Good day, ladies and gentlemen, and thank you for your patience. You've joined the PTC Therapeutics Second Quarter Corporate Update and Financial Results Conference Call. And instructions will be given at As a reminder, this conference may be recorded. I would now like to turn the call over to your host, Chief of Staff to the CEO Timothy Dyer, Sir, you may begin.
Hello. Good afternoon and thank you for joining us to discuss our 2019 second 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 Chief Financial Officer, Emily Hill. Before we start, let me remind you that today's call will include forward looking statements based on current expectations. Please take a moment to review our slide our simultaneous presentation, which contains our forward looking statements. Our actual results could materially differ from these forward looking statements as any and such risks can materially and adversely affect our and uncertainties, we encourage you to review the company's most recent quarterly report on Form 10 Q and annual report on Form 10 K filed with the Securities And Exchange Commission as well as the 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
Over the second quarter, we've made important progress growing the DMD franchise around the globe. In addition, we have increased the franchise value this quarter by expanding the Inflaza label to include 2 to five year old patients. Furthermore, following approval of Translarna in Brazil, we completed an annual contract with the Ministry of Health to provide Translarna to patients. We continue advancing the therapies in our pipeline with 2 programs on track to be submitted to regulatory authorities by the end of the year, including an NDA for risdiplam a small molecule identified from our splicing platform and a BLA for our first gene therapy product for the treatment of AADC deficiency. Moving these clinical programs to commercial stage products reflect our continued execution of the 5 year strategic plan that we described last year.
This vision elucidate's PTC's mission of bringing differentiated therapies to patients suffering from rare disorders with limited or no treatment options. By fulfilling this mission, we will be creating value for all of our stakeholders. Our one key pillar of our strategic plan is to continue to build a robust diversified orphan drug franchise. We believe that one of PTC's key differentiators is our ability to work across multiple scientific platforms to bring orphaned products to patients in need of new treatments. Our products and innovative programs currently span across 5 core platforms including nonsense mutation read through, alternative splicing, gene therapy, antisense DNA technology and on oncology.
We intentionally sought to develop products against targets with differentiated mechanisms of action that allow us to diversify our pipeline ensuring that we bring innovative products to patients with of the strategic plan. Because of these efforts, we are now in the position to have 4 products launches over the next year. Rizdiplam for SMA, TEGSEDI for HATTR, RayLIVRA for FCS and our gene therapy product for AADC deficiency. In addition, there is potential for U. S.
Approval of Translarna for DMD in 2020 based on the outcome of the dystrophin study. The combined potential revenue and royalty streams of these products, all of which are either already approved or will be submitted for approval this year is anticipated to grow in excess of one $500,000,000 in potential revenues by 2023. Our growing commercial infrastructure was strengthened over We have started to see early access sales of TEGSEDI in Latin America, bringing patients the benefit of in home injections to treat polyneuropathic hATTR. Because this rare disorder has a Portuguese ancestry, Brazil is one of the largest markets with an estimated 5000 patients. We know for market research these patients have a high degree of unmet medical needs.
And TEGSEDI offers important therapeutic benefit. To bring therapy to patients as quickly as possible, we have submitted the application for TEGSEDI registration in Brazil and expect to significant progress in Brazil for Translarna. As I mentioned on the last call Translarna received regulatory approval in Brazil in the second quarter for non transmutation DMD patients over five years of age. Having received the approval, We have now completed our negotiations for an annual contract to sell directly to Brazilian Ministry of Health. This contract and the Enviso approval will allow for broader patient access in Brazil.
As I mentioned earlier, we also expanded Emflaza access to patients in the second quarter. The FDA granted our inflow label expansion for patients two to five years old. This is critical. As treating patients earlier can preserve muscle mass and delay loss of ambulation. Multiple publications from clinical studies as well as long term natural history data show that Emflaza is the superior product compared to prednisone.
Our DMD franchise continues to produce robust revenues and provides a strong base in which we are continuing to grow the business. We are reporting that the DMD franchise revenue was approximately $85,000,000 we remain confident in our DMD revenue guidance of $285,000,000 to $305,000,000 for full year 2019. The teams have also been working hard to advance our clinical programs. To treat AADC deficiency and are on track to submit the BLA this year with a potential approval next year. We are also excited to Roche oversees the Risdiplam NDA and we are supporting this effort.
