Conference Transcript - PTCT 2026-05-20

Brian Abrahams, Analyst — RBC Capital Markets

with RBC Capital Markets. Our next company is PTC Therapeutics, represented by their CEO, Matt Klein, and their CFO, Pierre Gravier. Matt and Pierre, thanks so much for being here. Good to see you, Brian. Thank you. Good to see you guys. So let's get started. I wanted to first start with the launch of Suffiance. Launch has obviously been going really well for you guys. Can you talk a little bit about what specifically has been driving the strength of the recent launched maybe the patterns of prescribing that you guys are seeing in the real world where the prescription is coming from how are you looking to potentially expand beyond kind of the initial centers of excellence and then we'll kind of build off that yeah absolutely look we're we're incredibly excited about the start to the launch and incredibly excited about what we see as sustained momentum in some cases growing momentum and a really overall overall significant opportunity.

Matthew Klein, CEO

You've heard us refer to as $2 billion plus, multi-billion, but everything we're seeing thus far reaffirms our confidence in that. I think the keys to early success were a few. One, we have a really good drug in suffiance. The dual mechanism of action allows suffiance to potentially provide benefit for the full spectrum of PKU patients, including the most severe patients. And thus far in the launch, that's exactly what we're hearing. Folks are responding. Folks are liberalizing their diet. And more and more, we've been hearing about other benefits like decreased anxiety, improved mood, improved cognitive function. A lot of that likely tied to the fact that the drug gets across the blood-brain barrier. So that's been there. Two, population size. This is 17,000 patients or so of PKU in the U.S., 58,000 globally in markets where we believe we can access. And so in terms of rare disease, that's a healthy population. All the trappings for commercial success have been there. Newborn screening, centers of excellence identified, payers that understand the disease. And we have a team, a global commercial team, that's used to executing on rare disease drugs, right? And I think we've done it before. I think we can even say we've done it before, done it really well with much more challenging data packages and much more complex competitive landscapes. And then finally, the fact that there is this large population was significant on that need. So it was all there. We had the time to do market development. We had gotten to all the 103 centers of excellence in the U.S., understand the prescribing patterns, the patient patterns, and things like that. And I think that's what really allowed this acceleration out of the gate. There were waiting lists and such. and then the other i think theme early on has been breadth the breadth of the launch in in every way you could think about it for the pku population so where we've got we said we've gotten prescriptions from over 90 percent of the centers of excellence that's really good two and a half quarters into a launch right so at this point in a launch you're you sort of maybe we're focused in some of the larger centers then you've got to expand that we've actually had the we're in all these centers and now it's a matter of penetrating deeper into those centers. In terms of patient segments, well, coming into the launch, one of the, I think, let's call it a misconception, was that the launch early on would be driven by those who are on Cuvan switching to Sofiance, and, in fact, a lot of KOLs said that. But that's not been the prescribing pattern. What we've seen early on was more that the largest bucket has been those who've tried and failed therapies. we're seeing a larger number early on than expected of therapy naive patients and also again in those early dialogues of kols the therapy naive segment was thought to be adults remote from the center who are not accessible maybe later in the launch you could hope to bring them in and we're seeing them come in and we have had some switches so and is that just because cuvan really hasn't been as actively detailed or is there is it intrinsic advantages of the drug of suffiance's properties So I think it's the advantages of the drug and another factor, which is the prescribing decisions at a lot of these centers are made by nurse practitioners, physician's assistants, with a lot of input from dieticians. And so I think some of the early interviews that were done with folks was a perception, but not the reality of what was going on actually inside their center in part. And the second one I'm going to mention now makes a lot of sense. If you, look, no one spends their entire day at these centers going through just PKU. They see a lot of different patients with a lot of different metabolic diseases. And it's saying, okay, if I've got time to start this drug, why not start it for someone who doesn't have a therapy, right? If you're on an existing therapy, if you're on Kuven, and you've been on Kuven for years, you're likely getting some benefit. and even though 100% of patients we've seen will do better in terms of fee lowering, dialerization, other benefits with suffiance, they're at least stable on a therapy. But then you've got 85 plus percent of your patients who are not on any therapy. And you might say, if all things be equal, let me give someone who doesn't have something to try. I think there was also an interest in some of the centers to, how can I say this, put suffiance to the test. Let's see how it is going to do in some of these patients who've tried and failed other therapies and see if they respond. And I think one piece of feedback we've gotten so far in the launch has been really positive in saying, there was one KOL who I know a lot of folks have spoken to who said, I put my hardest classical patient on it and a 90% drop of phenylalanine right away, and now I'm convinced everyone's going to get tried. So in a way, the launch has also benefited from that because you try your hardest patients, they do well and then there's now this prevailing uh sentiment that folks are going to try all of their patients on on suffiance now that's going to take time right if there's 17 000 patients in the u.s the vast majority of emerald centers of excellence and that's why you hear us talk about saying look we're off to a strong start we think we've settled into a pretty reasonable pace now that's sustainable why because there's a lot more patients to go at these centers and and we don't have the work now of having to say oh my god how do we activate the other 80 centers no we're

