Q4 2023 PTC Therapeutics Inc Earnings Call
Participants
Ron Aldridge; Investor Relations; PTC Therapeutics Inc
Matthew Klein; Independent Director; PTC Therapeutics Inc
Eric Pauwels; Chief Business Officer; PTC Therapeutics Inc
Kylie O'Keefe; Chief Commercial Officer; PTC Therapeutics Inc
Pierre Gravier; Chief Financial Officer; PTC Therapeutics Inc
Sami Corwin; Analyst; William Blair & Co LLC
Rick Miller; Analyst; Cantor Fitzgerald & Co.
Kelly Shi; Analyst; Jefferies & Company, Inc.
Eric Joseph; Analyst; JPMorgan Chase & Co.
Jeff Hung; Analyst; Morgan Stanley
Brian Abrahams; Analyst; RBC Capital Markets
Peyton Bohnsack; Analyst; TD Cowen
David Lebowitz; Analyst; Citigroup Inc.
Gena Wang; Analyst; Barclays Capital Inc
Paul Choi; Analyst; The Goldman Sachs Group, Inc
Alex Brown; Analyst; Raymond James Financial, Inc.
Joseph Schwartz; Analyst; Leerink Partners LLC
Presentation
Operator
Good day, and thank you for standing by, and welcome to PTC fourth-quarter 2023 financial results. (Operator Instructions) Again, please note that today's conference is being recorded. I would now like to pass the call over to the Senior Director of Investor Relations, Ron Aldridge.
Ron Aldridge
Good afternoon, and thank you for joining us today to discuss PTC Therapeutics Fourth Quarter and Full Year 2023 corporate update and financial results. I'm joined today by our Chief Executive Officer, Dr. Matthew Klein; our Chief Business Officer, Eric Pauwels; our Chief Commercial Officer, Kylie O'Keefe; and our Chief Financial Officer, Pierre Gravier.
Today's call will include forward-looking statements based on our current expectations. Please take a moment to review the slides posted on our Investor Relations website in conjunction with the call, which contains our forward-looking statements. Our actual results could materially differ from these forward-looking statements. As such, statements are subject to risks that can materially and adversely affect our business and results of operations. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent annual report on Form 10 K filed with the Securities 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 to non-GAAP financial measures and a reconciliation of GAAP to non-GAAP are available in today's earnings release.
With that, let me pass the call over to our CEO, Matthew Klein.
Matt?
Matthew Klein
Thank you, Ron, and good afternoon, and thank you all for joining today's call, I'm pleased to share our fourth quarter and full year 2023 results and to provide an update on the progress of our pipeline programs as we move into what will be an exciting 2024 with a number of potential significant milestones as we closed out 2023, we had another solid quarter commercial performance with total fourth quarter revenue of $307 billion and full year 2023 revenue of $938 million, representing 34% growth over 2020 to our DMD franchise revenue totaled $143 million in the quarter and $611 million for the full year. Harrison Kylie will provide additional detail on our commercial performance shortly. Our revenue performance reflects the continued outstanding work of our global customer facing teams and our successful efforts in geographic expansion. With this infrastructure and track record of execution. I remain confident in our team's ability to succeed with our next product launches, including CP parent, for the treatment of PKU. Most of you are aware in January, we received a negative opinion from the CHMP on the continued conditional marketing authorization for Translarna in the EU. This opinion is expected to be ratified by the EC in late March or early April. Importantly, Translarna remains on the market until ratification occurs. In addition, we continue to commercialize Translarna in several regions outside of the EU where independent authorizations exist while we are, of course, disappointed in the CHMP opinion and the potential impact it has on patients in Europe. PTC. is well positioned to withstand this up as I have previously emphasized through our efforts to focus our R&D portfolio, rightsize the organization and strengthen our balance sheet. We have a solid foundation for building the Company forward and continuing to deliver on our goal of discovering, developing and commercializing transformative therapies for patients.
As we look forward to 2024, we have a number of important potential regulatory and clinical milestones for a number of our programs will begin with our CP parent program for the treatment of children and adults with PKU, we remain on schedule to submit M&A per se, deterrent to the EMA in the first quarter of this year and to submit the NDA in the United States no later than the third quarter of this year as we continue to collect data from the open-label extension study following the Phase three AFFINITY trial, we continue to see durability of CP apparent treatment effect and the ability of patients on secret parent to tolerate increases in dietary protein intake beyond the recommended daily allowance. This liberalization of diet is incredibly meaningful to patients and further supports the potential of CP parents to fill the persistent unmet medical need of the majority of the 58,000 PKU patients worldwide.
Moving to our particular program for Friedreich's ataxia, we had a Type C meeting with the FDA earlier this quarter. Based on discussions with FDA, we now have a path to potential NDA filing based on the placebo-controlled results from the move of a study in combination with long-term open label extension data currently being collected. The open-label data will be compared to a natural history population from the robust Friedreich ataxia patient registry using analyses similar to those provided to FDA by Reata as part of this quite high-risk NDA. Based on the time needed to collect sufficient long term open label data, we expect to be able to submit an NDA in late 2024. We are very excited about the potential of particular note to fill the significant remaining unmet need for pediatric and adolescent FA patients.
