Ladies and gentlemen, thank you for standing by, and welcome to the PTC Therapeutics 2 2019 Third Quarter Corporate Update And Financial Results. At this time, all participants are in a listen only mode. After the speaker presentation, there will be a question on your telephone. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Alex Kane, Head of Investor Relations.
Thank you. Please go ahead, sir.
Thank you, and hello, everybody. Good afternoon. Thank you for joining us to discuss our 2019 third quarter corporate updates and financial results. Joining me on today's call is our CEO, Stuart Peltz, our Chief Operating Officer, Marcio Souza, and our Chief Financial Officer, Emily Hill. Before we start, let me remind you that today's call will include forward looking statements based 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 business and results of operation. For a detailed description of applicable risks and uncertainties, We encourage you to review the company's most recent quarterly 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 the call over to our CEO, Stuart Peltz.
Thanks, Alex. Thank you for joining us this afternoon as we provide an update on the third quarter. As you heard, On the call with me today will be our COO and CFO, Marcio and Emily. Marcio will provide commercial and clinical development updates Additionally, Emily will provide update on of creating a diversified fully integrated biotech company with multiple platforms. And we have previously described Our strategic vision is to be a leading diversified rare disorder company that through the combination of both using our internal innovative scientific platforms as well as business development, we will have multiple products and programs and anticipate approximately $1,500,000,000 in revenue we will continue to discuss our efforts in building out this vision of the company and how we are executing across a number of programs.
We will also review the results presented during the World Muscle Society that highlighted the continued clinical benefits and competitive advantage seen with Risdiplam. I'm proud to report that in October, TEGSEDI was approved in Brazil by ANVISA. Along with Translarna, this marks the second approval that we have successfully achieved in Latin America in this year. The opportunity to treat hATTR in Latin America is important because the disease has a Portuguese founder's effect Brazil is the largest country with Portuguese ancestry with 1 of the largest markets worldwide with approximately 5000 patients. Additionally, TEGSEDI has the advantage of being delivered by subcutaneous injection as infusion centers in Latin America are often saturated or hard to access.
Through our early access programs, we are seeing that there is a high unmet medical need in Latin America. We have continued to educate the community on the importance of identifying patients and ensuring that these patients gain access to medicine. The ANVISA approval will allow us to initiate TEGSEDI's launch, giving us the opportunity for direct physician outreach. We have also been continuing to grow our DMD franchise. As you will hear about this in more detail, we reported top line combined commercial revenues of $71,400,000 in the third quarter of 2019 when compared to previous year third quarter of $53,000,000.
We have also shared results from the Stride registry this quarter. Which is the 1st international registry for patients with DMD due to analysis mutation receiving Translarna. I'm also pleased to announce that This asset targets a key enzyme involving the regulation of oxidative stress and inflammation. The compound is ready to be in pivotal trials for select CNS rare disorders and has the potential to be used in combination for with existing programs in our pipeline. We have agreed to pay success based milestone that are due 1 year after certain regulatory approvals.
We believe this is an exciting opportunity because of the novel approach in treating rare CNS anti inflammatory disorders. I now like to turn to our programs in gene therapy. As we previously mentioned, we are on track to submit a BLA to the FDA by the end of the the necessary manufacturing run of AADC gene therapy product required for the BLA submission. We also plan to file an MAA in Europe for AADC deficiency following our submission to the FDA. We are proud to potentially be in a position to launch 1 of the 1st gene therapy programs worldwide.
As Marcio will discuss with you in more detail, We have ramped up our patient's finding efforts and expect to be in a good position to have a strong launch for this product next year. Our gene therapy program in Frederick ataxia continues to move forward. However, because of manufacturing timelines, we now expect to enter the clinic mid next year. Let me now switch gears to update you on the progress we've been making using our splicing platform. Our collaboration with Roche and the SMA Foundation on Risdiplam for the treatment of SMA is progressing very well.
Recently, we shared updated clinical information from the pivotal Firefish and Sunfish studies. At the World Muscle Society meeting, we reported that SMA patients demonstrated continued improvement including observing babies that are beginning to walk and stand. These are milestones that would have otherwise not have been achieved. Additionally, Risdiplan continues to be well tolerated with no drop offs reported from adverse events. Given that Resciplined has been stubbing in a broad cohort of SMA patients, we would expect a potential approval to be for a broad label The importance of the SMA program is that it's the first small molecule drug that is orally bioavailable that is systemic that goes to all tissues affected that lacked the FMM protein.
