same period in 2017 excluding $3,600,000 in non cash stock based compensation expense.
This increase in R&D expense reflects increased investment in our research programs and the advancement of our clinical pipeline as well as the Akcea upfront licensing fee of $12,000,000 paid during the third quarter. Non GAAP SG and A expenses were $33,900,000 for the third quarter of 2018 excluding $4,500,000 in non cash stock based compensation expense compared to 27 $900,000 for the same period in 2017, excluding $3,500,000 in non cash stock based compensation expense. Reflecting continued investment in commercial activities to support our DMD franchise Net Loss for the third quarter of 2018 was $51,000,000 compared to a net loss of $33,700,000 for the same period in 2017. Cash, cash equivalents and marketable securities totaled approximately $249,000,000 at September 30, 2018, compared to approximately $191,000,000 at December 31, 2017. We are proud of these transactions we announced R and D and SG and A expense guidance for the full year 2018 to $280,000,000 to $290,000,000 from the previous guidance of $250,000,000 to $260,000,000.
This increase reflects our investment in the gene therapy programs, and also includes the upfront licensing fee to Akcea paid in the third quarter. This non GAAP guidance excludes estimated non cash stock based compensation expense of approximately $35,000,000. Operator?
Our first question comes from the line of Ritu Baral with Cowen. Your line is open.
Could you walk us through a little more about the dynamics that you're seeing with Emflaza that's leading you to sort of tighten the range forgive me if I missed it, but is it connected to the discontinuation of the bridge program in some capacity Can you talk about what you're seeing? And I've got one follow-up.
Sure. Hey, Marcio.
Yes, of course, hey, too. So it is and it isn't, right? So it is in a sense that we that was one of the drivers I discussed last quarter in terms of accelerating the conversion that we were looking to this at the beginning of the year, as I mentioned before, we normally expect the conversion between prescription, to dispense around 3 to 6 months or trailing more towards the upper end of this guidance. Part of this was a large number of patients that we had on this program, on this bridge program, where we saw some efficacy on the patient and on the physician side give us information to continue to move forward. So one of the decisions we made was to terminate this program.
So, the sense of fusions would be skills and to move things forward. And this is having an impact, and it is, moving. So with that, we are being able to model when you're looking to individual patients. Now the dynamics of the market in general, when you're looking to individual patient conversion, the number of prescriptions we have right now ordering patterns for the, special pharmacies, what is letting us or getting us to narrow the range. Since we are relatively close to the end of the year.
So that's the main reason why, considering the base of patients we have in the number of scripts we are seeing per day.
Okay. So is it fair to say your time to fill is continuing to improve and that your insurance discussions and coverage is is not getting worse?
Oh, no, it's definitely fair to say it's not getting worse. And if anything, our team is is out there really trying to remove some of the barriers. I mentioned this before as well in previous call. The most common a step added we have is around 6 months on prednisone previous to start in Plaza. What we are seeing is a number of plans and it's still a small number, but we see this improving moving forward, removing that altogether or reducing to like a number of weeks reducing to 1 or 2 months.
So we're seeing an improvement on the general condition and now it's really getting this paperwork through getting this patients that we're having out is still on the order of 100 that we're having out like move to commercial, while we build the new prescription. So in a sense, like the entire team focus is twofold, right? So one, for this year, and to get, like, to the numbers that was just discussed since continue to execute on the conversion. But keep me an eye on building the number of prescriptions for year as well. And we have a lot of focus and like great daily calls and with different accounts and moving like I'm pretty confident as we move forward to have a good end of the year.
And I think it's also we're trying to remove the impediments as Marcio said. And we're helping them by the number of publications that continue to come out demonstrating that, in flaws that has superiority over prednisone and now that not only the, the, synergies databases that came out that publication the paper on the ActMD trial and those others that are coming out as well. So I think that's helping as well.
That's definitely helping. Yes.
I was able follow that. And then, can you characterize, persistence on treatment and how that figures into everything?
Yeah. So, so persistence like in the U. S, one of the advantages that we can track and we do track patients like every order. And we are seeing a very good persistent on treatment one of the things that we didn't quite tackle this year to the extent that we'd like to is adjustment of those two are those that is more in our view more associated with better therapeutic index on these patients So that's something moving forward. We're going to put a little bit more focus on, since we discussed this before, but maybe it was not clear, some of these patients are like half of the therapeutic dose, for example, with and we're discussing actively with the prescribers if this is a leftover from the previous regimen or if it's really something they want to focus.
