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

All right. Good morning, and welcome to the 40th Annual JPMorgan Healthcare Conference. I'm Eric Joseph, senior biotech analyst at the firm, and I want to thank everybody for joining us this week. Our first presenting company is PTC Therapeutics. And it's my pleasure to welcome CEO, Stuart Peltz, to talk to us a little bit about the company. Just a quick formatting note. There is a Q&A session after the presentation. So I'm inviting everybody, all of our viewers to -- if you'd like to submit a question, I should say, just click the blue Ask a Question icon, and I'll work those questions and where appropriate. With that, Stu, let me pass it over to you for the presentation.

Well, thanks, Eric, and thanks for this introduction. I'm excited to provide an update on our achievements and upcoming milestones. Before I get started, I'll refer you to our forward-looking statements and our SEC filings for information on risks and uncertainties. So we're proud to have built a fully integrated biopharmaceutical company that discovers, develops and commercializes therapies for rare disorders. We have a track record of utilizing our strong drug discovery platform to bring first and best-in-class drugs to the market for diseases with little to no treatment options. Our strategy is to build a sustainable, robust pipeline that at steady state will develop new therapies that we can commercialize every 2 to 3 years, creating short- and long-term value for all our stakeholders. We were established almost a quarter century ago, and we've -- we have grown and expanded into a global biopharmaceutical company with multiple drug discovery platforms, ease based on innovative pioneering signs. We've grown to over 1,200 employees with 20 offices worldwide, distribute our therapies in 50 countries around the world, so we bring them to as many patients as possible. Our corporate headquarters and research are situated in New Jersey, Massachusetts and California, and we have international headquarters in Dublin, Zug and São Paulo. The strategy is to continue to innovate to aggressively build our pipeline so that we have multiple shots on go that leads to a stream of potential new therapies. This has been a successful strategy for us as evidenced through our growing commercial portfolio, our ongoing near-term registration-directed trials and our research and development pipeline. This visual exemplifies how our pipeline continues to mature. And with success in our ongoing registration trials, we anticipate to expand the number of patients treated from 50,000 patients today to over 700,000 patients by 2030. We have grown our business for both homegrown therapeutics and by seizing strategic business development opportunities. We're proud to say that we have delivered $536 million in total revenue in 2021. We are providing updated long-term guidance where we expect to grow to potentially $3 billion in revenue by 2026 and towards an updated anticipated $8 billion of revenue in 2030. The innovation revenue cycle described here is our vision for how we will continue to create significant value for all our stakeholders. And while we continue to see robust growth from our existing commercial portfolio, we anticipate that beginning in 2024, a steadily increasing portion of the revenue will come from products currently in our pipeline. This proportion will increase over time to reach more than 50% of the $3 billion in 2026. We're proud of how our team kept its head down during the pandemic in 2021 and made significant progress across our pipeline, setting up key value drivers for this coming year. These included completing Phase I trials for 2 new chemical entities, PTC518 and PTC857, with both compounds moving into Phase II trials; completing enrollment in the registration-directed MOVE-FA trial for Friedreich ataxia, achieving important 2- to 5-year-old DMD label expansion for Translarna in Brazil, continue to have strong commercial year with impressive growth in our DMD franchise, with continued success of Evrysdi for SMA with approvals in 68 countries in the important category 1 pricing approvals for Tegsedi and Waylivra. As part of our vision for continued company growth, obtaining strong revenue feeds allows for continued investment into our innovative pipeline. We had strong commercial performance in 2021, with unaudited total revenue of $536 million, with $424 million being from our DMD franchise. We expect continued growth of our commercial portfolio and are guiding between $700 million to $750 million in total revenue in 2022 and DMD franchise net product guidance of $475 million to $495 million. Now I'd like to focus on updates from our development portfolio. We have several important near-term drivers. I'm proud of the remarkable progress of our teams of need to bring each of these programs forward. The strength of our pipeline becomes evident with 5 ongoing registration-directed trials and with 4 readouts planned for 2022. We're excited about Translarna Study 41 reading out this year. Based on our previous learnings, we understood that choosing the right patient