This is the first small molecule that has been shown to be selectively affecting splicing and leads to modulating gene expression. Therefore validating our splicing platform. We anticipate this to be widely used in all types of SMA patients. Based on success of this program, we have used our platform to identify other splicing modulators that affects splicing to treat diseases. In particular, we have discussed 2 programs that have identified molecules that selectively is specifically impact splicing that have the potential to treat orphan disease disorders.
One compound was identified to treat patients suffering familial dysautonomia or FD and the other program is to treat patients suffering from Huntington's disease. Or HD. I will now discuss these programs. PTC258 is an orally bioavailable highly potent splicing molecule that has been shown to effectively correct the splicing defect in FD. This is an ultra orphan disorder with small patient population of only a few 100 patients in the U.
S. And Israel resulting from a founder's mutation predominantly found in DASHkenazi. Jewish population. The FDA briefly indicated that the clinical development path of FD would require a long and complex 2 years or greater placebo controlled trial. This trial design is not feasible in this small patient population.
At this point, there is not a development path that allows us to move forward in FD. Unfortunately, in drug development, we have to make difficult decisions. And as such, we have discontinued this program. We are disappointed for We will continue to work with the rare disease community for ultra rare disorders in difficult diseases to move forward. Let me now switch to discuss our HD program.
We are highly focused on rapidly advancing our Huntington's program. Slicing modifiers and showing reduction of the HTT protein in all areas of the brain as well as other tissues in the HD mouse model. We are now in the process of performing larger scale GMP production of 1 HD compounds to perform GLP safety toxicology. As the program is advancing rapidly, we continue to expect that the Huntington's disease program will enter the clinic in 2020. Like SMA, there are a number of advantages and having an orally bioavailable compound that is systemically delivered through the blood and has broad distribution to tissues.
Including all tissues in the brain. We believe that a therapeutic that a systemic and simple to deliver will bring a strong competitive advantage to the Huntington's disease landscape. As you can see, we have a number of exciting milestones coming up. We will be hosting an Analyst Day on March 5 and we look forward to sharing more detailed information on our pipeline at that time. I'd like to turn the call over to Marcio so he can provide an update on the commercial clinic and development programs at PT see.
Marcio?
Hey, thanks, too. Let me start with our DMD franchise. Emflaza, our treatment approved for all DMD patients 2 and older in the U. S, reported revenues of approximately $68,000,000 year to date. In the 3rd quarter, We saw strong prescription growth.
However, the net sales were impacted primarily by 2 factors. The first related to our Special Pharmacy transition to Accredo, where we faced challenge while processing all the new Ks transitions. Have completed the transition and we do not expect to have any further impacts in the following quarters. The other factor affects net sales, was the mix of Medicaid's utilization. In order to align with our expected privates to public payer mix, both now and in the future.
In the marked access fronts, we have been working diligently to educate payers on the benefits of Emflaza. Recently, we have seen an improvement in the conditions by which some important plans are operating, including removing requirements for prednisone treatment as a step edits. To further demonstrate Emflaza's benefits, during WMS, Data collected as Cincinnati Children on more than 400 GMD boys was presented. This data showed clear motor and pulmonary of Emphaza when compared to other corticosteroids. This is one of the largest cohorts ever observed and studied in GMD.
The data reinforced the importance of correct use of steroids in the management of this disorder, and you continue to work with physicians and payers to understand the benefits of Emflaza. Now switching gears to Translarna, we have seen a strong year to date performance, with revenues of approximately $141,000,000. We continue to see growth in demand and support from physicians and patients in all territories Translarna is available. And we continue to execute in our geographic expansion. Most recently with addition of a PTC subsidiary in Russia, which we believe will enable the growth in the region.
In addition, as Stuart mentioned, we're excited with the body of evidence supports Translarna's effectiveness. Including the data coming from the first Duchenne product registry, strides, which is following up more than 200 patients with nonsense mutation DMT who are receiving Translarna globally. We reported real work long term evidence from Translarna treated patients coming from this registry. The data shows that long term treatment with Translarna is low disease progression by preserving both pulmonary and motor function in all patients observed in the registry. As you know, patients die due to respiratory and cardiac failure.