Risdiplam results were showcased at 2 medical meetings this quarter. The American Academy of Neurology Meeting and the Cure SMA meeting. KOL feedback was overwhelmingly positive. With increase in support for the need We believe Risdiplan will be the most competitive therapy in the SMA space. The SMA program was the first project demonstrating that small molecules targeting the splicing apparatus to modulate gene expression can selectively have specifically changed the course of disease progression.
We are the leaders of the small molecule splicing modulator field. Discovering the first small molecule drug to affect F and A splicing that will be submitted to the FDA for approval is something that we are all proud of accomplishing. It is an important achievement. We have also investigated Risdiplan's mechanism of action, which has been productive and incredibly valuable We have synthesized these efforts to create a splicing platform that we have utilized to discover other tentro small molecule splicing modulators to treat diseases. Moving forward, we intend to substantially increase our focus on the splicing platform with the objective to generate several new transformational therapies for Our unique understanding of the splicing mechanism and how it can be modulated by small molecules is a key competitive advantage that we are working hard to continuously improve.
We have already produced another candidate within the platform for familial dysautonomia or FD for short. Which is expected to enter the clinic soon and we anticipate entering the clinic next year for Huntington's disease. But the work does not end there and we intend to generate a significant number of drug candidates using the splicing platform in the coming years. Splicing modulation is expected to be a key source of innovation and value for all our stakeholders. Like Risdiplam, both the FD and HD molecules have the potential to demonstrate rapid changes in RNA and protein levels in the blood and other tissue, allowing the ability to show an early proof of concept next year.
You may recall that for the SMA molecules, we show that increases of protein levels were observed in the blood and reflected its clinical activity in the CNS. Let me turn now to another strategic priority for PTC, our gene therapy platform align with our strategic imperative to advance the gene therapy portfolio and infrastructure, we are proud to report that PTC has signed a long term lease agreement with Bristol Myers Squibb Company under which we gained access to approximately 185,000 square feet of space. This includes an existing state of the art biologics production facility and supporting research and operations buildings on the BMS campus in Hopewell, New Jersey. We plan to further develop the Biologics facility to support gene therapy production and also plan to move The buildings we are leasing are located on an existing BMS property of over a million square feet, which is being transitioned to a multi tenant research and development campus. The existing GMP Suites on the site were recently renovated will be used to produce material to serve multiple preclinical and clinical gene therapy programs.
This adds to our current preclinical production capacity in Bridge And Water, New Jersey. These efforts underscore our commitment to our internal gene therapy programs. I'll now turn the call over to our COO, Marcio Souza, to discuss the details of our commercial and clinical progress. Marcio?
Thanks, Stu. We're very excited with the results in the first half of the year. And remain constant about the full year performance. I'd like to start by reviewing some of the key business dynamics for our commercial portfolio. So far, 2019 has been the strongest commercial performance in the history of PGC.
It's especially humbling to be in the position of delivering 4 distinct therapy for rare disorders, all with high medical unmet needs. We're proud to be delivering differentiated therapies for thousands of patients globally. Let me start by reviewing Emflaza. The only treatment approved in the United States for all DMD patients older than two years of age. Demand for Emflaza continues to grow and we have seen compliance of patients on drug of around 90%.
To date more than 400 physicians prescribed Emflaza and our focus remain on the continued growth for the brands including leveraging new data on differentiation. We expect the continued growth to come mainly from patients that might have decreased those to manage safety while sacrificing efficacy with presence on. As well as expensing into segments that might not be as engaged or have equal access to standard of care in the past. Another area of growth is a recently approved label expansion for Emflaza. The promotional launch is going well with the focus on updating payer policies and educating healthcare professionals on the benefit of early intervention.
As noted last quarter, we have switched to a new specialty pharmacy in the U. S. And expect temporary operational inefficiencies to be resolved by theendofthethirdquarter. Now focusing on Translarna, our ex U. S.
Business remained very healthy. With organic growth of patients in all regions. At the time of that approval, long term effectiveness of Translarna in nonsense mutation, commercial patients treated in a real setting. We are delighted with the results coming out of STRIDE, including benefits in ambulatory and non ambulatory patients. This data for more than 200 patients have now been presented at several Congress demonstrating significant delays in loss of formulation and improved ventilatory function when compared to match natural history controls.
Additionally, we have received a significant order in second quarter from the Brazilian government following the approval of Translarna by ANVISA. The number of patients identified in Latin America continue to grow and we continue to work with the payers worldwide to provide Translarna broadly to patients in needs. Supporting the DMD community globally has been our very fabric for many years. We have initiatives for both prescribers and patient groups to advance the needs of DMD patients. Our strive award for patients and patient advocacy is in its 5th year.
