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

All right. Welcome, everyone, to this session of the Morgan Stanley Global Healthcare Conference. I'm pleased to welcome PTC, Matt and Pierre representing the company. Just I'll read a quick disclosure before we get started. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. So with that out of the way, thank you both for coming. It's been an exciting year for PTC between regulatory decisions and clinical readouts. Before we dive in, maybe can you give the audience a quick intro of the company for those who may be less familiar with the story and maybe highlight how strategy may have changed in the last couple of years.

Yes. Thanks, Judah. So PTC is a global biopharmaceutical company that discovers, develops and commercializes differentiated therapies for diseases of high unmet need. We have a global commercial infrastructure that markets 6 products around the world. We have a highly differentiated R&D portfolio, including our small molecule splicing platform, which has yielded Evrysdi for SMA, Votoplam for Huntington's disease and an additional number of programs in the works. And we're well capitalized. We closed the second quarter with over $1.9 billion on the balance sheet. This is an incredibly exciting time for the company coming off the heels of approval for Sephience for PKU in the U.S. and Europe and the recent global launches. And we've been very clear that Sephience is a foundational product for PTC that's going to lead us to be cash flow breakeven and profitability in the near future. So I'd like to say that a lot of the work we've been doing for the past 1.5 years, 2 years to really turn the company and evolve the company into where we are today, which is a well-capitalized focused execution-oriented company now with a foundational product and all of the key factors in place for near-term and long-term growth and success.

Okay. Great. And we will spend a decent amount of time on PKU, but we will get to other programs as well. So starting out with Sephience, congrats on the approval. It is your first full approval in the U.S., and you've got the commercial launch underway. You provided a bit of color on the very early days of the launch with your second quarter update. We're a bit further in now. How would you characterize launch progress, whether that's quantitatively or qualitatively? I think it's about 104 centers of excellence that you're targeting and have interactions been consistent across those?

Yes. So I'd say things are off to a great start. No surprises. A lot of that comes from the preparations we've been doing over the past couple of years. And we've talked a lot about how the opportunity for Sephience is quite unique in terms of rare disease launches. While there are 2 approved therapies for PKU, the vast majority of patients are not on those therapies. We said somewhere over 85% of patients are not on current therapies. So it sets up this really unique situation where you have all the pillars for commercial success in place. You have newborn screening, physicians that understand how to prescribe therapies, patients who know it's like to have to go and get a therapy, payers who know PKU, they know the high value to phenylalanine lowering, a well-aggregated patient community that communicates very well that's well networked through social media and other channels. All the things that we have to usually build, they are in place. Plus we have a team that's experienced. We have been selling -- this is a team that's been selling Emflaza in the U.S. for over 10 years. So let's just say battle proven in genericized and competitive market. We know how to do rare disease drug development. We have a patient services team that provides the necessary white glove service to both the physicians and the families to ensure that we get start forms so get patients quickly on therapy and get them to stay on therapy. So with all of that backdrop, working -- mapping those 104 centers of excellence, understanding the dynamics of those centers who are the prescription decision makers. It's the physicians, yes, but in some cases, nurse practitioners and dietitians who really spend a lot of time with the patients, even those who are currently on therapies rely heavily, heavily on the dieticians at these centers to manage their diet, which is their standard of care. So with all the work we've done, all those pillars in place, our experience, our know-how, there have been no surprises and things are off to a really good start.

Okay. Great. And you talked about sort of layers to the launch. So for patients that have started on commercial drugs, do you have a sense for their prior treatment history as uptake mostly been in Kuvan failures and poor responders? I know you said those would be your initial targets. Are you seeing interest from patients that are treatment naive? Maybe you could help us with what you're seeing thus far on what the stage...