In these cohorts, we observed that 32% of patients receiving standard of care has an ADC of less than 50%. Which is in line with the decline in lung function expected in this disease. Only 2.2% of patients who received Translarna achieving such milestone. Additionally, patients receiving Translarna had a prolonged ability to extend from supine by 3 years when compared to untreated patient population. Continuing with our commercial portfolio, we're happy to have received regulatory approval by ANVISA for tax aid this week.
Is an important milestone, which enabled pricing registration and negotiations with the Brazilian government. To make TEGSEDI available to all patients who may benefit in the country. We had the team in place for market developments and medical support since the beginning of this year and now intends to start launching activity for TEGSEDI immediately in Brazil. We are proud to add this important regulatory approval, and are committed to serve all the patients in Eastern Latin America. Our next major regulatory step in the region is to file for the approval of Waylivra.
Now focusing on the ADC deficiency. We are preparing for a successful launch in the United States next year with the expected FDA submission this quarter and subsequent approval in 2020. Market preparation is well underway with a clear plan to cover both the prescribing population but also the centers of excellence conducting the neurosurgical procedure. In terms of patient finding, our approach involve multiple channels. 1st, our field based personnel are distributing at no cost testing kids for any clinicians that suspects an ADC deficient patient within their practice.
A protocol driven broad based screening programs of cerebral palsy is also advancing. And our social media initiatives have launched with good success rate to date. Additionally, we have recently established a partnership 2nd tier newborn screening panel in the United States. And we are working together on the tax validation. We expect more than 200,000 babies to be screened at birth for ADC deficiency next year, and more than $1,000,000 in 2021.
Our goal is to have more than 300 addressable patients available before launch to be converted to commercial in key territories we are on track to We have completed enrollments in Study 45, which is our dystrophin management study in the United States for Translarna. This study is positive, will serve for the NDA resubmission in the U. S. We have also had the last patient, last visit for our unreaded study for Translarna, which should readouts at the beginning of next year. Our Friedreich's Ataxi clinical development program is progressing well as we prepare to dose the first patient next year.
Lastly, Stu just mentioned, we have acquired some assets from Biolectron. We intend to initiate a clinical trial mitochondrial epilepsis with the most advanced compound early next year. The trial has been designed based on scientific advice received from the European Medicines Agency. We also intend to explore other use considering the anti inflammatory properties of these compounds, which are going to be disclosing in the near future. I'll now hand the call over
also wanted to take a moment to acknowledge a new member of the Investor Relations team, Alex Chang. Alex joins us from the agency side and Nasdaq he spent almost a decade focused on biotech Companies. We are very happy to have him join us at PTC. As you know, our third quarter press release was glued shortly before today's call, which summarizes the details of our financial results. Please see that release for further detail.
I'll start with a few comments on our financial performance in the quarter and our guidance for the full year 2019. Starting with our top line results we reported $71,400,000 in combined net revenue across our commercial portfolio in the third quarter of 2019. Compared to combined net revenue of $53,000,000 for the third quarter of 2018. Translarna net product revenues were $48,300,000 for the quarter, This compares to $30,400,000 in third quarter of 2018. This growth includes the expansion of Translarna ex U.
S, including regulatory approval and then annual contracts with Brazil. For Emflaza, we reported net product revenues of approximately $22,900,000 for the third quarter of 2019. Which compares to $22,600,000 reported in the third quarter of 2018. We are working towards establishing Emflaza as a standard of care for all patients in the U. S.
And are happy to be able to bring Symflaza now to patients as young as two years of age. Continued growth of the DMD franchise and our annual contract Brazil for Translarna give us confidence to reiterate our 2019 DMD franchise revenue guidance of $285,000,000 to 305,000,000 We've 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 $58,100,000 for the third quarter of 2019, excluding any non cash stock based compensation expense, compared to $49.9 expenses reflect our strategic investment in advancing the gene therapy platforms, splicing programs and other research programs as well as the advancement of the clinical pipeline. Non GAAP SG and A expenses were $43,800,000 for the third quarter of 2019, excluding $5,500,000 in non cash stock based compensation expense compared to $33,900,000 in the third quarter of 2018, excluding $4,500,000 in non cash stock based compensation expense. Reflecting continued investment in support of our commercial activities, launch preparedness in Latin America and global patient finding efforts.
