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

Good morning, everyone. I'm Paul Choi, and I cover the biotechnology sector here at the firm. And it's my pleasure to welcome PTC Therapeutics for our next session here. To my immediate left is our CEO, Matt Klein, and to my far left, Pierre Gravier, CFO. Maybe what we'll do is turn it over to Matt to kick it off maybe with some high-level comments just on sort of the course of the year ahead. And then maybe we'll get into Q&A, talk a little bit about the commercial side, but what is obviously a very exciting pipeline stage period for the company.

Yes. Thanks a lot, Paul. It's great to be here. And indeed, we're at a very exciting time for the company. We're coming off an incredibly successful 2024, where we had outstanding execution across every part of the company. We had 4 FDA NDA submissions, all of which were accepted for review with one approval coming last year and now it's 3 approval applications pending, including our Sephience NDA from which we expect an approval within the next 6 weeks or so. So really coming up fast. We had another year of strong revenue performance, and effective operating expense management that put us in a very strong cash position. We closed Q1 with over $2 billion in cash in the bank. And that really provides us a solid foundation to successfully [indiscernible] the planned launches, continue to advance our R&D portfolios and also think about strategic business development to complement our existing R&D and commercial portfolios. So as we sit here today, we have a solid foundation in terms of cash on the balance sheet, a solid revenue opportunity forthcoming with PKU, potential upside scenarios, including the Friedreich's Ataxia program, potential approval in August, Translarna in the U.S. as well as our PTC518 program for which we announced a successful Phase II data package last month. So really a lot of exciting things going on and look forward to discussing.

Great. Maybe we can just start with sort of the existing commercial portfolio and talking a little bit about the sort of legacy products for lack of a better term, and given the regulatory change with Translarna in Europe, maybe just to kick it off there. You've previously talked about maybe roughly 1/4 of that business being maintained. How is that transition going since the decision, sort of intra-quarter, what updates can you give there? And then maybe just how you're thinking about that on the forward as sort of you're thinking about strategic landing and sort of the base case?

Absolutely. I think Translarna in Europe is again proving to be an unprecedented story. We had the adoption by the European Commission of the CHMP opinion at the end of March. So while in first quarter revenue was in line with that run rate for 2024, we did share that given that the European Commission invoked something called Article 117, which enables each individual country within Europe to make a decision to potentially continue to commercialize Translarna in spite of the lack of renewal of the marketing authorization. And this is something our team has been planning for. And in fact, as we sit here today, more than half of the countries in Europe have expressed the desire to continue to commercialize the drug. We've been importing drug into a number of countries. This has included providing continuity of Translarna therapy for those who've previously been on drug, and in some cases, even discussion about starting new patients. So we're, again, in these unprecedented waters that despite not having the marketing authorization, we are still able to commercialize the therapy. And so this -- as we said, we believe can allow us to maintain about 25% to 30% of the European revenue which represented about 40% of the overall Translarna revenue for 2024. And so exactly as you framed it, Paul, these are, sort of the legacy products that have been able to bridge us quite well to the future products, PKU and others. And we're still in a position to garner meaningful revenue, both in Europe and outside of Europe and other countries with Translarna as we continue to move forward.

Right. Maybe one more question on the topic before moving on is just how you think about the potential durability of that revenue in Europe. I think a lot of investors when they ask what's an analog here, I'm like, I really can't think of one. And so how does the investment community model this and think about [indiscernible] you just take it out of the model altogether. .

Yes, I think there's no analog. I think we're comfortable with that 25% to 30% for the foreseeable future, in particular because there's really no therapy that can supplant Translarna even if you look at what may or may not happen with gene therapy in Europe. We know that many of the nonsense mutations that the Translarna patients have sit in exons that may be relatively contraindicated for the gene therapy. And when you also consider that CHMP, I believe, is looking at a potential label of 4- to 7-year olds. So again, so there's no situation we see in the near future, intermediate-term future, where there'll be a replacement for Translarna.

Great. Maybe turning to some of your pending commercial stage assets and starting with Sephience. I think this is the asset that investors primarily focused on as they think about what PTC looks like in the future here. Maybe you could frame for us, you've characterized it as potentially $1 billion opportunity, but the analog drugs in the PKU space have certainly not come up to that level of sales. So can you maybe just frame for us what is the unmet need, I guess, in the PKU community right now, that's not addressed by the currently available therapies?