population was key to showing clinical benefit. We use this inclusion criteria to choose the best population to show benefit in the clinical trial. We anticipate that results from this trial will allow DMD patients in the United States to be able to obtain Translarna commercially, which we know has been a long way. In addition, the results from the vatiquinone MIT-E registration-directed study, who mitochondrial disease associated seizures, that's the AFFINITY trial for PKU and the FITE19 COVID trial will all read out in 2022. The MOVE-FA trial is ongoing, and the results for FA will read out in the second quarter of 2023. Clearly, we have a number of trial readouts that are potential value-generating milestones for all of our stakeholders. In addition to the registration-directed studies, we have been building PTC's R&D pipeline. Our next most advanced placing compound is PTC518 for HD or Huntington's disease, and we'll be initiating the PIVOT Phase II study in this quarter. We'll also initiate the CardinALS Phase II clinical trial for our second Bio-e compound, PTC857, for potential treatment of ALS. We're also proud to report that we have completed 2 niche oncology trials with unesbulin, and we'll be advancing these programs and the registration-directed trials this year. Will all of these readouts, we expect 2022 to be a very pivotal year. Let me now go through in more detail, some of the key programs so you can see why we are so excited about that. Let's start with the Bio-e program. This platform focuses on diseases of oxidative stress, which is due to excess electrons causing high levels of oxidative stress. The oxidated stress response pathway is controlled by oxidoreductase enzymes that regulate neural inflammation. Like other inflammatory pathways, oxidoreductases, are tightly regulated and over activation of the pathway causes cell and tissue damage. The first oxidoreductase enzyme we are targeting is 15 lipoxygenase or 15-LO, which is a key regulator and when activated induces neuroinflammation in a number of disease states. Our first compound for this platform is vatiquinone, and is in Phase III trials for mitochondrial disease associated seizures and Friedreich ataxia. PTC857 is the next-generation Bio-e molecule and is well suited for adult neurodegenerative diseases, including ALS. So let's start with our registration-directed MIT-E trial of vatiquinone for mitochondrial disease associated seizures. Now while mitochondrial diseases can affect every organ in the body, they most severely affect the brain to its high energy demand. Mitochondrial disease-associated seizures is the highly morbid condition of refractory seizures in patients with inherited mitochondrial disease. These are devastating diseases typically diagnosed in the first 1 or 2 years alike. They're rapidly progressive, highly morbid and usually fatal in childhood. The global prevalence is approximately 20,000 patients. There are no approved disease-modifying treatments for these patients. Now vatiquinone targets, the energetic and oxidated stress regulatory pathways that underpin seizures in these patients. So the MIT-E study is a randomized placebo-controlled study. It has a 28-day run-in period to establish the baseline seizure frequency. The primary endpoint is the change in frequency of observable motor seizures. The study will enroll 30 patients in each arm and patients will receive study drug for 24 weeks and transition to open label. Enrollment is ongoing and results are expected by the end of the year. Now let me turn to our MOVE-FA registration-directed trial for Friedreich ataxia. Friedreich ataxia is a rare inherited progressive neuromuscular disease that mainly affects the CNS and [indiscernible]. Onset occurs in childhood, with a global prevalence of approximately 25,000 patients. There are no approved disease-modifying therapies. Oxidative stress-mediated cell death plays a key role in the pathology of FA, making vatiquinone potentially an important drug for FA patients. MOVE-FA is a randomized placebo-controlled 72-week trial with the primary endpoint being change in [ Empire ] scale and secondary being improvements in activity of daily living. There's been substantial enthusiasm for this trial, with 146 patients enrolled -- and enrollment is completed. We expect results in the second quarter next year. Let me switch to PTC857. Last year, we completed the PTC857 Phase I healthy volunteer study, and we're initiating a Phase II ALS trial. ALS, is a rapidly progressing fatal neurodegenerative disorder. While the precise pathological mechanism is unknown, oxidated stress can cause neuronal cell death and this mechanism has been implicated in ALS disease progression. There are no disease-modifying therapies for ALS. PTC857 is an inhibitor of 15-LO enzyme and blocks key oxidoreductases [indiscernible] pathways. These are key pathways in the pathology of neurodegenerative diseases like ALS and Parkinson's, inhibiting them should protect motor neurons from these cell death pathways. The ALS trial has the potential to be a registration trial and is a placebo-controlled 24-week trial followed by a long-term