Good day, ladies and gentlemen, and welcome to the PTC Second Quarter Financial Results and Corporate Update. At this time As a reminder, this call is being recorded. I would now like to turn the conference over to Emily Hill, Head of Investor Relations. Ma'am, you may begin. Hello, good afternoon, and thank you for joining us to discuss our 2018 second quarter corporate updates and financial results.
Joining me on today's call is our CEO, Stuart Peltz, Chief Operating Officer, Marcio Souza and our Principal Financial Officer, Christine Utter. Before we start, let me remind you that today's call will include 4 looking statements based on current expectations. Please take a moment to review our slide on our simultaneous presentation, which contains our forward looking statements. Our actual results could materially differ from those forward looking statements as any and such risks can materially and adversely affect our business and results of operations. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's recent quarterly report on Form 10 Q and annual report on Form 10 K filed with the Securities And Exchange Commission as well as company's other SEC filings.
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 Pupp.
Thanks Emily and thanks for joining us this afternoon. Joining me on the call today are Marcio and Christine. Marcia will provide the commercial and clinical development update. Christine will end the call with a review of our financials. The first half of twenty eighteen has clearly been transformative for PTC.
As I outlined at our 20th anniversary Analyst Day, We have a strategy to build out PTC as a rare disease leading biotech company. While we provided a 3 to 5 year plan, I hope you can see taking the outline of the strategic vision and aggressively executing on it in the first half of this year. We continue to successfully grow And most recently, we have announced 2 important transactions that strengthen our pipeline with late stage and commercial assets. Let me discuss each of those now. Which allows us to commercialize 2 rare disease drugs in Latin America, TEGSEDI and Waylivra TEGSEDI has been approved by the European Commission for treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary trends thyretin amyloidosis or hATTR.
The approval by the European Commission is important as it is critical in Latin America. The polyneuropathy form of hATTR which TEGSEDI has indicated for occurs more frequently in individuals of Portuguese Ancestry. Because Latin America, and in particular, Brazil contains a large portion of polyneuropathic hATTR patients The region is strategically important one for TEGSEDI. TEGSEDI is also under review by the United States FDA with a PDUFA of October 6th. The second product Waylivra is under regulatory review in the United States and Europe for the treatment of people with familial chylomicronemia syndrome or FCS, with the PDUFA coming up later this month on August 30th.
This collaboration reflects our strategic initiative to leverage PTC's global infrastructure and our successes in bringing innovative drugs to patients in Latin America. We are eager to bring these important therapies to patients in these regions as quickly as possible. The next transaction I'll review, the Agilis acquisition puts us on the forefront of gene therapy. On July 19th, we announced our agreement to acquire Agilis Biotherapeutics. The Agilis gene therapy platform for treating orphan monogenic CNS disorders is an ideal fit with our strategy of building out a leading rare disease biotech company.
This transaction places us in including a late stage CNS gene therapy program. We plan to file a BLA in 2019 for the lead program for the treatment of AADC deficiency. We are very excited by the lead asset as well as the technology behind Our DMD franchise was strengthened in the first half of this year on several fronts. The EMEA approved the label expansion for Translarna in non transmutation Duchenne muscular dystrophy patients ages two to five years old. CMD is a degenerative disease, treated patients earlier allows for better preservation of muscle function.
Importantly, this label expansion allows patients in countries that recognize the EMA approval to gain access to the therapy at a younger age. Our DMD franchise also includes Emflaza for all United States DMD patients over age five. We are working hard to establish Emflaza as the standard of care in the United States. Recent DMD guidelines reinforce this effort. The guidelines state that Emflaza should be initiated for all of DMD patients as early as possible.
Our commercial execution has led to strong year over year revenue growth. In the second quarter 2018, our revenue for the DMD franchise totaled approximately $68,000,000. Our guidance for full year 2018 remains $260,000,000 to $295,000,000. Beyond the current growth opportunity for Translarna, outside the United States, we are also looking to expand and bring Translarna to U S patients. We plan to initiate a dystrophin study this year to submit to the FDA next year for potential United States accelerated approval of Translarna.
Let me now turn to our internal splicing platform. We have an oral small molecule as a treatment for SMA advancing in the clinic. This program is currently in pivotal studies in partnership with Roche and the FME Foundation. The ongoing pivotal studies include Firefish, for type 1 SMA instance and SUNFISH for type 2 and 3 SMA patients. Encouraging interim data from the dose finding portion of both studies were recently presented at the Cure SMA meeting in Dallas, During the clinical presentation of the Firefish dose finding study, a video was shown of 3 babies sitting independently.