In other regulatory updates, we remain on track to submit the BLA for Stavzor to the FDA in March and are also scheduled to meet with FDA in March to discuss the contents of a potential NDA resubmission for Translarna.
Turning to our ongoing clinical trials, we expect to share interim 12-month results from the pivotal Phase three trial of PTC. five or eight in HD patients in the second quarter of this year from the initial cohort of subjects on whom we reported data last summer. The 12 month results will include additional safety and tolerability data as well as biomarker data, including CSF huntingtin protein levels, NfL levels in the blood and in the CSF and volumetric changes on MRI. We will also be sharing data from the clinical outcome measures collected as part of this study. Finally, we expect to share top line results from the Cardinals registration directed trial of mutual access data in ALS patients in the fourth quarter of this year.
In closing, we are well positioned for an exciting 2024. We have the team, the capital and the strategy that position us to execute on the many impactful opportunities that lie ahead.
I will now turn the call over to Eric and Kyle to discuss our commercial performance.
Eric Pauwels
Eric facemask, our global customer facing team has delivered yet another strong quarter, continuing the significant momentum we have built, we see ongoing growth from our portfolio products in more mature markets such as the US and EU and also new markets where we have invested in geographic expansion in Latin America, the Middle East, North Africa, and the Commonwealth of Independent States, where there has been robust year-over-year growth in the fourth quarter. We delivered $155 million of revenue for PTC marketed products, which represents 22% growth year over year.
For the DMD franchise, we closed out the year with a strong fourth quarter for both Translarna and Emflaza, delivering an impressive $143 million in net revenue, which is 25% growth compared to the fourth quarter of 2022 with a strong full year performance of $611 million. For Translarna, we achieved 75 million in revenue this quarter with annual sales of $356 million, which is a robust 23% growth over the same annual period last year. I'm very proud of the team's efforts and determination these last few months as they have worked tirelessly to ensure that every single Translarna patient in Europe continues to receive treatment until the ratification of the CHMP opinion. And we are actively evaluating local country options for ongoing access to treatment. Additionally, we continue to diversify our trends and Florida franchise globally as we brought this treatment to patients in seven new countries last year as part of our ongoing expansion geographically around the world.
Now turning to Emflaza. Quarterly, net revenue was $67 million with 255 million of net revenue in 2023, which is a 17% growth over 2022. The team has implemented a multi-prong strategy to ensure that we protect our Emflaza business in anticipation of a loss of exclusivity in Q1 this year, our U.S. team continues to engage with health care professionals by providing meaningful clinical differentiation compared to prednisone and have implemented other strategies to ensure Emflaza brand loyalty for new and existing patients. We continue to support DMD patients and their caregivers with outstanding service from our PTC. cares teams by enhancing customer experience, providing easier access to treatment, facilitating co-pay assistance and improving adherence for patients in the US. Ptc is also partnering with our specialty pharmacies and contracting with targeted payers to dispense the Emflaza brand. We continue to communicate and support our exclusivity for two to five year old DMD patients, which continues into 2026. And we are also leveraging patient advocacy in support of the benefits and value of Emflaza.
Now I will ask Kylie to update the progress of our current and future new product launches.
Kylie?
Kylie O'Keefe
Thanks, Eric. Let me begin with UPS data, the first and only approved gene therapy infused directly into the brain, where we continued to see transformative results. In October, we presented updated data at the CNS. conference, showing cognitive improvement and continued increase in long-term motor milestones. Our rollout across Europe continues to progress with new patients treated in the quarter. Furthermore, we are continuing the global expansion of the franchise with additional regulatory filings in Asia Pacific countries and have recently received regulatory approval in Israel where the team is working actively to treat our first patients globally, patient identification, treatment center readiness and access and reimbursement discussions continue to advance.
Moving to Texas and Waylivra.
In Latin America, we closed out the year with robust growth for both Tegsedi and Waylivra, more than doubling our revenue in the region. Patient identification is robust and the number of patients on treatment continues to grow across the region, including first time revenue in new countries. In Brazil, we received a new group purchase order for Waylivra, which is in recognition of the increased number of patients that rely on these life-changing treatments. We anticipate fulfilling this grew purchase order in the first quarter. As previously discussed, we are updating our total revenue guidance following the CHMP opinion for Translarna with growth continuing across the portfolio for everybody upstairs at Tech city and Waylivra, our efforts to protect the Emflaza business and expected Translarna revenue in geographies outside of Europe, we are updating our annual total revenue guidance to 600, 680 million. We continue to plan for our global launch of SAP. You, Tara and feedback from the PKU community is extremely positive and there's a widespread recognition amongst metabolic specialists, geneticists and dietitians of the potential of Serbia Taryn to meet the significant unmet needs for many of their PKU patients, not just patients who have been unresponsive to Kuvan, but also those who are poorly controlled on this drug and could potentially do significantly better on safety, a turn as we saw for numerous patients in the AFFINITY trial as well as classical PKU patients. More importantly, we continue to see durability of treatment effect and the ability for patients on therapy adherence to increase their dietary protein intake beyond the recommended daily allowance while still maintaining control of Phe levels in the long-term extension study. In addition, we have heard from patient advocacy groups around the world that PKU patients are excited as they've been waiting for a therapy that combines efficacy through both Phe reduction and improved Phe tolerance with tolerability. Both the physician and patient excitement continues to give us the confidence that we can reach over $1 billion opportunity. And we look forward to taking a step closer to realizing this upon our first global approval.