extension. The primary endpoint will be the change in the ALS Functional Rating Scale, or ALSFRS. And the secondary endpoints would be safety and PK. The ALSFRS assesses subject capability and independence in 12 functional activities across 4 functional subdomains. There'll be a run-in phase to define the patients change in the ALS Functional Rating Scale. This study will be initiated in the second quarter of this year. So let me turn to our splicing platform, which we've developed over the last 2 decades. It's an innovative platform of breakthrough science that first showed that oral small [ molecule ] can modulate splicing, making it a druggable target. Our splicing platform, first success culminated with the commercializing the first oral therapy of risdi for the treatment of SMA. We have established a sophisticated splicing platform that integrates biological and chemical informatics as well as high-throughput technologies that allow us to monitor large numbers of splicing sites, all at once for both identifying splice targets and to subsequently optimize selectivity and specificity of compound that modulates splicing. This has allowed us over the last 2 decades, to build and develop a proprietary [ LIBOR ] compounds that modulates splicing. So we've built the science, the infrastructure, the chemical libraries and a world-class group of scientists that allow us to be leaders in utilizing splicing as a target to develop new therapies. So let me now turn to the splicing modulated PTC518 that will be entering a Phase II trial to treat Huntington's disease patients. Huntington's disease, or HD, is a progressive, debilitating neurodegenerative disorder that is caused by CAG repeat expansion in the HTT gene that results in brain cell death. HD has broad impact on a person's motor and function of capabilities that results in both movement disorders and cognitive loss. HD has an estimated global prevalence of around 135,000 patients. And there are no disease-modifying therapies to treat the underlying cause of the disease. PTC518 is orally bioavailable, penetrates the blood-brain barrier, it's selective, it's titratable and not efflux. And not only uniformly lowers HTT across all sections of the brain, but also reduces mRNA and protein levels uniformly in the periphery. The Phase I study was unique in that PTC518 analogous to [indiscernible] was able to cause a targeted [ 30 to 50 ] reduction in HTT mRNA and protein levels in healthy subjects, demonstrating proof of mechanism. This gives us great confidence of the activity of the drug. Importantly, PTC518 also crossed the blood-brain barrier in the defined plasma of the CSF ratio. The next step will be to demonstrate activity in Huntington's disease patients. The Phase II trial called PIVOT HD, in which the first phase will be a 12-week placebo-controlled study, comparing placebo to 5 with 10 mg doses. The study is planned to continue for a total of 12 months of placebo-controlled data. There will also be an option to initiate a third dosing arm leveraging the titratability of PTC518. Endpoints in the Phase II study will measure PD biomarkers, including HTT protein reduction in the plasma and CSF and neurofilament light chain levels in the CSF and plasma and preservation of brand volume as assessed by MRI imaging. We'll also explore the possibility of an accelerated approval pathway based on biomarker results. Our experience is that to be successful in neuromuscular and neurodegenerative trials. We need to know which patients are in the so-called Goldilocks Population. They need to be a patient population that are showing disease progression, but early enough in this disorder so that an active therapy can demonstrate improvement. To pinpoint this population, we're using the scoring system that uses a combination of components of the UHDRS, does a cognitive function as well as motor and PIN scores, which are validated predictors of disease progression. We're also preparing to do a longer duration Phase III efficacy study, which will be completed regardless of whether the trial is done as part of a clinical data approval pathway or as a confirmatory trial following an accelerated approval. We plan to release the results from the placebo-controlled to our re-portion of the trial when it's complete. Let me now switch to describe our plans for PTC923 for PKU. We believe that this is another important near-term value driver. So PKU is a monogenetic disorder in which patients like significant phenylalanine hydroxylase activity leading to high levels of phenylalanine that causes cognitive disabilities and seizures. Well, there are therapies for PKU patients, there is significant unmet medical need. Many PKU patients remain either untreated or poorly controlled on the 2 available therapeutics. In our Phase II study, approximately 50% more patients responded to PTC923 than Kuvan. These responders showed twice the reduction in phenylalanine levels compared to Kuvan even in the class of PKU patients, which are the most severely affected and do not respond to Kuvan. We view PKU as a significant opportunity as there is a well-defined patient population through newborn