I'll provide more details have validated our splicing platform, which we've expanded to include Huntington's disease to familial dysautonomia. These are progressing and are currently in lead optimization stages. We expect both programs to advance into the clinic by 2020. Let me now pass the call over to Marcio to update you on our clinical and commercial efforts. Marcio?
Thanks, Steve. As Stu just mentioned, we continue to advance towards our objective for the DMD franchise in 2018. Increasing the use of Translarna globally and transforming Emflaza into the standard of care in the United States. We are pleased with DMA translarna label expansion to include patients aged 2 to five years old. The launch process has now started and I'm optimistic about the additional patients to be treated with Translarna in this expanded patient population.
We have been working very hard to help the communities in lowering the age of diagnosed for DMT. Before our launch of Translarna 4 years ago, the average age of diagnosed was around 6 to 8 years old. Depending on the country. In most geographies where we operate, DH has been reduced by at least 6 months and as much as 2 years. We continue to invest in improving disease awareness patient identification and genotyping to further advance this agenda.
We are committed to continue to drive earlier diagnosed efforts to improve patient's outcomes. We have a similar commitment to improve patient outcomes with Emflaza. We are marching forward to establish Emflaza as the standard of care for DMD patients in the U. S. I'm happy to report the first wave of transitioning the flasaccord experience patients to commercial therapy is complete.
We are now expanding Emflaza use to the segment of patients who have been previously or are currently on prednisone. This second phase has been slower than expected. Completion on the payer side is happening but has been more time consuming than we previously anticipated, mostly due to the doctor's office burden of paperwork and processing. We have a number of key initiatives underway to ensure Emflaza uptake continues and accelerate. This includes improving administrative support and continuing to remove barriers with payers.
Based on increased information around Emflaza's benefits. 2 important publications demonstrating the effect of Emflaza over prednisone have recently been published. We just announced an important publication in Muscular nerve comparing the efficacy and safes of the Fazalore in prednisone from the placebo arm of the XTNG study. The results demonstrated a clinically differentiated benefit of the Plazacore overpresence on in its low disease progression, as measured using physical function endpoints and the time to delay of loss of ambulation. Reaching naive patients is yet another critical step in our long term strategy.
In the United States, about half of the DMD patients are still not currently treated with any Portquoise steroids treatment. The current DMD treatment guidelines recommends starting in flaza treatment upon diagnosed. We have a long term strategy to penetrate the segment of untreated DMD patients as well as to expand the label to address the youngest patients age two to five. Our highly differentiated DMG franchise has been growing year over year. In the first half of twenty eighteen, the combined franchise reported revenue growth of 67% versus the same periods in the prior year.
We are reiterating our expected guidance for The global commercial Translarna business and Emflaza acquisition have diversified our product portfolio, revenue and geographic footprint. Positioning PTC as an outstanding rare disease BT partner. We have now demonstrated our ability to integrate and rapidly launch products for rare disease. In line with our strategy, we had 2 transformative transactions in the past month, Most recently, we announced a collaboration with Akcea to commercialize 2 rare disease drugs in Latin America. TEGSEDI and Waylivra.
For our commercialization efforts with Translarna, we have established a strong presence in key countries including Brazil, Argentina, Chile and Colombia. Our patient identification efforts have resulted in strong year over year growth in these countries. TEGSEDI has received marked authorization approval from the European Commission for the treatment of stage 1 or 2 polyneuropathy in adults with ATTR. HATTR is a devastating disease with limited treatment options. As Stu said, Latin America and in particular, Brazil contains many such patients.
So the region is a strategically important one for TEGSEDI. We anticipate Brazil to be 1 of the largest spot neuropathy ATTR market worldwide. In Latin America, we understand to be more than 6000 patients eligible for treatment. Our team is working hard with the Akcea Ionis teams to execute on a robust regulatory and go to market strategies. For the region.
We are uniquely positioned from a competitive standpoint to execute in Latin America. The second product Waylivra is in the regulatory review in the U. S. And Europe for the treatment of FCS. When LIVRA has the potential to be the 1st and only therapy indicated for SCS.
We expect the market opportunity for Waylivra to have the potential to be similar to the one of Translarna in Latin America. FCS has been historically misdiagnosed and we expect patient identification to be the gating factor for launch. At CFS calls by impaired function of the enzyme lipoprotein lipase and is characterized by a risk of unpredictable and potentially fatal acute pancreatitis. We're excited with the opportunity to bring these life changing drugs to patients. Let me now turn to planned acquisition of Agilis Biotherapeutics.