Brian Abrahams, Analyst — RBC Capital Markets

activated in a majority yes we still have less than 10 percent of centers to go we think we're going to get prescriptions there there's always late adopters that's typical launch dynamics and and we know that there's centers that are not quote unquote centers of excellence but still have patients and we're starting to get traction there too so so how do you think about sort of what comes next in terms of the patient segments like how many more how much more of the population is out there at these centers who are plugged in but untreated that haven't already started on suffiance and then secondarily how and when do you think you'll start to capture the kuvan switchers i think we'll start seeing more and more switches come and again the value

Matthew Klein, CEO

proposition here is pretty straightforward right if you have a response to kuven you know it's just physiology you're going to do better on the supplies right so that that's there and and benefit means a lot right especially if it's greater diet liberalization lower fee all those different things so that's there but i think we still have a long way to go in these other buckets as well right and so because if you consider the the majority of patients are tried and failed just generally and so that's a long way to go and a lot of them are tied to centers and and i think again one of the early misconceptions as well before starting the launch was that if you're not on a therapy you're not tied to a center if you're not on a therapy you may not be seeing the physician however for if you're not on a therapy your mainstay of management is diet management right and so you are likely in touch with the dieticians at the centers you know we've heard you know we've obviously spent you know one of the key recipes for success in rare disease is making sure you're integrated in the patient community we've been very well integrated in the patient community both in terms of disease state education disease state awareness and education but also obviously understanding how suffiance can fit in the community and we hear from folks who haven't been on a therapy talk about their relationship with dieticians and even if it's not we're seeing them every three months it could be an email here an email there and in the world we live in that's a connection that that's helping getting getting folks back i think the other part of this launch that's really important to understand is the international component yeah you know i i think ptc you know part of our commercial legacy was outside the u.s we actually built the business outside the u.s first and to be able to have that existing infrastructure and be able to leverage that infrastructure we said we expect to be having commercial patients in up to 30 countries by the end of the year you know for a company our size that's pretty impressive uh we've we launched in europe we launched japan we launched in the u.s all within six months uh we had to build the team in japan and that launches off to a great start and so i think that that's really could be a source as we get into the back end of the year of accelerated growth we're just going to have more patients on drug as we enter countries as we start completing pricing and reimbursement discussions, and I think that can be, if we think about the U.S. as being a sort of source of steady growth, we can have acceleration outside the U.S. in a meaningful way over the long term.

Brian Abrahams, Analyst — RBC Capital Markets

Can you talk a little bit more about the ex-U.S., just the general pricing dynamics you expect for Europe versus the U.S., degree of availability to a branded BH4 therapy, and just, I guess, how you would gauge the overall long-term market opportunity there, Europe and Japan versus the U.S.?