And we have received more than 30 qualified applications, which will support better standard of care for patients globally. Moving on paid patients in Latin America for TEGSEDI and first prescriptions for Waylivra. We're excited with the potential of both products and our ability to leverage PTC's infrastructure and knowledge base. TEGSED is expected to be approved by Envisia in the following months which would trigger pricing including our nurse network support is in place in all key countries to support a smooth launch. We are working or FPL to determine the potential commercial strategy in Latin America.
Now switching gears to gene therapy. As we approach the ADC deficiency PLA submission later this year, The teams are busy finding patients and preparing the ground for a successful launch. In terms of patient identification, our global large scale screening programs continue to roll out to all targeted regions and countries. For instance, we have recently agreed to partner with a key host in Germany to initiate a pilot's newborn screening projects in more than 90,000 newborn screens using the 3 OMC methods. The important initiative to realize our long term vision to include ADC deficiency in newborn screening panels globally.
In the U. S, the protocol driven ADC deficiency screening in cryptogenic cerebral palsy we will start screening patients this quarter and the non protocol screening systems are in place globally. On the location of France, we're busy providing resource to physicians and caregivers to identify and provide best care for ADC patients, including a series of webinars specifically targeting increasing diagnose in AADC. We have all the requests a specific ICT10 code for ADC deficiency, which we expect to be accepted. This will allow for better follow-up of patients in the future.
Moving to some key clinical development updates. First on at Lorne, we have finished enrolling in Study of 45, our dystrophin assessment study, which, if positive, would support the resubmission of the Translarna NDA in the United States for nonsense mutation CMG. With the enrollment now completes, we expect the readouts in the first half of next year. As previously reported, we have requested a reexamination for the non ambulatory label expansion in Europe. And our tentative date for an opinion is in October.
We are working diligently on the resubmission to support the documentation for the European Medicines invasion. For our ADC gene therapy, On top of the preparations for the PLA submission later this year, we have received approval for our pediatric investigation plan in Europe. Which is a critical step towards the market authorization application submission. Our FA program readiness is evolving well. And we have selected Emory as the first site for the initial trial.
Since this is the it's key that we assess in this trial proper dosing and safety. But at the same time, we intend to assess both imaging and functional endpoints. Because this is an open label study, we would expect to report on progress for the first few patients in late 2020. These are exciting times for PTC as we continue to deliver on our therapies to support the rare disease patients. I'll now hand the call over to our Chief Financial Officer, Emily Hill Emily?
Thanks, Marcio. I'm happy to be joining the call today for the first time in the CFO capacity. It's been a great experience to be part of PTC's growth in the last 5 years as we've developed from an R and D stage company to a global commercial company still driving innovative R and D. I'm eager to continue to be an integral part and the advancement of several R and D programs. As you know, our second quarter press release was issued a short while ago, which summarizes the details of our detail.
I'll start with a few comments on our financial performance in the quarter and then reiterate our guidance for the full year 2019. Starting with our top line results, we reported $85,400,000 in combined net revenue across our commercial portfolio in the second quarter of 2019. Compared to combined revenue of $68,100,000 for the second quarter of 2018 Translarna net product revenues were $57,800,000 for the quarter. This compares to $47,800,000 in the second quarter of 2018. This growth includes the expansion of Translarna ex UF, including regulatory approval and an annual contract with Brazil.
For Emflaza, we reported net product revenues of approximately $27,600,000 for the second quarter of 2019. Which compares to $20,300,000 reported in the second quarter of 2018. We are working towards establishing inflows as the standard of care for all patients in the U. S. And are happy to be able to Brazil for Translarna gives us confidence to reiterate our 2019 DMD franchise revenue guidance of 2.85 $305,000,000.
We have also outlined the opportunity for our pipeline to generate potential combined revenue in excess of $1,500,000,000 by 2023. Non GAAP R and D expenses were $54,500,000 for the second quarter of 2019. Excluding $5,500,000 in non cash stock based compensation expense compared to $28,700,000 for the second quarter of 2018, excluding $3,900,000 in non cash stock based compensation expense. The increase in R and D expense reflects strategic investment in advancing the gene therapy platforms, slicing programs and other research programs as well as the advancement of the clinical pipeline. Non GAAP SG and A expenses dollars in non cash stock based compensation expense compared to $29,400,000 in the second quarter of 2018, excluding $4,100,000 in non cash stock based compensation expense, reflecting continued investment to support our commercial activities, including expanding our commercial portfolio.