The acquisition brings us 4 gene therapy programs at various stages of development. All focused on treating CNS disorders. It's starting with a late stage program in AADC deficiency for which we plan to submit a BLA in 2019. This is followed by programs including Friedrechtia, in Engerment Syndrome as well as other cognitive disorders. This acquisition as a cutting edge gene therapy platform and strength our pipeline, adding both late and early stage gene therapy programs.
Which we are eager to bring to patients. Many of these gene therapy programs will benefit from the advantage of targeted microdosing directly to specific structures in the CNS. Michael dozing of the viral vectors bring many advantages because that allows for a small scale manufacturing, reduce risk of immunogenicity, while maximizing efficacy in the CNS. These transactions align with our strategic priorities. Bringing in late stage therapies for rare disease and leveraging our global infrastructure We are confident that they are well equipped to drive value with both strong commercial and clinical capabilities.
And a continued focus on transforming lives of patients with rare disorders. I'll now hand the call back to Stuart. Stuart? Thanks, Marcio. I'd like
to share more detail on data recently generated in our SMA program. Most of you are familiar cover potential new therapies for spinal muscular atrophy or SMA, a rare genetic neuromuscular disorder that generally manifests early in life 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 of its broad tissue distribution and ease of administration. Earlier clinical data has shown that RG-seven thousand nine hundred and sixteen drives SMN2 splicing towards a 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, 3 patients. The JEWELFISH study will not registrational is also enrolling patients from other splicing therapies. Data from JELDfish and from the dose finding portions of Firefish and Sunfish were presented in June at the Cure SMA meeting in Dallas demonstrating sustained benefit and safety and tolerability. Data from the 21 babies in the dose finding portion of Firefish highlighted continued survival.
During the presentation, the investigator of the study showed a video of these babies demonstrating improved motor function including head control, rolling from supine and Citi. 3 babies were depicted sitting independently. The first baby received their first dose 6.8 months of age and was depicted sitting at week 35. The second baby received their 1st dose at four months of age and was depicted sitting at week 26. The 3rd baby was first dosed at 5 months and since sitting at week 26.
Notably, The last baby was also depicted riding a dragon ride on toy across the hospital. Previously published natural history data indicate that the meeting age of event free survival for SMA Type 1 infants to be between 8 10.5 months. Of the 21 babies presented already, 13 have surpassed the natural history expectations of 10.5 months survival. It was also noted no babies have required a tracheostomy or permanent ventilation to study initiation and no baby has lost the ability to swallow. The meeting age of the first dose was 6.7 months and babies have received RG-seven thousand nine hundred and sixteen for a duration of up to 24 months.
As of the June presentation, RG-seven thousand nine hundred and sixty has been well tolerated at all dose levels and there has been no drug related safety findings leading to withdrawal. 2 deaths were previously reported due to disease progression and were determined not to be drug related. The firefish dose finding study is now complete and all babies have a transition to the therapeutic dose for an extension trial. Ongoing data presentations from this trial are expected throughout 2018, including additional survival data chopping ten scores and other motor milestones. We look forward to sharing these developing data with you.
The next anticipated medical meeting presentation is at the World Muscle Society Congress in early October. Data on additional sitting SMA Babies will be shared at this point. Based on reports of an increasing number of sitting babies, We and the collaborators believe there is a potential to file an NDA in 2019. Recruitment is ongoing globally for the pivotal registrational portion of the Firefish and Sunfish studies and enrollment is expected to complete this year. The Sunfish is a blinded study with the primary endpoint of motor function at 12 months.
The primary endpoint of the open label Fireflies study is a percentage of infants who are sitting without support at 12 months of treatment as assessed by the Bailey infant scale. The SMA program is not only progressing towards the oral and systemic treatment for SMA patients. It also validates that our splicing platform technology can identify selective compounds than modulate pre mRNA splicing. We are now applying our expertise These include programs in Huntington's disease and familial dysautonomia. We expect both programs to enter the clinic by 2020.
We are very excited about our splicing programs and covered them in-depth at our Analyst Day. And I would refer you to those slides on our website for full details. I'd now like to turn the call over to Christine Otter, our Principal Financial Officer. Christine?
Thanks, Sue. Earlier today, we issued a press release summarizing the details of our financial results for the second quarter of 2018, and I refer you to that release for full details. Financial performance and our guidance for 2018. Starting with our top line results we reported strong performance across our DMD franchise. As Stew mentioned, our results for second quarter of 2018 for total net product revenue of $68,200,000 compared to $47,900,000 in the second quarter of 2017.