Yes. It's early days. And we've talked a lot about our excitement over the launch of the commercial opportunity of Sephience is because our data demonstrate the ability to access all the different segments, right? So you have patients who are currently on therapies, including BH4 whether branded or generic. We've consistently shown as recently as data we presented last week in Japan at the International Metabolism Meeting that if you have a response at all to BH4, you get a much greater response to Sephience. The most recent data we shared last week was a 70% greater reduction on average with Sephience when that was in a head-to-head study, so same patients. We also have data showing that we can have significant effect in the more severe patients, those with classical PKU or mutations known as BH4 nonresponsive mutations, even those with the most severe genetic scores. We shown that these patients respond well to Sephience. And in fact, we have a manuscript that's going to be coming out shortly that's going to highlight the ability to have significant effect in these most severe patients who are in that therapy naive bucket. And then, of course, we have those who've tried and failed. So we've been very clear that different centers may have different priorities. Some may say we're going to switch those who are on therapies because it's quite -- on current therapies, it's quite easy to go from once-a-day therapy to another one, especially when you know the response is going to be greater. Others have said, look, we want to get therapies to those who aren't on them. And what we're seeing in the early days of the launch is all those segments. We've seen patients all over. Now it's early days, but we are seeing therapy naive, those currently on therapies. And when we listen, for example, I think a recent interview with the Head of the Children's Hospital of Philadelphia, PKU center, he said, look, I got about 200 patients and my expectation is to try all those patients on drug, looking to get 2 or 3 prescriptions written a week. So when we hear that, it lends further support to our belief that we can access all those segments and that there's going to be a very wide funnel of patients getting on drug. And when you look at the response rates that we've had in the trials, 2/3 of patients are higher responding, again, setting up for a strong launch.

Okay. Great. And you touched on this, but in terms of the clinician specialties that are driving uptake, right, like can you maybe reemphasize kind of how doctors versus nurse practitioners versus dieticians are impacting the launch? Is it going according to how you expected?

Yes. Again, yes, no surprises. We're seeing prescriptions from physicians. We're seeing prescriptions from nurse practitioners. And we're spending a lot of time engaging with the dietitians. They're so important because as this new therapy is introduced, especially one that holds the promise for potential diet stabilization, it's going to be very important that the dietitians work with those who get on the drug to carefully titrate their current restrictive diet and gradually introduce new foods. We want to make sure that expectations are appropriate and that we do this very carefully. While I think the patients themselves see on social media reports from their peers saying, I just had a double cheeseburger for the first time ever or my child just went to a pizza party and had pizza for the first time. We're incredibly excited about that, but we want to make sure that there's sort of a gradual liberalization of the diet. And so we are working very closely with the centers to make sure that all the key aspects of supporting a new start and Sephience are in place.

Okay. That makes sense. And just moving to kind of the revenue opportunity here, right? I think you've said you're comfortable with where consensus numbers are for this year. I guess, can you help us with moving from where we are today to this blockbuster opportunity that you talked about in PKU? And I think maybe we can tie into that question also this sense that so many of these PKU patients have been lost, whether it's the follow-up or just are not seeing specialists. So how do you kind of marry blockbuster sales potential with the patient population?

Yes. So again, it's our belief that we can access all patient segments. And I think we've encountered a number of misconceptions on this journey. The first ones were the opportunity is limited to what BioMarin had with Kuvan, clearly not the case given the differentiated nature of Sephience. This is only going to be for the more mild, not the more severe patients. Well, our data have shown time and time again, the more severe patients are responding in our pivotal trial, the more severe patients actually had a greater amount of phenylalanine lowering. They're also enjoying the liberalization we're talking about in our study. So the data clearly support that we get to all those patients. This misconception that their patients are "lost follow-up." We've heard from a couple of patients. It's great they're like, I'm not lost. I'm not here. I know exactly where I am. Just because I'm not seeing the doctor because there's no therapy they're going to give me to change my life, it doesn't mean I don't want that opportunity. And these individuals are well networked. We've talked to some of them. There's actually social media influencers that interact with them. I was at a national PKU conference this past weekend in San Diego and heard from a man who's in his 40s who was talking about his experience with classical PKU, tried and failed BH4. And he said, I still talk to my dietitian. I'm still in touch with that individual at the center. And I'd like to try an effective therapy. So I think that we're now understanding that this sort of mythical loss of follow-up is, in fact, mythical. And then we talked about the opportunity. We've been quite consistent in saying we believe this can be an at least $1 billion opportunity in the U.S. And when you think about where we priced the drug, that would require modest penetration. We think the opportunity could be much bigger. I think if you think about Sephience as a highly differentiated oral therapy for a rare disease that can become the standard of care in PKU, penetration rates for those type of products are clearly much higher than the ones that would get us to the $1 billion. So it's early days. We're excited that things are off to a great start. As we get further into launch, we'll be able to give think more reasonable projections on where this can go. But right now, we see it as a large opportunity given the size of the market, 17,000 patients, the highly differentiated profile of the drug, the ability to access all the patient segments and quite honestly, our proven track record of success in commercializing rare disease therapies.

