Thank you for standing by and welcome to the PTC Therapeutics Third Quarter 2023 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. [Operator Instructions] Please be advised that today’s call is being recorded. I would now turn the conference call over to your host, Jane Hanlon, Associate Director of Investor Relations. Please go ahead.

Good afternoon, and thank you for joining us today to discuss PTC Therapeutics' third quarter 2023 corporate update and financial results. I'm joined today by our Chief Executive Officer, Dr. Matthew Klein; our Chief Business Officer, Eric Pauwels; 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 slide 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 quarterly report on 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 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?

Thank you, Jane. Good afternoon and thank you for joining the call. I'm pleased to share our third quarter results and outlook for the remainder of the year, including an update on our development programs. I will begin with the recent announcement of our agreement with Royalty Pharma to monetize up to $1.5 billion of the Evrysdi royalty stream. This non-dilutive financing provides PTC to capital to support planned operations and allowed us to retire the Blackstone debt obligation. In addition, the deal structure includes flexibility for accessing additional capital over the next two years. Notably, PTC maintains its right to the remaining $250 million of milestones related to Evrysdi global net sales. The royalty financing deal, along with the operating expense reductions announced in September, put PTC on very strong financial footing as we continue to focus our resources on our differentiated, high potential R&D program and robust global commercial infrastructure. Now, I'll turn to our third quarter results. We had another solid quarter with total revenue of $197 million, which keeps us on target for meeting our 2023 total revenue guidance of $940 million to $1 billion. Our DMD franchise revenue in the quarter totaled $136 million. This strong performance allows us to update our 2023 DMD revenue guidance to between $565 million and $595 million from between $545 million and $575 million. Eric and Kylie will provide additional details on our commercial performance shortly. I'd like to now provide an update on recent regulatory activities for several of our programs. Let me begin with an update on Translarna. Following the negative opinion from the CHMP on the conversion of the conditional marketing authorization to full marketing authorization and on the renewal of the conditional authorization, CHMP gave us the option to request reexamination of both opinions or…

Thanks Matt. We are proud of the accomplishments of our global customer-facing team, which continues to deliver revenue growth and build on our success as we focus on a strong close to the year for our commercial portfolio of products. Once again, our global DMD franchise delivered a strong quarter with continued growth from new patient starts, high compliance, low discontinuation, dose adjustments and geographic expansion. Let me focus on our two key products in the DMD franchise. Translarna and Emflaza continues to be important growth drivers, delivering $136 million in net revenue for the third quarter, which is 4% compared -- growth compared to the third quarter of 2022. With strong year-to-date performance, we are raising our DMD revenue guidance from $545 million to $575 million to $565 million to $595 million. For Translarna, we achieved $69 million in quarterly revenue. Year-to-date sales were $281 million. The team has worked tirelessly to continue to bring this important treatment to existing as well as new patients in our markets around the world. The recently concluded World Muscle Society meeting was an opportunity to present and discuss with healthcare providers the totality of data and real-world evidence supporting the efficacy of Translarna and reemphasizing the significant life-changing impact this treatment had on young boys suffering from this devastating disease for whom Translarna is their only therapy that specifically targets nonsense mutation DMD. Our customer-facing teams have increased communications with healthcare providers in Europe, providing medical information on Translarna and its continued availability for all new and existing patients. Now turning to Emflaza. The Emflaza business continues to be solid. Quarterly net revenues was $67 million, which is 23% growth over the prior year quarter. We have had $188 million in year-to-date sales. We continue to see strong trends in the new patient start forms and high compliance. The continued Emflaza growth is impressive and highlights the brand loyalty in the DMD community in the United States as our team is actively implementing plans to defend and protect the Emflaza brand ahead of loss of exclusivity next year. Now, I will ask Kylie to update the progress of our current and future new product launches. Kylie?

Thanks Eric. Let me begin with Upstaza, the first and only approved gene therapy infused directly into the brand. We continue to see transformative results for the patients we have treated thus far. Our rollout across Europe is progressing well with our first patient treated in the U.K. this quarter following the positive NICE recommendation earlier in the year. Patient identification, treatment and readiness and access and reimbursement discussions continue to advance. We also continue to leverage early access programs and cross-border treatment opportunities with the patient from the Middle East also receiving treatment in France this quarter. Moving to Tegsedi and Waylivra in Latin America. We continue to grow our franchise in the region with recent MAA approvals for Tegsedi in Argentina and Waylivra in Mexico. Patient identification is robust and patient on treatment continue to grow across the region. In Brazil, we anticipate receiving new group purchase orders for both Tegsedi and Waylivra before the end of this year, which is in recognition of the increased number of patients who rely on these life-changing treatments. Lastly, as Matt mentioned, we are extremely excited about the sepiapterin opportunity. The APHENITY Phase 3 data and the long-term extension study preliminary data were presented at the recent SSIEM Congress and were very well received by physicians and the PKU community. They are excited about the opportunity to bring a differentiated therapy to PKU patients in need. With strong differentiation from the mechanism of action and the APHENITY results, coupled with our global commercial infrastructure and proven track record in commercializing rare diseases, the team is actively working on launch activities to ensure a fast uptake upon approval. The potential market opportunity for sepiapterin is composed of a number of key PKU patient segments, all of which our APHENITY data suggest we…

