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spk01: Thank you for standing by, and welcome to the PTC Therapeutics Third Quarter 2023 Financial Resorts Conference Call. At this time, all participants are on a listen-only mode. After the speaker's presentations, there will be a question-and-answer session. To ask a question at that time, please press star 11 on your telephone. Please be advised today's call is being recorded. I will now turn the conference to your host, Jane Hanlon, Associate Director of Investor Relations. Please go ahead.
spk08: Good afternoon, and thank you for joining us today to discuss PCC 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 Powles, 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 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 the 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 Form 10-Q and annual report on Form 10-K filed with the Securities and Exchange Commission, as well as the company's other SEC filings. We will disclose certain non-GAAP information during this call. Information regarding our use of GAAP to non-GAAP financial measures and a reconciliation of GAAP to non-GAAP are available in today's earning release. With that, Let me pass the call over to our CEO, Matthew Klein. Matt?
spk03: Thank you, Jane. Good afternoon, and thank you all 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 Abrisdy royalty stream. This non-dilutive financing provides PTC the capital to support planned operations and allowed us to retire the Blackstone debt obligations. In addition, the deal structure includes flexibility for accessing additional capital over the next two years. Notably, PTC maintains its rights to the remaining $250 million of milestones related to the RISD 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 programs 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 DMV franchise revenue in the quarter totaled $136 million. This strong performance allows us to update our 2023 DMV 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 Transline. 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 only one opinion. We decided to pursue reexamination of the negative opinion on renewal of the conditional authorization only. As such, the reexamination process will focus solely on the allowance of continued conditional authorization of TransLarna in Europe. We remain optimistic that we can address key concerns raised by the CHMP on the evidence of benefit in the TransLarna clinical trials, as well as concerns raised on the methodological robustness of the STRIDE data analyses. As previously discussed, in accordance with EMA guidelines, we expect the opinion from the reexamination procedure in late January with adoption of that opinion by the European Commission 67 days later. The U.S., a Type C meeting with FDA to discuss a potential path to NDA resubmission, is scheduled for this quarter. Turning to CpEuterin, we held a pre-NDA meeting in the third quarter with FDA to discuss the NDA submission. At the meeting, FDA stated that the CpEuterin clinical safety and efficacy data supported NDA submission for the treatment of pediatric and adult PKU patients. However, they requested that we complete a 26-week non-clinical mouse study to assess potential carcinogenicity risk of sepia-tarian prior to submission. This non-clinical study was initially not required when sepia-tarian was acquired from CENSA as the NDA submission was planned under the Section 505B2 pathway. With our decision to file under the 505B1 pathway, the 26-week study is considered a required NDA component if needed to inform labeling. we will continue to discuss with FDA the potential to submit the mouse study results during the NDA review process. We now expect NDA submission to occur no later than the third quarter of 2024. This submission could occur in the second quarter if FDA allows submission of the nonclinical study report during the review process. For the EU, we expect to submit a marketing authorization application to EMA in the first half of 2024. The delay in NDA submission in no way mitigates the strength of the affinity data. Given the highly meaningful clinical effects observed in the trial, as well as the continued evidence of providing phenylalanine tolerance benefits to the full spectrum of PKU patients in the long-term open-label extension study, we remain incredibly enthusiastic about the potential billion-dollar-plus global commercial opportunity for C. peterin. Moving to the PTC518 Huntington's disease program, Enrollment is ongoing in the PIVOT-HD study for both the Stage 2 and early Stage 3 cohorts. We expect the next data update to occur in the first half of 2024. This update will include 12-month data on the initial group of subjects on whom we reported data in June of this year. Regarding the status of the trial in the United States, we had a Type A meeting with FDA to discuss the clinical safety data needed to enable resumption of enrollment of the PIVOT-HD trial at U.S. study sites. At the meeting, FDA stated that the existing three months of safety data could support 12-week dosing at 5 milligrams and 10 milligram dose levels, and that six months of clinical safety data demonstrating a similar favorable safety profile could support 12-month dosing in the PIVOT-HD trial. This is very good news, as it suggests that the safety data being generated from PIVOT-HD should be sufficient to lift a partial hold in the United States. Turning to vitiquinone, the data in the MOVE-FA study demonstrated vitiquinone's treatment benefit across several disease endpoints, including favorable effects on the upright stability subscale of the mFARS assessment, which is predictive of time to loss of ambulation. We had a type C written response only meeting with FDA in the third quarter to determine whether the data from MOVE-FA would be sufficient to support an NDA for accelerated approval. In the written response, the FDA stated that while they see the value of upright stability as a clinically meaningful endpoint, they believe the confirmatory study would likely be needed to support NDA submission. As this was a written response only, and we believe we can address the concerns raised by the FDA, we have requested a follow-up live meeting. In parallel, we are participating in a scientific advice procedure with the EMA to determine if the MOVE-FA data could support a conditional marketing authorization application in the EU. We expect to have the outcome of this procedure in the first quarter of 2024. Turning to Upstaza, we had an informal meeting with FDA in the third quarter, at which time they said that the data we have provided to support comparability between the clinical drug product and the intended commercial drug product were still not sufficient. However, in that meeting, the FDA said that the available data from the clinical study in the United States assessing the safety of the drug delivery cannula could be used to support a BLA for accelerated approval based on biomarker data demonstrating a treatment-related increase in de novo dopamine production. FDA suggested that we conduct a pre-BLA meeting to review the contents of the planned BLA. This meeting has been scheduled for December, and pending the outcome, we expect to submit the BLA shortly thereafter. Let me conclude by saying I'm incredibly proud of our team's continued ability to execute on all fronts. The recent Royalty Pharma financing deal, along with our operating expense reductions, position PTC as strongly as possible for future growth as we realize the potential of our many promising programs. I will now turn the call over to Eric and Kylie to discuss our strong commercial performance in the quarter. Eric.