Yes. I think Sephience is a highly differentiated therapy. Its efficacy and safety package is highly differentiated from the current approved therapies, which is why the market opportunity far surpasses that which has been achieved in the current therapies. It's estimated that roughly about 10% to 15% of the 15,000 to 17,000 patients in the U.S. are on these therapies, which leaves a significant unmet need of 85% to 90% of the population. And so we've talked a lot about the significant opportunity that's based in part on the size of this population, the strength of our data, which supports that we can address every key patient segment including the more severe classical PKU patients. We've shared that we have plans to price this at a premium to Palynziq, which is supported by the payers. In fact, there was a note recently that came out on payers' response and the net conclusion was, as we said, there should be no barriers to getting Sephience to all of these patients. And finally, our established commercial team. We have -- this is the team that has successfully commercialized Emflaza has continued to enjoy significant revenues post loss of exclusivity, they've been able to successfully navigate competitive and genericized markets. And that's not only our field force teams, but also having things like our PTC Cares patient services team that ensures high levels of adherence to therapy, helps navigate through prior auths and re-auths in DMD, which is far more complex than PKU. And now we're seeing more and more research done by others which is supporting that, I think numbers such as over 80% of physicians are going to switch their -- or physicians think over 80% of their patients on current therapies, they'll look to switch. Over 50% say that they're going to look to try all patients on PKU. So when you start looking at what penetration could look like in a market of 15,000 to 17,000 patients with the potential net pricing we've talked about, the math to get to $1 billion alone in the United States is quite easy. And then when you layer on top of that, that we have a team in place that knows how to successfully commercialize rare disease therapies.

Great. Maybe can you remind us like in terms of the treating community within PKU and endocrinologists, metabology-focused treatment centers versus sort of your rare neuro orphan call points, how much of that is overlapping and just how much will require a bit of a new build out to hit these new call points?

So there's about -- there's 103 PKU expert centers in the U.S. and a lot of those centers overlap with the centers that we have worked at before, which is what's really important, while the specific physicians may differ, you're in the same hospitals, same pharmacies, same things to navigate in terms of getting on formulary and getting all that is -- and we've done the work already to -- we've mapped those centers, map the KOLs, understanding the treatment teams. It's very important in PKU to understand that not only are there physicians driving prescribing decisions, but nurse practitioners and also importantly, dieticians. . Patients who have PKU may not be on an existing therapy, yet they remain -- they maintain their connections with these specialty centers, in particular, with the nutritionists and dieticians because then the mainstay of their therapy is the diet. And so understanding those interactions at each center, understanding who we need to work with to drive prescriptions and manage patient care. We've been doing all that. I mean this is an advantage, not only of having an experienced commercial team, but coming into a commercial landscape where there have been therapies because often, what we'll have to do when you're first to a therapeutic area is talk to centers and educate them about prescribing a commercial drug, you have to aggregate the patient communities. In many cases, you have to do patient finding. Well, we're in a situation now where there's newborn screening for PKU. So the patients are all identified. And there's about 300 to 350 new patients identified every year, not by us, just by newborn screening. The centers are identified, centers of excellence are there. There's an understanding and a culture of understanding about what it's like to prescribe a therapy. When we talk to payers, they [indiscernible] and importantly, they understand that you could tie value to phenylalanine levels so that when we're able to come in and say, look at our clinical trials at the high level of phenylalanine lowering we're achieving, 69% on average in classic PKU patients, getting 84% of patients to less than 360, which is the threshold for desired phenylalanine where you can start liberalizing. All those things are really, really important and facilitate our launch.

Great. I think in terms of time lines, Europe might be a little bit ahead, and so is the thinking that you'll presumably launch ahead in Europe, just given the regulatory time line on the calendars as a little bit in advance of the U.S. PDUFA here?

Yes, they will actually be very close in time. So the plan, we're expecting to have the approval in Europe before the end of June. Our plan is to launch first in Germany, taking advantage of that 6 months of free pricing. A certain advanced notice needed before you list the price in the [indiscernible] tax in Germany, which is what kicks off your launch and your IRAD review and so forth. And so we'll probably then be in close to the same time. And obviously, we're thinking a lot about the free pricing level. What we've done in preparation in Germany where we think there's 8,000 patients, we've initiated an early access program. So we've already gotten a number of patients on drug in this period waiting for approval and launch, and we've gotten into a lot of the key centers in Germany. And that's really important because in Germany, once you're approved and launched and list the price of [indiscernible], those patients on early access right away by loss switch to commercial therapy. So we're doing everything we can to make that launch in Germany as robust as possible, as quickly as possible.