Thank you, Kylie. I would like to begin by discussing the financing with Royalty Pharma that we announced last week. That deal, together with the pipeline reprioritizations and OpEx reductions that we announced in May and September puts PTC in a very strong financial position. We are pleased to work again with Royalty Pharma on this win-win transaction. The non-dilutive financing provides PTC with the capital to support operations and allow for increased operational and financial flexibility by removing the Blackstone debt obligation from our balance sheet. In addition, the deal structure provides the potential for additional non-diluted capital over the next two years. To recap the details of the deal, PTC monetize up to $1.5 billion of the Evrysdi royalty stream. Royalty Pharma acquired additional works on equity for $1 billion upfront. The agreement included options for PTC to sell up to an additional $500 million or for Royalty Pharma to acquire half of such retained royalties for up to $250 million at a later date, less royalties received by PTC. PTC maintains all economics associated with up to $250 million in the remaining commercial sales milestone associated with every global net sales. The agreement builds on the previous strategic partnership establishes Royalty Pharma in 2020. The initial agreement was for the monetization of approximately 43% of the Evrysdi royalty stream. As a result of the current agreement, PTC will maintain ownership of approximately 19% of the total Evrysdi royalty stream, pending any exercise of future options by PTC or Royalty Pharma or the achievements of the cap from the 2020 royalty agreement. I'll now share the financial highlights of our third quarter 2023. Please refer to the third quarter earnings press release issued this afternoon for additional details. Beginning with top line results. Total revenue for third quarter…

Thank you. [Operator Instructions] Our first question comes from the line of Eric Joseph of J.P. Morgan. Your line is open.

Hi. Good afternoon. Thanks for taking the question. Just a couple on PKU from us. Really, just around this regulatory path here. I guess, can you just clarify when the decision was made to pursue a 505(b)(1) path for sepiapterin over a 505(b)(2) and maybe what cross that decision? And then I guess, electing to go with the 505(b)(1), was it not clear that carcinogenicity study would be needed, would likely be a requirement? And really, ultimately, I guess, just looking forward, what should give investors confidence that assuming that the carcinogenicity study turns up nothing that the NDA submission and review cycle should otherwise be straightforward. Thank you.

Thanks for the questions, Eric. So let me just first start with a little bit about 505(b)(1) versus 505(b)(2). The 505(b)(2) pathway is typically used for Me2 compounds where there's already been -- and then there's an existing approval for the active ingredient in the compound for which one seeks approval. Alternately, the 505(b)(1) pathway is for innovative therapies, which is much more appropriate for something on sepiapterin, which while its active ingredient is BH4, which is basically the active component of Kuvan, it has many factors that make it differentiated, which underlies the superior efficacy we've observed to date and why this is such a promising therapy. Since initially was in thinking about the 505(b)(2) pathway, that's where things were lined up, but we acquired it and after we did our own analysis and understanding of the relative benefits of each pathway, it became clear that the 505(b)(1) was much more appropriate. Now with the 505(b)(2) pathway since here, it is an active ingredient already approved, you can utilize the study not safety and efficacy studies, but other supportive studies like nonclinical studies that were used to support that approval. With the 505(b)(1) pathway, you don't have the ability to rely on those existing studies. Now the decision to switch is based on a couple of things. One, Stepan is quite differentiated in terms of its efficacy profile from Kuvan. Second, if you go 505(b)(2) pathway, the companies product, the company whose products you refer to, to utilize their studies can actually block you from launching the therapy for up to 30 months if they still have an orange for listed at. So obviously, we did not want to be in a situation where we would risk the launch of the compound. And then again, this really is a…

Our next question comes from the line of Kristen Kluska of Cantor Fitzgerald. Kristen Kluska, your line is open.

Hi, everyone. First, just wanted to congratulate you on the Royalty Pharma deal. And I had a question about Translarna. Can you talk about why you're only pursuing reexamination of the conditional authorization? I guess, what advantages do you see going this way versus both? And assuming that you do get the green light, how are things going to be moving forward? Will it be kind of similar, like what we've seen over the last eight years when they've given you the green light, or will you be required to conduct any type of work in the background? Thank you.