spk02: 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 Inflaza continue to be important growth drivers, delivering $136 million in net revenue for the third quarter. which is 4% 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 TransLarner. and reemphasizing the significant life-changing impact this treatment has 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 Inflaza, the Inflaza 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 Implaza 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 Implaza 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.
spk09: Let me begin with Upstazer, the first and only approved gene therapy infused directly into the brain. 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 UK this quarter, following the positive NICE recommendation earlier in the year. Patient identification, treatment center readiness, and access and reimbursement discussions continue to advance. We also continue to leverage early access programs and cross-border treatment opportunities with a patient from the Middle East also receiving treatment in France this quarter. Moving to Tegceti and Weylivra in Latin America. We continue to grow our franchise in the region with recent MAA approvals for Tegceti in Argentina and Weylivra in Mexico. Patient identification is robust and patients on treatment continue to grow across the region. In Brazil, we anticipate receiving new group purchase orders for both Tegceti and Weylivra 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 sepia-tarrant opportunity. The affinity phase three 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 affinity 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 sepiaterin is composed of a number of key PKU patient segments, all of which our affinity data suggests we can address. First, patients who have not been trialed on cuvan or are considered therapy naive. This includes many of the classical PKU patients where we have demonstrated benefit in both the phase two study and the affinity study. Second, patients who have not responded to cuvan. Third, patients who have achieved some level of blood fee reduction from KUVAN, but are not well controlled, and for whom sepiauterin may deliver a better reduction in blood fee levels. For these patients, a reduction in blood fee to target fee levels is clinically meaningful, potentially allowing them to substantially increase their protein intake and significantly enhance their quality of life. Many experts who have treated patients with PKU across the world have indicated that based on the data they have seen from our affinity study and from their understanding of the mechanistic benefits of sepiaterin, all interested patients should be trialed on sepiaterin. With an expected addressable population of approximately 15 to 30% of the overall global PKU population, this would put us above a billion dollar market opportunity. In conclusion, our third quarter builds on an excellent first half of 2023. With significant progress across all of our commercial products and across all geographies, our customer-facing team is set to have a very strong close-up to the year and set ourselves up for continued success in the future by continuing to build on our commercial capabilities and to execute pre-launch strategies for our future product pipeline. Now let me turn the call over to Pierre for a financial update. Pierre? Thank you, Kylie.
spk16: 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 allows 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-dilutive capital over the next two years. To recap the details of the deal, PTC monetized up to $1.5 billion of the FHD royalty stream. Royalty Pharma acquired additional royalties on FED for $1 billion upfront. The agreements 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 EverySD Global Net Sales. The agreement builds on the previous strategic partnership established with RoyaltyParma in 2020. The initial agreement was for the monetization of approximately 43% of the EverySD royalty stream. As a result of the current agreement, PTC will maintain ownership of approximately 19% of the total everyday royalty stream, pending any exercise of future options by PTC or royalty farmer 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 the third quarter was $197 million. This consisted of D&D franchise revenue of $136 million and other revenue of $61 million. Starting with the D&D franchise. Translona net product revenue in the quarter was $69 million, while M-Flazza net product revenue of $67 million. Moving to Evisdee. Third quarter global revenue of 360 million Swiss francs, which equates to over 400 million US dollars, was achieved by Roche, earning royalty revenue of 50 million dollars for PTC. As Matt mentioned, the third quarter performance puts us in a strong position to achieve 2023 total revenue guidance of 940 million to 1 billion dollars, including an expected 100 million dollars milestones whenever this year passes $1.5 billion in annual net sales. Non-GAAP R&D expenses were $150 million for the third quarter of 2023, excluding $14 million in non-cash stock-based compensation expense compared to $150 million for the third quarter of 2022, excluding $15 million in non-cash stock-based compensation expense. Non-GAAP SG&A expenses were $68 million for the third quarter of 2023, excluding $13 million in non-cash stock-based comp expense, compared to $67 million for the third quarter of 2022, excluding $14 million in non-cash stock-based compensation expense. Cash. Cash equivalents and marketable securities total approximately $295 million as of September 30, 2023, compared to $411 million as of December 31st, 2022. I will now turn the call over to the operator for Q&A. Operator?
