PTC Therapeutics, Inc. (PTCT) Earnings Call Transcript & Summary

[Audio Gap] My name is Geoff Meacham. I'm the senior biopharma analyst here, and I have Jarwei Fang from my team on here as well. We're thrilled today to have PTC Therapeutics. With us on stage is Matt Klein, CEO. Matt, welcome. Good to see you.

Thanks Geoff. Great to be here.

So lots of questions on Sephience and on your R&D Day. But maybe just for those on the webcast, just give us a bit of a quick background or overall, and then we can get right into it.

Yes, absolutely. So PTC is a global biopharmaceutical company. We are focused in rare diseases and other disorders of high unmet need. We have a robust commercial portfolio with 6 products that we market around the globe as well as an innovative R&D pipeline highlighted by our differentiated oral small molecule splicing programs. 2025 has been an incredibly successful year for us, highlighted by the U.S. and EU approval of Sephience, our oral therapy for PKU. As we shared at Q3 earnings, the launch is off to an incredibly strong start. And I'm proud to report we're seeing continued strong momentum into the fourth quarter. And as we've described, this is really a foundational product for PTC that will lead us to cash flow breakeven and beyond in the near future. So really excited to get into the questions and talk about the launch.

Yes. Yes. Let's do that. So when you think about PKU and the 341 patients on therapy, it looks pretty good for the first quarter, right? So what were the -- I know you had from the clinical development, a pretty good idea of the backlog of patients. But help us with kind of the execution of the early part of the launch with the time from diagnosis to script to getting a paid for to delivering drug. How seamless are you? And where could you go?

Yes, absolutely. So we've said all along that we believe that the opportunity in PKU for Sephience was pretty unique. It's a rare disease in the U.S. There's about 17,000 patients. And despite there being 2 approved therapies, there remains a significant unmet need for the vast majority of patients. So in one way, you have a lot of the pillars for commercial success already in place with newborn screening, centers of excellence identified, a well-aggregated patient community, given the fact that there have been previously approved therapies, you have payers that understand the disease. They know how to tie value for a product to phenylalanine lowering. And this is the context we walked into with Sephience, which is a highly differentiated product. It has a dual mechanism of action, allowing it to have effect in those who may have benefited from the oral therapy, sepiapterin. And also, given the second mechanism of action as a chaperone allows us to have benefit in the more severe patients, classical PKU patients who currently aren't met by the existing oral therapy or not met by the injection therapy, which has a challenging tolerability and safety profile. And so we basically had a drug that could be for the full spectrum of patients which obviously, in this context of 17,000 patients with large unmet need, really represented a big opportunity. I would also add that we have a commercial team, customer-facing teams that's well experienced in rare disease drug launches. We understand what it takes to get patients on drug, keep them on drug, actively engage with the patient community. We have our PTC Cares team, which is our patient services team, which provides the necessary white glove service from PSF to prescription fill to refill. So that's really the backdrop that we -- the launch had. And so when we see the early success, for us, it really wasn't surprising. It was really a product of the context of the commercial landscape, a highly differentiated product and a really experienced team. And so with the early launch numbers being so strong, we see continued momentum into the fourth quarter, and we'll obviously give the next update at JPMorgan, but we're continuing to see strong enthusiasm from the prescriber community across all patient segments, including the most severe patients, strong enthusiasm from the patient community and simply looking on social media and hearing patients tell the stories about being able to have foods that they never tried before, what that means to kids, what it means to adults, what it means to families. These are incredibly compelling stories that continue to fuel the interest to be on Sephience. In terms of the time, you had asked about the time it's taking to get on drug. We're seeing -- in the early days, it's been quite fast. I think we said on average, we're seeing 2 to 4 weeks from PSF to getting on drug. Those numbers are continuing thus far. And again, we think part of that is the the fact that there is this unmet need. We have an experienced team that knows how to get PSFs in, get them processed quickly and get to patients quickly and also knowing how to appropriately work with the prescribers' offices and work with payers and things so that if there are questions or if there is a need for a prior auth, if there's a need for a letter medical exception, that can all get accomplished pretty quickly.

Let me follow up on that. So if you have prior auth or step edits or a letter of exception, are there success stories that maybe to go through that at an accelerated path that you can maybe translate as you roll out across the U.S. and more -- maybe on a more global basis?