Kristen, thank you very much for the question. So as I mentioned in our prepared comments, in the previous procedure, there were two opinions. There's actually two procedures in one. One was the conversion of the conditional marketing authorization to full marketing authorization. And the other was continuation of the conditional authorization. Through nuances of the procedural elements in Europe, they had brought that together and said, we're going to issue two opinions that really get together. So, when they went negative on the conversion to full authorization, they elected to go negative as well for the renewal of the condition. Then they gave us the option to say, do you want to pursue one or both? Look, our priority here is to make sure this drug stays on the market, stays available for the boys in Europe, when there's no other targeted therapy for nonsense mutation available. And we believe that best chance of doing that is to focus solely on maintenance of the conditional authorization for now. We also believe in a way that by not asking for a conversion to a full approval, that the issues -- some of the issues with having a negative primary analysis population analysis in Study 041 may become less of an issue. Really, you can focus on the other important and strong data in Study 041, including in the ITT population, where we have clear evidence of benefit over a number of different endpoints, as well as obviously the long-term STRIDE data. So we really feel that by focusing this question on just renewal of the conditional authorization, that we can provide the necessary evidence that can get this opinion from negative to positive. Now, as you mentioned, what happens from -- as you asked, what happens from there? Well, if…

And just second part of that, I would imagine since you had the announcement that the community was probably pretty upset, especially the ones that have been on the therapy long-term. So wondering if there's anything you can collect from them, anecdotes, stories, et cetera, and if they can be of any help ahead of this upcoming meeting and decision.

Yeah, Kristen, good question. I think needless to say, the physician and the patient community was surprised, disappointed, and quite honestly scared for the patients. Obviously, this is the only therapy they have that is directed for nonsense mutation patient. Many of them have been on the therapy for years and observed the benefits that we've been reporting. For physicians, they understand the context of the disease. They understand the strength of the data that we produce, and they can't, as many have said, they can't imagine having to take patients off a drug that's safe and effective. The patients on their own have the ability on their own to reach out and let their voice be heard. I'm sure in many parts of Europe that will happen given the fear and concern they have. And I think similarly for the physician community, they'll want to speak on that. Our sense here is that most people, as we were, we never thought this date would come or this would be a reality. So I think this is a little bit for them, a call to speak up and let their voice be heard. And importantly, as you say, share their story, share their experience, particularly the physicians who are experts and can truly articulate the benefits they've observed and the importance of this therapy for patients with nonsense mutation DMD.

Thank you. One moment please. Our next question comes from the line of Sami Corwin of William Blair.

On the topic of Translarna, I guess since the negative opinion, have you seen any change in how physicians are writing scripts or if patients are accumulating medication ahead of the potential that the opinion does not reverse? And then can you speak a little bit as to if you've increased your sales efforts in non-EU areas since the negative opinion as well?

Yeah, Sami, thank you for the question. Again, I think in the physicians we've spoken with, the first response was clarifying and you confirmed that in no way does things change. Patients can stay on the drug, they can write new prescriptions and obviously everyone's going to do everything they can to make sure patients stay on therapies. But let me take it over to Eric and if you want give some more detail on prescriptions.

First of all, we haven't actually seen an impact since CHMP has issued their opinion. In fact, we've seen physicians who have actually been very -- they've been very, very supportive. In fact, our customer-facing team has actually stepped up their interactions with healthcare providers, the advocacy groups and others to emphasize that the drug is actually available. And I think that's one of the most important things. We've made specific calls to every prescribing physician and we've worked with them, because we've had relationships now for many, many years with many of these physicians. They know about the treatment, they've been treating patients for many years and we've been reaffirming that Translarna is not only just available, it's available for existing patients, but it's also, we've seen new prescriptions as well. The fundamentals that we see, Sami, is basically there's been limited to no discontinuations because of the CHMP information. New patients continue to get scripts. Compliances actually remain very high and we've been able to maintain dose adjustments. We've had even patients that have gone from ambulatory to non-ambulatory and been maintained as well. And then to your question about geographic expansion outside, while some of the information has gone out to other countries. We've actually been able to continue to work with healthcare providers in other parts of the world and still continue to generate and see growth from Translarna in the quarter. So the simple answer, of course, is that we have not seen any discontinuations and the fundamentals remain strong. And as I mentioned earlier in my talk, we're not only very confident in what we did this quarter, but we're very confident in how we'll finish 2023. And we've actually raised guidance and our DMD guidance is now $565 million to $595 million, which includes Translarna growth in the fourth quarter. And combined, that would equal about 11% to 17% year-over-year growth for the DMD franchise compared to last year.

Great, thank you.

Thank you. One moment please. Our next question comes from the line of David Lebowitz of Citi.