spk01: Thank you. Again, ladies and gentlemen, if you'd like to ask a question, please press star 1-1 on your touchtone telephone. Again, to ask a question, please press star 1-1. One moment for our first question. Our first question comes from the line of Eric Joseph of JP Morgan. Your line is open.
spk12: Hi. Good afternoon. Thanks for taking the question. Just a couple on PKU from us. Really, just around this regulatory path here, can you just clarify when the decision was made to pursue a 505 path for sepiauterine over a 505 ? And maybe what prompted that decision? I guess, in electing to go with the 505B1, was it not clear that a carcinogenicity study would be needed, would likely be a requirement? And really, ultimately, I guess just looking forward, what should give inventors confidence that, you know, assuming that a carcinogenicity study turns up nothing, that the NDA submission and review cycle should otherwise be straightforward? Thank you.
spk03: Thanks for the questions, Eric. Let me just first start with a little bit about 505 versus 505 . The 505 pathway is typically used for Me Too compounds where it has already been, and there's an existing approval for the active ingredient in the compound for which one seeks approval. Alternatively, the 505 pathway is for innovative therapies, which is much more appropriate for something like sepia-carin, 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. SENSA initially was thinking about the 505 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 to us that 505 was much more appropriate. Now, with the 505 pathway, since there is an active ingredient already approved, you can utilize the studies, not safety and efficacy studies, but other supportive studies like nonclinical studies that were used to support that approval. With the 505 pathway, you don't have the ability to rely on those existing studies. Now, the decision to switch was based on a couple of things. CP Tarin is quite differentiated in terms of its efficacy profile from Kuban. Second, if you go 505B2 pathway, the company's product, the company whose product 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 book listed patent. 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 novel, innovative compound, much more suited to the 505 pathway. We then obviously had interactions with the agency to understand what would be required under the 505 pathway. And that included things like juvenile toxicity and , all of which studies will be conducted, including the NDA, no issues there. And then for carcinogenicity, What's typically required is that you submit to the agency a weight of evidence request to request a waiver for carcinogenicity. Now, obviously, we were quite confident in getting that waiver. One, there's no evidence of genotoxicity of CpEuterin. In the CpEuterin non-clinical studies, the six-month and nine-month studies, there was no evidence of CpEuterin-related Carcinogenicity, pre-neoplastic lesions, and neoplastic lesions. Furthermore, while we weren't referring to the Cuvan NDA, the clinical experience with Cuvan over many years clearly demonstrates that there's no carcinogenicity risk associated with BH4. So we submitted all of that to the agency. Now, the agency obviously came back and said that there's two different carcinogenicity studies. One is a two-year rat study. They said, fine, do that post-approval, no problem. But since you're in the 505 pathway, they would want the 26-week mouse study to inform the label, because in the label, they have to say whether or not there's a potential carcinogenicity risk. And while we were under 505B2 pathway, they could use the labeling in the CUVAN label, which referred to risk of adrenal tumors, which has never been seen clinically. But they said, look, we have nothing to refer to. We have nothing to inform the label. So we need you to do this study. And since it's a standard part, would be considered a standard part of the 505B1 pathway, it would be something you would need to submit with the NDA. Now, I'll also say, and just the other part of your question, in our discussions, it was clearly stated that the safety and efficacy data we have with sepia-carin could support the full spectrum of patients, which would be our desired label. So we fully expect that once we get the study results, if it's required to have the study report for the mouse study for submission, once we have that, we expect a very smooth path from there. Again, given the incredible strength of the efficacy data we have, the safety data we have, and obviously what's far from ideal. the additional time we're going to have now is only going to build that DAPCA further with greater length of exposure, greater ability to show more durability and effect, the kinds of things we're seeing in the long-term open-label study. And obviously, we're going to have even more data showing C-tolerance. We recently reported the latest update in the C-tolerance data at the Siam meeting in September, again, showing that patients are able to tolerate beyond the recommended daily allowance of protein and still have control of fetal immunity. So the strength of this data is It is in no way impacted by the need to do this non-clinical study. It is an unfortunate delay. We're going to continue discussions with the agency if we could submit the application sooner. But the bottom line is, this is a strong differentiator compound. The data we have to date, the studies we've done, show there's been no evidence of carcinogenicity risk. According to the study reports, we have genotoxicity and the like. And again, this continues to be a very, this will be a very strong package.
spk00: Thank you. One moment, please.