Great. Maybe in terms of the insurance preparations and your payer discussions, I'm just curious in terms of like the metrics and how payers will assess that. Clearly, the drug works very well on reducing fee levels. How does the diet liberalization sort of potentially figure in down the road after patients have been on therapy for future renewals, and continuous approval?

Yes. I think our feedback is there will, of course, be some payers for some patients that will want to ensure that patients are having a response to the drug. Our understanding is that's more going to be linked to fee reduction and not diet liberalization. Diet liberalization is incredibly important for patient uptake and physician uptake because for patients really, the holy grail is to be able to get to a point where they have control over their phenylalanine levels so that they can start to liberalize what is a debilitating a restricted diet. And so we fully expect that payers may, in certain cases, will want to see evidence of phenylalanine reduction, not necessarily liberalization, but blood test, which is objectively measured is in line with what we saw in clinical trials. So we're fully prepared for that. .

Great. You've also talked about a little bit -- you mentioned that you have some early access in Germany and just in terms of patient identification and potential pent-up demand here with the earliest part of the U.S. launch. Should we think about the early launches potentially having a bit of a bolus just given awareness of Sephience in the PKU community and just -- is that how you would sort of guide [indiscernible] to think about this an early buildup demand? .

Yes, there certainly is a pent-up demand, and that comes from several things, right? It comes from the fact that the data have been so strong that we've been able to show the diet liberalization. I just look on social media, and you see the patient's community generating their own buzz about the ability to liberalize their diet in a meaningful way. And the fact that you now have physicians, again, I said we've seen a number of these surveys saying that most physicians want to try all their patients on the drug. . Now what that first group looks like in the launch will differ center by center. We've had physicians say, look, we're going to take our patients who are on existing therapies and just switch them because we know if you've been on sepiapterin, either branded or generic, time and time again, you're going to have a much better response to Sephience. So that's what the data suggests. So it's very easy to take patients who are on a once-a-day therapy and switch them. Others say, look, we've got a bunch of therapy-naive or tried and failed patients tried existing therapies, have failed them, who we want to get on a therapy right away. And so I think we will see a lot of patients come on in the first phases of the launch, and that's due to the pent-up demand, due to the fact that these are centers that are used to the idea of having to prescribed drugs and the patients are identified, prevalent and desiring a safe and effective therapy.

Great. I think one question that our understanding of PKU outlook for you guys is just understanding how much of your IP is dependent on orphan or regulatory exclusivity versus other patent exclusivity? And I think it probably goes out further than people realize. And so can you maybe just remind us on what that IP landscape both on the regulatory side and the patent side looks like? .

Yes. So we'll certainly have the orphan exclusivity of 7 years, and we expect the pediatric add-on for 6 months. But we also have patent protection. We're guiding folks to 2039. We have 2038 in a very -- what we believe will be a very durable and strong polymorph patent that we've been able to further support with additional IP. And as is always the case, we're continuing to expand the IP landscape to keep putting fences around what we have. So for today, we're guiding to '39 on the back of patent protection, to '38 and what we believe conservatively is 1 year of patent term extension based on orange replicable patents.

Right. And one more for the investment community. Is this something they will be able to track through standard data sources like IQVIA? Will it be censored? Just how are we going to be able to sort of track the launch metrics?

It's going to come through us. So we're dealing with a closed specialty pharmacy network, so the prescription data will not be available. But when we get to launch when we get to approval in the U.S., we will share the metrics that we'll be sharing with everyone so we could track along and understand what the uptake is like and what adherence is like.

And maybe just at a high level, what would be the key things we should look for? Number of physicians, new prescribers, switches, what just -- maybe wrong things that we should look for? .

Yes. I think right now, as we're thinking about it, it is going to be patients on drug, and that's something that we can -- we should follow. And look, I think what we've talked a lot about is we expect, given the pent-up demand and all the things that we've talked about so far, Paul, is that you're going to see -- we expect a lot of patients to come on early, but we expect it to continue to grow. And we've talked a lot about these different patient segments. And again, I keep coming back to what we initially thought and what we're seeing more and more in surveys that are out there that there's a majority of physicians wanting to try all of their patients. And a lot of that is coming from the physician's own view of the drug, including recent data we've put out on mutation data, which shows that if you look purely on a mutation basis, over 70% of the patients in the APHENITY Phase III trial, technically have classical PKU. And if you see the level of phenylalanine reduction we're having there and the fact that we're having 2/3 of the patients get to over 30% reduction, 75% of patients get over 15% reduction, it's very easy to understand how this is a drug that can be a therapy for the majority of patients with PKU. And that's a very large opportunity.