Okay. Great. And maybe just to round out the topic, is there anything you can share on kind of initial payer interactions, how those are going also kind of relative to plan?

Yes. Again, we spent a lot of time with payers prior to setting the price and prior to launch. And I think, as I mentioned, one of the important early takeaways from our discussion was the familiarity payers have with PKU because there've been previous therapy and the idea that value can be tied to phenylalanine lowering. Furthermore, again, a kind of unique situation in PKU where you can understand and you can quantify if a therapy is working. We're used to working in the neurology space with neuromuscular diseases and neurological disorders where it's hard to quantify in the short term if the therapy is in fact working because the goal of therapy is to slow progression over time. Here, we know within a few weeks, we can get a blood test and provide an objective assessment of phenylalanine lowering. That gives payers a lot of comfort. They can be sure that they're paying for a drug that works. And again, that went a long way into understanding or informing our decisions around pricing and the ability to get patients covered. And I'd say as well, it's not only our experience, but I think that there have been a few interviews published with payers where their feedback is consistent with what we're saying. There's very few barriers to access anticipated.

Okay. That's great. All right. Maybe kind of turning to PTC518 in Huntington's and kind of setting the stage for some who may be less familiar, can you briefly outline the partnership terms you struck with Novartis for this program and maybe also tie in how that effectively recapitalized the company?

Yes. So the terms, we received the billion upfront and up to $1.9 billion of milestones, 40% profit share in the U.S. and double-digit royalties ex U.S. So -- and all the Phase III costs are all on Novartis. So we don't pay anything after that. So very, very strong partnership. I think in the rare disease space with Phase II data or Phase II -- preliminary Phase II data, this is probably the highest upfront deal ever done. And we kept a very large portion of the economics. So we're very pleased with the partnership, and that obviously allowed us to close Q2 with $1.99 billion of cash, very strong financial position. We worked really hard for it. And Judah, you followed PTC for a while, you know that's probably the highest cash balance we ever had. And in this environment it is especially important because it allows us full flexibility to operate and get to cash flow breakeven and profitability without the need to raise additional capital.

Okay. That's a good backdrop. And maybe just diving into the data a little bit. You had 12-month Phase II data earlier this year. Can you remind us of what we saw in that update? What are the implications of different responses in Stage 2 versus Stage III patients? And then we can get into kind of next steps for the program, but maybe just kind of how you viewed the data and kind of the different responses by patient type?

Look, we were very excited about the results of that study. It was the primary endpoint of the study and basically achieved everything in Phase II we wanted to and that one we could hope for, for a CNS drug, right? We've showed that the drug works the way it's supposed to work. We had dose-dependent lowering in mutant Huntingtin protein levels, very, very important. We showed that the drug going where it's supposed to go. We're achieving the exposure in the CNS, which is necessary for this drug to be successful. We're getting full brain biodistribution, which is essential for a disease like Huntington's, which affects all regions of the brain. Drug was safe and well tolerated. We saw early signs of efficacy. We saw dose-dependent effects on cUHDRS as well as a few of the subscales of cUHDRS in 12 months relative to placebo in the Stage 2 patients. And then when we look longer term after 24 months, we saw a significant effect versus cUHDRS for those treated for 24 months. And then we also saw a dose-dependent lowering of NfL, which is also another important sign that the drug is working the way it's supposed to work in terms of providing neuroprotection. We also learned a lot about who the right clinical trial population is. That was one of the goals of the study was we had always believed that you likely need to go a little bit earlier in Huntington's disease, particularly with the Huntington lowering drug that's acting by targeting all the way upstream of the disease pathogenesis. And so it makes sense that there's probably the sweet spot in that patients who are too advanced might not respond as well in a short period of time. And that's what we saw. We saw a much better effect in the Stage II patients in the Stage III patients. So for us, that was a very important learning as we move forward in designing the next efficacy trial because the key to success in every CNS program is not only having a safe and effective drug, but the right study population and the right endpoint. So to have made that learning in Phase II was really an important box to tick as we move the program forward.

Okay. And maybe just in kind of thinking about addressable market, I think there was this initial reaction that you're potentially excluding Stage II patients from the market, maybe you're losing some large chunk of the addressable market, but it doesn't seem like it should be the case.