So persistence being really good. What we ideally want is persistence at the best those for that given patient, and we're moving towards that as well.
Our next question is from the line of Martin Auster with Credit Suisse. Your line is open.
I had a question.
I was wondering if you could give us an update on when you expect the, enrollment in Firefish to complete. And then also just with the Sunfish phase pivotal part of that trial completed. Is there anything you can tell us about the, baseline characteristics around the age of the patients or the SNN32 status or things like that? Thanks.
Sure. Yes. So thanks for that question, Martin. So two things. One is the, as we all know, that the fire the SUNfish trial has completed enrollment and probably at the appropriate, meeting, we'll be describing what what the baseline characteristics are like.
So we'll be, we'll do that at a meeting most likely. And then in terms of firefish, Yes, things that, as we said, that we anticipate that it would be completed by the end of this year, and then we fully expect that to be the case, so that it would be, completed enrollment would be completed by theendofthisyear, and the trial would be finished next year. So we fully expect that to occur. So we're, we're, we believe that we're well on track to finish enrolling the that trial.
Thanks. And if I can maybe ask a follow-up, I had a question about the AADC gene therapy program. Thanks for giving us a little bit. Sort of deeper look in your gene therapy, programs overall. Curious.
What, what can you tell us about the differences of your approach versus, other clinical stage AADC approaches that are directed at Park And then is there a long term opportunity for this product to potentially be developed for that market as well? Thanks.
So, yeah, it's our view of the ADC in terms of its, is obviously, in this case, the deficiency of the decarbox delays gene. Where we think by injecting into the butaneum gives the results that you see here that we showed within the the video, and there's many videos that do that. So we think that's clearly, you know, versus parkinson or something else, which is probably This is more for the direct effect of the disease, not for the symptoms of it. So it's a difference in that perspective. Maybe you want to
Yeah. So, too, on the biology itself, right. The cells are preserved here. That we are you're injecting on the area. We have we can go to the general area, in the determined maybe this was not clear before So the precision of the procedure obviously has to be precise, but it's not as precise since it's largely preserved.
So these are normal brands. Of in terms of neuroanatomy, where you are just trying to get dopamine to be produced. And as you probably seen before, margins like in the past, scan images we're seeing all the way to 5 years. That's why we have pet scans. We're seeing the production.
In Parkinson, one of the potential issues here is where you have the generation, right? And what you're trying to do is to find the cells that are still able to have an effect. So underlying costs versus potentially reducing the effects, that those are likely or are in reality, the models should be quite different here as well. You might have a little bit different constructs. But if you look forward, it wouldn't be outside of the things we are considering potentially expanding this program.
The current focus of the company, I think we've been clear is on rare disease, and we're going to continue to plow through that and to deliver this treatment. The agency team is laser focused on getting the BLA filed next year and getting like everything ready. But, we continue to discuss our management and other areas of the company, potentially expanding.
Yeah. And in that view also, we know that just it could be, for this, we know it's due to specifically for mutations and the in the DDC gene, in the case of Parkinson, there could be multiple other genes that could be involved in this as well. So even for making for dopamine, it might be one of the other genes. So you might have to when you think about how to do this, you may do it in a way where you have multiple genes being expressed. So there's more things to think about in general of how you would do a general gene therapy perhaps for treatings, Parkinson's patients.
Our next question is from the line of Joel Beatty with Citi. Your line is open.
First one is on Emflaza. Given the hundreds of patients that have a script, but it's waiting to be fully processed. Do you anticipate that most of those patients will go on to be started at Emflaza at some point in time, or, you know, could there be a sizable number of those patients that may eventually not be able to transition for whatever reason to Emflaza.
We are committed to get every patient who is prescribed them for us to eventually get it, right? The conversion rate is actually very high. And in the order like very, very high, as you would expect, It's just a matter of time, in general. Obviously, some of these patients never qualify for one reason or another, and we have PAP program as well where some of those patients go through. We continue to look into ways for them to be on therapy.
Sometimes they do have 2, they never had exposure presence on and they are in a plan that really requires that and they have to have the exposure But at the end of the day, we're seeing like a terminal conversion, very extremely high and we're considering like dark talking about these numbers in the next call as we finish the year and so on. So not as much of a problem in terms of getting them there, eventually, but it's more on the timing of getting them there. And when a physician prescribed and flatter right now what we are seeing and still always highlights the publications and so on. They really believe it. It's more of a question of really the back and forth insurance that, I guess, you're not you're always hearing from other companies as well as we are, right, on how much back and forth has been happening right now and we are no different than that.