Based on where we stand today, we are reiterating our 2018 revenue guidance of $260,000,000 to $295,000,000. Translarna net product revenues were $47,800,000 the second quarter of 2018, representing 4% growth over the prior year period, mostly as a result of increased in existing geographies. Which make quarter over quarter comparisons less representative of underlying growth. Our Translarna guidance contemplates this lumpiness and reflects the total patient demand for the year. Emflaza reported net product revenues of $20,300,000 in second quarter of 2018.
Non GAAP R and D expenses were $28,700,000 for the second quarter of 2018, excluding $3,900,000 in non cash stock based compensation expense. Compared to $26,900,000 for the same period stock based compensation expense. This increase in R&D expense reflects increased investment in our research program. And the advancement of our clinical pipeline. Non GAAP SG and A expenses were $29,400,000 18, excluding $4,100,000 2017, excluding $4,000,000 in non cash stock based compensation expense, reflecting continued investment in commercial activities to support our DMD franchise.
Net loss for the second quarter of 2018 was $9,500,000 compared to a net loss reflects our growing revenue base as we continued to leverage our successful international corporate infrastructure. Cash, cash equivalents and marketable securities totaled approximately $296,000,000 at June 30, 2018, compared to approximately $191 As we close on these transactions and move forward with integration, we will provide updates to our expected spend for the year. I will now
Thank And our first question from Brian Abrahams with RBC Capital Markets.
Hi, this is actually Rick on the line for Brian. Thanks for taking questions and congrats on all the progress. First, I just wanted to follow-up, Steve, on your comments about the potential for accelerated approval of RG79 Dean. Based on the data emerging out of Firefish, what is your current understanding on what the bar for the potential for accelerated approval is? Is there a threshold number of babies achieving the sitting up unassessed milestone you think that would be supportive of accelerated approval?
Or are there any other motor milestones you think could play into accelerated approval?
Yes, thanks for the question. We think that's an important question. And maybe as you might remember at the, what we reported at the Cure SMA meeting where We saw a number of babies being able to have development milestones that included being able to raise the head, being able to turn over as well as being able to see. We're sitting as the endpoint for the trial. And in that in the in the Part 1 of that, where there were 21 babies within that trial, we had reported at the Cure SMA meeting in June that there were 3 babies that were able to be sitting.
So we thought that was actually really quite important. Over time now, what we're saying is that there are, as a consequence of more time passing that there are additional baby sitting since that time on top of the 3 that we had. And so we wanted at this point and probably you've heard from before where, Roche had disclosed last week that there's a potential filing in 2019. And I think that just reflects the potential to file for that reflects that the increased number of of babysitting, that will probably be presented at the World Muscle Meeting at that time. But what we wanted to do here is really reflect the increase in number of synonyms since that is the endpoint and we're seeing increased numbers.
And I think we've always said before that 5 out of 40 would be statistically significant in the part 2 of that trial, seeing additional fitters in in the part, in this part, just gives us more confidence for potential. So I think it's obviously going to require additional conversation with regulators so that they look at both safety and efficacy for a potential filing. But just the fact that we continue to see such exciting results makes us think about how to move this as rapidly as possible for the patient.
That's great. That's very helpful. I have a follow-up. So assuming positive results from the fire for study in type 1 patients, what kind of implications would that have for a potential expedited approval pathway in type 2 and type 3 SMA patients? Since they all have the same underlying genetic defects, but the progression of disease in type 1, SMA is much quicker.
Is there the potential for some sort of, submission package where you could maybe combine the achievement of motor milestone data from type 1 patients, with biomarker and safety data from type 2 and 3 patients?
Yes, I think that's, again, a really good question that would require additional conversations with the regulators to see how they would think about it in terms of the of knowing what you see in type 1 and extrapolating to type 2 others, which is not uncommon in the orphan disease space. So it's certainly a conversation we would have and we have an ongoing Sunfish trial, that certainly would then be continuing on as well.
Did you Yes. Maybe just to add a little bit, right. So some fish, our trial for Type 2 and 3 is, as we mentioned before, we expect these trials to be enrolled relatively soon by the end of the year. So we see that both parts 1 in SUNFISH where we collect the like safe data and the sending those and now this pivotal phase for Sanfex are going to be fundamental. So while they are expecting of the disease, they fundamentally different in terms how they progress, but the program is so comprehensive and there is so much data in terms of like the number of patients that being the exposure, our understanding of the PK and PT relationships and so on that we believe is by far the one in development most advanced in terms of just how comprehensive and large it is.