Matthew Klein, CEO

Yeah, absolutely. So a few things. I think, so we launched in Japan. Pricing is set. The list price there is on par with the U.S. It's fixed for 10 years. That's tied to the fact being an orphan drug. About 1,000 patients in Japan. And as I said, I think we're off to a good start there, and we see very good long-term potential there. We launched in Germany first, as it's typically done. There, the list price again was on par with the U.S. We're going through the pricing negotiations now i will note that the free pricing period ended in january and we started accruing in january for what could be a reasonable estimate of what the ultimate discount to the to the list price would be but we expect the list price to be there and then there'll be some negotiated rebate around that in other countries in europe we again are leveraging our understanding of how the systems work in each different country to begin with name patient programs so when you have named patient programs that gives us the ability to set the price but it's a smaller number of patients while we go through formal pricing and reimbursement. So you'll get through formal pricing and reimbursement, the price will come down a bit, but then you have access to the full population of patients. What's been really helpful in the discussions we're having, including initial feedback in Germany, was the differentiated profiles of science to your question and then the fact that we had the Amplify study completed. The Amplify study was a crossover study where folks were given in order A or order B, BH4, then suffiance or suffiance and BH4. So really allowed for rigorous intra-individual assessment of superiority. And on average, suffiance resulted in a 70% greater lowering of phenylalanine. So to be able to go into a European, quite frankly, a U.S. payer or a payer anywhere, and have head-to-head data in a well-controlled study as you start negotiations really answers any question about differentiation and clinical superiority.

Brian Abrahams, Analyst — RBC Capital Markets

One more question about suffiance, and then I'd love to talk more about Huntington's as well. Providing guidance at an early stage of the launch is always a challenge, and there's always a needle to thread there. How did you guys sort of think about that?

Matthew Klein, CEO

What is your guidance overall imply in terms of a lot of these dynamics that that you talked about and also patient persistence and i guess is this yeah okay so i i think we've we've traditionally and i think many have not issued product guidance in the first year on the launch for all the reasons there's a lot of dynamics to play out here and and you know we've been very clear that while we still need a couple more dots on the you know to make a line and give guidance we're very confident in a long-term trajectory here uh and you know i think as we get a little further into the launch we'll be able to give guidance and you know we had a lot of discussions about our product guidance for this year we started the year 700 800 and we said look we've got a couple different things uh we know for sure one we're very confident long-term potential suffiance how things play out we'll see we need a few more quarters under our belt and we've got a dmd franchise that we know is waning at and a lot of exceptional circumstances of selling in europe with that license uh you know 10 generics for plaza so the durability there's hard to predict now we had obviously had an incredibly strong quarter with 226 million of product revenue that allowed us to comfortably raise guidance i would say the lower end raise was based on what we were seeing uh with the duchenne franchise right that gave us assurances on the lower end to raise and the upper end was what we're seeing in terms of suffiance like that gave us confidence we can go even higher uh and as we've been as we've said as we get into the next quarter or so if we need to adjust raise again we will i think for us what we're going to be looking for now and understanding is you know seeing the trajectory uh the continued growth in the u.s which we expect and then understanding what that acceleration outside the u.s looks like i think i think we've and we've said this that we expect probably the ex-us market to really start having a big impact in the second half of the year as we get pricing and reimbursement on board as we start going through the process in brazil of the judicialization that we did with trans lana um look we've said all along you know trans lana did about i think a peak around 360 million outside the U.S., excluding Japan, and we were never into any countries at the same time with trends, and here we are with PKU, you know, about 10x the population of nonsense mutation, DMD, maybe a little more, a well-owned machine in terms of commercialization and the ability to launch simultaneously now. So that's all I'll say. We think the XUS opportunity over time can be really meaningful here.

Brian Abrahams, Analyst — RBC Capital Markets

Great. You recently presented long, shifting gears, you recently presented long-term data, open-label data for Vodoplame in Huntington's relative to natural history, match natural history. You maybe just start with what excites you guys most about the data.