Would also like to update non GAAP R and D and SG and A expense guidance for full year 2019 to $380,000,000 to 390,000,000 excluding non cash stock based compensation expense of approximately $40,000,000, an increase from $360,000,000 to $370,000,000 including estimated non cash stock based compensation expense of approximately $35,000,000. This increase in operating expense is primarily to business development activities and investment in gene therapy manufacturing. Net loss for third quarter of 2019 was $60,000,000 compared to a net loss $51,000,000 for the third quarter of 2018. Cash, cash equivalents and marketable securities totaled $708,600,000 2019 compared to $227,600,000 at December 31, 2018. In September, we completed a finance in $5,000,000, resulting in net offering proceeds of approximately $376,000,000.
Q on many fronts towards achieving our $1,500,000,000 20.23 revenue target. I will now hand the call over to the operator to start our question and answer session. Operator?
Our first question comes from Alethia Young from Cantor.
On all the progress. Maybe 2 for me. Just one, I feel like you snuck in this Bioelectron. And I was looking on the on the website, are you guys going to using the this EPI-seven forty three like and using the same combination of other assets? I just maybe can you talk a little bit more in detail as it relates to your platform?
I'm not sure if it's too early. And then on the second side of things, I wanted to check on the USDAMD study, which it sounds like it's still reading out sometime relatively soon. And I guess, how are you thinking about potentially filing? I mean, I know some people have paid attention to what's happened with like Sarepta in the case of Golodirsen. I mean, do you you feel confident in the agreement in which you have with the FDA around, dystrophin here at this point?
Thank you.
Yes. Hey, thanks, Alethia, for the question. Yes. Biolectronic, we thought was a very interesting company with a strong scientific platform that's hit Okta data strat for redox. And this turns out to be quite important for mitochondrial function and neural inflammation or inflammation in general.
And so we were very excited about it in Epi743, as you see, is their most advanced program that we think is, in a sense, pivotal ready program, study regularly for potentially a number of different disorders. Maybe I'll have Marcio talk a little bit about that. But that's what we thought was really quite exciting and what we're going to be focused on is as what I talked about in the script originally, this is really a success based milestones to on success of the of approval on trials to move forward. So we're excited. We think it's a very important asset that can complement not only new diseases, but can work in inflammation where you can explore in other diseases like DMD as well.
So we're excited about that. Do you want to talk about that?
Yes, absolutely, Stu. And thanks, Alicia, for the call. So 1st and foremost, so extremely excited is to just add about bringing the portfolio here through these assets agreements with Biolectron, specifically I wanted to call out that some of the team members are coming as well and are joining PTC. I'm especially proud to have Matt Klein, who is the CEO now by Alexron joining the team and leading the efforts with 743 and other assets here. We're going to be focusing on some of the diseases I mentioned on my prepared remarks.
The first one is mitochondrial epilepsis. We see a very high unmet need there, several 1000 patients in the U. S, several 1000 patients outside of the U. S. So relatively large market opportunity, but yet relatively small clinical trial to get to development, very interesting phase 2 proof of concept already in house with this.
So we're going to move that quickly and then going to go from a rigorous process to prioritizing the other indications to see what makes sense. Obviously, inflammation is in the core of a lot of the things we do right now like GMD and you're going to take a look and look at what really matters in terms of patients and whether or not we should move forward in other indications as well.
And then in terms of the DMD, we're pretty confident we had long discussions with Janet Wilcock on what was required. And just to remind you that it was, anything above background with the clinical data that we currently have on hand should be sufficient for approval. So we've had substantial discussion, they feel comfortable that we have an agreement to move forward based on that.
Great. Thanks.
Thank you.
Our next question comes from Vincent Chen from Bernstein. Please go ahead.
Great. Congratulations. Thanks for taking the questions. A couple of them on the Huntington's disease program. First, I was wondering if you could provide some detail on what are some of the assays that you used to the risk of off target splicing in different cell types and so forth.
What preclinical studies are the potential candidates subject to? I guess, which of these have been completed dates, what remains to be done on this front? And then secondly, how do you think about the target product profile you'd be aiming for? In particular, I guess if you think about, you've shown pretty substantial knockdown in the preclinical studies. Level of knockdown would you be looking to target in a clinical program?
Sure. Thanks for that. And so in general, our approach is really we use in the sense of chemical genomics approach in terms of identifying molecules versus the high throughput screen and then going into cell and animal based molecules. And they're always counterscreens against a number of other, what we think are similar yet not identical splicing events to watch. And so we look very carefully at that as well.
Then also used in a sense safety toxicology as an important measure as well. Because at the end of the day, whether it's on target or off target is what we tend to want to find that out. So this occurs quite early within our screening tier. And so We build a screening tear, both at looking at, in a sense, the effectiveness of the compounds for selectivity and specificity. We also do a deep sequencing and RNA seek to monitor White House.