Thank you for taking my question. When looking at the Translarna European sales, could you please, or overseas sales, can you please give us a breakdown of what those sales are in Europe versus rest of the world? Also, could you give us insight as to what other geographies might have their opinion affected by the EU opinion?

David, thank you for the question. Let me start and start with your second part first. As we've talked about in the past, many of our largest markets outside of Europe have independent regulatory agencies that do their independent assessments and will continue to make their independent regulatory decisions independent of the CHMP and European authorization. In terms of revenue, we have said in the past that while many years ago, Europe would have been the primary source of our Translarna revenue, we've done a lot of work over the past years to diversify our business. I know, Kylie, do you want to go into a bit more detail about the breakdown of revenue?

Yeah. Absolutely. As Matt was just saying, we've spent substantial effort and time over the last couple of years to geographically diversify the business. And this is the intent of evening out and sort of ensuring that we have contribution from a number of regions to total Translarna revenue. So where we stand today, we have a number of growth markets that have continued to grow over the last couple of quarters in last year. And this has allowed us to have a little less than half of EU revenue contribution to total revenue, and then the remainder being ex-US.

Sure, I mean, is there any way you can let us, I guess, zero in on what the particular number might be in the range of, just in case things don't work out in Europe, we're trying to understand what the implications might be going forward with respect to our projections.

Yeah, so David, I think from that perspective, I think it's roughly around 45% to 48%. But the one thing I would say, and what's important to note is those European markets are some of our more mature markets. And so as you look over time, you would expect that the contribution to total revenue for more mature markets doesn't have the growth trajectory as some of our newer and growth markets. And so while it currently sits around the 45% to 48%, currently you wouldn't expect that number to remain flat over the coming years.

Got it. And with respect to expenses going forward, is there any way you can give us, I guess, some level of bandwidth on what to expect for 2024 and beyond when the restructuring is in full place?

Yeah. David, we announced the revised our OpEx guidance previously to $810 million to $860 million. And also, we then announced the subsequent cuts and how that would have an impact of additionally approximately 20% in January 2024. Obviously, we'll give the updated our OpEx guidance at JP Morgan in January.

Thank you for taking my questions.

Thank you. One moment please. Our next question comes from the line of Kelly Shi of Jefferies. Your line is open.

Hi. This is Yun [ph] for Kelly. Thank you very much for taking the question. So the first question on Translarna, assume that you're able to get the negative opinion reversed. Is there a deadline for you to eventually have to convert that conditional approval to full approval? And then on the pre-BLA meeting for AADC deficiency, on the comparability in terms of manufacturing, are there any specific assays that you have to develop before the meeting?

Yeah. Thank you very much for the question. So on your first question regarding the positive opinion, if we're able to convert that to a positive opinion, the continued conditional marketing authorization in Europe. There's typically not a fixed timeline to that. Typically, what goes along with the conditional marketing authorization in Europe is something called a specific obligation. And that specific obligation is typically some requirement to collect additional data to support the benefit and risk profile of the therapy. So there's no timeline per se, but there would be a specific obligation that would require us to collect data. And obviously the shape or form of that and design of that data collection study would have some timeline likely tied to it. Also as part of a conditional marketing authorization, as we've done for years, requires an annual renewal. For the past several years, we've done that. And that's -- a lot of that is relied on the continued evidence of safety you're seeing in STRIDE as well as benefit that you're seeing in STRIDE. There are therapies that have been, have had conditional marketing authorization status for decade, 2 decades. So this would not be the first time that a therapy continued in a conditional frame for a bit more time. On your second question regarding the pre-BLA meeting and the issue of comparability. So comparability analyses are done to show that the material that we use in the clinical studies is as similar as possible to the material that we intend to use commercially. And usually that includes, as you referred to a number of different analytical assays. One of the challenges that we had is that the clinical trial material that we, for which we had to establish comparability with the commercial process is over…

Thank you. One moment please. Our next question comes from the line of Brian Abrahams of RBC Capital Markets. Brian Abrahams, your line is open.

Hey, good afternoon. Thanks for taking my questions. As you prepare for the MAA filing for sepiapterin next year, what are your expectations for what the CARC study requirements will be for Europe approval? And then secondarily, I guess, on Translarna in the US, where do you stand in terms of key discussion items and potential areas of focus that you're expecting for the Type C meeting? And when might we see an update from that? We'll be shortly after the meeting or should we expect a little bit of a time gap to allow for the minutes to be collected? Thanks.