spk01: Our next question comes from the line of Kristen Kluska of Cantor Fitzgerald. Kristen Kluska, your line is open.
spk11: Hi, everyone. First, just wanted to congratulate you on the Royalty Farm 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.
spk03: Kristen, thank you very much for the question. So, as we mentioned in our prepared comments, 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. nuances of the procedural elements in Europe, they had brought that together and said, we're going to issue two opinions, but 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, and there's no other targeted therapies for non-sensitive 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 they raise with having a negative primary analysis population analysis in study 41, may become less of an issue. Really, we can focus on the other important and strong data in Study 41, 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, as you asked, what happens from there? Well, if you have a conditional marketing authorization in Europe, you are required to conduct or collect additional evidence to continue to support the benefit. Now, we believe there's many potential sources of this, including continuing to collect data in stride. While we've obviously been able to show clear benefit in delaying time to loss of ambulation by three and a half years in the most recent analysis and continue to show meaningful multi-year delay loss of pulmonary function, as we can continue to collect more data over time, there'll be even more patients informing the loss of ambulation analysis, even more patients informing the pulmonary function analysis, and hopefully, ultimately, cardiac function and mortality. So, there's still a lot more meaningful data that can truly inform the long-term benefit of trans-autism stride. There's also the possibility to talk about bolstering stride, either with additional analyses or a second registry. That's a possibility. I think in the universe of possibilities, because they asked us to do another clinical trial, I think that's possible, probably not likely, given a lot of the feedback that the scientific experts gave and the scientific advice portion of the procedure last time was that clinical studies for genetic-directed therapies in DMD are really hard and really difficult to produce meaningful data, and the experts have told us They believe that these longer term data collection mechanisms that are really most useful for understanding the true benefits. So that's a long answer. The short answer is, look, we'll have to collect additional data. We'll be well positioned and quite honestly pleased to do so. The priority now is to keep this therapy on the market in Europe. And we believe by pursuing just the renewal of the condition, it puts us in the strongest position to do that.
spk11: Okay, thanks. 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. Thanks again.
spk03: Yeah, Kristen, good question. I think needless to say the physician's 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 non-sense mutation patients. 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've produced. And many have said they can't imagine having to take patients off a drug that's safe and effective. They'll, the patients on their own, you know, have the ability on their own to reach out and let their voice be heard. I'm sure in many parts of Europe that'll happen given the fear and concern they have. And I think similarly for the physician community, they'll want to speak up. You know, our sense here is that most people, as we were, never thought this state would come or this would be a reality. So I think the... 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 non-sense mutation DMD.
spk01: Thank you. One moment, please. Our next question comes from the line of Sammy Corwin of William Blair. Sammy Corwin of William Blair, your line is open.
spk10: Great. Thanks so much. 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 is not reversed? 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? Thank you.
spk03: Yes, Amy, thank you for the question. Again, I think in the physicians we've spoken with, the first response was clarifying and we confirmed that in no way did 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 kick it over to Erica, and if you want to give some more detail on prescriptions.
spk02: Yeah, thanks for the question, Sammy. First of all, we haven't actually seen an impact since CHMP has issued their opinion. In fact, you know, 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, 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 they've been limited to no discontinuations because of the CHMP information. New patients continue to get scripts. Compliance has actually remained 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 and 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 TransLorna growth in the fourth quarter. And combined, that would equal about 11% to 17% year-over-year growth for the DMV franchise compared to last year.
spk01: Great. Thank you. Thank you. One moment, please. Our next question comes from the line of David Lebowitz of Citi. Your line is open.
spk04: 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?
spk03: David, thank you for the question. Let me 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 the 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 TransLondon 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 little bit more detail about the breakdown of revenue?
spk09: Yes, 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 TransLana revenue. So where we stand today, we have a number of growth markets that have continued to grow over the last couple of quarters and 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.
spk04: 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.
spk09: Yeah. So, David, I think from that perspective, I think it sits 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.
spk04: 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?
spk05: David, we announced the revised ROPEX guidance.
spk03: previously to 810 to 860, and also we then announced the subsequent cuts and how that would have an impact of additionally another approximately 20% that went in run rate 2024. Obviously, we'll give the updated OpEx guidance at JPMorgan in January.
spk04: Thank you for taking my questions.
spk01: Thank you. One moment, please. Our next question comes from the line of Kelly Shee of Jefferies. Your line is open.
spk15: Hi. This is Yun for Kelly. Thanks very much for taking the question. So the first question on Translana, assume that you are 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 ADC deficiency. On the comparability in terms of manufacturing, are there any specific assays that you have to develop before the meeting?