Within the genome they may hit. So and we continue to try and improve not only the efficacy, but the select activity of that. We find that we're capable of doing that and as the molecules become more effective, you tend to be in the lone animal or range. They tend to be far more selective as consequence of that. And then obviously, we put them in through pharmaceutical, not only due to the Epic CSC at Safe Steve, but look at the pharmaceutical properties that go along with that.
And that's a long laundry list of of things that we look at, whether it induces SIP or aims assay issues, all the things that we look that is known to look for that we if we find some issue with it, we work it out and try and that out until finally we get a compound that we want to move forward on to do what we'd say is to move forward like a development compounds that we then do larger GMP scaling of the product. So we have that synthesized in the GMP manner than those do GMP safety toxicology studies. What we've talked about in the past for a Honey Tins Disease is that this we think that an orally bioavailable product, much like analogous to SMA, would really be the most competitive product. And so there's a very important program for us where we would anticipate as need be to continue to have as many compounds to move forward as we can. As I said in my prepared remarks, we already have a compound that we are doing TMP scaling and going to be moving in the state to toxicology such that as we've always said, anticipate to have it in the clinic, next year.
So I think that's an exciting point here that we're moving forward on a compound continue. We lead to build out the patent IP profile around all of that. And then And we've already shown in animal models that it reduces, HTT, not only in the brain, but also in other tissues as well. And we'll have the advantage that we'll be able to look into blood and see a reduction of that. These compounds are highly effective.
We're shooting for probably reduction. These molecules are effective enough to go pretty low. And so we're capable. I think the nice thing about a small molecule also is that not only do we know it penetrates the blood brain barrier and gets into and obviously it's because of the blood exposure gets to all cells within the brain, but it also gets into blood and skin and we're capable of actually monitoring with the effect of what exposure causes a reduction. And the fact that is that we could then go and figure that out to what effect reduction you see in brain.
So we have a very good ways of titrating what the appropriate, what the appropriate exposure is to get a 50%, 60% reduction. And that's the way that we're that's the way we pick the compounds and begin to define what in the blood, we're able to say what reduction we're able to see. And I think one thing that we probably didn't push hard enough in the SMA program is that very early on in healthy volunteers, we were able to show that there was a reduction of SMA analogous to that. We're going to be able to show that the molecule that we chose, we'll be able to say with the hypothesis, do you reduce HTT and can you observe that in the blood? We did that in SMA and that gave us a lot of confidence to be able to move forward because of what you see in the blood is what we saw in the brain.
So that's in the sense one of the first even in healthy volunteers, I think we're going to have a good idea whether we hit the target we want, affect the splice, reduce the splicing, and then move on. And then in terms of the product profiles, I think We'll be sort of talking about that in more detail over the next call.
Great.
Thank you very much. Appreciate the insight.
Thank you. Our next question comes from Joe Thomey from Cowen And Company. Please go ahead.
There. Congratulations on the quarter and thank you for taking my questions. Maybe your first one on the acquisition of the new products. I know you mentioned there was a success based milestones associated with the programs, but was there any upfront costs associated with the development And then maybe a second on the dysautonomia program. I know you outlined the reasons that's why you're not moving forward with that, but is there any read through to your oral splicing platform as a whole?
And maybe how has this interaction changed your future development plans for rare diseases? Thank you.
Sure. I'll take the second one first and then I'll have Emily discuss the cost. I think I think this is an important point. And, early on, when we chose to look at FD, it was really a consequence of it was unique and that it had a founders effect in terms of the mutation. It has a single point mutation that actually affect the splicing of the L1 gene.
That prevented the production of the protein and that lead to the disease. So it was very much a consequence of altered splicing. And just based on our understanding of it, we could fix it. But we knew that it was a relatively small patient population But we thought it was just teaching the importance to see if we could find another molecule, which I'm excited to say that we did and it's highly effective but it's a very small patient population. And we said to ourselves that, and it's a dwindling population that they now longer have additional patients because they screened for this.
And so we said that the best we thought that the best approach for such a small patient population would be a biomarker study that is that we show that you reduce the level of the protein. And then if possible, then to go into registry where you would follow it over time. We measure as we had in the bars for about a year, but then go on and do a post marketing registry study. And unfortunately, the FDA wanted to have or suggested to us that we have a placebo controlled study on perhaps look for other endpoints. And so in this case and selective specifically for FD, the small patient population, the fact that it would be placebo controlled, we just didn't think there would be enough patients to be able to power be able to do this in the long term 2 or 3 year study.