The order of magnitudes for Emflaza for our neuromuscular clinic is much higher than for the other product. So it's a lot of their attention and paperwork and we've seen that's taken a little bit of the, kind of slowing down that we mentioned before. And that's why we put extra incentives for people to really pay attention and give, the attention this deserve and we're seeing some good traction there.
Yeah, I think also, as Mauricio said, is that there's while we had a large number of patients who were in the bridge program that transitioned over, and this is sort of, there's always some where if we don't if you don't put in there some sort of an additional pressure, it would stay on until until a pressure is being put on. And so This is our way now of sort of moving those patients through the process. And that, that additional pressure just seems to be working sort of, reminder that it's not that it's not just that it's not here forever and that you have to move on to commercial truck.
That's right.
Got it. That makes sense. If I could ask a question on the AADC program. Could you give us an update on the key steps that still need to take place before filing the BLA in 2019.
Sure. I'll start and then I'll so just to remind you, the ADC program, as we have discussed previously, and I even think I had talked, here, is that, obviously, we think the data is is quite good in that it's really now, you know, and from the regulatory discussions that it was a matter of, that it's ready to be filed. And so, really, we're having discussions now in terms of that. And obviously, what the next step is to make sure the CMC is ready the sizing. And so, let me pass that to Marcus to focus on that.
Of course, thanks too. So, we have our strategic partnership with Mav Biologics to manufacture this. The key step here, I would say the most important steps really to continue to produce material towards they want to be commercialized. We mentioned previously, and I believe we filed in the queue that we had some interactions with the FDA. We're expecting to have more interactions with the FDA.
This is progressing nicely in terms of like conversations we had before and parameters and strategy for CMC that we had discussed continue to look positively for what we doing with Mass Biologics and internally here at PTC as well. We reaffirm today that we are filing the PLA neck year, right? So this is all progressing nicely on the clinical models of the BLA on the preclinical models of the BLA We're all now moving towards finalizing the documentation. So we want to be as ahead as possible in terms of everything that is not rate limiting. And I'm very happy with the progress that that's taken.
So at the moment we have the final CNC package, we can submit it next year. So everything is moving, from a regulatory perspective with the U. S. Very nicely. And the package for Europe is very similar.
So that's all based on the same. Our team in Europe is working towards that submission as well that includes few other steps, as you know, like pediatric investigation plan and so on. So everything is progressing. We should be able to file a BLA and an MAA in Europe and potentially other jurisdictions in a very short period of time to each other. So were very happy.
Again, I'm just going to put, I know it was not in your question, but one last thing here, the patient that then has been going very well as well, as I mentioned on the, on my remarks, because obviously we want to make sure to get the launch and to have a good base of patients to benefit from this launch. So they're going hand in hand.
Great. Thank you.
Our next question is from Gena Wang with Barclays. Your line is open.
Hey, this is Xiaobin dialing in for Gena. Thank you so much for taking our questions. Maybe just a couple from me, for Charles Lana, Can you, give us more color regarding the the girls in different geographies? Also, if you can excludes the Latin America part. And the second part is, can you update us, regarding the US regulatory status?
Like, when do you plan to start the dystrophin biomarker study?
Sure. Okay. So maybe I'll start and then we'll go in From the, the regulatory status for the dystrophin study, I think as we've said, we plan to start the been studied by the end of this year, so that it would be completed by the end of next year and would be filed after that. And so, we're on target to do that as well. So we feel good about getting that going to then be able to be able and therefore, it's anything really above background.
In terms of the amount of dystrophin that would actually give us the accelerated approval. So we feel good about moving about that. In terms of Translarna's growth and development. I guess what I could say on the high level is that we continue to grow Translarna in all these area in all the areas And maybe I'll let Marcio go into some details in terms of the dynamics of the areas. Sure.
Sure. So like 2 major areas for us, right? So the European and Middle East area in the Americas. And that's how we look. It's a basket of counties in each one of them.