Thanks for the question, Brian. So on the question regarding the MAA in Europe, I think this is another example of how regulatory authorities tend to look at things differently. The feedback we have gotten from Europe regarding carcinogenicity is they understand very well that the active metabolite for sepiapterin is BH4. And they understand that BH4 and sepiapterin are both naturally occurring cofactors. They understand the data we've collected to date in terms of carcinogenicity risk. And they have said, they would like us to not only have our own data, but that we can rely on the data and the experience include Kuvan for many years, there's a knowledge base that exists that there's been no carcinogenicity risk associated with BH4 used clinically for many years. So we don't believe that the issue we have at FDA will be an issue with Europe for that reason. So again, different authorities looking at things differently. And again that's why we're able to move forward with that submission as we said in the first half of 2024. On your question regarding the Type C meeting for Translarna, the purpose of that meeting is really to focus on the evidence that we have, the many sources of evidence we have showing that not only there's clear evidence of benefit in studies such as Study 041, but that could be confirmed in a number of ways, including meta-analysis, the long-term real-world STRIDE registry. And so really working constructively with the division to say, what are the components we need and how do we formulate them in order to support the end of the submission? As we typically do, once we have clarity in the outcome of the meeting, sometimes that can come from the meeting itself, sometimes that requires minutes, sometimes that requires some back and forth afterwards. As soon as we have clarity, we'll certainly share it. Obviously, we know a lot of people are quite interested in the outcome of this meeting, not the least of which are the boys in nonsense mutation DMD in the US who have waited years for therapy. And then also the large number of boys in the US who've been on Translarna for a number of years for their participation in clinical studies and beyond, all of whom are quite interested in ensuring that this drug can be available in the US for them.

That’s really helpful. Thanks for that.

Thank you. One moment please. Our next question comes from the line of Colin Bristow of UBS. Your line is open.

Good afternoon. Thanks for taking the questions. On the sepiapterin NDA filing timeline, I am just curious, what is the latter end of your guidance 3Q 2024? I am curious, can you confirm whether the study has started? And it just seems like a sort of extreme upper bound of this timeline if this study is all that's needed. And then on the AADC, could you just put a little more detail on why FDA thinks the comparability data is still not sufficient? And then what are you sort of hoping or what will be discussed at the pre-BLA meeting in December? Thank you.

Thanks for the questions Colin. So -- the -- if you just -- when you find out you have to do a study, it takes a little bit of time to actually organize the study, get the slide at the CRO, get the animals ordered, get the doses confirmed, get the protocol set, get the protocol agreed upon and start the study. We expect to begin dosing in the study, have all those things ready and dosing that study to start in December. That's a six-month study. So by the clock that all the animals get dosed in December, that's the in-life portion should be done in June. Once the in-life portion is done in June, they have to sacrifice the animals, go through the histological studies, all the histological analysis and write their report. We're obviously going to work as quickly as we can to accelerate those timelines. Obviously, we can't shorten the 26 weeks, but we're doing everything we can to shorten the time for data analysis, as well as getting the audited draft report, which is necessary for submission. So that's where you get the 3Q time back from. It's nearly the reality to do a 26-week study that takes more than 26 weeks. And we wanted to give an accurate depiction of what we think could be the longest possible date or the latest possible time for that submission. Obviously, as we mentioned, the vaccine received, we're able to work out something with the agency where perhaps we could submit those data during the day 120 safety review and late stage review. And that's going to be the basis of our ongoing conversations, because otherwise we believe we have a package that has every other component there. And again, as the agency indicated in our discussions…

Great. Thank you for that.

Thank you. One moment please. Our next question comes from the line of Jeff Hung of Morgan Stanley.

A question, in your discussions with the EMA on vatiquinone, what gives you confidence that it makes that move up day for conditional market authorization? Is there anything that you can update in terms of analysis or presentation that would increase your confidence for a positive outcome on the conditional marketing authorization given the feedback you've received from FDA? Thanks.

Yeah. Thanks Jeff, for the question. So the frameworks in FDA may slightly different, and the discussions we're having with FDA are around the potential for accelerated approval based on upright stability being an intermediate clinical endpoint. Obviously, upright stability, we've talked about is all the four sections of the mFARS, which was the primary endpoint, the one that is shown to be most important in pediatric and in adult patients, particularly ambulatory patients because it's been shown to be able to predict time loss of ambulation. Obviously, with future ataxia for ambulatory patients, the key thing for a therapy to do is to delay that time to loss of ambulation, loss of angulation and so you have an endpoint that can do it, we believe meets that criteria for an intermediate clinical endpoint. We look forward to continuing the discussions with the AGC as is often necessary in real diseases. There's a lot of back and forth to talk about the analysis we have. And as you indicated, could we provide some additional supportive analysis and MOVE-FA in particular the fact that we have a six-month open-label extension study during which all subjects are blinded so that gives us an opportunity to look at changes in trajectory, for example, for the placebo patients once we switched on taken. That's the US. In terms of Europe, the conditional marketing authorization, there's a number of criteria set out for conditional marketing authorization. Do you have initial data that shows that there's a favorable benefit risk of a therapy? Are you meaning an unmet medical need getting -- is getting this therapy to patients sooner potential public health benefit. And I think when you consider vatiquinone and MOVE-FA study and the other data we have, we clearly meet all of those criteria.…

Great. Thank you.