That's great. Maybe switching gears to Friedreich's Ataxia. I think investors are watching the SKYCLARYS launch in Biogen. And which has been going reasonably well. But maybe you can highlight for us what are the sort of the key differences mechanistically for Vatiquinone versus SKYCLARYS to start? And then I have some commercial questions after that.

I think there's several important differences between the 2 therapies. Now mechanistically, there are different. SKYCLARYS the Nrf2 response pathway, which is part of the downstream antioxidant response pathway. We've talked about how Vatiquinone target 15-lipoxygenase, which is a key regulator of the oxidative stress and cell death pathway that's been intimately linked to Friedreich's Ataxia pathology, but perhaps from a practical standpoint and a commercial standpoint, what's more important is the fact that Vatiquinone would be a therapy for both children and adults. There's a large volume of safety and tolerability data accumulated in pediatric patients with Vatiquinone down to less than 1 year of age. And then, of course, the MOVE-FA trial was really focused in pediatric and young adult patients. And so to be able to now have efficacy data along with safety data, will allow Vatiquinone to be a patient -- a therapy for all patients with Friedreich's Ataxia regardless of age and regardless of disease stage. So as we think towards moving into a commercial landscape, I think clearly, the pediatric populations, we see about 6,000 patients with Friedreich's Ataxia in the U.S. and about 1/3 of them are pediatric. You're looking at the only therapy available for those patients. And then, of course, if you look to the experience with SKYCLARYS, which has at a lot of patient starts, but also patients who have challenges based on the tolerability profile, the monitoring requirements, we believe that Vatiquinone could also be a very meaningful treatment option for adults.

Okay. Great. Maybe parsing the commercial strategy for the 2 populations between the adult population and the pediatric population. As you think about the sort of the selling message for those 2 distinct populations, is it your thinking that you'll be able to primarily get adult patients who are treatment-naive or treatment-inexperience versus SKYCLARYS experience? How -- sort of what's the sort of low-hanging fruit in your mind? .

Yes. So the low-hanging fruit for sure, is the pediatric population. And the dynamics of the pediatric population differ quite a bit from the adult population. The pediatric FA patients, as we said, it's about 1/3 of population. They tend to be clustered at a small number of specialty centers that are pediatric neurology centers. We've worked with all of these centers. They've been in our trials, many of them have extensive experience with the drug. And again, if you read what the physicians are saying in different surveys of them, these doctors are saying they will look to get all of their pediatric and adolescent patients on Vatiquinone, if approved. So that's really good. That's the low-hanging fruit. Then you talk about a migration into the adult population, and we see that in 2 different buckets. One, as you said, is the sort of tried but didn't stay on SKYCLARYS due to monitoring issues, lipid level issues, LFT problems or other tolerability issues, and we see that as also sort of the second bucket of patients that we can easily access. And then I think you have those adults who are therapy or SKYCLARYS-naive, I think we can penetrate as well given what we expect to be the lack of a monitoring requirement, the lack of potentially need to go on a lipid-lowering therapy or having LFT abnormality. So I think that there's a very large opportunity for the drug. If you have -- unlike PKU, where we believe we would look at all of those segments pretty much at the time of launch. I think for Friedreich's Ataxia, we think it's going to be sort of the kids first. It's a significant unmet need. One of the interesting dynamics in the community, as always happens when a first drug is approved, is there's an increase in diagnosis of the disease, right? Is it just heightened disease awareness. And this has happened in Friedreich's Ataxia with the approval of SKYCLARYS. However, the patients getting diagnosed are younger. Again, not surprisingly, typically, what you'll see is the age of diagnosis move lower and lower as there's heightened disease awareness and a motivation to get a diagnosis. And so if anything, the approval of SKYCLARYS has heightened, heightened the unmet need in the younger patients, increase the numbers and increase the desire not only on patients but to physicians to be able to have a therapy that they can give to younger patients because, of course, if you're trying to slow progression of the disease, it's best to start as soon as possible.

Okay. Great. And then maybe just in terms of your latest thinking on pricing, there is there's a commercial analog out there in terms of SKYCLARYS, is that sort of a reasonable benchmark as investors model out this opportunity, both in the pediatric and adult segments?

Yes, I think so.

