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

Good morning, everyone, and welcome to the 2021 Credit Suisse Healthcare Conference. We're thrilled to have PTC with us this morning. We have CEO, Stuart Peltz, along with Matthew Klein and Kylie O'Keefe. And with that, I think we could get started with Q&A. [Operator Instructions]

So Stuart, we thought we could start out with a brief introduction to the business. You have several marketed products, along with a robust pipeline across a number of modalities. So what are the key highlights for someone less familiar with the PTC story?

Yes. Judah, thanks for having us today. For those who don't know us too well, we're -- PTC is a global biopharmaceutical company that we are focused on discovering, developing and commercializing innovative therapies to treat disorders, particularly higher medical need. I started the company about 23 years ago. We built the foundation on really our innovative RNA biology and now other platforms as well. We have multiple platforms really that does innovative science. We're focusing on discovering and developing therapies that treat rare disorders. And you probably know we've used multiple pathways, including splicing, gene therapy, the Bio-e are just an example. So we've been building really the company and driving innovation to create value on the number of products. And so we have -- we're well-poised for not only commercialization now but in the future. And the DMD franchise, it really does continue to grow. We've had a quarterly net revenue of -- that we anticipate to be around $400 million to $420 million this year. We'll see geographic -- we continue to see geographic expansion for Translarna for all nonsense mutation patients. We also have Study 41, which is fully enrolled. We anticipate that this trial will provide commercial product for nonsense mutations to [ stent ] patients in the U.S. when completed, this being the third quarter of 2022. We're excited about that program. So as I said, the franchise is doing well. Revenue keeps increasing. We also are going to be seeing revenue in with TEGSEDI and WAYLIVRA as well as the collaboration revenue from Evrysdi. And so we anticipate this to continue to grow over the years. And this year, we expect to exceed $0.5 billion in 2021. The pipeline, I'd say, we're really excited about it. We have a number of near-term revenue generators of potential revenue drivers. We have 5 ongoing registration-directed trials of [ STRIDE ]. Two are now reticle known from our Bio-e platform. We have one is a registration study for the MIT-E trial. It's a mitochondrial -- it's a therapy for a mitochondrial disease that's associated with seizures. We also have with vatiquinone, what we call the MOVE-FA is for Friedreich ataxia trial. Again, it's a registration trial. The MIT-E trial will be completed next year and the MOVE-FA trial will be completed the following year. I'm also pleased to say that we have initiated our Affinity trial for our compound for PTC923 and for PKU. Again, this is a registration program that will be completed next year. In addition to these trials, in terms of the registration directed trials, we'll soon initiate 2 Phase II trials with one for PTC518 for Huntington's disease and PTC857 will also -- will be in the ALS. So we'll be talking more about these and sharing more details on these programs.

Great. And I figured we'd kind of go platform by platform, maybe start out with splicing. And we figured we could jump in with Evrysdi. How should we think about the U.S. launch trajectory for Evrysdi? And kind of what is the latest in terms of payer discussions? And what can you tell us about access to the drug at this time?

Sure. As I'm sure you know well, it's -- the uptick has been really phenomenal. And we're very proud of the success of Evrysdi that we've seen. We're not really surprised, however, with the launch since the majority of the global SMA patients weren't being treated. So the nice thing about Evrysdi is it's an oral small molecule that has broad tissue distribution and it's allowed patients to get access to the effective treatment even during the pandemic. It's highly selective and specific. It's very convenient and that Roche has reported that is expected to be the treatment of choice for SMA patients with over 2,100 patients in the U.S. and since the launch in over 4,000 globally. So it's been really a tremendous success. It shows you the -- what we -- and what now Roche is feeling more and more comfortable with this. And the -- I think what they think now is that the market is going to be multiple of what they previously thought where it can get up to about $5 billion in terms of the overall SMA market. And it's really showing that the uptick of Evrysdi is doing as well, really demonstrating the unmet medical need despite existing therapies. Evrysdi has actually proven its efficacy and safety profile and has the added advantage of really simple at-home administration. As I said, it's now the most prescribed SMA treatment in the U.S. and the fastest take up for a disease-modifying therapy in SMA. So we're seeing all types of Evrysdi being taken, type 1, type 2, type 3, all range of all ages from naive to previously treated. More than 550 HCP have actually prescribed it.

Got it. Okay. And in terms of competitive positioning relative to Spinraza or Zolgensma, how do those conversations go either with payers, physicians or patients?