We see progression like when you look into the full year and we always look into full year because inside each one of those regions, there is several countries with very uneven order pattern. So it doesn't make sense to look quarter on quarter for us. So when I look into my full year, latest estimates that we always run periodically here that is double digit growth in each one of them, which is exactly where we'd like to be which put us in a position to continue to reinforce and reaffirm the 15% long term goal to 2022 that we mentioned before, specifically on Latin America, right, that we called out in the in the Collins part of your question, like Brazil, Argentina, a longer important business for us. And we always monitor there, there are countries that are used to only order periodically through the year in lump sum, I would say, orders for several patients. So we receive one of this order after Q3 ended for, for Latin America specifically working through the paperwork right now to get it shipped, but that, something that sometimes got a little bit delayed from one quarter to another, and that's why we always, messaged that and talk to all of you, a how lumpy it is.
So having that enhanced relatively early on Q4, give us confidence to get the guidance where we are, for the year. Does that help?
Yeah. That's very helpful. Thank you so much.
You mean, it's also worth, though, just for everyone to know is we always talk about lumpiness of Latin America. But even country by country over time, maybe it's worth talking a little bit about well. Sure.
And that's what I was mentioning in terms of even Europe, right? We like. We are shipping to more than 40 countries now And when you look into the combination of all of them, several of them have like orders for more than 3 months throughout the years, just because of that, how their supply agreements work. So end up being lumpy in general. And one of the reasons why we got this question before, why not looking to quarter by quarter.
But for us, it's really not possible right now. We have a exclusive ex U. S. Business for Translarna. And it's fairly unusual.
There's not a lot of other products there like that, but it's a very common pattern that to Stu's point. We have highlighted more or less in America before, but it's really in general in our business.
So we sort of know how many patients there are and how much we get over the year. But the ordering patterns could vary. And that's just, I think, important for people to understand over the time within Europe.
Okay. Thank you so much.
Our next question is from Brian Adams with RBC Capital Markets. Your line is open.
Hi, this is Bert on for Brian. Thanks for taking our question. I wanted to ask on your new oncology studies. Could you just remind us of the pharmacology of 596299 and maybe talk a little bit about the DIPG, like the incidence and prevalence in the clinical course of that disease. Sure.
So you and so the I think you're referring to what's the mechanism of action. So, yeah, sure. So maybe we'll start with PTC299, which is, an inhibitor for dihydrolortate dehydrogenase, So, it's a very potent effective inhibitor of that. That turns out to be important in particular in leukemic cells where you need polychromidines to be made. And if you inhibit that, you can actually cause differentiation of leukemic cells into that, and that's been seeing not only over in the diverse array of leukemias, but in particular in AML itself.
So we think this has a very promising effect possibility of having effects in these diseases. We also know already just because of our previous clinical studies in this that we know we can it is we do see inhibition in patients of DHODH by seeing increased levels of the dihydro ordatase in the bodies when you treat patients with PTC299. So we know we're on target So it looks, you know, so now all we need really to go is to prove the next hypothesis, which is that will cause, leukemia Excel to differentiate. So we feel pretty good about that. PTC596 is, inhibits was identified as an inhibitor of BMI, which is a stem cell regulated protein that is important in many different tumors in particular in brain tumors.
The other thing is that, when we selected it as a molecule, in particular, we selected it for being able to go to the brain and actually stay in the brain. And so we know that it's not inhibited or pumped out by brain pump. So I think that's an important aspect of this being an effective molecule that could get to the brain and stay into the brain. Want to talk a little bit.
Yes, let me talk a little bit about the numbers that you mentioned, right? So the IPG, so the trials just to remind everyone, right? 299, we started an ML. It's a dose escalating trial right now. We're trying to get to the dose that is the most efficient and most efficacious, and at the same time, confirmed toxicity as we normally do here.
I think the ML markets as well understood in general. For the IPG, for the IPG is a pediatric brain cancer, relatively rare about 1000 U. Ks per year in the United States. The age of onset or the age of symptoms is between 5 6 years of age in these patients is absolutely devastating. If you look it up, you're going to see for all the pediatric cancers is the one with the lowest 5 year survival.
So the median survival once the patient is diagnosed, it's 9 months. So they virtually all die unfortunately before the 2nd year with the disease is only 2% survival at 2 years 1% at 5 years. The trial that we are doing right now is with the DIPG network. I'm very happy to work with and they're well established out there. The game plan right now is really a numbers 1, right?
So we need to get sites open throughout the United States. And that's what we are doing because these patients buy so quickly, we need to be able to get them. In terms of design, the trials in combination with standard of care that is radiation on this patient. So we have to have the courses back to back and one more reason to have a number of sites. We have sites open right now.