Matthew Klein, CEO

Look, we, if we zoom out, Huntington's disease is a complicated, heterogeneous, neurodegenerative disorder without any treatments. Okay, that's code for it's hard. And so you think about what you want to do in a drug development program, and you come into phase two, what you really want to do is make sure that you come through phase two knowing that your drug works, does what it's supposed to do, and in this case, lowering Huntington protein, which we believe is a very rational approach to this disease. The drug goes where it's supposed to go. It gets into the brain, a very good exposure. That's important. It's safe and well-tolerated. You understand what dose you need. You know who to study it in. And you have signs that it could actually long-term have meaningful efficacy. And so when we looked at the data that we shared at the end of April, you know, all those boxes are now ticked. And being able to see that dose-dependent effect with a 52% slowing of disease progression at 24 months relative to well-matched natural history gives us a lot of confidence. And seeing the dose dependence, the focus of the first 12-month study was really on lowering Huntington protein. We said the blood is a very good way to understand what the drug is doing. By the way, that was borrowed from the Avrisdi playbook where we used blood cells in Avrisdi to predict what we were doing to SMN protein in the brain. Same thing we were doing here with HCT lowering. And to be able to say, okay, we showed that if if you're making if you if you lower Huntington protein twice as much you're getting twice as much benefit at 24 months now I'm not saying that's a one-to-one you know expect to think but in that ballpark that's a pretty good sign yeah and to see contributions across several different scales and some of the other things we understood looking at the data we thought was really really good okay and and gave us confidence that this is a very well-designed phase three study it's a very well-powered phase three study it has an interim analysis to get to an answer sooner and you know i'm very proud of our company but novartis is a machine in terms of being able to get get get up and running and execute from a technical aspect a phase three trial with 770 or so patients in you know many many countries so i think it was seeing that proof of efficacy at 24 months and knowing now that we really as much as you can have de-risked a phase three trial for neurodegender disease where there's no approved disease modifying therapies.

Brian Abrahams, Analyst — RBC Capital Markets

It sounds like the phase three, this really validated the approach that's up and running. What are you going to be looking for to decide whether to engage the FDA around potential accelerated approval discussions and how and when might you announce potential next steps in that regard?

Matthew Klein, CEO

Yeah, absolutely. Look, I think both companies have been clear that if there's an accelerated path, we want to get this drug to patients as soon as possible. I mean, Vardis is very clear about that we've been clear about that and as Voss outlined in the Novartis earnings you know the plan is let's continue going through the data let's talk with PTC and come up with a plan for regulatory interaction so I think that's there is there anyone left at the FDA to interact well that becomes a quite well so in terms of you know that plays into it as well right it is just understanding what we have in terms of data and what's the best argument you can make and what's you know what's the temperature in silver spring i think one thing people are maybe confusing but govartis has been very clear when they acquired the drug that they believe in it their base case was phase three but if they can accelerate things they will and they did a great job of getting the phase three trial up and running i think everyone's excited about what these data showed i think everyone agrees these data what we've seen so far support exactly what's planned in phase three and de-risks it and i think for them getting phase three up and running and going is a is a corporate priority they're not a small mid-cap biotech company that everything stops and we run for accelerated approval and that's what we're doing it's okay we'll look at we'll get the data and we'll look at how the discussion so i think people shouldn't confuse the fact that you know they're not coming out tomorrow and everything's fast track to make a decision about the fda with one not having an interest in not believing in the data it's just the dynamics of companies operate differently so we look forward to the data being completed you know as you know we shared the data novartis had earnings on the um april 28th that's when we shared the data there was still more data to go through we'll have a discussion and we'll come up with a point of view and and yes we'll understand what's the temperature um in in uh in in at fda in maryland and then make a decision to go and then just in terms of leveraging the interim analysis from the phase three to potentially get this to uh over the line more quickly i guess what are you going to be looking for in a potential interim cut uh to support a filing i guess how do you balance the importance of having sufficiently long follow-up and enough

Brian Abrahams, Analyst — RBC Capital Markets

patients to fully elucidate the profile not compromise the integrity of the of the data against also, I guess, balancing against the importance of trying to get this to patients as quickly as possible if there is going to be a profound effect that could have for them.