Thank you. One moment please. Our next question comes from the line of Alexander Xenakis of Truist Securities. Your line is open.

Hi. Thanks for taking my questions. Congrats, first of all, on securing the royalty financing deal. That's great. Maybe two for me. One on sepiapterin. When might we see another cut of the Phe tolerance data? And then one on Translarna. And if you are able to overturn the conditional marketing -- these ongoing conditional marketing motorization and have that ongoing study, but you don't have the official sold marketing authorization. Have you done any market research to see how that would affect referencing countries worldwide and if they would be required to whole sales or not? Thanks.

Thanks for the questions, Alex. So first on the Phe tolerance, as we shared, we gave an update on the Phe tolerance data at the sepiapterin IEM meeting in Israel in September. Those were again really great data showing now with over 40 patients enrolled in the Phe tolerance protocol that we're seeing patients move through and get to levels get to levels of Phe tolerance beyond the recommended daily labs. These are incredibly important data. As we said all along, the Phe tolerance component is brilliant for regulatory purposes necessarily, we have the sufficient efficacy data for that and we're able to show in the long-term extension that we're adding important durability of sepiapterin treatment effect as well as long-term safety. This is really quite important one for differentiation is something Kuvan is never able to demonstrate and for physician adoption and for payer discussions, particularly outside of the US. On the Translarna front, the -- look, again, we see the ability to keep the conditional authorization as a big win, not only how is doing for us, but really most importantly for the patients. I turn it over to Kylie, a few comments, Kylie, on the -- what you think the global payer, in fact, could be a conditional authorization.

Yeah. I think from a paper impact, I think it will be quite minimal, Alex. I think one of the things that the team has done an incredible job is with the conditional authorization that we've had over the last nine years is being able to secure a favorable pricing corridor and reimbursement and being able to maintain that over the years. So I think at this stage, where we stand, we don't see any sort of negative impact from the continuing conditional authorization. And of course, we'll continue to focus on it.

Okay. Thanks for taking the questions.

Thank you. One moment please. Our next question comes from the line of Joseph Schwartz of Leerink Partners. Your line is open.

Hey, thanks very much. I was wondering if you could talk about your publication plans for the APHENITY sepiapterin data. Will we see that published in a peer-review journal any time soon? And then I believe you have the option to go up to a 20-milligram dose of PTC518 in PIVOT-HD patients outside the US. So where do you stand on implementing that decision?

Yeah. Absolutely. I'll take the -- I think let me take the second question first, and then I'll let Kylie answer the first question, second. So on 518. So we -- as we talked about we shared the results from the 5 and 10-milligram dose groups, the first cohort of 32 in June. Those data from our standpoint were as good as they can be. We achieved every objective of that 12-week portion study in that first cohort of patients demonstrated a dose-dependent lowering of Huntington protein in the blood, seeing the differential exposure of PTC518 in the CSF relative to the plasma as a 10-milligram dosing seeing that, that ratio is 1.5:1 suggest that we're getting even greater exposure, 518 in the brain and even potentially higher levels or greater lowering of Huntington proteins in the brain all of which is very, very important. And of course, the other key plan is that we are doing all of this safely. The safety profile of the drug was quite strong in those first 12 weeks. We had no terminated serious adverse events. There were no NFL spikes, all very, very important, particularly given concerns that were raised over other HTT lowering therapies that have drawbacks that we've talked a lot about in the past. We said based on those data, we believe we may have the dose levels we need right now to get us where we want to be in terms of the ultimate goal of the program, which is being able to lower brain cell Huntington protein levels 30% to 50%. And so with the decision with those early data, while we had the ability to go up to 20 milligrams, the DSMB has supported us starting 20-milligram cohort. The regulatory authorities and local ethics communities have approved us going into 2020. We're still in a holding pattern. We want to understand a little bit more what the biomarker effects are with the dose levels we have now 5 and 10, but those very well may be sufficient to forget they want to be. So we haven't issued those -- the 20-milligram dosing yet. I'm not sure we're going to need to, and we want to better understand the longer-term bile marker effects of the current levels before revisiting that decision. Why don't I turn it over to Kylie to answer your questions around publication strategy for PKU.