In conclusion, a strong fourth quarter rounds out what was a strong 2023 for our commercial team, our team is well positioned to continue to execute across all our commercial products and across all geographies. Together with building out the foundation for SAP at Heron for success in 2024 and beyond.
I will now turn the call over to Pierre for a financial update.
Pierre Gravier
Pf centric IT.
I'll now share the financial highlights of our fourth quarter of full year 2020. Please refer to the earnings press release issued this afternoon for additional details beginning with top line results. Total revenue for the fourth quarter was 307 million. This consisted of DMD franchise revenue of 143 million and other revenue of $164 million.
Starting with the DMD franchise, Translarna net product revenue in the quarter was 75 million, while Emflaza net product revenue of 67 million moving to everything. Fourth quarter global revenue of CHF354 million, which equates to about USD400 million, was achieved by was earning royalty revenue of 51 million for PTC. We also earn 100 million milestone for Vizzy, achieving more than $1.5 billion in 2020. Our total revenue for full year 2023 was EUR938 million for year-over-year growth of 34%. This included DMD revenue of 611 million, which represented 21% year-over-year growth. Everybody royalties for the year grew 49% to 169 million year over year. Non-gaap R&D expense was 113 million for the fourth quarter of 2023, excluding 8 million in noncash stock-based compensation expense compared to EUR175 million for the fourth quarter of 2020, excluding 14 million in noncash stock-based compensation expense. The year-over-year reduction in R&D expenses reflects the strategic portfolio. Prioritization of the Company continues to focus its resources on its differentiated high-potential R&D programs. Non-gaap SG&A expense was 68 million for the fourth quarter of 2023, excluding 8 million in noncash stock-based compensation expense compared to EUR79 million for the fourth quarter of 2022, excluding EUR13 million in noncash stock-based compensation. This expense reduction reflects lower operating cost as a result of the reduction in the workforce. We're maintaining our guidance. We provided in January for GAAP R&D and SG&A expense of between 740 and 835 million. We are also maintaining our guidance for non-GAAP R&D and SG&A expense of between 660 and EUR755 million, including expected R&D expense, milestone payments of up to EUR65 million and excluding estimated non-cash stock-based compensation expense of 80 million.
Cash, cash equivalents and marketable securities totaled approximately EUR877 million as of December 31st, 2023, compared to EUR411 million as of December 31st, 2020. The strong balance sheet provides PTC with the resources to execute on our strategy and to achieve our milestones over the next several years, including the anticipated pickup there in August.
And I will now turn the call over to the operator for Q&A. Operator?
Question and Answer Session
Operator
(Operator Instructions) Sami Corwin, William Blair.
Sami Corwin
Hi, this is Brad Shuster on for Samuel and thanks for taking our question. We were wondering if you could provide more details on the transition of the sales forces of resources for Translarna with the removal of the EU market. And if there be any effect on the SG&A outlook, spring 2024 Okay.
Matthew Klein
Thank you very much booked out for the question. As we talked about previously, the obviously we still are marketing Translarna in the first quarter in Europe until the ratification and with CHMP opinion occurs, and then it will be a very rapid transition of that infrastructure to get ready for that.
The city town launch, as we've discussed, we'll be submitting in a PCP, Tarragona, Spain, the first quarter and that infrastructure that we've built will be well positioned for a successful what we plan to be a successful launch of CP. tariff in Europe. So the the OpEx guidance that we've given for the year incorporates what we plan to have today and also already account for what we're going to need tomorrow for the CPU TAM launch and any other product launches that we have.
Thank you.
Operator
Kristen Kluska, Cantor Fitzgerald.
Rick Miller
Hi, this is Rick Miller on for Christine. Thanks for taking our questions. Maybe on FA. for vatiquinone, can you speak to anything on kind of the ongoing regulatory strategy in the US versus Europe with two guided regulatory interactions. Do you plan on making similar arguments around the data and move FA. to the different regulatory bodies? Or could there be sort of different strategies when it comes to the FDA and EMA based on what they're looking for? Any color here could be helpful. Thank you.
Eric Pauwels
Sure, Rick.
As we shared on the call, we were very pleased to announce that we had a very productive discussion with the FDA regarding the Friedreich ataxia program earlier in within the first quarter. Based on those discussions, we now have a path to NDA submission. We believe in a year it was a sensitive discussion regarding the clear evidence of benefit in the move FA placebo-controlled study, particularly an upright stability scale, which is now clearly recognized as the most applicable part of the entire end far score for assessing ambulatory pediatric adolescent and young adult patients that made up the majority of the population of the MOVE EPIC study. So after that discussion, it was agreed that we have the ability to potentially submit an NDA based on move FA along with confirmatory evidence from the long term open label extension portion of move assay, comparing those data to natural history data, very much like periodic, it's just by clarifying the idea that we're combining solid, reliable, strong evidence of clinical benefit, and we'll get a study along with confirmatory evidence from the open label portion of that study. So we're very excited about product.