Matthew Klein, CEO

And balance is a good word, Brian. And Novartis hasn't disclosed the details of the interim yet. You know, we've made clear, obviously, it's going to be sooner in a smaller, you know, a sooner time point, potentially, in a smaller number of patients. But it's been very well thought out and just about when you think about the cadence of enrollment uh and the fact that we'll also have experience longer term in terms certainly in terms of safety from pivot hd and that study is going to enroll 770 patients i think there'll be a very uh if there was a situation where the interim analysis was successful i i think you'll have the ability to have a very strong robust dossier to support a filing is there also a superiority interim analysis baked in at some point or is it just kind of that one interim that would potentially dictate a more rapid approval yeah it's basically a one a single efficacy and futility okay again i think giving a

Brian Abrahams, Analyst — RBC Capital Markets

lot of credit to the thoughtfulness of the novarius team it's been very well thought out in terms of setting up for for potential success got it um maybe moving to vitiquinone you're now conducting a 24-month study versus the 12-month time frame in the prior study, I guess how confident are you that upright stability, that that subscale is going to remain the most sensitive measure here for the full 24-month duration? And maybe talk about the trial design and plan there.

Matthew Klein, CEO

Absolutely. So this was, I'll say, a pleasant surprise for us that FDA suggested that we could use we could potentially use an open label study to support nda resubmission uh comparing to natural history and i think part of that comes from their uh understanding of of the natural history database the fact that in our move fa study uh that the placebo trajectory and the natural history trajectory were pretty consistent the fact that safety is pretty well understood for vitiquinone it's not that we don't need a blinded placebo study to better characterize safety so all the elements were there, and we were able to use the 2023 guidance on external controls to show how well this study could fit. The decision to do the 24 months was, again, based on having time points when natural history is collected and allowing for a result that would be interpretable. But we believe that the best endpoint at 24 months is actually the entire MFAR score. And this may be what your question was alluding to, because while upright stability subscale has been shown to be most sensitive to change over the short term right if you look at all the natural history studies they say from about 12 to 18 months that's the subscale of interest but given to the nature of that scale the fact that you it's kind of binary whether you have or lose something and the fact that it's usually two to three years between losing a step what all the natural history studies show is that as you go out further 18 months 24 months you start seeing contributions from upper limb and limb and so and if you look at the move fa data at 18 months yes it was driven and our data showed by upright by uh upright stability but you start seeing lower limb kick in and as we went to 24 months it was the same thing so now you think about designing a 24-month study where you've all if you're doing a natural history control you know what that control group is going to do more or less based on natural history so what you want to do to capture treatment effect is make sure you can capture any element where treatment effect can be measured yes and so that's why we we believe that mfars is probably the best got it at 24 months makes sense um p.r question for for you um you guys have a pretty robust balance sheet i think one close to two billion um you know i and you've said that there's a lot of leverageability in the existing commercial

Brian Abrahams, Analyst — RBC Capital Markets

infrastructure that you have for the suffiance launch um so there's not going to be a ton of additional expense necessarily there um you have a number of internal r&d programs but many of them are quite early stage and i imagine are not super capital intensive at this point so i guess what do you want to do with the cash like wow how are you prioritizing use of capital now across internal versus external versus uh internal r&d external commercial so the beauty in having such you know solid balance sheet we should agree you know gives us all the flexibility yeah and that's very important obviously we'll continue to deliver safe finance across the globe we'll continue to invest in our own r&d pipeline and then we look as well at ways to accelerate potentially

Speaker 1

structure that is you know highly capable they demonstrate it with emplaza with transfer now with obviously safe finance they have capacity um and we've we're going to be very thoughtful foreign discipline our approach needs to be strategic we're not going to do you know an ebay gamestop type of transaction uh and uh and that's how we think about it is let's be very disciplined let's find you know accretive transactions that accelerates that path right we're going to get two billion pixels plus at least two billion plus with the fans are there ways to accelerate that uh with our commercial infrastructure do you think there's anything interesting out there do you think valuations have now come up to a more prohibitive question yes there are opportunities of course if you come you know and maybe you can share some of that those multiples with us but you know we're going to be again we're going to look at creating value for our shareholders thanks guys great to catch up thanks everyone thanks brian