Absolutely. So first, a couple of things. One is the prior auths, we're getting a prior auth to the label. The label is incredibly broad. It's basically 1 month of age and above. That's in the U.S.. Outside of the U.S. and Europe, there's no lower age limit. So a prior auth to the label is really easily achieved. In terms of other things that we have in cases of -- we haven't really seen step edit issues. One of the important data pieces we have is our AMPLIFY study. And this was a study we shared the results from -- in September at the International Metabolic meeting. This was a head-to-head study with BH4. It was a crossover study. So while in our Phase III study, we had very good data on patients who had been on Kuvan previously generic or branded, showing superiority with Sephience, while based on mechanism of action, it's very clear that if you have a response to sepiapterin, you're going to have a much greater response to Sephience. This was a head-to-head study. So we could say within each subject, how does Sephience perform. And the key data result from that was the fact that we had 70%, 7-0 percent greater lowering with Sephience relative to BH4. So when you have that data piece and you could give that to a payer, it substantiates that we have a highly differentiated therapy and that an individual who may have been on Kuvan brand that are generic or had not tried it is going to do better on our therapy.

So maybe on the differentiated data, you mentioned that there is extreme -- a lot of excitement on social media for Sephience and also among docs that we've spoken with, right? There's a pretty high awareness of the product. I'd love to hear your thoughts on how adoption patterns are looking across different patient segments, whether it be classical versus nonclassical, naive versus switches and how the conversion and persistence may be differ by the different segments of patients?

Yes, absolutely. I think one of the things we shared at Q3 earnings at the first update that was really exciting is in these early days of the launch, we're seeing uptake across every segment. We are seeing some switches from Kuvan. We've even seen switch or 2 from Palynziq, which was not expected early on. We're seeing therapy-naive patients who maybe weren't tried on existing therapies because they had mutations that were thought to be "non-BH4 responsive". And with the data we have showing ability to treat those patients, they're getting on drug. We've had patients as young as 2 months of age. We had a 79-year-old get on drug. And all of these things really go to say -- go to substantiate this idea that we have the ability to address the full spectrum of disease. We're seeing early uptake from the full spectrum. We're getting patients. We're getting feedback, social media, physicians giving feedback saying, "Look, I'm trying my more severe patients on first." We had one prominent KOL talk about a severe and classical patient had 90% reduction in Phe very quickly. So those stories go a long way in continuing to drive enthusiasm for each of those segments. I think it's also important to highlight that the early success, the early numbers were not driven solely by Kuvan switches. A lot of people said, oh, that's going to be the low-hanging fruit because, of course, if there's any response at all to Kuvan branded a generic, there will be a more -- a greater response, whether that be in Phe lowering or Phe lowering and diet liberization. And afore, that made that easy population to get on drug because you'd be swapping one once-a-day for a more effective once-a-day therapy. The fact that these early numbers weren't driven by that really supports the fact that we've got a long way to go in penetrating each of these segments, which again gives us the tremendous enthusiasm that this is going to be a very successful product, certainly when you consider the size of the population and what one would think about in terms of potential penetration for a differentiated rare disease product.

So you mentioned that one of the patients were in their 70s, which is honestly incredible, right? Because a lot of times in these rare disease spaces such as PKU, if patients aren't well controlled, they kind of just drop off and they are not followed up anymore. And the fact that you guys were able to get somebody like that is pretty astounding, really. And then you also mentioned that you have diet liberalization data. So maybe tell us a bit about how getting those loss to follow-up patients and how dilberalization data, how do they all tie in together to help get patients that maybe you didn't initially plan on capturing so early?