So that gives us confidence that if you were to find path forward with the regulators to file for type 1, we could follow shortly thereafter with a type 2, 3 or even all together So stay tuned and we're going to keep you guys updated.
Thank you. Our next question comes from Joel Beatty with Citi.
Hi guys, this is Sean calling in for Joel. Guys. I'm such a busy and an eventful quarter. So I've got a few questions. Just kind of a follow-up on SMA I think we're going to see, I have your first efficacy data at World Muscle Society for Ascendfish.
Could you just review what are the most important that we should be looking for? Yes.
Thanks for that. Yes. So SUNFISH That's for part 1 where we've, in the past, showed both the RNA as well as protein level And over time, appropriately, we're going to we're measuring MFM and others as well. So it's obviously open label there, but we'll be looking at the MFM scores and things like that as well.
Excellent. And then I just have 2 follow-up questions on the HAATR program. Can you just briefly describe any work you've done give us confidence in the estimate 6000 patient population? Can I help you out there?
Sure. Yes. I think there's been a lot of prevalence in diligence in terms of looking at this. Marcy, why don't you go through a little bit on what we've done?
Absolutely. So, Mike, as you might know, we, we mentioned like during the press release last week, right from the collaboration. So let me first say how excited we are. We think that at C and I own is our incredible partners like the collaboration so far has been tremendous. And there was a lot of data they had collected during the due diligence in the last several months, we met with all the key opinion leaders in the country.
Are we looking to both primary research and secondary research, but also we have a network of labs that we've been working on in lab in America that collects genetic information, epidemiological information. So we rely on all of that and considering just how large the Ancestry background in terms of like DV3M mutation in Brazil alone, for example, it is, we feel very confident on the numbers that we provided is about 6000 patients in the region. It is mostly concentrated in the south of South America. So Brazil and Argentina, for example, are the 2 most important countries on that regard, but we see the potential across the region just with a slightly different genetic background in the other countries.
So we feel good about the notion that while we think there's around 10,000 to 15,000 patients with the polyneuropathy that really this area gives us between a third and a half of those patients ships. And we feel pretty comfortable that this is a really important valuable area for the drug.
Thank you for that. That makes a lot of sense. And just as a brief follow-up, can you talk a little bit on your strategy to best identify these patients considering it is such a heterogeneous be?
Yes, absolutely. So we're doing a lot of things already. And part of the joins development and diligence with the Akcea group, right? We exchanged a lot of ideas. We're going to be updating all of you, like in future quarters in terms of what we are doing.
But one of the key things is really mapping these patients that have the clinical diagnose but not the genetic diagnose to the sites. We know where these patients are concentrated right now. We believe that there are areas outside of the main centers that have been historically treating HTTR patients where there's large pools. We're focusing on those large pools. Having the team already present in all these colleges make a huge difference, right?
To have medical directors and MSLs and like a field team that is really like going through all these accounts already. That is a very large overlap in terms of the neurologists with the accounts that we've been already developing relationships or have relationships for Translarna. So it's kind of a perfect fit We're going to be giving updates. Now in a sense, it's a competitive space and we believe that we have a competitive advantage here. We're not going to be sharing as much as we shared before in relationship Translarna since we believe we are ahead at least few years ahead of the competitors here and you want to make sure we'll remain so.
Excellent. Thank you so much guys. Appreciate it.
Thank
you. Our next question comes from Gena Lang with Barclays.
Thank you for taking my questions. Just wondering, I think in the press release, you also commented the 5 year net product net product revenue growth rate 15 percent compound annual growth rate into 2022. So that translates into, I think, roughly $350,000,000 in 20.22. Just wondering what are the assumptions for this $350,000,000 in 20.22? And do you think are you being a little bit conservative in terms of that assumption?
Hey, Gena, thanks. Thank you so much for the question. The way we look into guidance and we mentioned this before, right, in our future guidance as well is it's always in terms of like the midpoint or so of what we are expecting. So there is a number of initiatives that we are doing to gaps that fit 18%. 1, they just wanted to highlight, we just got the 2 to 5 label ratified by DEC So that alone in total of the population, we're talking about a very large number of patients.
I mentioned in my prepared remarks, as you probably saw that a lot of those patients are not identified yet, but I'm extremely happy with the progress that was done in all the counties we operate in terms of identifying patients genotyping, reducing. So a lot of our assumptions are both for identification and conversion, but they don't differ much in terms of what we are seeing right now in terms of the trajectories. There are a few territories that we're going to be adding and increasing the penetration. We mentioned that before specifically like Latin America, where we just discussed recently our presence there, we are intensifying the presence we feel that the deal with Akcea very synergistic on that regards, it's going to put more people on the ground, more efforts, it's going to help with Translarna as well. And the Middle East region as well.