Not even close. First of all, those data didn't -- all those data set is in 12 months, you're recording much -- it's easier to record effect in Stage II and Stage II. So there is nothing about working or indications or label. But even in that case is [ Stage III ] is probably one of the smallest segments of the population. Stage II is much larger. And if you think about the goal of a Huntingtin lowering therapy, it's to go earlier and earlier, right? The benefit of -- first of all, the benefit in Huntington's disease that we don't have in other neurodegenerative diseases is that we understand for the entire population, what causes the disease. It's a genetic mutation that leads to the production of a toxic mutant Huntingtin protein. So if you know that you can target that and that drug does, you talk to the physicians, you talk to patients who diagnose, they want to start as early as possible. So really, the key is unlocking the stage 0 patients or the patients who are not even in stage 0, those who may not have wanted to get genetic testing before. And if you think about the market opportunity, there's probably 3x the number of patients who are earlier than Stage 2. So that's where the large market opportunity is. So the ability to have an oral therapy that is safe and well tolerated is titratable, and you can measure the effects of Huntingtin protein by -- through a blood test that's a really great setup not only for the Stage 2 patients, but then to access the larger buckets of patients who are earlier stage. And in our discussions with Novartis, of course, we're all keenly aware of that opportunity and are thinking a lot about the tactical map that gets us to where we are now studying patients in whom we can register efficacy in the course of the trial and then how would you think about migrating earlier and earlier.

And that's where having a partner such as Novartis is very, very important. They understand the full potential of the disease. And as you know, I mean, big pharma are set up to unlock the full potential. It's a bone crushing machine that really understand the 40,000 U.S. patients that are diagnosed and to Matt's point, probably 4 or 5x that number that are undiagnosed. And it's going to take a lot of work, obviously, to access this and Novartis fully understand the full potential here.

Okay. Great. So speaking of your partner, I guess, is there anything you can share on interactions post data related to trial design? And can you help us with time lines on how discussions with the partner as well as discussions with FDA are going to factor into what that next study could look like?

Yes. The answer is full speed ahead with the next study. So we've shared that there's going to be a meeting with FDA in the fourth quarter of this year with 2 objectives: one, to align on the design of that study, longer placebo-controlled is really a finite universe of endpoints in Huntington's disease and the idea is to leave that meeting ready to go. Novartis has recently messaged through the European Huntington's Disease Network. There was something out a few weeks ago that the patient community is getting ready. This trial is getting ready to start soon. And that trial, of course, will be -- is incredibly important, both as a potential confirmatory study in the context of an accelerated approval. And if there's not an accelerated approval, then obviously, getting that study started as soon as possible is going to get you to approval as soon as possible. The second objective of the FDA meeting, though, is to discuss the pathway to accelerated approval, understanding the types of endpoints we have, the types of data we could provide in an accelerated approval filing. Of course, we'll be having all the patients across 24 months next year. So with that in mind, the idea will be to align with FDA on what a package could look like. And then, of course, we're following very closely the gene therapy and the pathway that's been seemingly open there, which again, I think just gives us more optionality in what we could provide in a data package.

Okay. And maybe just -- you mentioned the gene therapy. I think kind of some of the buzzwords on endpoints that come out of there, right, NfL, cUHDRS, external controls. It seems like there may be some folks that would prefer total functional capacity as a functional endpoint, maybe more confirmatory. I guess how are you thinking about which components of their program are translatable to yours?

So we've said all along that any success with the gene therapy leads to very well to us. First of all, the gene therapy lowers Huntingtin protein, but in a limited -- in one region of the brain. So again, with Huntington's disease being a whole brain disease, the ability to provide durable Huntingtin lowering as you can get with a repeat administered oral agent in every region of the brain is clearly an advantage. And then on the regulatory front as well, we shared in the May readout data we had relative to natural history, showed significant effect relative to cUHDRS, significant effect on total functional capacity. And then in addition, we have NfL. We have evidence of target engagement, Huntingtin protein lowering with the blood levels, which you can't provide with a centrally administered gene therapy. So that's why I think that we -- things read through very well to us, but we also have additional optionality you would get from an oral therapy and also having 12 months of placebo controlled data, right? Because we're able to show these trends of dose-dependent benefit on cUHDRS relative to placebo that continue out into an open-label extension phase. And again, that just gives a bit more confidence that what you're observing is, in fact, real because as we know, it's always a little bit challenging to interpret purely open-label data in these types of diseases.