Yes. I think, Jarwei, this concept of loss to follow-up, I think, is a little bit -- I think it's a misconception. I think we hear -- I can say this as a physician. Physicians like to talk a lot about patients are lost to follow-up. And one shouldn't confuse someone not coming to clinic with not being interested in being on a therapy that could help them. The reason they don't come to clinic is because they're not getting something from the clinic that's helping them. In fact, if you listen to some of the adult patients who are thrown in that loss to follow-up bucket, they'll say, "I'm not lost, I'm right here. I have social media. I actually want to be on a therapy. And I don't go to the doctor's office because I don't want to be yelled that for having Phe levels that are out of control." Many of them will say that while I don't see the physician, I'm in touch with the dietitian because they really help me manage my diet. And so I think this concept of this loss to followup bucket is a little bit of a construct of docs thinking just because someone doesn't see them doesn't want me they want to be on therapy. Now admittedly, these are -- we would not have thought that, that was the -- I also hate the term low-hanging fruit, but let's just say the first layer of patients to get on a launch, but what it speaks to, I think, is what we knew to be true. that there's a strong desire for folks to get on a drug that can make them feel better because having lowering phenylalanine can help in terms of neurological function, executive function, cognitive function, and as you alluded to, the potential to liberalize your diet. In PKU, if you're not on a therapy and even if you are on one, really your standard of care is a highly restrictive onerous diet. And so the ability to get on a drug like Sephience that has the potential to allow you to start to scale back from that and enjoy foods that you never enjoyed before. I think it's so hard for us to imagine what that's like. And you look on social media and you see these stories of kid eating a cheeseburger for the first time, a mom talking about being able to have breakfast, the same breakfast with their kid for the first time, these are transformational stories. These are really meaningful testimony that not only supports the benefit of the drug, but also helps spread the word about the benefit and obviously garners tremendous interest for individuals with PKU to try the drug.

Matt, I wanted to ask you, as you think about the globalization of the launch, so Europe, maybe Brazil, Japan, broadly, what are the nuances in each of the markets from standards of care that you'll have to navigate that -- obviously, you have a super experienced commercial team, but that's going to have to be part of the conversation, right?

Yes, absolutely, Geoff. And we spent a lot of time planning for this launch. We said this would be a global launch. And in fact, we launched in Europe and the U.S. almost the same time, which is pretty unique, but we have the infrastructure, the experience to do it. We mentioned that later this year, I know we're in December, but we're still expecting before the end of the year approvals as well in Japan and Brazil, where we have infrastructure and teams ready to go in terms of launch. And we've been very thoughtful about price corridor. That's something that we take very seriously always. And I think in the era of MFN, it's something that we have to really think about, and we said that we have a price in the U.S. and Germany that are currently on par. We have patients outside of Germany who are looking to get on drug through early access programs, again, where we can help control the price as we go through pricing and reimbursement negotiations. And it may be in certain countries, to your question that we'll have to have discussions around price and volume and are there going to be certain patients who may get covered, may not get or get covered at different levels. And those are all things that we'll navigate in Europe. In Japan, this is a country where Kuvan and Palynziq, it's called Biopterin and Palynziq in Japan are actually priced at a premium to the U.S. And so again, in terms of maintaining the corridor, we expect to be able to do so there. And in Brazil, our teams have a lot of experience. I mean we market Translarna, Tegsedi, Waylivra there. And so introducing Sephience and understanding the dynamics and our teams there are fantastic. They've already done a great deal of work mapping different clinics, understanding where -- which are the patient groups that we think we could access early on through the judicialization process before we get formal access and coverage. And so we have all of that mapped out.

Do you have to navigate guidelines or quality analyses like as you look to some of these markets?

I think the big thing here is there are guidelines. And again, this is when we talk about coming into a well-organized community, it includes having guidelines in terms of targets for Phe lowering. In the U.S., the target for Phe lowering is 360 like the [indiscernible] leaders. Yes. And so -- and that's why in our trial being able to have 84% of patients get below 360 is really a strong data point. In Europe, it's 600 in some cases. So these are -- so that number is out there, and that's the threshold. And the other trick question in Europe is, in many cases, medical foods and formulas are. So having, Jarwei, as you mentioned, the diet liberalization data where we had 97 patients -- 97% of patients in the open-label extension be able to liberalize their diet at all, 2/3 of patients being able to get to levels of protein beyond the recommended daily allowance allows us to say when we talk to go through payer negotiations in Europe that we have data to say that this drug will actually lower the need to support medical foods in part. So that becomes an important part of the discussion.

Yes. And just in that same context, what investments -- have you seen the early part of the launch here? And I imagine you see the anticipated future demand, what investments incrementally are you investing in manufacturing, supply chain kind of thing, just to make sure that you can meet the demand?

Yes. This is I'm smiling as I answered it because these are the kinds of things we do in-house, right? We say what -- I'm very -- our teams and management teams what could go wrong from day 1 and have plan A, plan B, plan C, plan D, right? We're always thinking about these things. And so clearly, when we -- as we think about the tremendous potential demand for the drug, having supply is key, right, maintaining supply. So we've done this. We started with initially API manufacturer. We've now expanded to 2. We're going to be looking to possibly add a third. We have additional drug product manufacturers, making sure that we can meet what we believe will be very strong global demand.