I think the ease of convenience, its proven efficacy profile has made it really, I think the... [Technical Difficulty]

We may have lost Stuart there for a minute.

Yes, I think we might have lost him. I think what he was talking about from a competitive positioning point of view was just around I think the fact that the Evrysdi has a proven efficacy and safety profile with the added convenience of an at-home administration. And I think this has been both valued both from a health care professional point of view and from a patient point of view, and this is not just applicable to the pandemic, but also well beyond the pandemic. As where possible where patients and physicians can avoid unnecessary hospital visits, anesthesia and lumbar function procedures, these can all be extremely cumbersome. And so that at-home administration and convenience of that is particularly pertinent in the pandemic, but also beyond the pandemic. And I think that, coupled with a strong efficacy and safety profile, has really set up the competitive positioning. And as Stu just said, Evrysdi is now the most prescribed treatment for SMA in the U.S. And so I think that that competitive positioning is being well accepted by patients, health care professionals and payers as we see majority of commercial lives being covered in the U.S. and broad and rapid access across other countries as they establish pricing and reimbursement.

Got it. We can do one more on Evrysdi while we're maybe waiting for Stuart to come back if that works for you guys.

Yes.

Okay. Yes. So Stuart mentioned the relationship with Roche. Maybe you can just remind us of the economics around registering the partnership with Roche. And then the rationale for the Royalty Pharma arrangement. And would you say these are emblematic of kind of a broader strategy to monetize commercial assets early on and reinvest in R&D? But aside from the actual Evrysdi relationships, maybe just what it says about how you think about kind of asset development and modernization?

Yes, absolutely. So I think let's start with our agreement with Roche and then jump across to Royalty Pharma. So in our agreement with Roche, we have tiered royalties of 8% to 16% in addition to both regulatory and sales-based milestones. So we received the final regulatory milestone of $10 million with the first commercial sale in Japan, and this totals out $72.5 million in regulatory milestone payments that PTC has received. We're also in addition to that eligible for a total of $325 million in sales-based milestones, with the first payment of $25 million to be reached when we hit the $500 million in sales. So in addition to the economics with Roche, we see the Royalty Pharma from our perspective as a win-win for all stakeholders. It allowed us to diversify our market risk by transforming Evrysdi's potential future cash flows into a $650 million cash asset. This has created real value for PTC's financial position as the cash, as you alluded to, is being invested to support PTC's research and development platforms and also to be able to continue the geographic expansion efforts commercially as well which we've been undertaking particularly in relation to Translarna. So as a reminder, the terms of the Royalty Pharma deal specified that PTC retains approximately 57% of the Evrysdi royalty stream until Royalty Pharma receives a return of $1.3 billion, and that's when all of the upside or 100% of the royalties revert to PTC. We really brokered this arrangement because we know the market -- the biotech market is volatile, and we wanted to proactively make sure that we had an ability to shore up our cash balance to provide stability moving forward, and we're now in a strong financial position to be able to continue to invest in our business. And in regard to your question around whether this is something to see for the future, I think one of the things that's important to note is PTC was a very different company when we brokered this arrangement. And so while our cash balance was different and also our infrastructure was different, we now have a strong cash balance. We have a big, large global infrastructure that's poised to be able to have plug-and-play commercialization. And so I think what we're looking to do with our pipeline moving forward is use our own commercial infrastructure to be able to pursue the watch.

That makes a lot of sense. And I think you guys are well equipped with the team here to answer the rest of our questions. So we'll keep going.

Yes.

All right. So within the splicing platform, moving on to PTC518 and Huntington's, right, there's clearly a large investor focus here. Can you first just walk us through maybe mechanism of PTC518, the Phase I trial design and what has you excited in the data that you've shown so far?