screening and known centers of excellence. There is also a clear pathway to approval with blood-based biomarker endpoint and an enriched population, increasing success in the AFFINITY study. As planned in the third quarter of 2021, we initiated enrollment in the AFFINITY trial, our global Phase III registration-directed trial of PTC923 in pediatric and adult PKU patients. The double-blinded placebo-controlled trial will include a run-in phase to identify responders to PTC923 who would then be randomized to receive either PTC923 or placebo for 6 weeks. As with previous approved therapies for PKU, the primary endpoint of the AFFINITY trial is reduction of blood phenylalanine levels. Following completion of the placebo-controlled trial, subjects would then be enrolled in long-term open-label extension. We expect to have results from the placebo-controlled trial by the end of this year. I'll now turn to our oncology platform. We are making significant progress and plans to initiate 2 potential registration-directed trials with unesbulin, our oral, small molecule tubulin inhibitor. One trial is in DIPG, a severe, rapidly progressing pediatric brain tumor. Radiation is the standard of care and offers an overall survival benefit of between 9 and 11 months. The 2-year survival rate is only 10%. The Phase I trial is now complete and define the Phase II dose. We look forward to initiating the Phase II study this year and plan to provide more details as the plans -- as the plans are finalized. The second indication of for unesbulin is leiomyosarcoma or LMS. It's a rare and aggressive cancer found in smooth muscle tissue. It's also 1 of the more aggressive sarcoma subtypes and has a high risk of recurrence, leading to a poor clinical prognosis. Several chemotherapeutic regimes are utilized for relapsed or refractory LMS, but was an objective response rate between 7% to 9%, they offer minimal benefit. We recently completed a dose escalation study in unesbulin in patients with relapsed or refractory advanced LMS, and who already have either had third, fourth or even fifth line of therapy. Results of unesbulin in combination with dacarbazine were impressive and demonstrated a 70% ORR and was tolerated in Phase I studies. The 300-milligram was chosen as a dose for subsequent trials. These results give us great confidence as we progress towards a registration-directed trial. unesbulin showed this activity in refractory patients that were highly pretreated. We will shortly initiate a registration-directed Phase II/III trial called Sunrise LMS. It's a global placebo-controlled study in combination with dacarbazine in relapse and refractory LMS and will enroll approximately 345 patients. They'll be treated with either a combination of unesbulin and dacarbazine or placebo in the dacarbazine. The primary endpoint is progression-free survival, with additional secondary end points focused on overall survival, duration of response and objective response rate. We plan to initiate the trial by the second quarter and are looking forward to providing updates as the trial progresses. So turning now to updates on our commercial progress. We're very proud of our robust commercial portfolio, including our homegrown products, Translarna and Evrysdi. We have a strong foundation with substantial revenue of $536 million in 2021 from our current portfolio. Let's start with Tegsedi and Waylivra, which hold commercial rights to -- which we own commercial rights in Latin America. Last year, they both received Category 1 pricing in Brazil. We also submitted for a approval of Waylivra in Brazil for an additional indication, FPL. This would be the first global approval for FPL, which has no effective treatment options. The DMD franchise showed strong growth last year, and we project to continue the growth through the geographic expansion, new patient starts for Translarna and new patients and continued high compliance for Emflaza. The franchise has produced $424 million in total unaudited net product revenue in 2021 and is expected to grow to $475 million to $495 million of this year. So I'm also looking forward to the launch of our first gene therapy product this year for AADC deficiency. We expect to [ seiche ] an opinion this April. We are also on track to submit the BLA to the FDA in the first quarter of this year. We've been preparing for the AADC launch and have held many key activities, including disease education programs and webinars, virtual congresses and have initiated more than 100 screening programs in cerebral palsy and epilepsy centers to identify patients in over 20 countries. We're making good progress and have identified approximately 300 patients. We will continue to identify new patients well after the approval and launch. And as we shift towards commercialization, we'll focus on treating patients as rapidly as possible. So I think you could see that with all these efforts, our strong commercial performance and diverse pipeline, we're in a great position to continue to build value for many years to come. So thank you for your attention. And now let's open it up for questions. I'll turn it back to Joseph -- Eric.