So it's multi pronged in a sense approach, but patient identification expansion of the label and these new geographies are going to be the key drivers here. The interesting thing that I believe sometimes got lost is even on the key EU counties where we launched it way back 4 years ago, we're still seeing fairly robust growth in the number of patients and identification and so on. What gives us extra confidence of this long term?
Yes. And then I think your point is a good one is there is potential upsides we have depending on things like we're working now for the non ambulatory, in Europe, if you may remember the pulmonary function data, which was really quite quite strong. And so we're in the process of trying to get label expansion of that. And that could be considerable upside. That could be a 40% upside in terms of that.
So yes, there is potential for greater growth as well.
Okay. And then just want another also revenue related question in Plaza seems pretty flat. I think you also commented it seems like the conversion of new patient to the drug has been a little bit slow. I just wonder if you could provide, I don't know how much detail can give, but if you can just give a sense, how's this quarter compared to the last quarter in terms of the new patient growth?
Sure. So and much of my truth, give a little color on thinking, hon.
Of course. So there are 2 drivers here. Or may I say 3 drivers here that are impacting this quarter? So one is the gross to net is still fairly similar to what we're seeing last quarter. We mentioned was a little bit higher than we were expecting before.
So we have a little bit more on the gross genetic adjustments. We've seen growth in patients both on the prescriptions and on the conversions quarter over quarter, but what was happening is when we launched this last year, we mentioned about our expectation for the conversion between the time we get the prescription in house to the time the patient gets dispensed commercial product to be between 3 6 months. In the first quarter 2nd quarter of the launch, we mentioned as well that we are seeing more on the lower ends of that. So around the 3 to 4 months ish, and now we are seeing on the other end more on the 6 months ish. So what's happening is it's within our expected conversion timelines, but it's skewing in a sense towards the 6 months conversion.
So what we are doing right now in a very focused way is to go patient by patients, basically and help them reduce that. So we have hundreds of patients right now by which we have prescriptions that we are working with them. We're working with their providers. There's something new for the neuro, multiple accounts where now they have multiple products and they never had it, but they have to manage all those products. And some of them are Part D, some of them are Part B it's a little bit confusing for those accounts.
So we are seeing they need a little bit more support than not. And we are intensifying that we're making sure everything is in place. To bring that average down to where we'd like to be and driving. We've seen some movement already on the last several weeks and we expect that to improve and to get to the end of the year and be on where we want it to be there was pretty much where we were before.
And the other thing that's probably worth noting as well is the there's recently been 2 publications that have been really quite useful that are demonstrating the superiority of emflaza over prednisone. When was the synergy natural history study that showed just how much better Emflaza was over prednisone. And then the recent publication of our placebo data, looking comparing Emflaza to prednisone again showing improvement as well. And that's been very helpful in having the physicians understand the differences between steroids and then the payers as well. So that's a combination of all of that that we're working hard to make sure that it pushes through the large number of scriptures that we're already having the funnel to try and get it through that funnel.
Thank you. Our next question comes from Tazeen Ahmad with Bank of America.
Hi, good afternoon. Thanks so much for taking my questions. Stu, I just wanted to get your thoughts about your partnership with Akcea, you were very good at doing Akce West launches. You've demonstrated that very clearly. Just wanted to get a sense about how you're thinking about this particular opportunity with ATTR patients given, I guess, unlike some of your other launches, it's likely that at some point in time, there'll be more than one drug option available for this community of people?
Sure. Maybe I'll touch on this. I could pass on to Marcio as well. One of the I think this we're really excited about this obviously it's unique and that it's a polyneuropathy form of it. And that, it's in a way almost, I mean, some of the physicians there know it more as the Portuguese disease because it really is has a unique in for that particular, for that particular form of it.
And the fact that it's actually injectable versus infusion is a really major advantage in this area in which there there's not a lot of infusion support there as well. So there's not only is the drug quite efficacious, but route of administration and the simplicity of it is going to be a major advantage in that group as well. And so that's the work we've done and the due diligence of our and looking at this deal really suggested that that's having it's the the physicians there have looked at the efficacy and really believe that the efficacy of this drug is really quite good and similar. They're comparable, but the similarities of how it's administered gives this a major advantage.
Yes. No. And just to complement a little bit of what Stuart is saying, right? The one key thing here that we look when we're exploring several deals and this came to mind is our ability to compete. And an interesting analysis that we did with team is just going around and understanding how many competitive situations each one of us like myself included, all down to my team, like Eric and his team in Latin America and all the way to the ground and all of us, like from top to bottom have been on 1 or more competitive situations on the ground and being very successful on that.