Sure. So we're incredibly excited about this program, and it really does follow on the heels of the success of Evrysdi for SMA. We learned a great deal about both the preclinical and clinical development of a splicing molecule and obviously having Evrysdi as a model of success is incredibly helpful. So in designing PTC518, we incorporated many of the key learnings from Evrysdi, the importance of selectivity and specificity in a splicing molecule. They need to optimize our target activity. And also given that Huntington disease is a whole brain disease, the importance of designing a molecule that gets across the blood-brain barrier and doesn't get [ Eflux ], that as it gets into the brain stays there so that it can broadly biodistribute throughout every region of the brain, which we know is affected by Huntington disease. So just taking a step back and addressing your question about mechanism, Judah. So most folks know Huntington's disease is caused by a CAG repeat expansion in the Huntington gene. This results in the formation of a toxic Huntington protein which aggregates and basically injures and ultimately kills brain cells and leads to neurodegeneration. PTC518 modulates splicing within the Huntington mRNA to basically introduce a stop codon. It basically puts up a stop sign in the mRNA that prevents the production of the toxic Huntington protein by preventing the production of the mRNA protein that's toxic to the cell, obviously, the toxic protein levels go down, neural cell injury goes down and we're able to affect the process of neurodegeneration. And these are things that we were able to demonstrate preclinically, in particular in the Huntington mouse model, in which we could introduce a humanized Huntington gene. We were able to demonstrate 2 really, really key factors. One, that we have broad brain distribution of the molecule and that we affect Huntington mRNA and protein production in a dose-dependent fashion consistently in every region of the brain. One other thing we were able to do with this molecule, since it's orally administered, we can also look at peripheral blood cells which make Huntington and get a lead on what's going on inside the brain. That is by looking at blood cells, we can actually correlate the effect of Huntington reduction. And that's actually incredibly important in terms of biomarkers of disease and being able to understand PK/PD relationship as we move into humans. And so with that, let's move into humans in Phase I. So the Phase I trial was set up very much the same way that the Evrysdi Phase I trial was set up to demonstrate safety, pharmacology, that broad distribution throughout the body crossing the blood-brain barrier. And importantly, the dose-dependent reduction in contingent mRNA protein levels, which we are able to observe in the peripheral blood cells for the reasons I just explained. So what we did is we set up a single ascending dose -- series of single ascending dose cohorts, multiple ascending dose cohorts. We then had a protein expression cohort, where we wanted to look specifically over longer term exposure at the reduction of protein, given that it has a longer half-life than mRNA and then also look at CSF levels to ensure that we were getting across the blood-brain barrier and achieving exposure levels that we need to have that broad brain distribution. We were able to demonstrate all of those things. We demonstrated that PTC518 was well-tolerated. We were able to demonstrate the dose-dependent reduction in mRNA levels as well as protein levels. We also were able to demonstrate in that protein cohort that we were able to achieve the target levels of protein reduction that one would expect to see in steady state. And then looking at the CSF, we saw that the PTC518 crosses the blood-brain barrier and achieves those exposure levels necessary by design to ensure that we get the broad brain biodistribution to affect Huntington protein levels throughout the brain. So what we can say is what we set out to do, we did, we checked all the boxes. And again, we're able to avail ourselves of the ability to get important information about PK/PD activity given the fact that this is a systemically administered therapy, and we can get a reflection of what's going on in the brain from the blood cells. So when you put all that together and checking all the boxes, we're incredibly excited now to move into Phase II and move into Huntington's disease patients and continue to follow, again, a successful pathway of development that we established with Evrysdi.

Perfect. Stuart, we were just getting started on Huntington. So maybe I could throw you a follow-up just on kind of plasma versus CSF concentration. And correct me if I'm wrong, but I believe you were expecting kind of a one-to-one plasma to CSF concentration based on your nonhuman primate models, but it seems like the ratio in healthy volunteers could indicate a higher CSF concentration versus free plasma. So in general, how would you say your animal models are translating into the early human data that you've seen for PTC518? We've lost him again.

Yes, it looks like -- I can jump in till he -- till he get back. So one of the things I mentioned previously is that we -- intentional in the design of PTC518 was making sure that it's not efflux, that it gets across the blood-brain barrier, stays in, because that is necessary to ensure that it broadly biodistributes throughout the brain. And while there are some species to species variation that one would expect to see between animal models and humans, we did see consistent exposure in the animals and then we came to humans and what we saw was a higher concentration of PTC518 CSF relative to the plasma. We actually view that as a good feature. It actually validates the fact that the molecule is getting across the blood-brain barrier, it's staying in. It's not getting efflux, and it tells us now that what we can do is look at dose levels that achieve lower plasma exposure and will, therefore, have higher CSF exposure. So the way it gives us more flexibility, and again, an important learning. And of course, one of the things we'll do in the Phase II trial is measure the relative exposures in the plasma and the CSF in patients to ensure that that ratio holds. But again, one of the benefits of this molecule being an orally-administered therapy is a titratable. We have the ability to adjust that dose up, adjust the dose down as needed to achieve target exposure levels in the CSF which we understand will correlate with targeted levels of reduction in Huntington protein in the brain.