Okay. Great. Well, thanks for that presentation and overview. Before we move to the Q&A portion, maybe -- or as we do that, maybe, Stu, I could have you introduce other members of the leadership team who are on with you this morning.

Oh yes, sure. Well, maybe a quick hello, Matt, do you want to start, and then we'll move on.

Matt Klein, Chief Operating Officer.

Emily?

Emily Hill, CFO.

Kylie?

Kylie O'Keefe, Senior Vice President of Global Commercial and Corporate Strategy, good morning.

Eric?

Eric Pauwels, Chief Business Officer.

And [ Cassey ].

[ Cassey Seto ] IR.

Great. I thought we would start with the commercial side of the business and just kind of pick up from the fourth quarter performance as well as the outlook, the guidance outlook for 2022. At the midpoint for the DMD franchise, it looks from where -- from the implied print for fourth quarter with the DMD franchise, it implies sort of mid-single-digit growth, maybe it'd be helpful to have you sort of unpack what you anticipated some of the growth drivers for both Translarna and Emflaza, atleast within that guidance outlook. And then for the balance, sort of around $240 million non-DMD, can you just speak to some of the components within that, what some of the drivers are there?

Sure. So we -- I think 1 thing maybe is when we look at the growth of the company, we thought that the growth is actually it's still double digits, somewhere between 12% to 60%. So I think we're looking at within the growth of both of them, of both Translarna and Emflaza, continued strong growth both because of new patients and the geographic expansion. So we don't expect really much of a slowdown. And so I'll start with Eric and Kylie can talk through a bit more of what we're doing.

Sure. Yes, Eric. So first of all, I mean, it's been a remarkable year, right? We had our best year ever at $424 million for both DMD franchise, $236 million for Translarna, $188 million for Emflaza. These are the best years that we've ever had. And keep in mind, this is 7 years after the launch for Translarna, 4 years for Emflaza. So it's really a remarkable growth as we move into the eighth and fifth year of these brands, right? I think we continue to leverage this based on the totality of evidence for Translarna. And we have -- if I look back, and I look at the team's performance, there were already 40 papers and abstracts published for both products during the course of 2021, underlining the differentiated efforts of Emflaza versus prednisone. And with Translarna across a number of studies, real-world studies that show that the delays of loss in angulation and improve pulmonary function continue on for patients 2 years and older. So the foundation is that we've got really good science that's supporting the fact that these 2 treatments are incredibly important for patients 2 years and above. The key drivers really are kind of the same in many ways. Now first of all, we have executed extremely well with both products in finding new patients. We don't see that changing. We're continuing to find new patients for both products. We have high compliance rates. The compliance rates right now are in the 90s for both products, and that's incredibly good, and we're minimizing discontinuations. One thing we want to make sure that we're going to do to optimize these patients is to ensure that as they get reauthorized in the U.S. or new prescriptions are in at the beginning of this year, we will want to make sure that the physicians are looking at dose adjustments because that's critically important as patients get older for both products. The key growth driver for Translarna will continue to be not only main markets, but our big push geographically. Last year, in the fourth quarter, we also built an order for Brazil. And that was important. Brazil is a key market for us, and we continue to see orders coming in. And as we mentioned in our third quarter call, we launched in Russia very successfully, and we're able to secure orders in Russia as well. So while the revenues may seem a little bit lumpy from quarter-to-quarter. All I have to do is really look at the full course of the year. And I think the double-digit growth that we've been talking about over the last few years is going to be sustainable. We're looking at between 12% and 16% growth in the DMD franchise in 2022. So all these factors combined, and really proud of the team that have been executing against this across those [indiscernible] countries.

With Study 41 expected to read out middle of this year, maybe you can sort of set expectations with the readout there what would constitute good data. And then what additional -- well, and then the implications from a regulatory standpoint, right? This may enable registration in the U.S. And I guess, obviously, a related question is, whether -- if it doesn't go your way, whether there might be any sensitivities to Translarna's performance ex-U.S. Can you just speak to those factors there, what would constitute good data what would be registration enabling and any sensitivities?

Yes. So obviously, as I put on in my remarks, we all know that neurodegenerative, neuromuscular disease like Duchenne, like many others, it's -- they're variable and is to really define in a way what's the best patient population that you can actually see a difference within a clinical trial amount. And so I would say that if you think about we've done 2 placebo-controlled trials, and we've also had availability to the Lilly trial for DMD as well as the of BioMarin trials with placebo. So we have a huge amount of knowledge now on the natural history, the endpoints and what's the best patient population to be studying. And when you think about what we learned is that there's a -- there really is, in a sense, very similar. So we talked about HD as a Goldilocks Population, where not to early where we'll be stable or not do late where they're nonambulatory, and that we've been capable of defining what is the patients that are -- that you could see a change in because you could see the chain because they're having -- the disease is having an effect on that, but they're not so far gone that they're going to go nonambulatory very quickly. And that really came through all of that natural history and knowledge. And that's like sort of the 300 to 400 or what we used in our case was greater than 300 meters and time to get off the ground and 5 seconds or greater really define that population. And when you look at our data and all the others, and our -- even our controlled data was very clear that in that population the patients did incredibly well. So we feel pretty good about where we're at, and we make that the primary end point. So I think we're in a pretty good spot. We understand it. And we -- from our point of view, I should say, we're pretty confident the drug has shown [indiscernible]. We have striking revenue for 3 or 5 years. And when you look at long term patients in terms of their 5-year -- how they did in 5 years, is over 5.5 years of improvement where you don't see it saves ambulation by over 5 years. There's no 1 with less than a leader in pulmonary function, and that's a measure of people in a sense of like we heard a mortality within a few years. So it's done a very good job for patients. That's why you see continued growth and physicians know this data quite well. So we think we're in a very good position, that we're going to see positive results. As I said, we're already distributing in 50 countries. Really what we're trying now to is make sure that the U.S. patients, and on success with this trial, which is really just a statistical significant demonstration of that, we'll be able to transition into a [indiscernible] all the new [indiscernible] kids on to Translarna. So we think this is really important. It's an [indiscernible] important country to make sure that those kids had it and they've been waiting a long time. But I will say that -- what we also think if it doesn't come out as a home run, it's pretty clear from the long-term studies that these are -- that this drug is having a tremendous effect on these patients. So we would anticipate keeping it on the market and making those arguments. Does that help?