I would also like to reiterate our non GAAP R and D and SG and A expense guidance for full year 2019 of 360 $370,000,000, excluding non cash stock based compensation expense of approximately $35,000,000. Net loss for the second quarter quarter of 2018. Cash, cash equivalents and marketable securities totaled approximately 363,000,000 June 30, 2019 compared to approximately $227,000,000 at December 31, 2018. We are proud to have built a global biotech company that is in a financial position to continue to execute on our long term strategy. I'll now
Thank questions. Our first question comes from the line of Roger Prasad of William Blair. Your line is open.
Thanks for taking the question. Just a quick question
revenue guidance for 2019. I think you guys did $140,000,000 this year. I'm just trying to figure out with the naval expansion, and Brazil, what are you kind of expecting to get to the midpoint there from those new growth drivers? Thanks.
Thanks for the call. Emily,
Yeah, thanks for the color, Ajio. We are happy to be reiterating our revenue guidance for the 2019 of 2.85 $305,000,000 for our DMD franchise. That reflects the anticipated Brazil order for current patients' underlying demand does not contemplate the expansion of two to five year olds in the Emflaza label as that is a slower process.
Great. And just one on kind of your small molecule platform. Can you just talk
a little bit about some
of the learnings that you had with Resdiplam, and the prior formalized splicer that you're going to take forward?
Sure. Yes. So for the in the rest of the plan, obviously we've been doing this for some time. I think we've learned in terms of thinking about mechanism of action and how to focus on that. And over the years, we've built quite a proprietary library of small molecules that we think have that give us a unique advantage in being able to target splicing.
And then also we've learned a bit about in terms of the site, the first site that we're hitting, especially like Rinta plant, is a U1 binding site that has altered that has mismatches there. Now, as you probably remember, maybe from some of our calls, Most of the time it's a perfect interaction between the U1 and the 5 prime splice site. But in SMN, it's not in that's why it's leakier and our molecule in essence increases the interaction to allow the splicing efficiency to occur And we've learned a lot about that interaction that allows us in a sense to do a high throughput screen that lets us in more to other targets as well. And as a consequence of that we've been able to move quite rapidly for familial dysautonomia is a good example. So a lot of times when you did it once you're asking yourself can you do it multiple times and this is again a clear example of getting FD to a second molecule that's specific for that particular mutation.
And then we've gone on to do it on the third time and we're in late stage chemical optimization for Huntington's disease. So from a big picture perspective, I think you could see that what you'd like to be able to do is use a platform to be able to get multiple compounds out of that. You see that we're we've able to use our knowledge, the understanding the mechanism of action. To actually move into multiple other targets and move them quickly through the discovery process into the clinical development.
Our next question comes from Alethia Young of Cantor Fitzgerald. Your question please.
Hey guys, thanks for taking my question and congrats on the quarter too. Questions for you. Can you talk a little bit more about AADC deficiency and kind of what's going on with the manufacturing there and the progress toward getting an approval And then I was just curious if you guys might give an update on how many patients you found with ADC deficiency. I think the last time we got an update was in January. Thanks.
Yes. Hi, Alicia. Thanks for the other questions. Jeff, we're actually really quite excited about moving AADC deficiency as we've said, all things are on track for submitting the BLA this year for potential approval next year. And obviously, as you know, the key thing is on getting manufacturing completed and done.
And Marcy, you want to talk a little bit about that?
Sure, sure. Absolutely, Haley. Yes. So, a couple of steps here, right? Towards the submission of the BLA and hopefully the approval next year subsequent to that.
So the manufacturing group continue to work very hard on all the steps that we agree with the FDA, towards the, all the bets that have to be made before the submission. Obviously, the comparability on those, making sure all the analytical methods is validated in accordance to the discussions we had with the agency And then all the other parts of the BLA, we do expect to assume the meeting with the FDA in relation to the pre submission for the NDA itself. Which is a procedural step. It's normally taken on things like that where it's more structurally and administratively how the submission is going to be going. But from all the aspects, in general, it's all finalization of documents right now.