Got it. And speaking of the Phase II, maybe could you just give us a little more on the trial design there? How soon you can move into the Phase II? And if it's potentially registrational based on a biomarker, how and when do you discuss that with FDA? Or are you already doing that?

Yes. It's a good question. So obviously with the Phase I data being everything we wanted to demonstrate having been demonstrated, we're moving very rapidly now into Phase II. The Phase II study has 2 components to it. The first is a 12-week placebo-controlled phase, which is followed then by a 12-month open-label extension phase. The primary objective of the 12-week placebo-controlled phase is to demonstrate safety, pharmacology and the PK/PD relationship relative to Huntington mRNA and protein reduction levels in Huntington's disease patients. We think this is a very important step in the overall development program because this is really going to let us hone in on the optimal dose that we'll need for efficacy trials, whether that's done as a Phase III trial as part of the development or in an event we were able to avail ourselves in the accelerated approval pathway as a post-market commitment. So the first step of that program is really to do the key work we need to do from a drug development standpoint. Then as we move into the open-label extension phase, we are going to be looking at a number of biomarkers disease, including Huntington protein levels in the CSF, things like neurofilament-light chain and also volumetric changes on MRI. These are very important in increasing our understanding of the relationship between Huntington protein reduction and impact on markers of disease. And of course, we're also aware as everyone else is about the potential of biomarkers being used as a way to gain an accelerated approval based on surrogacy. So at this point in time, we're moving full speed ahead and getting the Phase II trial started. We believe that, again, the concept of biomarkers and approval from the FDA is well-established. It's in the statutes, the definition of accelerated approval, the separate issue of a surrogacy. And our plan really is to move forward to get this trial starting, collect data and have our conversation with the agency as time unfolds. But the priorities get to start as to the key development questions around pharmacology exposure and safety of Huntington disease patients and continue to progress the trial forward.

That makes a lot of sense. And the last 1 or 2 on Huntington's. Just given the various modalities out there investigating Huntington therapy, whether it's all of those gene therapies, your oral splicing molecule, how do you see the various modalities kind of participating in the market, assuming multiple are approved and commercialized? And how do you think about targeting mutant Huntington's gene versus the non-selective approach that you're taking?

Yes. I think we are incredibly confident in our approach. I think the value proposition of reducing Huntington protein, which is the toxic disease-causing protein in Huntington's disease, is incredibly promising, and we, as many others, believe there's nothing has -- no new information has changed that enthusiasm around this approach. We also know that having an oral small molecule that broadly biodistributes to every area of the brain is incredibly important. Huntington's disease is a whole brain disease and the ability to not have to sacrifice a part of the brain based on mechanism of delivery is an incredible advantage for PTC518. Also, as it's a oral molecule, the fact that you can titrate it to effect is also incredibly important. And again, these are all things that we've seen play out in the value proposition for Evrysdi and the benefits of having an oral small molecule, not having to have an invasive repeated procedure, not having peaks and valleys of therapeutic effect, not having complications of prolonged surgical procedures for gene therapy administration, getting whole brain distribution in a whole brain CNS disease where you can target all the different aspects of the disease. These are all incredible advantages that we see playing out with PTC518.

Got it. And speaking of kind of the various modalities, maybe we can move into your gene therapy platform. So you have an AADC deficiency program. Could you outline the clinical data that we've seen to date? And what are the gating steps going forward for a BLA filing?