Rick Miller
Okay. Thank you.
Operator
Kelly Shi, Jefferies.
Sami Corwin
Please proceed.
Kylie O'Keefe
Hi, this is for Kelly. Thanks very much for taking the question. A reception on Emflaza. Have you seen any patient switching from Emflaza to generic? And I know that you cannot speak for patient. But if a patient were to speak sorry, were to switch or were not to switch. Do you know what could be the reason driving patient decision, please?
And I have a follow-up question, please.
Matthew Klein
Thank you very much for the call are Harry, you want to comment on what leads a plaza, our revenue projections and potential impact of generics?
Yes, absolutely. So thank you very much for the question. As we've said in the past, we've obviously had the fact that loss of exclusivity has been on the horizon, and we've been preparing for this. The team is has a number of strategies in place to do everything they can to protect the business. And obviously Eric outlined a number of days in the prepared remarks. So I think from that perspective, we've talked about contracting with specialty pharmacies. We've talked about contracting with payers, number of initiatives, highlighting clinical differentiation to prednisone, ensuring brand loyalty through outpatient PTCCA. team. And so a number of these programs are in place to ensure that we can protect the business upon the loss of exclusivity from that perspective, I think it's too early to say flipping switches. There's nothing that we've seen so far. And I think what we have seen and understand through speaking to both physicians and patients in the community is that there is a strong brand loyalty to Emflaza. There's a number of programs in place to ensure that brand loyalty. And so from our perspective, we've done everything we can to maintain that business and our revenue guidance is projecting that as well.
Kelly Shi
Okay, great. And then on the Huntington's disease program, has the FDA give you giving you specific guidance in terms of firm criteria and time line to lift the clinical hold, please.
Matthew Klein
Thank you very much.
Yes, as we previously shared, we had a very productive discussion with the agency in the fall of last year where they shared that this data we've collected so far in the pivotal Phase three study in 12 weeks should be sufficient to allow conducted that study for 12 weeks duration. And if we wanted to be able to give a full protocol at 12 months that they would like to see six months worth of safety data. So that's obviously very encouraging because as we've shared last June, there's very strong evidence of safety and tolerability thus far with no evidence of it spikes seen and also by no treatment-related serious adverse events. The profile continues to be safe as we continue to collect more data. So we look forward to being able to share it with the FDA six month data they'd like to see to lift the partial clinical hold, which we expect to do is basically take those data.
Thank you.
Operator
Eric Joseph, JP Morgan.
Eric Joseph
Thank you.
Just wanted to touch on, particularly on MSA like to see that opportunity back on the table. Can you just talk a bit more about sort of what has got us a little more constructive on where they are?
Was any new data from the open-label extension discussed? Or is it more about just sort of getting them on board with upright stability or the key functional endpoint?
And just to it, so just kind of looking back on your commentary where the previously seem to want a confirmatory study.
If you proceed with an NDA submission here, that would be for full approval or accelerated approval next year.
Matthew Klein
Thanks.
For the question, Eric. So the discussion with the agency really focused on the upright stability scale. I think as we've talked about when we started the move at a study and what wasn't quite appreciated was that for the population you were looking at ambulatory patients, the only sensitive portion of that scale or them in the upright stability scale over the past couple of years, there's been several publications and there's also been an FTA funded study looking at pediatric Friedreich ataxia patients. All of these studies have shown clearly that if you want to assess the treatment effect in a young adolescent ambulant patient population that the upright stability is the only way to do it faster to even look at the placebo data in our trial, you see that the placebo group barely changed on any of the other parts of the Empire. It was really only on upfront stability that you see disease progression in that population over 72 weeks. And so when we are able to show those data and talk about those data and provide evidence to the agency, including evidence from the study they funded. It becomes very clear that while the primary endpoint itself, it imparts didn't hit, we demonstrated significant benefit on the only thing you possibly could show significant benefit on disease progression, and that's the upright stability and scale. So I think those data and that understanding, along with the supportive evidence on the Fitigues scale, which has also statistical significance, is well recognized as the most burdensome system for application, some correlation with a walk test. All of that together, I think was very helpful in having a constructive discussion with the agency and being able to talk about a path forward to NDA based on the data. We have not done the analysis yet of the open label data and those weren't share will obviously prepare an analysis plan. And for those for those data to share with the agency head of doing those analyses in terms of it being accelerated or full approval, we're still having those discussions at this point. But what we're most excited about obviously, is being able to have the potential to submit an NDA based on the move that a study and still what is still a significant unmet need for pediatric and adolescent Friedreich ataxia patients and also to be able to have a therapy that would provide benefit to you ambulatory patients who are who are young adults are at an adult one.
Eric Joseph
Okay.
I appreciate the commentary there. Maybe just on the sequencing of a shift in the open-label extension analysis and sharing those data with FDA, I guess, will we be updating the Street with those data ahead of further interactions with the agency?