Other than on the manufacturing that are we still working towards the release of the commercial batch based on the agreements we have with the agency. But since our last updates, that is nothing really major or even minor to that extent that happened that is not in the plan like it's all sequential at this point in time. I want to make sure we not only manufacture to the specs that we agree with the agency, but also have enough inventory for the time of launch and the technical operations group is working really hard with that together with and under the supervision of our quality team because we know how important it is to make sure our process are not only efficient, but compliance as well. In terms of the patient finding initiatives, as I mentioned on the prepared remarks, there's a number of things we are doing. One of them is the what we call non protocol screening and that's basically giving physicians the ability to screen the at risk or other patients that they might have misdiagnosed before with the DTC gene or the 3OMD methods in the blood.
This is going very well and we're being identifying patients like pretty much every week and progressing and I'm going to give an update in the future on the exact numbers. The second process, which we believe to actually yield more patients on the identification is the protocol driven. And that has to go through the IRB approvals, the contracting phase and up to a few weeks ago, there's been a little bit slow in a sense that you have to go through that all that steps and make sure they're all accomplished. Are now at the process to restart that and we expect to have the first patient screening in September. So our expectations that later in the year would be able to provide an update on the exact numbers.
And I think the work has been exciting and gratifying and that Just to remind you, we found there's over 80 different alleles that we've identified, which really gets by the notion when people thought there was the founders of fact So we get more and more convinced every day on the number that we had told you previously about 5000 patients commercially. So that are commercially viable. So we're excited to keep moving this forward. We're excited that the process thus far in the manufacturing is moving along and we anticipate the submission with the completion of the manufacturing of this year.
Thank you.
Thank you. Our next question comes from Brian Abrahams of RBC Capital Markets. Your line is open.
Hi. This is Bert on for Brian. And thank you guys for taking our question.
I
had a couple on the Friedreich's ataxia program. Can you talk about any preclinical, maybe functional data that you have to compliment the for tax and expression data you've shown in the porcine and non human primate models that gives you confidence that the level of expression you're able to achieve with the gene therapy will translate to functional improvements? And then also related to that, will you be building will the process of building out your own gene therapy manufacturing abilities to produce material for the clinical study be rate limiting for being able to start the clinical trial in FA patient?
Sure. Maybe let me start and then I could pass it on. So the FA program, as you alluded to, just to remind everyone else, the call, we were able to obviously inject into the cerebellum and be able to get a substantial production for tax in there to the levels that we would think, would be obviously to levels that we think would obviously change the course of the disease. So we were happy with the levels. There aren't any great models in the sense that we have that would be able to be able to do the functional comparisons But we feel pretty confident that, that we'll be able to bring it to the right place and that, in our discussions with all of the key opinion leaders, would anticipate that would have effects as a consequence of that.
In terms of the manufacturing, we're on target in terms of manufacturing getting ready to get manufacturer for the IND. That's ongoing now. We're not obviously as I think we mentioned, we have our a site that will be leasing, but this is being done initially at a different facility that will may ultimately come back later as the facility opens to produce it
there.
Comes from the line of Gena Wang of Barclays. Your question please.
Hi. This is Peter for Gena Wang. Thanks for taking our question. So I guess maybe 2 quick couple of ones for me. For TEGSEDI, how should we think about I guess, reimbursement decision process post approval and how would the pricing look like relative to the U.
S? And I guess, relatedly, And how should we think about revenue contributions from this region 1st few quarters?
So, thank you so much Peter for the questions. So, for so on TEGSEDI and what do we expect after the approval, which is upcoming from ANVISA. Obviously, that is 2 process, right? So as we described before, one is the individual patient's request, what we call named patient sales. And that should continue to be requested by the patients and approved individually.
And you might have seen that we got the 1st patients in the region are reimbursed, which we feel really proud of. And that's going to probably be anywhere between the U. S. Price and the European price based on the negotiations with the government. Now we have submitted for as is requested now by the regulation there, a price to be commercialized in the country.
We fully expected that's going to be some negotiation once it's approved. And then there is a cap, what it's called, it is a discount that is applied on top of that of around 20%. So it's going to be a reduction on the overall price that is normally anchored to the United States FSS price. So there is some reduction that it's going to be accounted for. We fully accounted for that in our internal projections on the model and the guidance for 2023 that we gave up $150,000,000 for the products.
Identification of patients and the lining up is being quite positive. So we see the long relates this year and next year to be while patient by patient in this 1st phase to be quite productive and positive for PTC. In terms of the contribution of the region for the overall mix of the company, as Emily mentioned, We did receive a large order for Translarna, which we're extremely proud of because it means that patients can have continuity of access it's for the entire year. So we know that it becomes a little bit more irregular, although it's still fairly lumpy in terms of the size of the orders, less irregular in terms of patient receiving. It's an important region for us, but it's not the biggest region in the world for Translarna.