spk03: 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 you're 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 Uh, study would have some timeline likely tied to it also as part of a conditional market 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. We're seeing in stride as well as benefit. that we've seen in stride. And there are therapies that have been, have had conditional marketing authorization status for, you know, decade, two decades. So, this would not be the first time that a therapy continued in the conditional frame for a bit more time. On your second question regarding the PBLA meaning and the issue of comparability. So, comparability analyses are done to show that the material that we used 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 for which we had to establish comparability with the commercial process is over a decade old. Those are clinical studies that were started in the early 2010s. And there simply is not enough of that residual clinical supply available to provide the additional replicates and additional data that the agency wanted us to have to finalize the comparability analysis. We obviously had data across all the assays that we believe show that the process is comparable. We've asked for some additional analyses. It's a bit challenging to get that. given the age of the material. Now, importantly, we were able to discuss with them the potential to leverage the accelerated approval pathway using our ongoing study in the U.S., which is using material made with the commercial process. So it is the commercial-like material for which there was no comparability assay. And what we're able to show in AADC, which is a genetic disease of dopamine deficiency, is that when we give the drug, we're able to measure increases in dopamine. Obviously, that's a reliable, quantifiable biomarker that's not only incredibly important to the disease pathology, but also logically will precede the subsequent development of dopamine-related motor function, which is exactly what we observed in the clinical study. So that fits squarely in the framework of accelerated approval. And I think everyone has seen lately in CBER, there has been increasing interest of Peter Marks has talked about this, the head of CBER, of using the accelerated pathway for rare disease gene therapies as a way to quickly get these therapies to patients. So, we're looking forward to a pre-BLA meeting in December. They asked us to do that to make sure we're aligned on the contents of that accelerated approval BLA package, and then pending the outcome of that meeting, we'd expect us to get the BLA shortly thereafter.
spk01: Thank you. One moment, please. Our next question comes from the line of Brian Abrams of RBC Capital Markets. Brian Abrams, your line is open.
spk19: Hey, good afternoon. Thanks for taking my questions. As you prepare for the MAA filing for sepiaptrin next year, what are your expectations for what the CAR study requirements will be for Europe approval? And then secondarily, I guess on Translarna in the U.S., 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? Will it 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.
spk03: Thanks for the questions, Brian. So, on the question regarding the MA 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 Cpterin is BH4, and they understand that BH4 and CpAsterin are both naturally occurring co-factors. 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 at KuVan Health for many years There's a knowledge base that exists that there's been no carcinogenic risk associated with H4 use 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. And so, again, just 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 meetings for translineups, 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 41, but that could be confirmed in a number of ways, including meta-analysing 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 NDA resubmission. 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, you know, boys with non-transmutation DND in the U.S. who have waited years for therapy, and then also the large number of boys in the U.S. who've been on for a number of years from their participation in clinical studies and beyond, all of whom are quite interested in ensuring that this drug can be available in the U.S. for them.
spk19: That's really helpful. Thanks, Matt.
spk01: Thank you. One moment, please. Our next question comes from the line of Colin Bristow of UBS. Your line is open.
spk17: Good afternoon. Thanks for taking the questions. On the Ceti Epta and NDA filing timeline, I'm just curious, why is the latter end of your guidance 3Q24? I'm 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 give 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.
spk03: Thanks for the question, Colin. The, if you just, you know, when you find out you have to do a study, it takes a little bit of time to actually organize the study, get the slot at the CRO, get the animals in order, 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, 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 reports. 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 this 3Q time bound from. It's merely the realities of to do a 26-week study 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, 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 with them they see our safety and efficacy data as being supportive of the NDA and so we look forward to being able to submit that as soon as possible. In terms of comparability this is simply a matter of not we had very limited supply of the clinical material. So there was only a certain number of assay runs we were able to do to provide data to compare to the assays that were conducted in the commercial material. They wanted additional data points, a greater number of samples that we simply couldn't provide due to limited supply. In terms of the pre-BLA meeting, it was suggested that we hold the pre-BLA meeting because they wanted to make sure that we're aligned on the contents of the package, how we're going to present their integrated safety summary from all the studies that are going to, how we're going to present the efficacy data, how are we going to include other components of the regulatory studies in the package. They thought it would be very important to make sure, as we were told in the meeting, It's not required, but we tell all companies it's important to have this, so we're sure that the file meets the formats and specifications we want to avoid any filing issues. So, we believe the most prudent thing to do is to have that pre-BLA meeting and then pending results be in a position to submit as quickly thereafter as possible.
spk05: Great.
spk00: Thank you for that. Thank you. One moment, please. Our next question comes from the line of Jeff Hung of Morgan Stanley.
spk01: Your line is open.
spk20: Question. In your discussions with the EMA on vaticanone, what gives you confidence that it may accept MOVE-FA for conditional marketing authorization? And is there anything that you can update in terms of analyses or presentation that would increase your confidence for a positive outcome on the conditional marketing authorization, given the feedback you've received from FDA?