Eric Pauwels
Yes, we expect those open label data to be collected over the next several months and would expect spending to complete the analyses once they collect. All the data will also be doing a, say analysis of the original study. As you know, we've previously shown that in the long-term follow-up from the initial, particularly on study, we had a highly significant benefit when looking at when comparing those patients treated for 24 months, versus a stage in natural history match. We'll be updating that analysis as well, including that as a source of confirmatory evidence as to the exact sequencing of having the data shared with the FDA and updating the Street, we'll certainly keep you posted as we move towards towards the NDA, including at the end of February, proficient taking the question.
Operator
Jeff Hung, Morgan Stanley.
Jeff Hung
Thanks for taking my questions. On for Translarna. Are you aware of any communication between the EMA and the Brazilian health regulatory agency after the recent EMA decision, given their data sharing agreement, roughly how much you got from Brazil? And then I have a follow-up.
Matthew Klein
Yes, Jeff, we're not aware of any correspondence, I think in Brazil has traditionally been quite independent, and we expect that to continue to be the case. So indications we have is that they will continue to act independently and making their assessment therapy have the benefit of translation.
Jeff Hung
Okay, thanks. And then for the SOP, after an NDA submission and what other data might be need beyond the tox data, could the FDA look for clinical data versus Ku-band and classical PKU patients? Or for have they ever asked you a sense about running a head-to-head study against Kuvan?
Pierre Gravier
Yes.
So as we've previously talked about, the only outstanding or the only gating item for the NDA submission was the completion of the mouse study. We started that as expected in December. And now that we have visibility to those time lines, we look forward to discussing being able to possibly submit the NDA news sooner than the third quarter and soon, obviously, look forward to those discussions in terms of comparison to two, then I think that's something we've never been asked for. In fact, what we've been able to show FDA and other regulatory authorities as well that we had to do Phase two study, which was a head-to-head comparison of Kuvan, and it showed statistically significant benefit out of CT's Hanover Ku-band and then, of course, the AFFINITY study where we had that number of patients, 27 patients who came in the study on Ku-band, we had washed out a bit negative at 50, a 50%, roughly 50% greater lowering effect, allowing alanine those patients, which should obviously be apparent again, clearly demonstrating that we're able to provide significant greater benefit to these patients. And then, of course, the evidence in the classical PKU patients. And then within the AFFINITY study with a mean reduction of 69% of the placebo-controlled portion, I think is, again, very supportive of the better the potential for CP Tarrant and provide benefits to the full spectrum of PKU patients of that being of all ages and all degrees of severity and also reinforcing that patients have demonstrated responsiveness to BH4 in the past, and we can certainly expect that much greater response once this put on super care.
Jeff Hung
Great. Thanks. So much.
Operator
Brian Adam Abrahams, RBC Capital Markets.
Brian Abrahams
Hey, good afternoon. Thank you for taking my questions on this five one eight Huntington's program. I guess two questions. First, I'm curious how your views have evolved on whether this could be a potential path for accelerated approval for that drug based on NFL. and or brain volume? And then secondly, and I know there's an additional cohort of patients that you guys were enrolling, the ones that weren't presented last year and included early stage three patients. Just wondering where you're at with that cohort. If we might see interim results from a from less than 12 months timeframe, in the second quarter as well and your latest thoughts on moving to a 20 milligram dose?
Matthew Klein
Well, thank you very much, Brian, for the questions. So on your first question, okay, okay. It's very clear that FDA and as a whole in the neurology division in particular, has been looking at the accelerated approval path as one that is rational for neurodegenerative diseases. Where it's typically many years of very, very large study needed to register clinically meaningful effect. So to be able to have a biomarker that is likely to predict clinical effect that makes perfect sense that you can have an accelerated approval in patients with either drug access to therapy. One Calypte, that longer-term data, obviously, if it makes sense for neurodegenerative disease in general certainly makes sense for a disease like Huntington's disease, which, of course is an indolent disease. The efficacy study will necessarily need to be large and long in terms of potential biomarkers for HD. We think there's several, as we mentioned, both NFL and brain volume, certainly in a disease of inflammation, oxidative stress to be able to show a benefit on a marker of inflammation. Oxidative stress like NFL certainly should be likely to predict clinical benefit. And similarly for something like brain volume, whether the pathogenesis of disease is selling to restart that loss of brain volume and then symptoms that present itself and ultimate clinical or degeneration. And you could sell that process brain atrophy, that certainly suggests you should be able to influence the progression of disease. So we see those both times as potential biomarkers. Of course, it's going to be a matter of having the data having the discussions with the agency because maybe it will be the first ones through that portal. But I definitely think that that the agency has shown an openness to leveraging the accelerated approval pathway in the case of diseases like HD., and we certainly would look to avail ourselves of that opportunity.