So that was a key component. You're absolutely right. We expect this to be competitive. We believe we have an advantage for multiple reasons. Time is one.
The acceptance of the physicians the interest of the patients for an SC drug versus having to be on a hospital, for example, are using steroids before the administration. But very importantly, it comes down to people being able to compete on the grounds. And we have this team that's highly motivated to make sure that they're going to make it happen for DTTR patients and make this drug successful.
So And the other one that you should touch on that's, I think, important Marcio that, that people it's a complex system in Brazil requiring licenses and analytical labs that we've spent the last 12 to 18 months building.
You may
want to talk a little bit about that as well.
Yes. Part of what we believe is the competitive here is just how established we are there. It takes a very long time, as Estu just mentioned, to just be ready get all the proper license, make sure you have the right relationships in place, that everything on from a compliance perspective is well established. Considering all the environment in Latin American. And we checked all the bots.
We went through several due diligence with our team and our systems and we're very confident we can deliver on that for patients because at the end of the day, that's why we are doing this, right? So there are thousands of patients there that needs the drug now and you're going to make sure to provide to them.
Okay. Thanks for all of that color. And then I'm sorry if you addressed this earlier, but similar to how you've talked about how long you think it'll take for you to address your estimated addressable gene therapy population? How long do you think it could take you to reach this documented 6000 population that you're going for?
Yes, that's definitely not going to happen overnight. And that are differently from the AADC deficiency that I believe that's the one you are referring to where there is very few patients identified and we're really doing the ground up in terms of the awareness. The biggest difference here with HATTR is like virtually every physician, if you go to Latin America specifically Brazil and Argentina, had treated a patient that seeing a patient have lost a patient or had someone in the family. So it's a little bit different in terms of the awareness it's mostly making sure they have the correct referral network, the genotyping and so on so forth. So we expect that to be faster Now at the same time, there are much more patients.
So logistically and the conversations with the government and so on, our little bit different than for ADC deficiency. So we don't see one necessarily taking precedent over the other we're going to put the best effort on both of them, but it is a multiyear process, not a few months.
Yes, the AATC, those more finding those patients because and we'll go to cerebral palsy clinics, severe epilepsy clinics to to try and find a lot is where we think a lot of those patients will be. In this case, as Marcio said, this is the awareness in these countries is really quite high. It's now about genotyping and then and getting them on to drug. So we think they're they're different, but it's as with all orphan diseases, as Marcio said, it takes some time to get to peak Thank
you.
Our next question comes from Raju Prasad with William Blair.
Thanks for taking the question. Can you just provide maybe some color on how you expect the ramp for some of these younger patients in in the EU on Translarna. Is this something where you've got several commercial sites already available in 28 countries. And maybe there'll be a little bit of a bolus of of commercial patients early on? And then as you continue to identify patients kind of a slower ramp or Is this something where it'll take some time to develop and hit peak?
Yes. So, Raju, thanks for the the question. So this is going to take probably a little bit of time. We don't see necessarily a bolus of patients pretty much anywhere, right? It is, as I mentioned before, that is very few patients until recently identified on this We made a lot of progress.
I'm very happy with the progress that was made, but now it's really getting patients access and there are several routes and some of them are individual patient requests that are happening already. Other counselors, you don't have to submit. I help technology assessment those and we're going through that. But the majority of the countries, we had to wait until the green light for the diversification to submit the dossier. So now we are in that phase where some is going to be granted faster than others.
So it's going to be a staggered in a sense launch which we accounted for when we are projecting our CAGR and getting to that point where we can maximize it There is a lot of enthusiasm from the patients and the physician's perspective, and that's what gives us confidence that you're going to penetrate this relatively fast. But just the way the system is in Europe, what is our priority markets right now for this, it takes some time to get this for the system.
Actually, let me just also, I think, kudos to the team because one of the things that, Marcio talked about is changing the time of diagnosis, which requires not only to do a lot of hard work on disease awareness and genotyping, But the change in average 6 months and in some cases much as 2 years is a tremendous effort in the 4 or so years that we've been doing that. And so that really then got as a consequence, well, it's not where we want it to be there then are starting to be patients that they're picking up earlier. And so we think that's the efforts are sort of paying off on all the hard work that's been done for the 4 years. So there will be patients that will be getting. And actually, we've even known patients for physicians who've decided when they find younger patients put them on earlier because I think the general notion is that when they're younger, they have more muscle.