We just didn't think it was viable. So that's why that stopped In the case of other things, we don't think that's the case. I mean, Huntington's disease is a much larger population. And we think there's the good news is that there's others who are doing substantial amount of work ahead of us so that are helping to find what are the best points was the best way to power it. So we feel in a much better position in the case of Huntington's and unfortunately for HD.
And I think that's relatively sad for the F. D patients. And one of the cause celebs, I think we want to work at the company is to is trying to it's trying to think of a way where there's a in a way like the Europeans have exceptional circumstance that can allow for these extremely small patient populations to have a means try and get approvals on drugs that could be beneficial. But that would obviously take time to change direction and loss for the company. But that's something I think we're going to try to work on in the long run.
And then an answer to your question about the upfront for the assets acquired for by Elektron, we were pleased to have structured that as a success based deal. The transaction has very little upfront payment, $10,000,000 upfront for these assets. And then obviously, as you mentioned, their success based milestones do 1 year after certain regulatory approval.
Great. Thank you.
Thank you. Our next question comes from Gena Wang from Barclays. Please go ahead.
Hi. This is Peter for Jeanette. I just had two quick questions. First on SUNFISH part 2, Could you give a sense of how, what format you would release the data? Would it be a press release followed by a medical conference?
And if so, What kind of information would be included in the top line? And I have a quick follow-up.
Hey, Peter, Mauricio. So first, as you might recall, right? The trial is reading out in Q4. We're trying to do this real time. We leave the top line data.
As it's practice, both for us and Roche is the more complete results are going to be shown early next year in a conference and a scientific conference. So we should be having before the end of the year, the top line, and then next year more complete response.
Got it. And, I guess, my follow-up question is, given that, I guess, part to data would be available to before the approval decision? Would that be part of the discussion as well? Thank you.
Yes, absolutely. I believe we mentioned something to this regard on the previous call as well, why it's not required for the submission as we made clear, it is courtesy and it's obviously we would be doing Roche in this case who are leading the submission would be submitting that to the FDA, the topline data. What is not required here is to have like a CSR format and all the data transfer and everything else that's normally would be, if it was a new submission, would be done. So the top line, again, as a matter of courtesy, but also as a matter of practice, to be shown to the agency presented to them if they have any questions and so on. Obviously, very excited.
I think the results of Part 1 and what we just show the WMS. And before that, at many conference shows incredible activity for this compound and in these patients in Type 2 and 3. Looking forward to these results later in the quarter.
Great. Thank you very much.
You're welcome.
Thank you. Our next question comes from Martin Auster from Credit Suisse. Please go ahead.
Hey, all. Thanks for taking the question. I had a couple. One was just from the press release you talked about the Risdipline NDA filing on plan for back half of the year. Just wanted confirm, are we going to just hear about this filing once FDA has accepted it?
And is that something we can expect by the end of the year? And then the second question was just on the Friedreich's ataxia gene therapy IND. Just wanted to see if you could add a little more color to the process that kind of led to the the slight push out from kind of end of this year towards middle of next year and how confident you feel about the revised timeline? Thanks.
Yes, sure. So I think the rhythm plan, I think we feel pretty confident that you're going to hear something by the end of the year. So we feel good about that. And terms of the FA, I think unlike ABC, it's a much larger population. We think about 25,000 patients And we what we did is we decided, that we wanted to optimize the sellout a bit to get larger quantities produced.
And so we decided to take the time to get that moving forward and to get that appropriately completed. To be able to do that. And so our timeline now have moved, but we still think that, and what we're saying still think that we will have IND next year, for FA. Okay.
I'll just do one quick follow-up on the Risdiplan NDA. There'll be an announcement when FDA has accepted the filing or when the filing has been submitted?
Accepted.
Okay, great. Thank you.
Our next question comes from Brian Abrahams from RBC Capital Markets. Please go ahead.
Hi, thank you very much for taking my questions. First one on Risdiplam and SMA. As the SMA market and the data continue to evolve, what's been your latest feedback from regulators, physicians and reimbursors as to the magnitude of benefit that would really resonate from the Sunfish Part 2. And then separately, you mentioned that you're tracking on the AADC program towards your patient identification goal. Just wondering if you could give us a little bit more granularity around that.
