Good morning, everyone. I'm Cc and I cover the biotechnology sector here at the firm. It's my pleasure to welcome PTC Therapeutics for our next session here. To my immediate left is CEO Matt Klein, and to my far left, Pierre Gravier, CFO. Maybe what we'll do is turn it over to Matthew to kick it off maybe with some high-level comments just on sort of the course of the year ahead. 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.
Yeah, thanks a lot, Paul. It's great to be here. 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 four FDA NDA submissions, all of which were accepted for review, with one approval coming last year. Now three approval applications are pending, including our Suppiance NDA, from which we expect an approval within the next six weeks or 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.
That really provides us a solid foundation to successfully complete 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. 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 PTC 518 program, for which we announced a successful uniQure two data package last month. Really a lot of exciting things going on, and look forward to discussing them.
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. Given the regulatory change with Translarna in Europe, maybe just to kick it off there, you've previously talked about maybe roughly a quarter of that business being maintained. How is that transition going since the decision sort of interquarter? What updates can you give there? Maybe just how you're thinking about that on the forward as sort of you're thinking about strategic planning and sort of the base case?
Yeah, 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. While first quarter revenue was in line with our 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. This is something that our team had been planning for. In fact, as we sit here today, more than half the countries in Europe have expressed a 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. We're again in these unprecedented waters that despite not having the marketing authorization, we are still able to commercialize the therapy. This, as we said, we believe can allow us to maintain about 25%-30% of the European revenue, which represented about 40% of the overall Translarna revenue for 2024. 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. 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. How does the investment community model this and think about it? Or can you just take it out of the model altogether?
Yeah, I think there's no analog. I think we're comfortable with that 25%-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. When you also consider that the PHMP, I believe, is looking at a potential label of four- to seven-year-olds. Again, there's no situation we see in the near future or intermediate-term future where there'll be a replacement for Translarna.
Okay. Great. Maybe turning to some of your pending commercial stage assets and starting with Sepiapterin, I think this is the asset that investors primarily focus 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 a billion-dollar opportunity, but the analog drugs in the PKU space have certainly not come up to that level of sale. 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?
Yeah, I think the SIFIANCE 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 with the current therapies. It's estimated that roughly about 10% to 15% of the 15,000-17,000 patients in the U.S. are on these therapies, which leaves a significant unmet need of 85% to 90% of the population. 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 supplies to all of these patients. Finally, our established commercial team. 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. 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 reauths in DMD, which is far more complex than PKU. 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. When you start now looking at what penetration could look like in a market of 15,000-17,000 patients with the potential net pricing we've talked about, the math to get to a billion dollars alone in the United States is quite easy. When you layer on top of that, that we have a team in place that knows how to successfully commercialize rare disease therapies.
Right. Maybe can you remind us in terms of the treating community within PKU and endocrinologist 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?
There are 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. We've done the work already to, we've mapped those centers, mapped 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 maintain their connections with these specialty centers, in particular with the nutritionists and dieticians, because the mainstay of their therapy is diet.
Understanding those interactions at each center, understanding who we need to work with to drive prescriptions and manage patient care, and 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. We're in a situation now where there's newborn screening for PKU. The patients are all identified, and there's about 300-350 new patients identified every year, not by us, just by newborn screening. The centers are identified, the 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 educate you . 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 classical PKU patients, getting 84% of patients to less than 360, which is the threshold for desired phenylalanine where you can start liberalizing diet. All those things are really, really important and facilitate our launch.
Great. I think in terms of timelines, Europe might be a little bit ahead. Is the thinking that you'll presumably launch ahead in Europe, just given the regulatory timeline on the calendars is a little bit in advance of the U.S. PDUFA here?
Yeah, they'll actually be very close in time. 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 six months of free pricing. There is certain advance notice needed before you list the price in the LAR t ax in Germany, which is what kicks off your launch.
Your IRAG review and so forth.
We will probably then be close to the same time. Obviously, we're thinking a lot about the free pricing level. What we've done in preparation in Germany, where we think there's about 8,000 patients, is we've initiated an early access program. We've already gotten a number of patients on drug in this period waiting for approval and launch. We've gotten into a lot of the key centers in Germany. That is really important because in Germany, once you're approved and launch and list the price in LAR tax, those patients on early access right away by law switch to commercial therapy. 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 the metrics and how payers will assess that. Clearly, the drug works very well in reducing Phe 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 approvals?