Therefore, there's more to help them. And we think that's going to bear out true as well.
Great. And any update on kind of FDA or high level discussions with the FDA on on the dystrophin study. I know that there was I know you guys are planning on trying to get a favorable study design, but anything you can kind of comment there?
Yes, I think what we've come is what we've said in the past is that, we anticipate starting the dystrophin study by the end of this year. Will be completed by theendofnextyear, we can then be filed for accelerated approval. And I think that we're on track to do that.
Great. And then just the last one. Can you just comment on the types of hospitals or specialty centers that you would expect AADC patients in the U S to show up at? Is there any overlap with some of the other rare diseases that obviously you guys are looking at like SMA or anything of that nature that you can leverage?
Sure. Hey, Marcy, you want to talk a little bit about that?
Yes, of course. So there are a couple of targets that we have mapped and that the Agilis team done a tremendous job on mapping before, like very happy with everything they've done and established relationship with key opinion leaders. So the key focus, I would say for the next few months is going to be on the cerebral palsy clinics, not only the United States, but globally in general by the patient journey mapping that we did and by the work that Agilis did. Seems to be that that's where the most patients are going to be concentrated. So we're going to focus there.
But also in patients with severe epilepsy, or with a diagnosis of severe epilepsy, they actually don't have a plastic crisis. This patient is a misdiagnosed and you're going to be looking there. I think the biggest overlap that you'll start to seeing is with some of the efforts that BioMarin is doing to diagnose the balance patients. So we've been hearing from some physicians that they are doing like a tremendous job on the identification there. And that's starting to raise the awareness of disease and genetic base of some of those CNS disease.
So that's helping. There's a little bit of spillover effect there. So nothing specifically that we've done before, definitely not SMA very little in terms of the differential diagnosis on the neuromuscular that is outside of the United states, a good overlap on the treating physicians, where in several countries, you don't see the neuromuscular expert taking care of DNG, but more a general neurologists or pediatric neurologists. And then you're going to have a little bit more of overlap. But in the U.
S, it's probably the CPA clinics and some of the epilepsy centers.
Great. Thank you.
Thank you.
Thank you. Our next question comes from Martin Auster with Credit Suisse.
Hey, all. Thanks for taking the question. Appreciate it. I guess, a couple of follow ups from some of the earlier questions on RG79 16 on the part 2 of the FIREFISH study, is your expectation that the data will be reported to the public at a in the press release or conference once the required number of, infants sitting up is achieved, or will it run to, some completion of that study that's kind of time dependent. And then on Sunfish, I had a question regarding, with SPINRAZA, the functional benefits SPINRAZA seemed to kind of separate out from Placebo around the 9 month endpoint.
I was wondering from your perspectives about how, 7916 functions and differences versus SPINRAZA in, in benefit in effect. Do you think that that's a reasonable time frame to see separation with this drug? Do you think that there's anything about it should make us expect something different. Thanks.
Hey, Martin. Thanks for the question. The first part of the question, 7916, part 2 of Firefish. I think that's a good question. And I think a lot will depend on how we think about into the 1st part of the Obviously, the second part of the Firefish is a pivotal study.
So we'll obviously think hard before when we talk about it, but it is an open label study. So we'll be able to be seen. So we'll have to be talking with our partners about what's the best way to start presenting that and putting that in in line with what's happening in the first part and how we move forward on that. On the Sunfish, side, I think that's a very interesting question. And that it's just going to require some time to see, I think you've even seen from some of the earlier parts of the Firefish data that even some of the patients that are older within the study you're still seeing improvements faster in the CHOP INTEND from the patients on RG7916.
And that in a way that's in line with how we thought that might be, especially when we look at the preclinical data where we were able to show previously that we can actually dose in the animal model much later even in the Fair Fair forums and be able to recover that. So we think it's a highly effective molecule. And I think only time will tell us how well that will, if that will bear out in the Type 23, but we're quite hopeful that, that will be the case.
Thanks for your thoughts and I appreciate taking the question.
Thank you.
Thank you. And I'm not showing any further questions from the queue. I would like to turn the call to Stuart Peltz for his final remarks.
Obviously what our vision is is to continue to build a fully integrated rare disease biotech company that really leverages the deep scientific expertise and world class commercial capabilities. The programs we'll obtain through these transactions along with our ongoing DMD splicing and niche oncology franchises really does provide, I think, a number of value creation opportunities over the next 2 years. I'll be on the call.
And ladies and gentlemen, thank you for participating in today's program. This concludes the conference and you may all disconnect. Have a wonderful