Welcome to our next session. We've got PTC Therapeutics presenting for the next 30 minutes. Sitting up here on stage with me are a couple folks that you definitely would recognize. Matthew Klein, who is, of course, Chief Executive Officer, as well as Pierre Gravier, who is Chief Financial Officer. We also have a couple folks in the audience from the team as well. We might yell out to Eric during Q&A as well. Let's maybe just do a quick overview of the company for the few people who might not know about PTC, Matt, and then we can go into to Q&A.
Absolutely. Thank you so much for having us, Tazeen. PTC is a global biopharmaceutical company that discovers, develops, and commercializes therapies for diseases of a high unmet need. We have six marketed products that we commercialize ourselves around the globe, as well as a robust R&D portfolio, including our validated and differentiated small molecule oral splicing platform. We're off to a great start in 2026. We delivered commercial revenue total revenue in the first quarter of $273 million, with product revenue of $226 million, allowing us to raise guidance for the year. That was really led by our another strong quarter for SEPHIENCE, which we launched last year for children and adults with PKU. We did $125 million in revenue globally.
This is a rare disease launch that's leveraging our established global infrastructure, and as I mentioned, we're off to a strong start with strong momentum, and I'm sure we'll talk a lot about that during the fireside. Also, we've made a number of advances in our R&D portfolio as well, sharing the positive data from the long-term extension of our oral Huntington's disease therapy votoplam, which is partnered with Novartis. We also shared that Novartis has initiated the phase III HD trial, which is up and running.
We also provided an update on our Friedreich's ataxia program, where we've discussed with the FDA being able to conduct a open label versus natural history study to support NDA resubmission. Our NLRP3 program we shared is now in phase I. A lot of great progress across both the commercial and R&D portfolios.
Okay, great. Yes. We wanted to talk a little bit about this new little launch you've got with SEPHIENCE, right? We've covered this company. I've covered this company for quite some time now. You've had an evolution. You were originally known as the DMD company. Now you've got PKU, and maybe just talk to us about the platform, how it's evo lved, and why you're excited about the early innings of the launch, and then we can talk about what your expectations going forward are.
Yeah, absolutely. The company has its roots in DMD, which was started with DMD and actually being one of the first RNA drugs in development. That experience with Translarna and then of course with Emflaza really allowed us to build a robust rare disease global commercial infrastructure with the ability to navigate regulatory authorities, pricing and reimbursement, and sales all over the globe. As we've continued to do work and focus on both the discovery and development of important therapies for rare diseases, the PKU program with SEPHIENCE fit very nicely into that. Of course, we have a number of other programs in the pipeline that are moving through. When it came time to file for SEPHIENCE and get ready to launch, this was really we saw as an exciting opportunity.
One, because the molecule, the therapy itself, SEPHIENCE, is highly differentiated. It has a novel dual mechanism of action, which is capable of providing potential benefit to the full spectrum of PKU patients. PKU is a disease approximately 17,000 individuals in the U.S., 58,000 globally in areas we can market the therapy. Despite there being approved therapies, there remains a significant unmet need for the vast majority of patients. Here we are with the opportunity to launch a product that has a highly differentiated profile, very strong safety profile, demonstrated efficacy across the full spectrum of patients, regulatory labels that are quite broad, a large patient population for rare diseases with significant unmet need, and this global team that's very used to launching and selling rare disease drugs.
You know, we've been able to, within six months, get approval in the U.S., Europe, and Japan. We have already launched in a number of countries. We said we should be in up to 30 by the end of this year. That's really impressive for a company our size and for a rare disease launch. I think it's really this combination of having a really good drug, a really experienced team that, you know, obviously being in place allowed us to spend a year and a half in market development, become very well integrated in the patient communities, understand their needs, have disease awareness and education programs. Like in the U.S., we had an opt-in program prior to launch. All these things that allowed us to hit the ground running.
Yeah.
As soon as we had authorization, and I think you're seeing the products of that with the strong launch, not only in the U.S., but now globally.
Yeah. You know, on the point of the strength of the launch, were you expecting a bolus when you first launched, and did you see that, and is that starting to fade?