And so maybe thinking about what you mentioned earlier about the different guidelines depending on country. So as you begin to engage with the regulatory entities in each of those geographies, what part of the data packages of Sephience do you think will be important to highlight? Would there be differences in Japan versus EU versus Brazil and...

Yes. I think one of the beauties of the Sephience data package -- of the regulatory package is just how strong the data are. I mean it's -- we look at it and see the primary endpoints and secondary endpoints with less than 0.0001 significance, right? I mean that's -- the whole package is so strong and the fact that we can -- we have data that speak to Phe lowering being incredibly strong, Phe lowering across the full population, the proportion of patients, we -- over 75% in the trial would have met the definition of responder with over 15% reduction. Then being able to bring in the guidelines, 84% getting below 360 micromolar per liter, then the diet liberalization data being able to show this proportion of patients has significant lowering and being able to say that we're seeing these benefits in every age group. So in a way, no matter what a regulatory agency may want to see, I think we have the luxury with the strength of this data package to be able to address any concern that comes at you. And I think we've all been around long enough. That's a pretty rare situation to be able to do that. And that's part of why this has been so exciting for us.

And I think earlier, it's apparent that excitement for Sephience on social media is quite large. And -- but maybe help us understand how -- I don't want to say ramping, but how wide is the awareness perhaps on a global scale, right? Is it just U.S.-centric? Or will social media help drive awareness of Sephience and its benefits on a global basis as you guys begin rolling out?

So the short answer is it's strong globally. In the U.S., we've done a lot of work. We've got -- and part of this is the drugs incredibly -- has an incredibly strong track record thus far. And there's no better spokesperson for the drug than someone who's been on it and had benefit. And so it's 2025, right? Social media and patient-to-patient communication is a very, very strong component of -- I'll put marketing in quotes, but just getting the word out about the therapy. But we're seeing as well that there's well-aggregated patient communities globally. We've been -- we went to the ES PKU meeting. Our teams were there in Hamburg, Germany in September, a very well-organized community in Europe. And then in each country in Europe, there's PKU groups. And again, I think this is something that having an experienced team that's a patient engagement team, global patient engagement team and understanding how important it is to work with the community and work with the community in a way that's not really -- it's not only about Sephience, it's about truly helping the community, helping with disease awareness, understanding what's important. All of those things go a really long way in igniting patient awareness and enthusiasm.

Matt, I want to ask you just -- you have some very good market data from the entire clinical development path and then the duration of therapy. But are there other insights you can gain from pre-approval that the development, things like what helps to keep people on compliant persistence rates, things like that?

Yes, absolutely. So we know that what really helps with adherence is one, do you feel better, which I know sounds obvious. But for a lot of individuals with PKU, they will tell you that their brain is like a Phe monitor. And when their levels get different from what they're used to or they go higher, they'll have brain fog. We had one individual who is speaking with us who said, she knows on days that her Phe levels off. She just used the GPS to get home from work, which just tell you, they know things. The other part is knowing the Phe levels lower and then, of course, diet liberalization, being able to liberalize diet is incredibly important. And we're continuing to garner data as well. For example, at the International Metabolism Meeting in Kyoto in September, we presented some QOL, quality of life data that included evidence of significant benefit after a relatively short period of time on executive functioning, on cognitive function, on mood. And these are things that are really, really important for individuals with PKU.

Yes. Makes sense.

So Matt, maybe thinking about the strategy of -- or maybe the future development of PKU treatment. Obviously, with Sephience, that's a novel new asset that's being marketed now. But there are other mechanisms such as SLCA or SLC6A19 my gosh, what a mouthful, inhibition that may be coming. Maybe help us understand where that might fit in the paradigm of PKU treatment and how maybe it may even be paired with Sephience use for...