Yeah. Thanks Joe. We are absolutely getting the APHENITY study published in a peer-review journal. The team is working on that as we speak and is looking to target a high impact journal. And so the timeline for getting that published is obviously driven by the journal of choice. So we work -- this is work in progress. The team is moving through this and we expect it to be published during 2024 pending the journal chosen.

Thank you.

Thank you. One moment please. Our next question comes from the line of Gena Wang of Barclays. Your line is open.

Hi. Thank you for taking my questions. So I do have, I think, three quick questions. The first one is regarding the PKU program. Since initially was thinking about 505(b)(2). Is that because of the lack of confidence of their IP position that this drug will be very different from Kuvan? That's the first question. And relatedly, how confident you are on the IP regarding this is a new composition of matter. And then for the PIVOT-HD, I don't know if I missed it. So have you like exactly what kind of data you would need in order to remove FDA clinical hold. So based on -- I think in your prepared remarks, you did mention certain months of the clinical safety data. When I look at the press release, the six months of the clinical safety data demonstrate similar favorable safety profile could support 12-month dosing? And what additional data that will require to dose more than 12 months? And what dose you can dose like beyond 10-milligram. So that's the second question. And a quickly last question regarding the Upstaza in AADC. So if you are using current US data for accelerated approval, what additional study you will need to do in order to get a full approval in the future?

Thank you very much for the questions, Gena. The first question for -- number one regarding PKU sense. Look, I think that was really what more reflection of sensing a very small virtual company and probably looking for what they thought at the time would be the quickest and least expensive development path forward. I think it's not uncommon for a smaller company to think about the development path that way. I think from our standpoint, the -- it's very clear that it's a highly differentiated therapy that is much more suited to the 505(b)(1) pathway. Obviously, we're in a position to have the resources to do the necessary studies and not have to rely on a other NDA and incur that risk of having a state based on the launch of the therapy follow approval. As we talked about, not only we have a great deal of confidence in how differentiated sepiapterin is and its ability to meet the persistent large on that medical need for PKU patients and as we put some positions, including Ania Muntau on a commercial [indiscernible] summer, a desire for physicians to even switch patients who maybe serve to some extent Kuvan to sepiapterin because of what we've been able to show in terms of the large magnitude of clinical benefit. We've also talked about the IP here. We obviously have orphan designation. We also have some potential patent extensions that we believe will extend the orphan exclusivity out several years. Your second question on PIVOT-HD. As we had talked about in the past, our discussions with the agency, they said that when they want to just see additional evidence that we can dose at the dose levels we intended in PIVOT-HD. Those additional data could take the form of non-clinical data. It could…

Thank you. One moment please. Our next question comes from the line of Paul Choi of Goldman Sachs. Your line is open.

Good afternoon and thank you for taking our questions. Two questions for me. First, on the commercial side, with the approval of Vamorolone today, can you maybe just comment on how you're thinking about the impact to Emflaza, and would you maybe consider pulling back on Salesforce resourcing for that product starting next year ahead of your expected loss of exclusivity? And then on the pipeline side, can you maybe comment on what you would intend to present in terms of your PIVOT-HD update next year? Should investors continue to expect plasma Huntington updates and neurofilament changes, or would you perhaps present some details on other endpoints, including clinical endpoints? Thank you very much.

Thanks Paul for the questions. Let me grab the second one first, and then I'll turn the other question over to our other Eric and Kylie. So first, in terms of the 518 data, so the 12-month data that we getting, Paul, that we would share in the first half of 2024, that will be data from the biomarker portion, right? We talked about PIVOT-HD as being a 12-month placebo-controlled study in two parts. The first part, the 12 weeks, focuses on pharmacodynamics and pharmacokinetics as well as safety. And then in that second portion, at the 12-month time point, we would have data, further data on neurofilament levels now less about safety, but maybe more about recording treatment benefits, CSF Huntington protein, mutant Huntington protein levels, volumetric changing on MRI. We also will have some clinical data at that time point, which are not main endpoints at the 12 months, but obviously we're collecting this data. I think -- and we would certainly share the biomarker data, share what clinical data we have with the obvious caveat that even the 12 months, it's very hard to have interpretable clinical effects on things like the UHDRS scale or even the total motor score for the different values that's just given to the rate of progression in the disease and the sensitivity of those instruments to change over a short period of time. And so the answers will have those data. The main focus will be the biomarker data, obviously in terms of safety. We'll also, when ready, have data on the additional subjects who are going to hit the 12-week time point and then ultimately hit the 12-month time point. And we haven't given a timeline to that, the timeline will be given. Obviously, the data point -- most are interested in which is that 12-month data point for the initial cohort of subjects on whom we shared the 12-week data. So in terms of your question on Vamorolone and Emflaza, Eric, do you want to take that?