Okay. Okay. Great. Maybe one on Vatiquinone, which is just that it's regulatory time frame is a little bit behind that of Sephience, and so just given that we still have several months for that to go, are there any other regulatory interactions that are going to happen along the way, beyond perhaps regular way of -- potential label discussions? Any other material meetings of note? .

Yes. So we -- so our PDUFA date is August 19, as you indicated a bit after Sephience. We've had the mid-cycle meeting that went well. It was at the mid-cycle meeting that the agency shared with us that they do not expect to hold an AdCom. So that was an important update. We still will have a late cycle meeting and then, of course, labeling discussions still to come. .

Okay. Great. I want to talk and maybe switch gears to your recent PTC518 Huntington's update. Maybe, Matt, you could just sort of recap for us the latest set of data you presented from that program and just sort of -- then I have some follow-up questions on just sort of the development path there. .

Yes, absolutely. So I think as we look at the PTC518 data package in the Phase II PIVOT H2 trial, it ticked all the boxes it had to. We achieved the primary endpoint, we demonstrated that the drug is working the way it needs to work with dose -- continued dose-dependent reduction in Huntington protein levels in the cells. The drug continues to be safe and well tolerated, which is very, very important as we go out to longer terms. We had continued confirmation of CNS exposure, incredibly important for the drug that's working the way it works. We know it's going to where it's supposed to go. . We also saw in the data readout continued evidence in the short term at 12 months, dose-dependent effects on stage 2 patients on cUHDRS, total motor score, in cognitive function very important. And then importantly, in this update, we had the first group of patients out to 2 years. And in 24 months, patients who've gotten PTC518, not only is it safe and well tolerated, but we're seeing dose-dependent benefit on the cUHDRS disease rating scale relative to natural history as well as benefit on the total functional capacity and cognitive scales relative to natural history that was statistically significant. And we saw out of 2 years dose-dependent benefit lowering on neurofilament light chain. The natural history of Huntington's disease is to see gradual increases, and we're seeing decreases now out at 24 months. So that's really important. We also learned about study populations. And this was one of objectives of the PIVOT HD study to try to figure out in which group of patients we think would be the optimal future efficacy trial population. And what we clearly saw is what we suspected is that likely the stage 2 patients are those that are moving at the appropriate rate and that may be best suited to the population in whom we could capture significant effect. So when you take everything as -- when you take the data package as a whole, we achieved all the objectives for Phase II which positions us well to move forward with an efficacy study. We believe that the data also can support further discussions on the potential for accelerated approval. I think we've long talked about the potential surrogate endpoint of lowering Huntington protein. I think the recent correspondence from uniQure on their conversations with FDA about a potential intermediate clinical endpoint approach using long-term cUHDRS versus natural history data and NFL. I think we, now with this data set, are in play for that option is what we think our optionality in terms of what we could talk about supporting accelerated approval has gone up.

Yes. I mean it certainly seems like, to your point, bringing out uniQure's recent disclosures, just on the regulatory landscape, still seems supportive of a mix of biomarker and quasi-functional or some sort of hybrid endpoint in the space. And so I guess, in terms of next steps. First, when would you present any additional detailed data from a recent update at a medical meeting? Are there plans to do that over the course of 2025? And then sort of when would you and your partner Novartis potentially have regulatory interactions on a Phase III design?

Yes. So the teams are working on that right now on the interaction standpoint. I think what we've said all along even before the readout was that we'd be doing these things in parallel, moving forward with the Phase III trial and having discussions about accelerated approval, and the plan would be to have an FDA meeting where both things would be discussed sort of an end of Phase II meeting that could talk about the data package that would be needed to support accelerated approval knowing that we're continuing to harvest data from the open-label extension of PIVOT HD, and then, of course, what does that efficacy trial look like and trying to move as quickly as possible on both fronts. So the teams are actively working on that right now. I think we also all have in mind as well that the significant opportunity in HD is in stage 2 patients and earlier, right? And also trying to think about how do we get into stage 1 patients and then even earlier stage 0 patients where there's the undiagnosed patients, which is that, that population is multiples of the identified patients. So there's a lot of thought going into how we migrate earlier and earlier, which is what the patients want and what the physicians want. In terms of presentations at medical meetings, I think the teams are still looking at that. There's some HD meetings in the fall. I think that would be a good opportunity to give updates.

Okay. Great. Maybe just on your last point, Matt, of finding and identifying or potentially including earlier stage patients, how are these patients typically identified versus like the more symptomatic stage 2 and stage 3 patients that were in PIVOT HD. I'm sure most doctors don't typically scan for CAG repeats, but just kind of how are these patients potentially identified? And how good does it expand the pool for you? .