Okay. Great. Really helpful. Maybe a quick one on the CRL for vatiquinone. What are next steps there? Any thoughts on your inclination to potentially run another trial in FA? Or I guess, what do you need to hear to help you make that decision?

Yes. Look, obviously, the CRL was disappointing. We had said all along that the main question on the review would be the potential application of flexibility to upright stability, meaning that, that itself was not prespecified as the primary endpoint. I think it's quite clear from the CRL that flexibility wasn't there. This was really a statistically based decision where formality of flexibility seem to be the prevailing force. We'll look forward to meeting with FDA, having a discussion with them, understanding what a trial would look like. Are there any other options here? Most likely scenario it would be as outlined in the CRL that need to do another randomized placebo-controlled trial. And if that's the case, we'll take a close look at it. We'll look at what we think the probability of success is, understanding what we do about the endpoints and study populations, what's the market opportunity, what's the cost of the trial, and we'll make an informed decision. I think we're certainly of the view that this is a safe drug, has efficacy and the CRL is really based on a statistical issue relative to learnings that were made while we were running the old trial. So we'll bring all of that to our thinking when we ultimately make the decision.

Okay. Great. And then one question I'm surprised we get as often as we do. Translarna in the U.S. I guess, just what's the latest thinking, how you think about time lines on an FDA decision? Or is it something that we should think of as -- we'll get an update when we get it. If it's good, great, if not, move on.

Yes. I think -- yes, what you said. Look, I think we work very hard to position the company where it is today. As I said in my opening comments, we sit here today with a foundational product in PKU that we believe is going to bring us tremendous success. We have a strong cash balance that as Pierre highlighted, will enable us to get to cash flow breakeven and profitability as well as give us the optionality to do strategic business development deals to complement the commercial and R&D portfolio when we see something that we think could be a really valuable opportunity for the company. We submitted the NDA for Translarna. If it gets through, great, it's great upside. We have over 100 patients on the drug in the U.S. This is something we can easily commercialize. And I think it would be great to be able to provide the boys and young men with nonsense mutation DMD with a safe option. Given the nature and the sort of history of Translarna, we don't have a PDUFA date. We're not in the PDUFA program. So we don't have mid-cycle, late cycle type of things. We have shared that it was quiet for a while. We did get a recent information request dealing with CMC asking us to either justify or modify specs for product release. So these are the types of questions we're getting. So it suggests that they are engaged with the application. But look, we're all very focused on the PKU opportunity, excitement around HD, things we have coming in the R&D portfolio. And if this comes through, it will be terrific. If it doesn't, we keep on our trajectory to success, it will have no impact.

Okay. Great. And I guess with all the focus on Sephience and the later-stage pipeline programs, maybe we just spend a minute touching on the earlier-stage pipeline. It is still there. Maybe it's been streamlined a bit. But what are you most excited about there? Are there any updates that investors should look forward to in the coming months?

Yes. So we have streamlined it quite a bit. I think we've spent a lot of time getting folks to focus on the near end value drivers for the company. But at the same time, behind the scenes, the same focus, the same execution approach that we've given to the late stage to regulatory and to commercial, we're bringing to the research stage as well. And we're going to be having an R&D Day later in the year in the fourth quarter to pull back the curtain on some of the things we're working on, in particular, what we've done in a way the company never has before is focused on the splicing platform. This is a highly differentiated platform that brought Evrysdi forward, Votoplam forward. And the simple question we ask is when you have this "golden goose," if you would, how can we make sure that we're resourcing it appropriately, we're disciplined appropriately to bring forward programs that can be successful for PTC and also use the platform as a source of strategic partnerships for other indications like oncology where we're not going to develop and commercialize therapies, but there's certainly oncology targets amenable to splicing, similar for larger neurodegenerative diseases. Again, we're not going to do that development and commercialization, but there are certainly attractive splicing targets. So how can we leverage our really valuable and unique understanding of developing these molecules to bring forward valuable products, both for us and for potential partners.