Absolutely. Yes. Shifting a little bit to the development portfolio and PTC518. Quite a bit more color here on the PIVOT HD trial, especially in terms of how you define the Goldilocks Population that you're looking to recruit here. I'm curious to get a sense of, I guess, how readily you'll be able to find patients that can meet these criteria to the extent that they are kind of assessed as part of their follow-up? I mean are these scales sort of readily used as is, we'll kind of take some time to kind of appropriately screen patients as you get underway is the first question. And secondly, given that there is the potential for dose titration longer term after 3 months, can you just speak to sort of where -- what range you'd want to see patients in after 3 months of 518 treatment in terms of their mRNA and protein decline?

Yes. So I'll start, and then I'll pass it on to Matt. So yes, I think as -- what we just talked about with in Duchenne muscular dystrophy, it's very similar thought processes for Huntington's, HD, right? This -- another neurodegenerative disease, where if you go too early, the patients are -- the disease is not involved enough that you won't see differences in the time of a clinical trial. If you wait and go too long, your -- the cognition and functions are so far gone that there's not a lot to measure in terms of that. So very similar to in a sense that what we just talked about, you need to get patients in line with those that the disease is affected, you can measure that disease, but they're not so far gone that you don't -- that there's nothing much left to measure, right? So -- and I think that is 1 of the biggest problems that when you talked about the previous study that was done, the patients were much further along the line within the disease state, the motor function and cognitive was pretty much at the lower end of the scale. So it would have been hard to see an effect. So what we've done is -- and we -- the group took apart the natural history data, and there's a lot of it. So you really can do this, to define what characteristics give you, in a sense, the appropriate Goldilocks, where they're declining, and they are -- and yet we don't think that there's plenty of room to measure improvement. So we feel pretty comfortable with that. Those are not difficult. Those are well-known measurements. We're using the current scales. So it's not going to be hard to do and there's 135,000 patients, and we're looking at all the sites, and we're going to sites that have plenty of them. So we don't anticipate a real problem. And Matt, maybe you want to go on a little bit more.

Yes, absolutely. As Stu said, we really undertook an exercise availing ourselves of available databases to really tone in that population. And it's important to remember, this is the continuous progressive disease. So we're not looking at some rare subset, but we're rather capturing a stage of the disease at a particular time where we believe we're in the best position to demonstrate an effect. So these patients are passing through that stage, virtually all then we'll go through it at some point. And what we've also found in getting this trial ready is there's an enormous amount of pull from the patient community and the physicians to be involved in this study. The concept of targeting HTT protein, mutant HTT protein is incredibly compelling, and the fact that this is an oral therapy and bioavailable is very, very attractive to patients as well as to the physician. So we expect to have quite fast enrollment for this trial given the enthusiasm we've seen across the centers worldwide. As we mentioned, we designed the study in 2 parts. The first phase is that 12-week portion, where we're going to focus on safety and pharmacology, really essential components to the drug development plan. This will be very important in informing dose levels for Phase III, whether we do that as a part of accelerated approval commitment or as a standard development program and then moving into longer phase where we're going to focus on biomarkers of disease that could put us in a position for the accelerated approval. As we said all along, we're targeting Huntingtin protein reduction of 30% to 50%. So that's really what we're going to be looking at after that first phase. Are we getting that targeted reduction at the doses we have, or do we leverage the titratability of this oral therapy and explore additional doses that can better get us in that targeted range of Huntingtin protein reduction.

Okay. Great. We've just barely scratched the surface given the breadth of the platform and pipeline, rather, but I'm being called for time here. So the PTC team, I want to thank you very much for joining us this morning, and everybody, have a great set of meetings and as the morning and day goes forward. Thank you.

Thank you.

Thank you.