Look, there's 2 therapies targeting that renal transporter of amino acids. I think it's a very interesting approach. Clearly, like most things early on, things could look good, but there's still a lot of questions, for example, what -- given the fact that this is a transporter in the renal tubule that's not only responsible for phenylalanine reabsorption, but all branch chain amino acids an important open question about potential effects of causing depletion of other amino acids that could be important. So that's an open question. And certainly, the Otsuka trial, I believe, is being conducted now in adults. So there's an open question, will it be in children? What's that about? And their protocol, in fact, allows for using that experimental therapy on top of existing therapies, Jarwei. So I think that answers your question. I think this is envisioned to be something that can be used on top of an existing therapy. Clearly, a lot to be learned a long way to go. We're also comforted by the fact that we're going to be well into our launch before these products come to market. So I think it could be an opportunity to see how they are on top of Sephience, but I expect by the time they come to market, we'll have very broad penetration.

We do want to give airtime to other parts of the business. But maybe, Matt, if you could talk through just the R&D Day, kind of some of the high-level takeaways, and then we can get into maybe Translarna and other elements.

Yes, absolutely. Happy to talk about the rest of the business. Clearly, the #1 focus for us inside PTC right now is, of course, the Sephience launch and continued execution on that launch because as I said, we think this is going to be incredibly successful for patients and for us. But we do have other parts of the business, and we do have the R&D Day. And part of that was to basically say, look, I think people have been paying a lot of attention to our focus and execution on the late-stage programs on the commercial front over the past couple of years. But behind the scenes, we've also been doing some work. Our R&D teams have been doing work to advance a whole new set of programs. I think one of the most exciting things that we were able to share at R&D Day is the incredible, really incredible evolution of our small molecule splicing platform. This 20 years ago, and we started working on small molecule splicing seemed like this radical concept that you would use an oral molecule to affect RNA, basically doing genetic manipulation with a pill seem crazy. How could you ever get the necessary sequence specificity and such? And now that's clearly a very well-validated approach with the success of Evrysdi, which was the first compound we discovered. Now Votoplam, which is in Phase II, which is the leading oral therapy for disease-modifying therapy for Huntington's disease. And so while the world has been focusing on those 2 drugs and their success, we've been able to make a number of important advances in the lab, the most significant of which is saying, while initially, we focused on a very small as a target for both Evrysdi and Votoplam, we've now found that there's about 256 additional sequences that could be targeted for small molecule splicing. That was something we elucidated. And we've also now gone and seen that we have chemical matter possibly talk to those new targets. So what we have basically is a highly differentiated, valuable small molecule RNA platform that we think holds tremendous potential to be a really incredibly important source of impactful and innovative therapies that PTC can develop and commercialize, but can also be the source of strategic partnerships because we know, for example, there's important splicing targets in oncology. There's important splicing targets in neurodegenerative disease. And so those may be areas where we're not going to go as a company, but we have certainly the ability to think about strategic partnerships. So as we think to the future of the company, clearly, we're focused on the Sephience launch and execution there, but we also have sort of a goose that's laid 2 golden eggs already that we've only gotten smarter and better at learning how to leverage for future therapies.

So I guess that's the follow-up is that the filter is rare for you'll keep in-house and opportunities outside of that more likely to out-license?

Absolutely. We shared a number of programs the other day. We shared 5 new splicing programs. They're all early stage, and we have small teams working on those. We also shared programs from our inflammation platform, which some targets that are very familiar to people that we have a very differentiated approach to. And the same thing there. There will be some that will be for us and some.

Do you have a number in mind in terms of the R&D and the D capacity? Is it 1 IND per year? Is it 2? So that used to be an old metric, right, but now people are talking about that.

Yes. Again, I think -- so I think we don't have a specific limit in mind. However, we -- I want to be very clear that one of the things that we've been extraordinarily thoughtful and careful about is managing our expenses. And that's something we're going to continue to do. We've committed the company 2 years ago, I stood up and said we're going to move to get to cash flow breakeven in the near future. I stand by that. We'll update that guidance at JPMorgan. Again, with a focus on the success of Sephience, that's going to drive our top line. We've said that we plan to reduce OpEx in '26 relative to '25. Very simple math tells you we're going to be getting very close to that point. And we're going to manage our expenses in the earlier parts of the pipeline to make sure that we're not violating that. And I think that's where this model of partnership as well as internal development, balancing that is one way to ensure that we're bringing things forward, but we're not overburdening our expense or our corporate focus.

And as you've had to invest in R&D, manufacturing and have had to acknowledge the MFN. Tell me about your engagement with the administration, how over the course of this year has it evolved?