spk03: Thanks, Jeff. Thanks, Jeff, for the question. So, you know, the frameworks in FDA and EMARE are 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, as we've talked about, is in all the four sections of the MFARS, which was the primary endpoint, the one that has been shown to be most important in pediatric and young adult patients, particularly ambulatory patients, because it's been shown to be able to predict time to loss of ambulation. Obviously, in future cataxia for ambulatory patients, the key thing for a therapy to do is to delay that time to loss of ambulation, delay loss of ambulation. And so to have an endpoint that can do it, we believe meets that criteria for intermediate clinical endpoints. We look forward to continuing the discussions with the agency as is often necessary in rare diseases. There's a lot of back and forth to talk about the analyses we have, and as you indicated, could we provide some additional supportive analyses to 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 they switched on to active. That's the U.S. In terms of Europe, The conditional marketing authorization, there's a number of criteria set out for a conditional marketing authorization. Do you have initial data that shows that there's a favorable benefit-risk of a therapy? Are you meeting a medical need? Is getting this therapy to patients sooner a potential public health benefit? And I think when you consider the Tiquinone and the MOVE-FA study and the other data we have, we clearly meet all of those criteria. While we didn't hit the primary endpoint of the overall MPHAR score, there's a number of important sources of benefit in the MOVE-FA study, not only in upright stability, on a bulbar subscale, also on fatigue, which is an important symptom for patients. And then if you look at the well-established safety profile of the tiquinone, particularly in pediatric patients, we can clearly demonstrate that this initial study has a favorable benefit-risk profile. Obviously, it's on that medical need, not only for pediatric patients, but there's no approved therapies for FA in Europe for patients of any age. And obviously, given when you have a therapy that can potentially slow the delay of loss of ambulation, that's an irreversible morbidity, and those patients would therefore benefit from access to therapy sooner. The final point, obviously, we know very well from the TransLarna experience, is to be able to be able to demonstrate that you can collect more data on FA patients to support the conditional approval and confirm that you have a favorable benefit-risk balance. We obviously believe there's many sources of additional data that we could generate to confirm the benefit-risk profile. So, again, we believe we meet all of the necessary criteria for conditional authorization, and we look forward to discussions with the EMA to gain alignment with them on those points.
spk20: Thank you.
spk01: Thank you. One moment, please. Our next question comes from the line of Alexander Xaniacs of Truist Securities. Your line is open.
spk21: Hi. Thanks for taking my question. Congrats. First of all, on securing the royalty financing deal. That's great. Maybe two for me. One on sepiaptorin. When might we see another cut of the OLE fee tolerance data? and then one on Translarna. If you are able to overturn the conditional marketing, the ongoing conditional marketing authorization and have that ongoing study, but you don't have the official full marketing authorization, have you done any market research to see how that would affect referencing countries worldwide and if they would be required to pull sales or not? Thanks.
spk03: Thanks for the questions, Alex. So first on the fee tolerance, As we shared, we gave an update on the fee tolerance data at the SSIEM meeting in Israel in September. Those were, again, really great data showing now with over 40 patients enrolled in that fee tolerance protocol that we're seeing patients move through and get to levels of fee tolerance beyond the recommended daily allowance. These are incredibly important data. As we said all along, The fee tolerance component is really not for regulatory purposes necessarily. We have the sufficient efficacy data for that and are able to show in a long-term extension that we're having important durability of CPI treatment effect as well as long-term safety. This is really the fee tolerance data are really quite important. One for differentiation is something Cougan was never able to demonstrate and for physician adoption and for payer discussions, particularly outside of the U.S. On the TransLARN upfront, look, again, we see the ability to keep the conditional authorization as a big win, not only obviously for us, but really most importantly for the patients. I'm going to turn it over to Kylie if you want to comment, Kylie, on what you think the global payer impact could be, if any, on a conditional authorization.
spk09: Yeah, I think from a pay 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 continuing conditional authorization. And of course, we'll continue to focus on that.
spk05: Thanks for taking the question.
spk01: Thank you. One moment, please. Our next question comes from the line of Joseph Schwartz of LeRinc Partners. Your line is open.
spk18: Great. Thanks very much. I was wondering if you could talk about your publication plans for the Affinity CEPI-Aptrin data. Will we see that published in a peer-reviewed journal any time soon? And then I believe you have the option to go up to a 20 milligram dose of PPC-518 in PIVOT-HD patients outside the U.S. So where do you stand on implementing that decision? Yeah, absolutely.