Yeah. Thanks for the question, Paul. I think with Emflaza, we know that Emflaza has been currently on the market for more than six years. It is currently the standard-of-care. We've established Emflaza as the standard-of-care because there's been a number of publications and there's also a lot of scientific evidence that has actually preserved greater motor function than prednisone. And we know that the data has continually supported that. And we have very, very strong relationships with each one of the healthcare providers in terms of showing them the evidence, but also providing patient support. We understand that the community wants options, but we know that right now we have been focused on and our field force has been focused on not only growing the brand this year, but also we have a number of strategies that will also protect the brand following a loss of exclusivity, because we don't necessarily see this as being a fall off, because of a generic or even a competitor. And we have a number of key strategies right now. And a lot of them are centered around leveraging our patient support programs, because we have that direct line with patients and we have more patients on Emflaza than any other DMD treatment. We can continue to leverage that support. And through that process, we'll continue to work with our specialty pharmacies. We'll be targeting key relationships with payers to obviously continue to, if you will, foster brand loyalty. So all the more alone is an additional option. We also know that clinically it hasn't been differentiated like Emflaza and that we have a very strong and loyal customer base.

Okay. Thank you for taking our questions.

Thank you. One moment please. Our next question comes from the line of Tazeen Ahmad of Bank of America.

Okay. Thanks so much for taking my questions A few quick ones from me, if I may. So to keep with the topic of the approval for Catalyst Pharma, how, if in any way, does that change your strategy for how you might want to look beyond the loss of exclusivity for Emflaza next year and beyond? And then second question, as it relates to sepiapterin milestone agreements with Censa, I believe you've already paid them $30 million for completing Phase 3 enrollment. I guess what other milestones should we anticipate either this year or next? And then lastly, to clarify on the conditional approval for Translarna, and I'm sorry if it was answered earlier, is there a set amount of time for which a conditional approval would need to be renewed on a go-forward basis? Thanks.

Thanks for the questions, Tazeen. Let me take the third one and then I'll pass to the team for the other two. So the conditional authorization, obviously, there's always comes with a specific obligation to collect additional data. So that's less of a time based, specific time based element, but rather the time is necessary for that data collection effort. Obviously, there have been therapies that have had conditional authorization for many, many years, even beyond a decade. So for us, what we would do is look forward to the opportunity to keep the therapy on the market and then continue to collect the data necessary. We do also have the obligation to submit for annual renewals, which we've been through before. That's what we've done for the past several years to show that we're, one, collecting the data that we've agreed to as part of a specific obligation, and then also providing any necessary updates, particularly around safety to the therapy that might emerge. Obviously, the safety story on Translarna is quite robust. And we've clearly been able to show that it is a therapy that is safe and long-term, just as we've been able to show the benefit long-term to the stride registry. In terms of your questions on Emflaza strategy and as well as milestone, Kylie, do you want to take Emflaza?

Yeah. Absolutely. So on the Emflaza front, Tazeen, I think what we continue to do Emflaza as the standard-of-care across all DMD patients. And we have been able to demonstrate the benefit of Emflaza in a number of different milestones and we continue to believe that that's not going to shift in the near-term. I think from a loss of exclusivity perspective, we have a number of strategies that we're looking at to be able to preserve the business, and again, that doesn't shift based on the Vamorolone approval. We have good, strong relationships across our customer base and with patient advocacy groups and we will continue to leverage those relationships as we move forward. On the milestone question…

Are you able to provide any color on the specific strategies that you're going to use for Emflaza?

Yeah. Absolutely. So there's four main pillars that we're focused on with regards to protecting the business. So one is ensuring that we have an enhanced patient support program, which is really, really important for particularly DMD patients those in Medicaid as an example, and then also partnering with specialty pharmacies, partnering with payers, and partnering with manufacturers to be able to ensure that, we're doing the best for the patients and protecting the business. So there are some of the key strategies that we're looking at, as well as a dispenses written program that the team is working on as we speak.

Okay. Thank you.

Thank you.

And then in your -- just to answer the last question, Tazeen, around the milestones for Censa. So you are correct. We obviously had paid the $30 million in equity in 2023. Don't expect any additional milestones for Censa in 2023, but we had shared in the Q that we expect $65 million worth of regulatory success based milestone for Censa in the next 12 months, so in 2024, and we haven't broken out the specifics around that.

I'm showing no further questions at this time. Let's turn the call back over to Dr. Matthew Klein, Chief Executive Officer, for any closing remarks. End of Q&A:

Great. Thank you. Thank you all for joining the call today. We look forward to a strong closeout in 2023 as we get ready for what's clearly also going to be a busy 2024. And we'll look forward to sharing updates with you as they become available. Thank you all again and have a good evening.

Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may now disconnect. Have a great day.