Okay. Great. And maybe last company-specific questions before we get into a little survey we're asking everybody. So can you talk a little bit about that cash flow to breakeven -- cash flow path to breakeven that you discussed. Is PKU kind of the linchpin there? Is there any way you can talk about profitability within the PKU program? And then given the path that you're on, how are you thinking about business development?

Absolutely. So I reassure everybody PKU gets us to profitability alone. We don't need anything else. Matt highlighted the fact that we believe we could do at least $1 billion in the U.S. could be much larger, and we don't need to get to that level to become profitable. So I think if Translarna obviously comes that will just accelerate everything. So we're very pleased with that position. And more to come on exact timing. It will depend on the uptake, but we're very confident we'll get there. And in terms of business development, Matt touched on that a little bit. We're in no rush. We obviously we're a strong position on cash. We are on PKU mode or on launch, and we want to make sure this goes really well. We'll be opportunistic. If we see something that makes sense that fit the commercial portfolio or the R&D portfolio will strike, but we want to be very disciplined. We want to make sure that when we look at opportunities, we create value for shareholders. That needs to be prime. So that's how we're thinking about it.

Okay. Great. So maybe that business development point takes us into kind of the mini survey we're asking all the biotech companies this year. So biotech does seem to be more exposed to external and macro factors of late. So like I said, we're going to ask these to everybody. The first question is on the topic of China. Business development certainly comes into the conversation when we're discussing China biotech. So how are you thinking about how the Chinese landscape in biotech could affect you, whether it's on the R&D side of your business or the business development side?

I'd say on the R&D side, one of the things we did in focusing our R&D activities was to focus on the 2 platforms that are unique to PTC that quite simply -- we have science that others don't. And I think splicing is a great example of that. Our inflammation platform is a great example of that. We have mechanisms and things that we're looking at that are pretty unique. So we feel pretty -- at least for today and for the foreseeable future, pretty insulated from that in terms of the competitive aspect. In terms of [ DND ] opportunities, of course, we are paying attention like everyone else is. And as Pierre said, our strategy for business development of being thoughtful and strategic is not limited to geography. So we'll be looking far and wide for good opportunities.

Okay. Helpful. The second topic is AI. How would you say PTC is currently leveraging AI or thinking about the potential for AI to disrupt the broader business model with [indiscernible] Biotech?

Yes. Look, I think we all acknowledge AI as a tool, and we've used it in some of our kind of regulatory work and legal work. But in terms of drug development, we've combined AI with sort of real intelligence and experience, particularly in the splicing platform, for example, where we've been able to leverage high throughput machine work to more rapidly and robustly match target noncanonical nucleotide sequences with splicing targets with splicing literature and our chemical library. So sort of make an earlier match, more reliable match with a potential splicing site, chemical matter we have and potential applications. That's just one example. Again, we're just using it as a tool to do some machine work a lot faster and also leverages the expertise that scientists have. So the computer could do that kind of tedious work where our scientists can do the creative work. And we've seen this actually accelerate the preclinical development time lines for some of the splicing candidates to bringing forward.

Okay. Great. And the last topic is on the regulatory side of things. I guess, what has been most impactful to your business? Some options could be changes at FDA, pricing conversations, tariffs, I guess, just on the regulatory side of things, what is impacting your day-to-day conversations?

Yes. I would say, certainly, we've talked a lot about how we don't see MFM impacting us very much. We've always, particularly in the Sephience launch, mindful of the maintaining a rigid pricing corridor. So we don't see any issues with MFM there. The IP for all of our products that are sold in the U.S. held in the U.S. So we don't see really tariffs having a significant impact. I'd say sure on the regulatory front, I mean, look, we will have -- we've had 4 applications in front of the FDA for approval for the past year. So far, we have 2 approvals. So we talked about vatiquinone and we have the Translarna under review. So naturally, the changes at FDA, whether it be changes in workload, the changes in leadership, I think that naturally has an effect on us. I think as most would agree, it's hard to understand what that effect is because it's a little bit difficult to predict. I think what we're all seeing though is desire from FDA leadership for greater flexibility and common wisdom, and we're all waiting to understand how that important philosophy for many rare disease companies gets translated or gets operationalized at the review level. So we'll continue to see that. But of course, we -- with so much activity in FDA, we're, of course, impacted by changes there.

Okay. All right. Very helpful. We might have time for one question in the room, if anybody has one? If not, that will take us to our time. So thanks again for being here.

Thank you, Judah.