spk03: So maybe I'll take the, I think let me take the second question first, and then I'll kind of answer the first question second. So on 518, so we, as we talked about, we share the results from the 5 and 10 milligram dose groups, the first cohort of 33 patients in June. Those data, from our standpoint, were as good as they can be. We achieved every objective of that 12-week portion of the study in that first cohort of patients, demonstrating the dose-dependent lowering of puntutinib protein in the blood, seeing the differential exposure of PTC518 in the CSS relative to the plasma at that 10-milligram dose, seeing that that ratio is 1.5 to 1, suggesting that we're getting even greater exposure of 518 in the brain at each potentially higher levels or greater lowering of Huntington, mutant Huntington protein in the brain, all of which was very, very important. And of course, the other key point is that we were doing all of this safely. The safety profile of the drug was quite strong in those first 12 weeks. We had no drug-related serious adverse events. There were no NFL spikes, all very, very important, particularly given concerns that were raised over other HCT 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 percent. 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 cohorts. The regulatory authorities and local ethics committees have approved us going to 20. 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, because those very well may be sufficient to move forward and get us where we want to be. So we haven't issued those 20 milligram doses yet. We're not sure we're going to need to, and we want to better understand the longer-term biomarker effects of the current dose levels before revisiting that decision. Let me turn it over to Kylie to answer your question on publication strategy for PKU.
spk09: Yeah, thanks, Joe. We are absolutely getting the affinity study published in a peer-reviewed journal. The team is working on that as we speak and is looking to target a high-impact journal. And so the timelines for getting that published is obviously driven by the journal of choice. So this is work in progress. The team is moving through this, and we expect it to be published during 2024 pending the journals chosen.
spk01: Thank you. Thank you. One moment, please. Our next question comes from the line of Gina Wang of Barclays. Your line is open.
spk07: Hi. Thank you for taking my questions. So I do have, I think, three quick questions. The first one is, Regarding the PTU program, since initially we're thinking about 505B2, is that because of the lack of confidence of their IP position that this drug will be very different from Kuvent? That's the first question. And then related to how confident you are on the IP regarding this is a new composition of a matter. And then for the Pivot HD, I don't know if I missed it, So have you mentioned, like, exactly what kind of data you would need in order to remove FDA clinical hold? So based on, you know, I think your prepared remark, you did mention certain months of clinical safety data. When I look at the press releases, six months of clinical safety data demonstrate similar favorable safety profile could support 12-month dosing. And what additional data that we'll require to can 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 APSTAS in AADC. So if you are using current U.S. data for accelerated approval, what additional study you will need to do in order to get a full approval in the future?
spk03: Great. Thank you very much for the questions, Gina. The first question for number one regarding PKU and SENSA. Look, I think that was really what more reflection of SENSA being 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, you know, it's not uncommon for a smaller company to think about the development path that way. You know, I think from our standpoint, the, you know, it's very clear this is a highly differentiated therapy that is much more suited to the 505 pathway. Obviously, we're in a position to have the resources to do the necessary studies and not have to rely on another MBA and incur that risk of having to stay placed on the launch of the therapy following approval. As we talked about, not only do we have a great deal of confidence in how differentiated sepia-tarrant is and its ability to meet the persistent large unmet medical need for PKU patients, and as we've heard from physicians, including Andre Montel on a commercial deep dive this summer, a desire for physicians to even switch patients who may be served to some extent, including van tube sepia-tarrant, because of what we've been able to show in terms of the large magnitude of clinical benefits. 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 PivotHD, as we had talked about in the past in our discussions with the agency, they've said that they wanted to see additional evidence that we can dose at the dose levels we intended in PivotHD. Those additional data could take the form of non-clinical data. It could also take the form of clinical data. And so we had made the decision since we were able to conduct this trial in many countries outside of the U.S. and enroll the study outside the U.S. that we would conduct the study, collect the clinical data in the study, and then provide those data as we had them to FDA in order to fulfill that need of demonstrating that PTC518 can be demonstrated safely. So once we had the 12-week data, we took those data that we presented, and obviously, since all patients aren't enrolled at the same time, we had some data beyond 12 weeks. We provided all of that to the agency, and that was clinical data. It included clinical laboratories. It included the NFL levels that we had shared at the earnings adverse event reports, the lack of serious adverse events, the DSMB minutes, letters from the DSMB chair, all of which were shared with FDA. As I mentioned in the prepared remarks during our discussion in the meeting, the FDA indicated that those data that we had at that point could be sufficient for 12 week dosing in 5 and 10 milligrams if that's what we wanted to start now. But obviously the goal here is to think about longer term dosing as your question suggested. And they said what they would like to see is data at the six-month time point, so basically a little bit longer than three months to support the duration of dosing that we had proposed in PIVOT-HD. We're right now quite simply doing the timing math. It's very possible by the time we got that data, sent it to the FDA, got the review, got sites ready, up and running in the U.S., it might very well be done with enrollment in PIVOT-HD. extremely close right now to completing enrollment in the Stage 2 patients, and enrollment is moving very quickly overall for the study, particularly after the June data release, when we were able to provide a lot of comfort to physicians and patients that Unlike other hunting and mowing therapies, we were able to achieve our objectives and do so safely. There's been a lot of interest in that study. There's obviously a lot of interest in the United States for patients and physicians. So we would love to be able to open sites here, but if the study is fully enrolled, then we'll look to start phase three here and be able to offer the opportunity for patients to participate in the PDC5-1A development. Your 3rd question was regarding upstairs and accelerated approval and confirmatory study. So we are using the existing clinical study now in the US, and we have the end point that we're using to support. The accelerated approval is an early end point of biochemical changes. Then you'll have a longer term extension component of that study, which will collect long term clinical data to provide the clinical evidence necessarily. to support the full approval. So this is really an example where we will have the study ongoing. It's going to be a long-term study that's going to look at the acquisition of motor developmental milestones over time, much in a way that we've been able to show previously in the clinical studies of STESA that were done previously, where over time we're able to show that these children develop the ability to first lift their head and be able to sit, crawl, and walk independently. That obviously takes many years, which is why in many ways this is a very good setup for an accelerated approval where we have biomarker evidence, dopamine increases, which is obviously likely to predict long-term clinical benefit of the acquisition of dopamine-related motor milestones.