So again, trying to balance the general demands globally while giving the emphasis that of all patients being on drug.
Great. Thank you. Sorry. A quick follow-up, if I may. When should we expect any updates from like a part 1 and part 2 of firefish and sausage?
Thank you very much.
So the updates, so we'll be doing that at subsequent meetings for park 1. And Part 1 of each of Firefish And CentroShip World Muscle WMS meeting that will be presenting the continuation of that for Part 1 Part 2 will be, next year sometime.
Great. Thank you very much for answering questions.
Thank you.
Thank you. Our next question comes from Martin Auster of Credit Suisse. Your line is open.
Hey, thanks for taking the question. Most of them have been asked maybe just to follow-up on that last theme there. Is there any plan to present or kind of publish any of the preclinical data from the Huntington's splicing program in the balance of this year or ahead of the IND next year? Thanks.
Yes, thanks. So we've been moving forward on the Huntington's program, we anticipate a clinical candidate this year with it going into the clinic next year. We're always careful in terms of timing of when we publish, the work on Huntington because it's a structure and we we take our time in terms of putting out the structures. So the publications of those are undefined as of that. But we'll probably be talking either the Science Day or Analyst Day about further on about what the about Huntington so that you get more information and more details about what we're doing.
Are you contemplating an Analyst Day later in 2019 or sometime next year?
Sometime next year.
Our next question comes from Vincent Chen Bernstein. Your line is open.
Congrats on for August and
thanks for taking the question. Another follow-up on Hunting Dunes.
I was wondering if you
could provide a little bit more detail and color on the status of the preclinical hunting test program and what's left to be done before you can get into the clinic. I guess a little bit more on where specifically are you in the lead optimization process? What are properties you're focused on? And I guess maybe point is late. Are you at a point where you have compounds clusters or compounds that appear adequately specific for the targeted pseudo exon?
Or is there more to be done on the specificity front and reducing risk off target effects?
Yes. Thanks. It's for the question. It's there's a lot of chemistry that's been ongoing. We're in the relatively late stages if we anticipate a picking of a clinical candidate.
Now a lot of it is moving it through the screening process, the safety toxicology studies that we do. And that just takes some time. So we have a set of of a small set of compounds from a scaffold that we've identified from a scaffold that we've identified that we like that we anticipate where the clinical candidate will come from. And it's just now going through the myriad of assays that are required when you think about of what I always call the underbelly of what you got to do for getting a small molecule through an I and D process. There's just a lot of testing to make sure that or having understanding of the chemical properties.
And then our own internal safety, toxicology that allow us to define what the threshold and window are. Marcie?
Yes, of course. And Vincent, just to add a little bit to everything that Stewart just said, right? So specific profits that we are looking at compounds, obviously distribution in the all the structures of the CNS is important for us. We see that as a shortcoming of the other approach to really having the reduction of the hunting tent and specifically on the deep structures. So that's what is important.
But at the same time, that is a lot of residual disease, peripherally. So it wants to make sure that is a distribution very therapeically as well. So being a normal molecule or molecules, as I'm going to explain in a minute, that's quite important. Stewart mentioned that we have a number of viable scaffodes that we've been working on. From then at this point in time, while we're still early since we're going to be going to GOP docs hopefully soon.
We have multiple viable candidates and we intend to continue with them. All the way potentially to the clinic, since safety margins and even the ability of them to penetrate different tissues or to have different properties on the spectrum of the disease since we know that Huntington is not necessarily just one manifestation, but that is like different types of patients that might benefit from different profiles. So very extensive approach to have like really dedicated and large number of people working on this, expect to declare 1 or more candidates this year and beyond the clinic next year. All right.
Thank you.
Thank you. Thank
you. Our next question comes from Joel Beatty of Citi. Your question please.
Hi guys. This is Sean Egan calling in for Joel. Thank you for taking my question. I have 3 today The first one is on heels of today's positive Phase III where the Eberdata and FPL, just try to frame any early work you've done on the LATAM opportunity there and you anticipate those fall through your with the sales force anyway?
Marcio? Yes, thanks Sean. That's a great question. And we're super proud of the work IONIS and Akcea has done here to help this community and with the results that they're sharing today and we shared as well. The opportunity basically doubles for us in Latin America when we add both FCS and SPL together.