Yes, absolutely. So just for reference, AADC deficiency is the deficiency of an enzyme due to a genetic mutation, a genetic mutation where basically the kids can't make dopamine and other neurotransmitters. So these kids don't develop the typical motor milestones such as being able to lift your head, being able to set up, be able to crawl, be able to walk. Obviously, that results in a devastating disease where it's highly morbid repeat infections, lots of time in the hospital, severe malnutrition. And in the severest case is death in early life. So the gene therapy is quite simply giving a working copy of the gene to the part of the brain that needs it so dopamine production could occur. The part of the brain where the dopamine is needed is the putamen. And so we're in the majority of the dopaminergic cell bodies, neuron cell bodies are located, and we achieved that delivery through a stereotactic neurosurgical procedure. Basically a stereotactic neurosurgical procedure uses MRIs and CT scans to create a rule of map that takes a surgeon from outside the skull through a small hole in the skull directly to the putamen where the gene therapy has to go, safely so they don't hit any blood vessels and -- or other structures that could get injured. And so this -- there have been 3 clinical studies conducted in the AADC program, and the data are incredibly compelling. First, we've been able to demonstrate that by replacing the provision of a working AADC gene, it allows for the production of dopamine, which we've been able to demonstrate on brain scans, so that gives evidence that the gene therapy is getting to the right destination, and it's working. And we've seen that over the course of years, 3, 4, 5 years and even longer persistence of dopamine production, which is also a testament to the longevity and durability of our gene therapy approach by delivering it to the right part of the brain into cells that don't turn over. What we then see in addition to the dopamine production increasing is improvement in motor function. So we're seeing not only biochemical effect, but then the important clinical effect. So we're seeing children being able to lift their heads and over time be able to gain other milestones like being able to crawl, being able to sit and in several cases, being able to walk. We see this benefit unfold over the course of the years. And we have follow-up data now going out 6, 7, 8, 9 years, even longer. Here we showed maintenance of benefit in terms of motor function, continued acquisition of milestones. And then we're also seeing other improvement in other aspects of disease morbidity such as decreasing respiratory infections, improved weight, improved nutrition. And so basically, a data package that continues to show the clinical benefit of the AC gene therapy administration. And also, over time, we've, of course, also been able to collect safety data showing that over the long term, the gene therapy is safe and well-tolerated. We've submitted the MAA in Europe, where we're moving through the process, have disclosed that we are expecting an opinion in Q4 this year. For the BLA, the process is a little bit behind the EMA process. One particular reason for that is the use of the device that introduces the gene therapy to that right part of the brain. We're using something called the [ Smart Canula ], which is using a number of neurosurgical procedures, has been CE marked in Europe for the administration of gene therapy, has not been specifically 510 clear -- 510(k) clear in the U.S., the administration of gene therapy. So that's one additional step that we needed to take in the U.S. that we didn't have to take in Europe, which explains that staggering of time lines of the process.

Got it. Okay. And maybe moving on to the FA program on this platform. Can you just remind us of the status of the Phase I program and kind of how the delivery method here compares to maybe others that are being investigated, systemic versus kind of direct to the brain? A little bit of an overview on FA would be great.

Yes, absolutely. So Friedreich's ataxia is a neuromuscular and neurological degenerative disorder that affects the whole body. Obviously, the brain, in particular, cerebellum is impacted. That's the ataxia and Friedreich ataxia, but we also know that it affects other organ systems, including the heart, which is a source of morbidity and mortality in Friedreich ataxia patients. As a company, we're proud to have 2 programs of Friedreich ataxia. As Stu mentioned in introductory comments, we have PTC743 and the MOVE-FA trial, which is a oral small molecule that distributes to every organ system in the body and targets a pathway of inflammation, oxidative stress that's known to be key to Friedreich ataxia. That Phase III study is ongoing now. And we're incredibly proud to be able to have that therapy to treat the whole body, but then also a gene therapy, which, following in the footsteps of AADC and our overall gene therapy strategy of targeted delivery, is given to one particular organ system that is relevant to the disease, and that's to the cerebellum. So our gene therapy is delivered to the dentate nucleus to the cerebellum and get to target a key aspect of disease pathology, the ataxia in Friedreich ataxia. This, again, will be achieved through a stereotactic delivery system that Google map. And this time, the map is going to take you right into the dentate nucleus, the cerebellum, where the gene therapy is delivered. We're in the process now of completing the gating preclinical safety toxicology studies and look forward to bringing the FA gene therapy into the clinic in 2022.

Okay. Perfect. And moving on to the Bio-e platform. Stuart mentioned kind of the excitement around the MIT-E trial. But maybe you can just remind us first within the Bio-e platform, kind of what drew you to targeting oxidoreductase enzymes? And then we can go from there into MIT-E maybe.