With the...

White House.

White House?

Usually, that's a large-cap conversation. But you guys are a global company and you've hitting all the right use of elements.

And we're quite aware of these things, right? I mean we have a very -- look, we have a very active government affairs team. We all spend a lot of time in D.C., making sure we're well aware of how specific topics can impact our business. We've taken the approach with MFN, as I mentioned. In fact, it wasn't a stretch because, again, our commitment to maintaining a narrow corridor really was consistent with what one would think about in MFN capacity. I mean there's other things that are very important to us as well. In rare disease, the renewal of the voucher has been something that's been very important. And with the House passing what we think will be a bill that will get through the Senate to renew the priority review voucher, that's very important to us. There's something about R&D amortization. Those types of things have been areas of active engagement for us as well. So we have been active on all those fronts. I don't expect we'll be...

Probably not on the radar...

Exactly. Yes. I think there's a lot of important things going on right now. I think the FDA, the commissioner has been quite outspoken. He was here a couple of days ago, reaffirming his commitment to flexibility and innovation, explicitly calling out neurology, I believe, as an area where the agency has to be forward thinking, and that's obviously near and dear to us with several things at FDA. And so we've been quite active, I'd say under the radar. But I think we've been making sure that we partner with the appropriate people where there's shared agendas to ensure that we can not only help our business but the global community.

So I think that would be a great segue over to Votoplam and the Huntington's disease program that you guys have partnered with Novartis. I mean, like you mentioned, Commissioner Makary highlighted that the agency is now very committed to increasing flexibility to get these drugs for high unmet need indications to market, and Huntington's is a great example of that, isn't it? And so as you guys are engaging with them, planning for Phase III and then maybe even potential for an accelerated approval pathway, how do you think this increased flexibility and then also your existence of placebo-controlled data differentiates Votoplam from maybe some of the other programs out there?

Yes. I think it's incredibly important to highlight how differentiated Votoplam is and from gene therapy, which may be what you're alluding to that there was news on this morning. I mean we have an oral small molecule. We have placebo-controlled data. We have a study with -- a Phase II study with open-label extension with over 140 patients. We also importantly have objective measurement of target engagement mechanism of action, which is really, really important when you think about the accelerated approval framework, right? Because an accelerated approval, the idea is you have to demonstrate that you have data to suggest that you're likely to have subsequent definitive clinical efficacy. But one important component of that is being able to show that the drug is working the way the drug has to work in order to register the efficacy. And so one of the primary endpoint of the Votoplam Phase II trial was Huntington lowering. Why? Because that's how the drug works. And if we're not -- if we're going to have ultimate clinical efficacy, we have to be having evidence that we're lowering Huntington protein, and we did. We had dose-dependent lowering and lowering with 2 different dose levels of a magnitude that has been associated with clinical benefit. So all that is to say, I think we have a very differentiated program that would address a lot of the concerns one may have had in looking at the gene therapy. So we're very -- we're differentiated. And then the second part is, I think Novartis shared they had a recent Meet the Management event in November, and there was a separate neurology group discussion, and they emphasized there how constructive our discussions with FDA have been and how there's a very clear shared view of the significant unmet need for Huntington's disease. And of course, I think the neurology division in Cedar has been -- has demonstrated itself to leverage flexibility certainly when it comes to devastating neurodegenerative disorders like ALS, like Alzheimer's. So we're excited to continue to work with them. Novartis also shared that they're full speed ahead on getting that next trial started, whether that's going to be a confirmatory study in the context of a potential accelerated approval or a registration trial if the accelerated approval portal is not available.

Can you just characterize maybe your level of engagement with them on trial design, regulatory strategy? I wasn't sure if it's more proactive, passive, active, like just help talk about that.

Yes. I think it's been an incredibly productive collaboration, Geoff. I think we -- from a corporate leadership level, I think we're very aligned in terms of our shared enthusiasm for Votoplam, our desire to move forward as quickly as possible. I think this is one of the things that we valued in selecting Novartis as a partner. And then the working groups, the joint clinical development teams work very closely together. And I think it's a great example of how I think the best of both companies comes together. There are certain strengths that I think PTC has and there's absolutely strength that Novartis has in experience and execution and thinking about a development program of things that you can do in parallel that may have been cost prohibitive for a company like PTC to do in parallel, they can deal in. And so I think we have a really promising molecule, a great collaboration and really a strong desire to bring this forward. And I think the recent news and the concern in the community with the discussions with uniQure and FDA, which have brought a lot of concern about the regulatory potential and also about whether there can be a drug for HD. I think, again, given the fact that we're in a much different context with this molecule continues to have us be very enthusiastic along with Novartis that there's a potential path here that we're keen to drive through.