In terms of your second question, that the Phase three enrollment has gone quite well in fact of overall enrollment, it really ticked up after we shared the June data and were able to reassure both the patient community and physician community that you can develop a drug for Huntington lowering that is safe and well tolerated and have the necessary bio distribution and pharmacodynamic effect necessary for therapeutic benefit. So we've seen excellent enrollment and we will be sharing in addition to the 12 month data in the second quarter, interim data from 12 weeks on the other stage two patients as well as some of the stage two patients. So we look forward to sharing all of those data wish you all in the second quarter.
Your third question regarding the 20 milligram dose, that's our view remains as it was when we talked about in June. I think what we're seeing with the 10 milligram dose and the time preferential distribution to the CNS with a 1 to 1.5 ratio of plasma CSF exposure that we very much believe that 10 milligrams is probably a dose that we need. So right now, we're committed to moving forward with five milligrams and 10 milligrams and learning more about it. Of course, we do have that opportunity to titrate up to 20 milligrams if need be. But right now, we believe that we may very well be sitting at dose levels that are the right ones to achieve to safely achieve the desired volumes of Huntington protein that can provide clinical benefit to patients.
Brian Abrahams
Thanks so much, Matt.
Operator
Peyton Bohnsack, TD Cowen.
Peyton Bohnsack
Hi, guys. On I guess for us, could you possibly elaborate on the reauthorization process for Translarna in Brazil and Russia and maybe the process for UM National Assessment in the United Kingdom? It looks like in Brazil specifically the renewal is up in April. Is that the case? And do you expect I know you mentioned earlier that there was a crossover between the two agencies, but do you expect the recent EU decision would have an implication here.
Matthew Klein
Thanks.
Yes, thank you. Thank you for the questions.
So as you mentioned, we were up for reauthorization of Brazil. That process is ongoing. Every indication we have is that this will continue to be an independent assessment and remain very interested in following their own assessment. The owns the view of KOLs and others in Brazil and are not influenced by the CHMP's decision. I would say that we are seeing similar things in the UK where they also have said that they want to do their own independent national review and a national authorization. So that signals that we're getting very clearly that there's a strong desire countries to do their own assessment and not follow the lead of the CHMP.
Great.
Peyton Bohnsack
Thank you. And then I guess maybe just a quick follow-up question on when you're looking at the open label data, have you guys reached alignment with exactly what the national history like external cohort group will look like with the FDA? Or is that still ongoing or something?
Matthew Klein
I think you're talking about for Friedreich ataxia?
Peyton Bohnsack
Yes, sorry, for PetroChina?
Matthew Klein
Yes.
Yes, I think where it becomes really luxury. The freezer capacity of community has really been a model community and doing the necessary hard work of creating a robust patient registry, the FACOMSFAC. homes natural history registry has a robust repository of patient data that has several years' worth of data on things like the NPRs, including the upright stability scale. And this is something that every auto was able to leverage as part of their NDA. And we would look forward to doing the same. I think the FDA acknowledged that I think the FDA publicly acknowledge the great work that the future for taxi community has done in building this registry. And honestly, that's something that's incredibly useful to develop drug developers like us like Reata and others who can now leverage that natural history database to contextualize the long-term beneficial effects of therapies. So I think there's no question that this is the registry we will has needed, develop a statistical analysis plan precisely details. I will do what will be a propensity score matched with to ensure that we have an apples to apples comparison between the patients and move FA and particularly in the natural history, patients home. And that should provide us the necessary natural history data needed for the long-term treatment data needed to provide that confirmatory evidence of FDA.
Peyton Bohnsack
Great. Thank you so much for taking our questions, and thank you.
Operator
David Lebowitz, Citi.
David Lebowitz
Thank you very much for taking my questions. But could you compare the regulatory process for five oh five and two and five or five being one. And talk about how the data at this point. First, if you turn fits into the submission and file and what additional components or different ways of looking at the data might be required?
Are the FDA?
Matthew Klein
Yes, I think, David, I think just for context, as we've talked about the initial sea deterrent development path was 5.5 b. two, which was a decision made by Censa when they were developing the compound. I think it was likely thought to be a path that would be maybe faster, less resource-intensive. But when that when we license the therapy and it's very clear, it is not the appropriate path. It's more of a feeling for a molecule like CVK Yucatan has novel composition, novel mechanism of action, novel biodistribution, novel pharmacology and clearly differentiated therapeutic benefit. So it doesn't fit into the sort of need to file by the two paradigm it's a novel therapy that is and should be part of the 5.5 b. one development pathway. As such, it's necessary then to provide a full slate of nonclinical studies including things like, right pharmacology studies, toxicology studies, maternal fetal study, all those types of juvenile toxicity. All of those studies then become necessary to be part of our program, all of which will have and in terms of being ready to submit the NDA.
And if I look at the one, as we said, the only outstanding item is the US study, which I mentioned earlier in the call. So it's really a matter. I think it was probably not appropriately started in five of the big five or five b. two pathway. It was really about putting it where it belongs for novel differentiated therapy like super Terrence, five of RBC. Does the FDA require any type of head-to-head comparisons in this particular process?