Where the patients being identified are coming from geographically through what channels that you're finding them? And I'll hop back in the queue. Thanks.
Sure. So on the Risdiplam, I think people have seen the data that we presented from part 1 of them. I think they feel pretty good about that. We're looking at the results, in a sense, the payment from the gene therapy program that seems that they're getting paid for. That's feel pretty good about where we're at.
We think obviously not only do people like the efficacy and the fact that it's systemic and actually hits other tissues, in which SMA is the lack of SMA effects, like liver, bone, muscle, other tissues as well. But the simplicity in the oral bioavailability of the drug, I think, is a real important factor. So we think the combination of of the quality of the data that we've shown thus far, the ease of use is going to really put us in a very good and competitive position. In terms of, the second question, let me pass that over to Marcio.
Sure. Hey, Brian. So the ATC patients had indication, as I mentioned on the in the prepared remarks, we're making some good progress here towards our goal to have 300 patients available at the time of launch. To convert them to reimbursements. The source, the main source of patients right now is twofold, right?
One is our efforts on really connecting with families and physicians through social media and that's been panning out quite nicely. And the second is our grass root approach in in terms
of
in the United States where we are providing this at no cost and outside as well. You mentioned about geography. In your question. So the key focus obviously is that you asked, that's the majority of our focus right now. That's where we expect to launch first.
But we are putting some real nice effort as well in some selective countries in Europe and in Brazil. So we have a relatively, I would say, strictive in terms of focus geographic spend for now for the next 12 months. We're going to build success and success. Trying to get to these patients on areas they're going to launch first. And the last source is the identification through screening programs.
So that's coming along. Now we have the sites open, as I mentioned in the previous quarter, we had a little slow down there. Mentioned, we expect to start newborn screening some patients in the United States. This is on top of the newborn screening program we announced last quarter. We're going to be a pilot in Germany.
So it's all coming out quite nicely for a successful launch. Thank you. Thanks, Bryce.
Thank you. Our next question comes from Raju Prasad from William Blair. Please go ahead.
Thanks for taking the question. 2 for me. On Emflaza, you mentioned the mix So what utilization of Medicaid, is that something that we should anticipate moving forward? And just maybe some general color on how the label explain is going so far for the product? And then on TEGSEDI, it looks like in your 2023 projections, you have about 200,000,000 Rentech setting.
Can you just provide some color on how we should anticipate that long as to go? I mean, in the process of what percent of that 200 is earmarked for Q3? Thanks.
Sure. Iris, it's Mauricio here. So, first on, on the question on Emflaza, right? So Medicaid, we constantly monitored the use as you can imagine, there's like new patients pretty much being added every day. We need to look into that on a rolling basis so we can meet our legal obligations with CMS and pay the rebates and so on quarterly.
So when you look into that in the last few quarters, it was trending at a higher in terms of the percents than we expected. So we had to make some adjustments to make sure like we're okay in terms of gross to net. That's resulted in a little bit of a negative impacts on the net revenue this quarter. When you're looking to that, it's not only for the past but very importantly, our we revise our projections for the future based on the rate of patients that are coming in and what the insurance plans are. So we should be our best expectation right now is that we should be covered for the subsequent quarters in terms of the mix we and you're going to update you properly, if not.
In terms of the label expansion, the key here is not necessarily to convert the patient. That actually a relatively easy task is really these patients are not getting diagnosed and they're not getting on sterile So we're doing our field forces working a lot in our medical, science liaisons and the patients advocates are working a lot on guaranteed identification. Very nice early progress, but it is still along our roads to go. So lastly, on the tech savvy, so extremely excited. Let just say that first since your question is the first about TEGSEDI officially published the approval today.
We received an advanced note for visa that would be coming. So, the very first approval in the world for any to include quality of life in the indication, I stay Mints. So as we talk about differentiation, competitive markets, we wanted to make sure we're always ahead of everyone. So that's very nice. When you look into our long term projections, Brazil is the most important market in the region, about 5000 patients.
It puts us ahead in terms of negotiations with the government, and that's what we're going to start now. But very importantly, while we've been preparing the market we have a decent number of prescriptions for already we couldn't promote. We couldn't say the word tech savvy. We couldn't talk about the label. So as of tomorrow, the team in Brazil is going to be talking about this to physicians.