We have patients like coming through through the network, but we really want to enroll this quickly because again, it's very unfortunate for the patients, but it's relatively good for drug developments that the mortality is so high. So as we see clinical benefit as we expect to do so would be able to see this relatively quickly. So this is moving forward and we expect to include the 2nd trial with 596 for Lioliosarcoma 3 starts later this year. So it's all lined up we just need to get the site open to start that trial.
And our next question is from Eric Joseph with JP Morgan. Your line is open.
Hey, guys. Thanks for taking the questions. I just wanted to follow-up on AADC Manufacturing. And, you previously talked about having a, a CMC meeting with FDA by your your expectation. And I'm curious to know how iterative, you expect that interaction to be.
And, also as it relates to manufacturing, I'm wondering to what extent your current efforts with Mass Biologics for AADC commonly applied to, the Friedreich Ataxia program, And is the idea to have mass mass bioproducing product that you'd be, taking into clinic when the IND gets underway? Thanks.
Hey, Eric, and thanks for the questions. So we have, discussed before, right? We're going to have a pipe C meeting with the FDA relation to CMC, or like before the end of the year and we had the meeting, and we're moving forward with the feedback that we got very productive in general like extremely happy with interactions with the doctors at the FDA and glad for all the feedback they've been giving It's more a strategy in how we go through finalizing the process with the with Mass biologic moving forward. But again, we got that milestone that we mentioned before. We normally don't give regulatory updates in general.
So I hope it's not expected that we're going to give play by play, but since this was important, we thought we would give like these updates right now. Metabolic is now fully focused on AADC. We see the capabilities there to expand to other programs. We obviously talk to them all the time. But part of the strategy here, and we do the same with Translarna just don't talk much about it.
Is have a diversified base for all the products we have. So we have other partners we're discussing with right now at the appropriate time, we're going to be disclosing who they are and which stage they are and looking through other options for manufacturing in general. While it's a still small volume for FA, it's obviously in general a bigger incidence and prevalence of a disease. We're going to need more material. And we are considering that as well as we expect to be successful with ATC, they're going to have a demand for mass biologics in terms of production versus having FA, which we are like getting to the point that the product has to be available for the clinical trial for next year as we mentioned before.
And I'm reaffirming now we're fighting an IND next year So we are considering all the needs on the short and long term for this product and what is the best strategy moving forward. But Neo and his team is really focusing on this and I think we're all very happy to get them out there and talking to different folks and getting the base expanded.
Great.
Thanks for taking the question.
Thank you.
Our next question is from Alethia Young with Kent Vatero. Your line is open.
Hi. This is Eileen on for Alethia. Thanks so much for taking the question. Just one on Joltfish. Can you kind of characterize what data you're looking for that would really change the prescribing behavior beyond what we might see from the Sunfish data set with respect to switching or anything that you guys are also thinking about.
And then, for TEGSEDI in Latin America, how many of the 6000 patients have been identified or do you estimate are under care right now? And have you gotten any, you know, feedback from regulators with respect to the safety or monitoring from a Latin America perspective?
Yes. So I think for the JUULFISH switch, it's really for those patients who want to move from one therapy to the next therapy. So that's really what that's really it's almost open label trial for that will be. But as you saw, probably what we did at the World Muscle, we did demonstrate as we've seen for all the other trials that the levels of the SMN protein went up to near normal levels that we saw in, in, in, in carrier. So again, you're, you know, to me, that's a very important point because at the end of the day, it's the loss of that protein that leads to disease.
And so you're getting to the, the right level for those patients, and then we'll be following them over time.
Yes. And I think one additional point here, right. So that obviously, as it gets to the launch and Roche, obviously thinking a lot about together with us in the collaboration. It's important to have some safety data that the patients can switch from one therapy to another. So that's going to give that data is to just mention, I just want to highlight that it's actual increase or change in SMN levels, not cartoonish chains like actual numbers, that is being out there.
I think some people believe that just showing illustrations is good enough. We don't. We believe that we have to be able to show, like growth in expression, increase. So that's, I think that's quite important. As we look into the numbers of TEGSEDI in Latin America, like the majority of those patients are identified some of them are not genotypes yet.