spk01: Thank you. Thank you. One moment, please. Our next question comes from the line of Paul Choi of Goldman Sachs. Your line is open.
spk06: Good afternoon, and thank you for taking our questions. Two questions for me. First, on the commercial side, with the approval of Emerilone today, can you maybe just comment on how you're thinking about the impact to Inflaza, 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.
spk03: Thanks, Paul, for the question. Let me grab the second one first, and then I'll turn the other question over to Kylie. So first, in terms of the 518 data, so the 12-month data that we said in the call that we would share in the first step of 2024, that'll be data from the biomarker portion, right? You talked about HBDHC as being a 12-month placebo-controlled study in two parts. The first part, the 12 weeks, focuses on pharmacodynamic 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 changes 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 we would certainly share the biomarker data, share what clinical data we have with the obvious caveat that even at 12 months, it's very hard to have interpretable clinical effect on things like the UHD-RS scale or even the total motor score, or just the rate of progression of the disease and the sensitivity of those instruments to change over a short period of time. So the answers will have those data. The main focus will be the biomarker data, obviously, continued 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. We haven't given a timeline for that. Obviously, the data point I think most are interested in, which is that 12-month data point to the initial cohort of subjects on whom we shared the 12-week data. So, in terms of your question on Velour alone and MFLASA, Alex, do you want to take that?
spk02: Yeah, thanks for the question, Paul. I think with MFLASA, you know, we know that MFLASA has been currently on the market for more than six years. It is currently the standard of care. We've established and flaws as a standard of care, because there's been a number of publications and there's also a lot of scientific, scientific evidence that is actually preserved greater motor function than, than prednisone. And, uh, we know that the data has continually supported that, and we have very, very strong relationships with each one of the healthcare providers, um, in terms of, um, showing them the evidence, but also providing patient support. Um, 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 the 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 influenza 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 in Plaza, and that we have a very strong and loyal customer base.
spk06: Okay. Thank you for taking our questions.
spk01: Thank you. One moment, please. Our next question comes from the line of Tazin Ahmad of Bank of America. Your line is open. Thank you.
spk13: 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 EMPLASA next year and beyond? And then second question, as it relates to SEPIAPTA and milestone agreements with SAMHSA, 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.
spk03: Sure. Thanks for the question, Suzanne. Let me take the third one, and then I'll pass to the team for the other two. So the conditional authorization, obviously, 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 1, collecting the data that we've agreed to as part of the specific obligation, and then also providing any necessary updates, particularly around safety to the therapy that that might emerge. Obviously that the safety story on on is quite robust. And what we've clearly been able to show that is a therapy that is safe and long term, just as we've been able to show that the benefit long term to the, to the stride registry. In terms of your questions on. and FLASA strategy, and as well as Myles and Peter's. Kyrie, do you want to take some FLASA?
spk09: Yeah, absolutely. So on the FLASA front to Dean, I think what we continue to do is see FLASA as the standard of care across all DMV patients, and we have been able to demonstrate the benefit of FLASA 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 memorial 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,
spk13: Are you able to provide any color on the specific strategies that you're going to use?
spk09: 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 DMV patients and 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 they're some of the key strategies that we're looking at, as well as a dispenser's written program that the team is working on as we speak.
spk13: Okay, thank you.
spk09: Thank you. And then in your... Just to answer the last question, Christine, around the milestones for CENSA, so you are correct, we obviously had paid the $30 million in equity in 2023. We don't expect any additional milestones for CENSA in 2023, but we had shared in the queue that we expect $65 million worth of regulatory success-based milestones for CENSA in the next 12 months, so in 2024. And we haven't broken out the specifics around that.
spk01: Thank you. I'm sure no further questions at this time. Let's turn the call back over to Dr. Matthew Klein, Chief Executive Officer, for any closing remarks.
spk03: 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.
spk01: Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may now disconnect. Have a great day.
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