Not at all, I think. But the one thing to say is, yes, I think we're in a we're in a situation that is precedented. There have been approved therapies for PKU. There's a well established. Of course, it's clinical trial design endpoints and what the FDA likes to see. And that's exactly what we saw happening, including the sea deterrent for registration program, looked a lot like the Kuvan program in terms of having a responder analysis to identify those and funded and then having a placebo-controlled study and then having the necessary data to demonstrate durability and long-term safety, all of which we have. I think the only difference in our program is significantly greater responder rate that's significantly greater magnitude of treatment benefit. So those are the components of the data needed to support the NDA submissions as well as the efficacy. It's the evidence of effectiveness that are needed as the evidence of effectiveness that we have and we look forward to being able to submit that NDA since.
David Lebowitz
Got it. And just jumping over to FA., have you received the minutes from the meeting yet? And what are the next steps?
Matthew Klein
Yes. Yes.
So I think at this point where we are is we're still, as I mentioned, having some back-and-forth with FDA regarding whether this could be a accelerated approval or full approval. That's something that we look forward to getting written correspondence on for the near future. And I think for us right now is also moving forward in collecting all the open label data and getting together statistical analysis plans that can support the confirmatory evidence. And so that's what our team is focused on.
David Lebowitz
Got it. Thank you for taking my question.
Operator
Gena Wang, Barclays.
Gena Wang
Thank you.
And we just ask one more question regarding fintech renewing SA. So did the FDA suggest any specific statistical methodology to analyzing data from 16 or this will be comparing to the natural history data as well as the open-label extension study?
Matthew Klein
Yes, thanks, Gena. But they were not prescriptive. I think we've gone to them. And this was that we would look to do a propensity analysis approach and again, we're in a round here of precedent and they recently approved an NDA for Scott Claros based on a study in particular, which all study along with open label data compare to the FACOMS. natural history, data of in-season propensity score matching. So we have a lot we can follow here and but to be sure we'll submit a statistical analysis plan analysis plan that we're fully detail our approach not only in the propensity model, but also into look likely to be a mixed effects modeling to provide the appropriate longitudinal estimate of treatment benefit relative to natural history.
Okay.
Gena Wang
And very quickly, you noted FD. give guidance what type of data you need to hit in order to in a could be approvable from the open-label registry for FAU. for the open label portion?
Matthew Klein
Yes, no, there was no specific phone knows. There was nothing restricted. I think this is viewed as the regulatory framework we have persuasive evidence of effectiveness from you would be putting together an NDA based on our ability to demonstrate persuasive evidence of effectiveness in the placebo-controlled portion of the move that they study along with confirmatory evidence that we said will consist of the compare and the open label data to natural history showing that there's a benefit over a longer period of time from both who, let's say as well as I mentioned earlier in that to Eric's question also, yes, with data open label data and natural history comparison from the first efficacy study that was in a slightly different population that consisted mostly of adults, both ambulatory and nonambulatory, where we've previously done these types of analyses to show significant long-term benefit relative to the natural history matched.
Gena Wang
Okay. Thank you.
Operator
Paul Choi, Goldman Sachs.
Paul Choi
Hi, good afternoon and thanks for taking our questions. I want to change gears for a moment and maybe ask about maybe trying to look at that. And I laughed. And I was wondering if you could maybe ahead of the CARDINAL study readout later this year, further frame your thoughts on potential plays a treatment effect and or areas of differentiation versus three approved therapies relative revenue from Amlin?
And my second question is on under a scenario where Amlin has a positive on Phoenix comps confirmatory study for Rogerio. Can you maybe just comment on what your regulatory strategy might be? Should they get garner for approval there off of their part of the confirmatory study?
Thanks for taking our questions.
Matthew Klein
Yes, thanks, very much, Paul, and thanks for the question on the initial asset ALS. program, and this is a program we're very excited about given what's become very clear now is that link between therapy, ptosis and ALS. I think that that dermatoses pathways and our team is really an important pathway in disease progression. And of course, two lots of side was developed to specifically target that pathway. We did a lot of the preclinical development work with huge losses that benchmarking to a year ago, which is also another approved therapy for ALS it has a much more sort of generic nonspecific effect on elements of oxidative stress and characterize this pathway. And as we've talked about, we've been able to show 25 to 30 times the potency and the spinal ash ash site model, how we've also been able to show important protective effects when benchmarked against their bone and number of other disease-relevant harm preclinical test models.
In terms of the study design, I think again, we're in an element, as I mentioned with David's question and PKU, where there's clearly precedents for the design of an ALS study and have had discussions with the FDA were very constructive and ensure that this is a protocol that could support registration. If positive, we designed was setting with a two-to-one randomization with a treatment effect. So roughly a 2.5 treatment difference between the treatment groups and placebo groups, which gives us roughly 85% power to detect that difference. And I think that positions us very well to capture significant treatment benefit. I think the regulatory pathway doesn't change at all based on what happens with Amil active compound and obviously, the commercial opportunity and the differentiation will be based on the data, what we see in ALS FRS. form of potentially we could see in terms of pulmonary function and also what we might see in terms of mortality. And you'll recall that the FDA has always been very key in understanding both changes in ALS, FRS. and mortality I think it's also become very well accepted in the ALS community, given the aggressiveness and the complexity of ALS that this is probably not going to be single therapy disease. I think it's probably going to require more than one. But again, I think the specifics are returning in terms of head to head comparison with analogues compounds really going to be data-driven and we look forward to seeing the results from from the CARDINAL study.