Yeah, 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 restricted diet. We fully expect that payers may, in certain cases, want to see evidence of phenylalanine reduction, not necessarily liberalization, but that the blood test, which is objectively measured, is in line with what we saw in clinical trials. We are 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 early part of the U.S. launch. Should we think about the early launches potentially having a bit of a bolus, just given awareness of sepiapterin in the PKU community? And just is that how you would sort of guide the street to think about an early built-up demand?
Yeah, 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 patients' community generating their own buzz about the ability to liberalize their diet in a meaningful way. The fact that you now have physicians, again, I said we've seen a number of these surveys saying that most physicians are going 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 sapropterin, either branded or generic, time and time again, you're going to have a much better response to sepiapterin. That's what the data suggests. It is 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 and failed them, who we want to get on a therapy right away.
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 prescribe drugs and the patients are identified, prevalent, and desiring a safe and effective therapy.
Right. I think one question that, or understanding of the PKU outlook for you guys is just understanding how much of your IP is dependent on orphan or regulatory exclusivity versus other patent exclusivity. I think it probably goes out further than people realize. Can you maybe just remind us on what that IP landscape, both on the regulatory side and the patent side, looks like?
Yeah, so we'll certainly have the orphan exclusivity of seven years, and we expect the pediatric add-on for six months. We also have patent protection. We're guiding folks to 2039. We have 2038 on 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. As is always the case, we're continuing to expand the IP landscape to keep putting fences around what we have. For today, we're guiding to 2039 on the back of patent protection to 2038 and what we believe conservatively is one year of patent term extension based on Orange Book list of patents.
Right. And one more for the investment community. Is this something they'll 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. We're dealing with a closed specialty pharmacy network. The prescription data will not be available. 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 uptake is like and what adherence is like.
Maybe just at a high level, what will be the key things we should look for? Number of physicians, new prescribers, switches, maybe some round things that we should look for?
Yeah, I think right now, as we're thinking about it, it's going to be patients on drug. That's something that we should follow. 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, you're going to see we expect a lot of patients to come on early, but we expect it to continue to grow. We've talked a lot about these different patient segments. 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.
A lot of that is coming from the physician's own view of the drug, including recent data we put out on mutation data, which shows that if you look purely on a mutation basis, over 70% of the patients in the affinity phase three trial technically have classical PKU. If you see the level of phenylalanine reduction we're having there and the fact that we're having two-thirds 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. That's a very large opportunity.
That's great. Maybe switching gears to free drugs like ataxia, I think the investors are watching the Skyclarys launch and Biogen, which has been going reasonably well. Maybe you can highlight for us what are sort of the key differences mechanistically for vatiquinone versus Skyclarys to start? I have some commercial questions after that.
Yeah, I think there's several important differences between the two therapies. Now, mechanistically, they're different. Skyclarys targets the NRF2 response pathway, which is part of the downstream antioxidant response pathway. We've talked about how vatiquinone targets 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. 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 one year of age. Of course, the MOVE-FA trial was really focused in pediatric and young adult patients.
To be able to now have efficacy data along with safety data will allow vatiquinone to be a therapy for all patients with Friedreich's ataxia, regardless of age and regardless of disease stage. 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., about a third of them are pediatric. You're looking at the only therapy available for those patients. If you look to the experience with Skyclarys, which has had 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 two populations between the adult population and the pediatric population. As you think about sort of the selling message for those two distinct populations, is it your thinking that you'll be able to primarily get adult patients who are treatment naive or treatment inexperienced versus Skyclarys experience? Or sort of what's the sort of low-hanging fruit in your mind?
Yeah, so the low-hanging fruit for sure is the pediatric population. The dynamics of the pediatric population differ quite a bit from the adult population. The pediatric FA patients, as we said, is about a third of the 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. 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. That's really good. That's the low-hanging fruit. You talk about a migration into the adult population, and we see that in two different buckets.
One, as you said, is the sort of tried but did not stay on Skyclarys due to monitoring issues, lipid level issues, LFT problems, or other tolerability issues. We see that as also sort of the second bucket of patients that we can easily access. 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 abnormalities. I think that there is 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 is 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? There's just heightened disease awareness. 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. If anything, the approval of Sconclaris has heightened the unmet need in the younger patients, increased the numbers, and increased the desire not only of patients, but of 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. Maybe just in terms of your latest thinking on pricing, 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 more on vatiquinone, which is just that its regulatory timeframe is a little bit behind that of sepiapterin. 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 potential label discussions? Any other material meetings of note?