So we're going to be seeing hopefully a very nice increase in demand. And going to convert to revenues. The 1st year is normally low, in terms of revenues, but we do obviously going to do our best and more than that even to deliver on results. But I would try if our modeling was in your shoes, I would be putting a little bit of a slower 1st 12 months and then ramping up from there. And one small just point was the $200,000,000 for TEGSEDI
was really I think what we put for TEGSEDI and we leave we had about $150,000,000 for TEGSEDI. So it's Okay, thanks.
Thank you.
Thank you. Our next question comes from Joel Beatty from Citi. Please go ahead.
Hi, thanks for taking the questions. First one is, could you just discuss the importance of showing a statistically significant benefit in Sunfish Part 2 compared to Placebo from both a regulatory standpoint as well as a commercial success standpoint? And then the second question is could you discuss, the confidence in DMD revenue guidance for the year? It implies uptick from where it was at this quarter? Any thoughts on whether it could be towards the bottom or the upper end of the range?
Go ahead.
Sure. So on the Sandish Part 2, right? And what do we expect from that? So obviously, extremely bullish. In terms of the program in general.
And this is based on what it look into part 1. So the way that trial was powered is in relation to, obviously, it's always a ratio between the point estimate change and the standard deviation. On this case, We expect it should be a 3 points change on the MFM32. That is the primary endpoint and a 6 standard deviation for that. This is pretty much what we're seeing with Part 1.
So in that regard, like there's all indicators that the trial is going in the right direction. The good thing is this population should be more or more genius. So one would expect that the results are a bit more on Virginia as well. It is important to have a positive trial and obviously that's what we are planning for, right, both for the regulators, payers, patients and so on. It's very hard for us you try to predict right now, where it's going to land, this trial was well conducted, extremely well conducted, more 186 patients are 168 patients, always inverts that your numbers, they are my apologies, and power properly.
So all we could do to derisk was done. And again, we're excited to hear about that before the end of the year and inform you guys. In terms of the GM the guidance for the year. It is trending positively. You're absolutely right.
We continue to just like our approach for guidance as we always say is to be realistic in terms of what can be achieved at this point in time because we do have some ordering patterns fluctuation We didn't feel it was the right thing to narrow the guidance. Obviously, excited and going to do our best and we are all pushing here should be as high as possible, but the most responsible thing for us was to keep the entire range of the guidance open.
Great. Thank you.
Thank you.
Thank you. Our last question comes from Eric Joseph from JP Morgan. Please go ahead.
Hey, good evening. This is Turner on for Eric. Just to follow-up on Huntington's and thinking about entering the clinic with healthy volunteers next year and
getting some initial PD data, do
you have a sense yet of what level of plasma MRNA and HTTP protein reduction would give you some confidence to meet the 56 a 50% or 60% reduction threshold in the CNS that would confirm efficacy? And then one other quick one, I'm just curious as to when we may anticipate updates for Tulfish and Rainbow Fish and any particular recruitment update for Rainbow Fish? Thank you.
Sure. In the case of HTT, we probably obviously we're looking to see some change of that. Obviously, what we're shooting for somewhere between 30% 60% reduction of the HTP protein. So that's what we would consider important. So we think, that we know that within the blood and brain the blood brain barrier that there's a good, almost a 1 to 1 ratio within the exposure that you see in blood is what you see in the brain.
So we'd be pretty confident that, 6 what the results that we get from blood would be indicative of what you're seeing in the brain. And again, I think the importance of that is that obviously, that because it's in blood, it would get distributed to all cells within the brain. And I think that's actually important point because it's there are certainly deep recesses within the brain that are difficult to get to. And we think by having the exposure and the blood really gives us a big advantage.
And maybe I can take the second on the other trials for SMA. So RIMOFISH is probably the one we're the most excited to CNX right? So you probably see our updates at WMS. Those diverse patients there are having really great interest several sites open globally that should as it comes, we're going to be showing updates. I think it's being practiced for this program to be presenting all the major scientific conference.
There are obvious ones in the beginning of the year, like AAN, and that's where you should expect to have a general update the program.
Great. Thank you.
Thank you. This concludes our Q and
again, let me just thank you all for joining the call today. We really appreciate it. And I think what you could see thus far is that we've really had a productive year thus far with a number of exciting milestones that will be coming. I think the coming weeks. And we look forward to sharing those with you.
Again, thanks for being a part of our call.
Ladies and gentlemen this concludes today's conference call. Thank you for participating. You may now disconnect. Good day.