Yes. So if you think about Huntington's disease is pretty unique, right? And 100% of the patients have a genetic defect, and it's also uniquely autosomal dominant, which means that if your parent has it, you have a 50% chance of passing that on to your children. So there is then a lot of work in the community to get genetically diagnosed before you start having symptoms. Of course, that has a downside, if there's no therapy available, then you've just basically found out that you have a fatal disease that will have an onset at a certain amount of time. So a lot of this is going to be walking hand-in-hand with having therapy available. As we think about Stage 1 patients, which there's a large pool of as well, again, when we talk about a clinical trial, it's very hard to have an efficacy trial in patients who are not progressing a lot clinically, but that's a group that we can think about a biomarker strategy or something to be able to get into to be able to show that we're slowing progression. And I think when you think about Huntington lowering and the potential of Huntington protein lowering, it really is one of these things where the sooner you can get to patients and forestall the onset of clinical symptoms, the better. That's why I think really that large population is a holy grail, if you will. Of course, we want to provide benefit to the prevalent patients who are rapidly progressing in Stage 2 and Stage 3. But is also a very large opportunity of earlier stage based .

And that's why the partnership with Novartis is highly valuable, because they can -- it will require a lot of work to unlock the full spectrum of the opportunity and a lot of investments. Novartis, I can think of a billion reason why they want to unlock the full patient population. Once you get a drug approved, of course, this is where diagnosis rate, you should expect that to go up because right now, even if you know your dad or mom has or had HD because it's fatal. So you don't want to know. Most patients don't want to know. [indiscernible] why would you want to know if there's no cure. If at some point, you can slow down the progress, we would expect this to increase. And this is where, again, Novartis is truly committed. They are designed to do this, right? Large pharma, bone crushing machine, this is their DNA. .

Great. One last one on PTC518, which is that uniQure, I think, is probably in a position to file their application early next year, so they'll be first to market. How do you think, I guess, about the commercial market post their approval and your approval evolving? Will the market be segmented out depending on it. Their drug obviously involves not a trivial procedure, right, and so forth? And just how do you think about that? .

Yes. I I'm not sure we're very worried or the Novartis team would be very worried about being second to market. As you pointed out, it's a very large 10 to 15 hour -- I've heard a 16-hour surgical procedure, right? It's clearly that, that alone is going to slow uptake, right? There's only a certain amount of centers and surgeons who could do that. You're asking a neurosurgeon to take their entire or his entire day to do that procedure, and probably is an opportunity cost that they're going to be very aware of and the centers are going to be very aware. If you're also using up 16 hours of MRI time. So there's a huge opportunity cost for center in terms of being able to do 10 or 15 different scans versus just 1 patient all day. So that's going to play into it. And then the other part is also the patients, right? I think most people realize there's probably a finite durability of a gene therapy. So this idea of getting into the larger patient buckets that may be earlier stage with minimal symptomology or no symptomology. That's a large part of this market that is unlikely to be one served by the gene therapy because, of course, by the time they get to the stage of disease where they're going to be fulminantly symptomatic and needing the therapy. The gene therapy pump may not be working anymore.

Great. We are almost out of time. So I want to ask maybe, Pierre, one question just on the balance sheet, which is, you have one of the largest cash balance sheets among the mid-cap biotechs here in the U.S., a little bit of debt as well. But just, I guess, as you think about your uses of cash here on the forward, how are you sort of rank ordering internal development versus maybe looking externally? .

Yes. So we're in a very strong position, as you mentioned, $2 billion of cash, and this gives us a number of -- quite frankly, we have the flexibility to do everything and not look over our shoulder and try to raise capital, especially in this tough environment. So this gets us through all our operations, the launch of PKU or Vatiquinone, Translarna U.S. and our own pipeline and the extra cash will be used for BD activities, for instance, we're actually looking at a number of opportunities. We have to turn our own trials first over the summer. And as we mentioned, if you zoom out, the goal is to get to $2 billion top line. We believe PKU would get us to $1 billion in the U.S. alone, let's say, half of that ex U.S. And then FA or Translarna U.S. will more than -- will be more than enough to get us there. And we'll accelerate all of that with BD and we have the global infrastructure and the know-how to push products to the finish line. So that's how we're thinking about our capital.

Okay. Great. We're out of time now. So my thanks to Matt and Pierre for joining us, and we'll end the session on that note. Thank you very much.

Thanks, Paul.

Thank you.