It's a perfect overlap is the same physician diagnosing this our screening and monitoring programs are already contemplating one of the reasons and we alluded to that before, but maybe not so explicitly that we did not submit to ANVISA or other regulatory agents because we're waiting for the readout of this trial to submit a broader label with a bigger indication, which we intend to do. We're going to be reviewing. We'll review the results, preliminary results with the Akcea team before today's disclosure, we shared their view and enthusiasm in relation to that. And we're going to review the full results soon as it is available and then file for the submission in Latin America. I think what you can say right now is that patient identification was always in our HADA screen.
We're going to continue to look into them. We have a number of cases already that being reported to us and you're going to definitely drive to get these patients the treatment they deserve.
And actually maybe from a point of view, the just based on what we talked about before, in terms of the vision and the 2023, the numbers that we gave previously didn't include FPL as part of a part of that. So that's something upside as well.
Great. Yeah, completely makes sense. For Marcio, you mentioned initial newborn screening efforts in Germany, Have you had any initial discussions with the Secretary Advisory Committee around getting AADC deficiency out of the National Risk?
Yes. So more generic discussions, to be honest, Sean, at this point in time, because the methods that we are validating, now Internationally like using the blood sample and being widely available has not been tested for MBS yet. One of the key things we're trying to do with this large hostel in Germany is to not only screen this babies and provide potentially like lifesaving diagnosis and treatment for them, but also to make sure that these tests work at scale so we can bring to other places like the United States. So all these conversations are ongoing. And as I mentioned, again, on the remarks, it's part of a broader strategy to make sure that the time of launch are chart thereafter, we have an available platform for newborn screening that can be readily deployed.
Great. And my last question is, can you provide any update on the enrollment for the presymptomatic brain blowfish study? And kind of when you're when we're evaluating those is that is it more important to kind of show comparability to Xinraz and Zolgensma or other point of differentiation that they're important to consider?
So I think we'll probably be giving an update on rainbowfish next year. From the comparability, I think obviously the asymptomatic patients, one would anticipate maybe having improvements and that's been seen within the data we'd expect results like that as well that the patients with ultimate approved. Obviously, we think that the advantage of being able to pass not only get to the blood brain barrier, but get into all of the tissues as an advantage, not only early, but also as the the baby is mature and their prevalence there is no longer as open that they'll still get the benefits of of a molecule that can both go to CNS as well as distribute into other tissues.
Great. Thank you for your answers.
Thank you.
Thank you. Our next question comes from Eric Joseph of JP Morgan. Your line is open.
Hey guys, thanks for taking the questions. Maybe just a biology question for the Huntington's oral splicing program. If you're understanding the mechanism correctly, you'd be promoting both the turnover of the mutant and the wild type Huntington Part D. So I'm just wondering if you could speak a little bit to the native function of Huntington and sort of how a biological perspective, how wide of a therapeutic window you'd anticipate with its approach? And how are you able to analyze the relative turnover of the mutant versus wild type versions of the protein?
And I guess if there are any different safety considerations or meaningfully different safety considerations with the systemic agent versus the the other approaches that are directly administered to the CMS? Thanks.
Yes. Thanks for the question. So as you know, actually, right, we are through a pseudo ex unable to promote the reduction of the Huntington's protein. I think it's It's widely believed that one can see efficacy by reducing it approximately 50%. We're able obviously to go lower.
It hits both wild type and mutant forms of that. And so, but we think that one could certainly establish or a knockdown of 50% without having any detrimental or toxicity. At least that's I think what we all believe is true and we'll be able to monitor that as well. So I think that's where we are within our thinking. Of being of what we'll be able to do in terms of the clinic to be able to get at least a 50% reduction.
Got it. That's helpful. And maybe just a follow-up here if I could on discipline. It sounds, from Roche's commentary earlier and also on your PR tonight that And MAA filing would be contingent on at least some part of the Part 2, Part 2 data from the ongoing studies. Can you clarify whether EMA is interested in particularly different, both SUNFISH and FireFISH or are they prioritizing 1?
And I guess as it relates to SUNFISH, can you just talk a little bit about expectations from the randomized portion of that study, what magnitude benefit in in M32, the trial is powered to detect and what would be viewed as regarded as clinically meaningful?