Yes. Our PDUFA date is August 19, as you indicated, a bit after Suffice. We have 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. That was an important update. We still will have a late-cycle meeting and then, of course, labeling discussion still to come.
Okay. Great. I want to talk and maybe switch gears to your recent PTC 518 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 some follow-up questions on just sort of the development path there.
Yeah, absolutely. I think as we look at the PTC 518 data package and the phase II PIVIT 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 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. A 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 of dose-dependent effects on stage two patients on CUHDRS, throat motor score, and cognitive function, very important.
Importantly, in this update, we had the first group of patients out to two years. At 24 months, patients who have gotten PTC 518, not only is it safe and well tolerated, but we are 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 were statistically significant. We saw out at two years dose-dependent benefit lowering on neurofilament light chain. The natural history of Huntington's disease is to see gradual increases, and we are seeing decreases now out at 24 months. That is really important. We also learned about study populations. This was one of the objectives of the PIVOT H2 study, to try to figure out in which group of patients we think would be the optimal future efficacy trial population.
What we clearly saw is what we suspected is that likely the stage two patients are those that are moving at the appropriate rate and that they'd be best suited to the population in whom we could capture significant effect. When you take the data package as a whole, we achieved all the objectives for phase two, 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 as well.
We think our optionality in terms of what we could talk about supporting accelerated approval has gone up.
Yeah. 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. I guess in terms of next steps, first, when would you present any additional detailed data from your recent update at a medical meeting? Are there plans to do that over the course of 2025? Then sort of when would you and your partner, Novartis, potentially have regulatory interactions on a phase III design?
Yep. 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. The plan would be to have an FDA meeting where both things would be discussed, sort of in a phase II meeting. I 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. Of course, what does that efficacy trial look like and trying to move as quickly as possible on both fronts so that 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 two patients and earlier, right? Also trying to think about how do we get into stage one patients and then even earlier stage zero patients where there is, and the undiagnosed patients, which is, that population is multiples of the identified patient now. There is 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 are 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 the more symptomatic stage two and stage three 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 could this expand the pool for you?
Yeah. If you think about Huntington's disease, it is pretty unique, right? And 100% of the patients have a genetic defect. It is also uniquely autosomal dominant, which means that if your parent has it, you have a 50% chance of passing that on to your children. 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 is no therapy available, then you have just basically found out that you have a fatal disease that will have an onset at a certain amount of time. A lot of this is going to be walking hand in hand with having a therapy available.
As we think about stage one 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 with patients who are not progressing a lot clinically, but that's a group that we could think about a biomarker strategy or something to be able to get into to be able to show that we're slowing progression. 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 two and stage three, but there's also a very large opportunity of earlier stage patients.
That is where the partnership with Novartis is highly valuable because 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 reasons 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 is fatal, you do not want to know. Most patients do not want to know. They want to live their life. Why would you want to know if there is no cure? If at some point you can slow down the progress, we will expect this to increase. 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 PTC 518, which is that uniQure, I think, is probably in a position to file their application early next year. They will 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. Just how do you think about that?
Yeah. I'm not sure we're very worried or the Novartis team would be very worried about that, about being second to market. As you pointed out, it's a very large 10-15-hour, I've heard 16-hour surgical procedure, right? It's clearly 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 his entire day to do that procedure. Probably there's an opportunity cost that they're going to be very aware of, and the center is going to be very aware of. You're also using up 16 hours of MRI time. There's a huge opportunity cost for a center in terms of being able to do 10 or 15 different scans versus just one patient all day. That's going to play into it.
The other part is also the patients, right? I think most people realize there's probably a finite durability of a gene therapy. 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 a therapy, the gene therapy may not be working anymore.
Right. We are almost out of time. 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. 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?
Yeah. We are in a very strong position, as you mentioned, to be on a lot of cash. 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. This gets us through all our operations, the launch of PKU, of vatiquinone, and Translarna U.S., and our own pipeline. The extra cash will be used for BD activities, for instance. We are actively looking at a number of opportunities. We have to turn our own cards first over the summer. 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.
FA or Translarna U.S. would be more than enough to get us there. We'll accelerate all of that with BD. We have the global infrastructure and the know-how to push products to the finish line. That's how we're thinking about our capital.
Okay. Great. We're at 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.