Great. And so maybe in the last 5 minutes, we can switch over to vatiquinone and then maybe real quick on Translarna at the end. So vatiquinone, we know that the CRL definitely was a disappointment. I'd love to hear your thoughts on were there any elements from FDA's feedback that surprised you given, again, like you guys hit on mFARS subdomains and upright stability with stat-sig. And then in your continued engagement with the agency, what have your feedback had been on maybe the path forward and how might perhaps a new Phase III be different from MOVE-FA?

Yes. I would say the CRL was disappointing, but the reasons for the CRL were not surprising in that we knew all along the major question in this review was whether they would say that the evidence of statistical significant benefit with the upright stability scale, though not prespecified as the primary endpoint, would it be sufficient to provide substantial evidence of effectiveness and approval. That was the question going into it. And I think if you look at the CRL, that was really the main point in the CRL. There are a few other things they threw in there were other sort of, let's just say, statistical pile on, but the real issue here was you prespecified the whole scale, you didn't prespecify upright stability you missed. And that's really interesting because that basically says this was -- not that the drug didn't work. It was that there was something about that endpoint that wasn't learned until after we started the Phase III trial. And it was the old thing if we knew now -- if we knew then what we knew now, we would have done things differently. And that was the discussion with FDA that ultimately led them to say, yes, let's -- you should submit. And this will be a review issue because it was very clear that the upright stability scale is the most sensitive and meaningful component of the mFARS for the pediatric and young adult population enrolled in the MOVE-FA study. And that was really driven home by the fact that when you looked at the placebo curves, the placebo group had no progression, no progression on 3 of the 4 scales. The only scale on which the placebo group progressed was upright stability. This wasn't a chance finding. It was the only subscale in which you could register disease -- slowing of disease progression because it was the only scale in which patients would progress. So that was all the evidence that led to FDA agreeing that these would be review things that we should submit. We look forward to having a meeting with FDA in the fourth quarter. I know we're December, but we're still in the fourth quarter, and there's still some quarter to go. And I think we look forward to those discussions to say, is there any other potential pathway here? Could upright stability be an intermediate clinical endpoint. If we're doing another Phase III trial, what would they like to see? And if the answer is it has to be another placebo-controlled trial, that's something we will look at. We'll look at -- do an assessment of the marketplace, the commercial opportunity today, the commercial opportunity when that study will be done, the cost of the study, whether we -- what we think is the likely outcome. So the typical things you would do in assessing initiation of a trial before we make the final decision.

And so just real quick, sorry. Maybe thinking about a global perspective, could there be a possibility that maybe other regulatory agencies, maybe EMA might be more amenable to move that data and perhaps you can progress there before a new Phase III were to start in the U.S.

Yes. Those are all things that we'll look at. I think what we -- we had had initial feedback from FDA and EMA, and we decided that the initial FDA feedback supported filing in the U.S. So we prioritize that. We will, of course, have conversations with EMA and FDA as we plot the next steps.

And last minute or last but not least, Translarna in Europe. Just tell us kind of the next steps from here.

Absolutely. So in Europe, we're in a unique situation where we have a therapy that's not licensed, but we're continuing to sell. And I hold that out as further evidence of the strength of our customer-facing teams. I mean the ability to be on the ground and understand how to navigate local regulatory authorities, be able to continue to manage selling a drug where it's not approved. We said that we expected in the short term to be able to maintain about 25% of the European business. That's what we're seeing. The drug is now available in about a little more than half of the countries in Europe. Over time, we'll see. We expect heading into '26 to be able to continue that momentum. One of the factors to watch is the availability of other therapies. There are no other genetic therapies targeting nonsense mutation. There was the potential theoretically for the gene therapy, but the CHMP gave that a negative opinion, so that's not coming. So there's not really another viable genetic targeted option in Europe, and we'll continue to work and keep patients on therapy as long as we can.

Okay. Thank you very much.

Thank you. Thank you both.