Paul Choi
Great. Thanks for that and taking our questions.
Operator
Danielle Brill, Raymond James.
Alex Brown
Hey, guys. This is Alex on for Danielle. I'm just looking to Huntington's. Just kind of curious about what assay you're using for CSF mutant Huntington detection. Wondering if you'd have expect to have similar issues that a recent competitor had and how reliable the results are in an early age of the population?
Matthew Klein
Yes, outside questions, I think there's two separate issues. There's assay reliability and then assay sensitivity based on the population. And let me take them each in turn. We've worked very hard, ensuring that we have robust assays that are accurate and precise. And I think one of the things we know very well about assays and clinical studies is it's not just the assay itself is making sure that you have care with sample acquisition, sample processing samples, stored samples, transport and then ultimately sample analysis. And those are things that we pay very close attention, obviously able to minimize any confounding elements that could influence the assay results. We know the other part that's important as well as incentives work much better when you have a larger number of samples. So something that we've been very thoughtful about is ensuring that we have batch Campbell. So each time we run these analyses, we do and how many samples has to make sense at that time. So again, all things that we can do to reduce the variability and increase the fidelity of those assay results.
You bring up another point. That's very, very important, which is assay sensitivity based on disease stage, how it's well known that at very early stage or presymptomatic at higher age, some patients, mutant huntingtin protein not detectable in CSF because it's incredibly of the competition is incredibly low picomolar concentrations and maybe even lower as we move into the Phase two patients we have in the Huntington trial. Of course, these are patients. We believe there is detectable huntingtin protein in the CSF, and we've seen that so far. But of course, obviously something we'll watch very carefully in those patients do, where are we on that on terms of the limit of detection for the asset. But that's something we're very thoughtful that, of course, we've done up to now have a Stage three patients. And those are patients that, of course, they're going to be a bit further in their progression and we will likely have much higher baseline huntingtin protein levels that will make that sensitivity issue really not an issue.
Alex Brown
Thanks so much and thank you.
Operator
Joseph Schwartz, Leerink Partners.
Joseph Schwartz
Thanks so much for fitting me in. So I wanted to ask since it's been a while since Kuvan and pegvaliase were approved.
I was wondering whether there's for app, we've been able to establish with the FDA that data focused on Phe lowering will be sufficient and that clinical outcomes assessments that will be required for approval in PKU. And then I have a follow-up.
And Joe, obviously, one of the most important things we did prior to commencing the Phase two study is to make sure we have full alignment on the study design, including the primary endpoint of Phe reduction. I think traditionally if you look at the FDA when they have made a decision on an approval based on something that doesn't change with time.
Matthew Klein
It actually gives them confidence that they can understand that they can interpret your study results in a meaningful way. So we, of course, make sure that there was alignment on fee as the endpoint fee was the endpoints. And of course, we're very happy to have seen not only that we had a significant effect, but as I talked about earlier on the call, the results are highly statistically significant and much greater magnitude than we've seen with previous all therapies. So I think that it becomes very easy for them to see the not only submit statistically significant and highly clinically meaningful benefit that we've been able to demonstrate in the AFFINITY trial. And of course, one of the elements of the pre-NDA meeting was ensuring that we had the safety and efficacy data that's necessary to support that NDA submission.
And the answer was yes, yes, we do. And then since strong patient advocacy seem to be a key for speculators to get traction with the FDA was on board with Reata being able to file a first.
Joseph Schwartz
I was wondering if you could give us any insight into how much the FA patient or physician community has been lending support behind your effort to pursue a filing for Verticalnet?
Matthew Klein
As I mentioned earlier, John, I think the Friedreich ataxia community led by the future strategic Ataxia Research Alliance is really a model disease community in terms of aggregating the patients, the physicians as well as industry and being able to really lead the charge is shown as therapies developed and develop successfully for the treatment of Friedreich's ataxia patients. I'm proud to say that we have partnered with Santarus since the beginning of the clinical development of particular ongoing many years back. And we've been incredibly grateful for their partnership, not only in helping us understand how to best design chart trials, their work in establishing a patient registry that are obviously very, very important in us putting together a data package for NDA. And quite frankly, the work that they've helped lead with the physician community and research community on demonstrating the importance of upright stability for pediatric and adolescent ambulatory patients. So I can proudly say that they've been a partner of ours. And we think that's an incredibly important part of that particular journey. And we think it will continue to be in and that partnership will continue to be an important part as we move forward.
Just a minute, Andy.
Joseph Schwartz
Great.
Operator
Thank you, and thank you. I would like to conclude the Q&A session now, and I thank you all who participated and turn it back to the CEO, Dr. Matthew clients, for additional comments.
Matthew Klein
I just want to thank everyone again for joining the call today. As we discuss, we look forward to an exciting 2024 with a number of important and valuable potential milestones ahead and look forward to sharing the journey with you all as we move forward.
Operator
So thank you, and thank you all for participating, and you may now disconnect.