Sure. Yes, so Yes, I think as Roche has recently discussed and actually in recent interactions with the EMA, that there was a change of heart and that they wanted to see part 2 of both firefish and sunfish. So that as we said previously, the fire the SUNFISH data, the SUNFISH data will be completed by the end of this year, that study as well as the Firefish early next year, all that data then will be compiled. There was no change just to be clear from any discussions from the FDA in terms of putting in based on Part 1 for both fire fish and sunfish. Marcie, do you want to take that?
Sure, sure. And just to clarify, right, Eric, to your questions. So we expect both, submissions to include or the submissions to include both Part Q for SUNFISH and Firefish. The main reason on the discussions with DMA is just how close to the completion of the trials it is. So they just want to make sure that they see the data.
So nothing really unusual here. I would say in terms of the originally planned to 186 patients, the expected point estimate chains between Placebo and the arm, it was 3 points with a 6 standard deviation. So a half a standardized measure there. This is less than what you've seen in the Part 1, if you were to look into the change compared to natural history. So if you're really good, since this group is expected to be less heterogeneous than the regional group was in the Part 1 of the tribe.
And we think such impressive results so far. So we feel like quite positive about the results.
Our last question comes from the line of Joseph Thome of Cowen and Company. Your line is open.
Hi there. Thank you for taking my questions and congratulations on the quarter. First on Translarna in Brazil. I was curious if you can give us a little bit more information maybe on ordering patterns there and the size of those orders. There was a post count line suggesting the size was around 45,000,000 you give us any indication of how this is going to be booked and maybe the frequency there?
And then second on Risdiplam, for the initial data from the rainbowfish study, are the FDA will the FDA receive some of these data and do you anticipate presymptomatic infants may be able to be on the initial labels either in the U. S. Or the EU? Thanks.
Greg, Marcio, do you want to take questions?
Yes. So I'll start a little bit on the pattern then they use in Brazil and maybe Emily can talk a little bit about the revenues, right? So, the expenses based on the patient consumptions and the amount of patients that are being accrued as Emily mentioned, and I mentioned on my remarks as well, this is for the current patients. It's being practiced in Brazil that the Ministry of Health does dispense to patients that are accrued throughout the year So we expect that potentially some of those patients are going to receive and new requests are going to be made periodically. I think what it does to us.
It's like that is this one shipment that was made this quarter, we expect they're going to have new shipments. It is very hard to some extent for us to anticipate if it's going to be during Q3 or the beginning of Q4, but we know for sure that it is required to be done during this year since the patients use, which has been pretty good in terms of compliance there. Going to require all the order to be. In terms of the amounts of the shipments and the revenue recognition, I'm going to handle to Emily to answer.
Thanks, Marcio. Yes, we're grateful to be in a position of having now a formal approval from the regulatory authorities in Brazil and now an annual contract. Really demonstrates the Brazilian government recognizes the benefit for non transmutation DMD patients. There is an annual contract that we have now entered in remember historically, we received a large order for Translarna in Q4 of twenty eighteen, which reflected the need for a number of months to pay and subsequently did not receive an order in Q1. So a large segment of the annual contract was booked in Q2 and the remainder will be booked in the second half of 2019.
This gives us confidence as I mentioned before to reiterate our DMD franchise guidance.
And then to your second question on the label for risdiplam, so the availability of data in terms of presymptomatic and whether or not that's going to be included. It's going to depends obviously on the amount of babies that are enrolled on the trial between now and the submission on the availability of data and the discussions with the agents during the review. So it would be premature probably responsible for us as well to comment this right now until we have that. What we know and the discussions that didn't happen with the FDA is that the label would be based on review of the current data for type 1s, QN3, which you consider quite important since the type QN3s are vastly under treated globally, and we see the differentiated profile offers the plan on those patients. And in overall, I believe and we all here concur and so does the community that there's a sewer remaining and may be growing unmet needs on type ones considering the market dynamics that are happening every day.
Great. Thank you.
Thank you. At this time, I'd like to turn the call back over to CEO, Stuart Peltz, for closing remarks. Sir,
Okay. Well, thank you all for joining the call today. As you could see, the team has been executing quite well and I'm very proud of what they've been able to get accomplished in this half year. I think it's really important for all our stakeholders to continue to build out the company that we talked about and it's gratifying to see the execution on the vision of building out a a rare disorders company. So thank you for joining the call.
Thank you, sir. Ladies and gentlemen, that concludes today's conference. Thank you for your participation. You may disconnect your lines at this time. Have a wonderful day.