Sure. Oxidoreductase enzymes are a class of enzymes that have been known for decades to be incredibly important in regulating energy production, inflammation and oxidative stress. What has prevented anyone from systematically targeting these enzymes previously is that they're special enzymes that if you're going to target them, you need to perform an area -- a special type of chemistry called electron transfer chemistry. What that basically means is that to turn these enzymes on and off and affect inflammation and oxidative stress, you have to have small molecules that can fit and interact with the enzyme and transfer an electron, which is very unique for a small molecule drug. What the Bio-e platform has, in addition to these oxidoreductase enzymes targets is an entire library of molecules who can do just that. They can target these enzymes and effectively transfer electrons, communicate with them and turn them on and off. And so the first enzyme target of the platform is the enzyme 15-lipoxygenase, which is a key regulator of inflammation and oxidative stress in a number of CNS disorders, including mitochondrial disease, including adult neurodegenerative disease. And vatiquinone basically targets that enzyme to turn off the enzyme and decrease inflammation, decrease oxidative stress, restore glutathione levels, which are -- and basically restore cell survival and prevent neurodegeneration. And so this compound, vatiquinone, has been in development for a number of years for mitochondrial disorders and for Friedreich ataxia, both which are known to have pathology in this pathway. And we're excited now to have the 2 potential registrational trials, the MOVE-FA trial, which we've mentioned before, for Friedreich ataxia and the MIT-E trial, which is targeting the severe and highly morbid symptom of refractory seizures in children with mitochondrial disorders.

Got it. Okay. And those readouts, I think they're a bit away. What should we expect in terms of updates for those programs kind of between now and the initial readouts?

Yes. So we're actually moving forward with enrollment quite well globally. Both trials are leveraging our global infrastructure and our global network of KOLs, given the many years that we have spent working in both therapeutic areas. And we're getting closer to readout. We're looking at Q3 2022 for MIT-E. And then in 2023 for MOVE-FA given that MOVE-FA trial has a 18-month placebo-controlled phase.

Got it. Okay. And then maybe we'll wrap up with PKU. So first, can you just remind us of the unmet need in PKU, maybe a little bit about screening procedures and why this is a highly addressable population?

Kylie, go ahead.

Yes, absolutely. So from a PTC perspective, we view PKU as a significant opportunity as there's high unmet medical need despite 2 existing therapies. So there's an estimated 58,000 patients globally. There's a well-defined patient population through newborn screening, so patients are identified at birth, and there's no incentives of excellence. So they're very comfortable with managing the diagnosis and treatment of these patients. So let me outline why we think there's an unmet need -- substantial unmet need in PKU. So roughly speaking, approximately 30% of the patients are currently treatment naive and they're not being treated by therapies. And the other remaining 70% have been treated with Kuvan. So of those 70%, very early on, almost 60% initially failed. So they are nonresponsive to treatment very early on. Of the remaining 30% to 40% of the patients that initially respond to Kuvan, almost 60% of those subsequently fail or are very poorly controlled over time. And so as you can see, there's a substantial unmet need in the sense of those patients that are therapy naive, so they're not on therapy at the moment, or even those that initially fail on Kuvan or over time become poorly controlled. And due to the large number of PKU patients globally, we see this as a significant unmet need and significant opportunity.

Great. Okay. And then maybe just the last one here as we're bumping up against time. But can you just remind us of the APHENITY trial designed specifically and how that can potentially improve POS there?

Yes, I can handle that. So we're basically designing a trial that's been used previously as an approval trial for PKU therapies. First subjects, so go through run-in phase where they'll be treated with PTC923 for 2 weeks. And then if they respond to PTC923 by a reduction in phenylalanine levels, the subjects will then be enrolled to receive either PTC923 or a placebo for 6 weeks. So essentially we're only enrolling in the randomized placebo portion of the trial patients that we know respond to PTC923. I'll also point out that this is a global trial that we're enrolling children and adults. So this is a therapy for all ages. Based on our Phase II study, we've been able to demonstrate significant greater responders to PTC923 relative to Kuvan. And then if you look at the subjects who demonstrate a response to both therapies, there's a 200% greater reduction in fail and allow any levels in the PTC923-treated population, 2 pieces of data that give us enormous confidence that we can really provide a therapy to address that unmet medical need. And also find that we've been able to demonstrate response in patients with classical PK. That's a 3-year PKU subtype or baseline phenylalanine levels are created to 1,200 micromol per liter. So again, really data demonstrating that we have a potential to address that unmet medical need.

Perfect. Okay. And that's time. And we're sorry Stuart dropped, but this was great. Thank you, Matthew and Kylie, for all the informative answers and for your participation. We really appreciate it.

Thank you. And thank you for having us.

Absolutely.