And some of them are not being followed by the centers as we would want them to be. So the effort right now is twofold, right, is to obviously, you can diagnose and especially in areas like Brazil or somewhat endemic, because of the genotypic populations, genotypic population by the clinic, But we believe that for the best interest of these patients, they should have a genotype, they should have a mutation on the gene. So we establish a very robust program, which is up and running, to, genotype these programs, the early feedback from the physicians that they really appreciates what we've been proposing. It's an exceptional program in my view because they can not only diagnose the HATTR patients, but also expands to other disease that might become a misdiagnosed. So, from the physician perspective, they are very happy.
We think only about like 20 to 25 percent of the patients are currently genotype. So we want to get this number to be much bigger. And we're moving towards that before the launch. In terms of the feedback for the monitoring program, we are discussing that as part of our regular interactions with ANVISA and other agencies, we do not expect that to be an issue for 2 reasons, right? So one, It is obviously can be, it's only a small percent of the patients that might drop the platelets.
But the second is, we have a very robust program in Brazil and Argentina and Colombia and the rest of Latin America in terms of monitoring the patients right now for Translarna Obviously, the monitoring is not as extensive as the one that is required for TEGSEDI and eventually Waylivra, but its presence what we did earlier in the year as we were discussing with Akcea, as we locked down the best vendor in the region, really the only one that can provide this kind of service to work exclusively with us. We have a process by which every patient's going to be visited on their house to get the blood draws and going to be sent to a central lab and the physician's going to receive the at the results. And just like couple of weeks ago, we had a large adviser board with a number of physicians there, and they all teamed this be more than appropriate and they're all happy actually that we're going to be doing that because it's not only the monitoring, it's making sure the products are using product correctly. And, obviously, in healthcare, everyone has interest for proper use. So we feel very good about that.
And actually to put it in perspective, when we think about, Ultra Orphan rare disorders, you know, Marceo said 25% we already know, that's a huge number when you think about it from a disease that had no real treatment for it before. And in a way, in Brazil, it many of physicians know it more of almost like the Portuguese disease so that they're highly aware of this. So this should really help quite a bit in terms of patient identification.
And our next question is from Raju Prasad with William Blair. Your line is open.
Thanks for taking the question. One for me on Translarna. Can you just kind of provide some color on non ambulatory patient population and how that contributes to the 50% CAGR through 2022?
Sure. So right now, obviously, as we said, we've already submitted in to get a label expansion. As of right now, we don't have anything into as part of the CAGR for that. So it's not really counted now. And as we've said before, this obviously could be quite extensive as there's 40 to 50% of the patient's increase.
So it would be an interesting addition, obviously, to the get it to these patients.
Great. And then on, On the on SMA, obviously, Novartis kind of discussed some some quality data today. You know, given the commentary in type 1 SMA, does that cut change at all. Your thoughts on on where ResiPlan may be used. And and pricing potential, obviously, that change at all based on, how a nexus 101 is priced?
You know, obviously, that's That's their consideration. From our point of view, what we think is that the Risdiplim has the potential to be best in class. Obviously, we're I think the only drug that's really been able to show protein levels to, to levels of what a carrier would have within patients And we can that's one of the ways we define what's the appropriate dose to go after. And so we think that based on the data that we hope to have both in the type 1s, as well as in the, in the type 2, 3 experiments of firefish and sunfish, that that's the potential to be best in class. So obviously, that's the way we're thinking about that now.
And, I know there was some discussion in their call today, but we think the fact that you have a drug that distributes not only to the CNS, but also as orally by available gets to every tissue that's affected, is what we think is a much bigger advantage to be able to get it both to muscle, bone, liver, as well as nerve and be able to treat the whole patient. We think is an important advantage, to treat an SMA patient. Both type ones, twos, and threes, In terms of, the pricing, actually what we think of that in terms of the, I think more of that in terms of the AAD C space where when you look at, the results that we currently have for AADC deficiency, where we have a fairly, a fair number of patients with who've been taking it up to 8 years that have demonstrated a very durable response. We think, if that's the pricing that's being considered, that really bodes well for the data that we have for AADC. And I think that's an important consideration.
So I'll now turn the call back over to Stuart for closing remarks.
Well, thank you all for, joining today. I hope that you've seen that our vision is really to continue to build this fully integrated reared disorder biotech company, and we're leveraging really our scientific expertise as well as the world class commercial capabilities that continuing on our 20 year history of innovative science I think there's a number of milestones in the coming year that's going to create value both to the patients and shareholders alike. So Thank you again for joining the call.
Ladies and gentlemen, this does conclude the program.