Yeah. I think the term bolus to me. The short answer is, we don't think we had a bolus because a bolus really means you had this flood of patients come in, and then it dwindles off. What we certainly had was an acceleration phase in the first couple of months, where since we had done so much work in market development and there were a lot of centers that had waiting lists of patients to come in, we had a really strong start to the launch and but we're still in a period of very strong momentum that we can maintain for the long term.
That's why we've really used the term an acceleration phase, where in the first few months, there are waiting lists, the centers brought in a lot of patients, and then somewhere around, middle of the 4th quarter, we started seeing we're getting into this sort of sustained cadence, whereas patients came in, they're being put on drug. We also noticed there are a lot of things in this launch that I think people misunderstood coming into it. One is I think there's a fundamental misunderstanding of the marketplace. A lot of folks thought that, you know, there's 17,000 patients, but a lot of patients have lost the follow-up, and you'll never get them in, and maybe you'll just get the patients who are on existing therapies switching. That's not what we observed at all.
In fact, what we saw across centers of excellence is that there's a preference for getting those who are not on a therapy on a therapy first. A number of these individuals who had fought to be lost to follow-up, such as adults, including those with classical and more severe form of the disease, they're coming back to the clinic. I think what we've been able to show early on is that the addressable market is the full patient population at PKU. These are people who want a therapy, so long as it's safe, well-tolerated, and it can make a difference in their life. We've been able to really, again, a lot of this was from the work we did beforehand, but we're already penetrated into over 90% of the centers of excellence in the U.S.
This early in the launch is pretty phenomenal, and we have penetration into all of the key patient segments, including those therapy naives, those who tried and failed other therapies, those who are switching from existing therapies. We've got, you know, infants on the drug. We have an 80-year-olds on the drug. We the breadth is really the story of this launch, and it's the fact that we have that breadth already and no matter how you segment the population. The fact that the population is so large is what gives us the confidence that we're really in this period of sustained momentum in the U.S. Outside the U.S., we're just getting started, right? We've launched in Germany, and that's going very well.
We launched in Japan, in March, now we're seeing that sort of accelerated phase in these other countries. That's what's so special is that we are now in a period with a strong start in the U.S., a strong base of patients with sustained momentum there, now accelerated momentum globally is really what we believe is going to take us to the levels of that we think we could achieve, you know, blockbuster status, multi-billion dollar status, as we've talked about.
Okay. We are in agreement with everything that you've said. We published a survey of physicians before you reported the quarter, which indicated, you know, strength of the quarter and beyond. Some folks are looking at data points that, you know, we'd like to hear, you know, what you think of, for example, you know, claims data. Some are of the view that claims data trends seem to indicate that there might be a plateauing of demand. Why would that be an incorrect interpretation?
I don't think the claims data are really reliable here for us. Also people are looking at prescription sources and such. We have two specialty pharmacies. It's a closed network. Everything's confidential. That's point one. Point two is that what we've talked a lot about is we saw at the end of the year holidays into early part of the year, typical dynamics you'd see with holidays and, you know, starts maybe going down a bit, shorter month in February. We see a really strong March, really strong April. There's no signs that this momentum is slowing. Yes, it's, you know, every week is not going to be the same. It never is in any launch. There's a lot of external factors.
If you can zoom out and look from around, you know, mid-November, till now, it's pretty consistent with the number we gave. I think people, you know, I know there's a lot of discussion about the first question you asked, you know, was there this bolus and now it's going away? No. There was this acceleration from all of the work we did, market preparation we did, and now what we're seeing over the past four or five months is sustained momentum that all the signals we have are going to continue.
You've used sustain a couple of times in this conversation. You used it a couple of times on the earnings call. As far as U.S., and then we'll talk about ex-U.S. in a second, Are you in a place where you think you'd start to feel comfortable providing, like, sales guidance?
Yeah. I think what we've talked about is we've typically had the practice of not giving guidance for the first year of a launch.
Yeah.
We've said that we see we believe we're in a period of sustained adds, which means if things continue to go the way we imagine as we get later into 2026 across the year point, and we have enough points on the map to give guidance, then, you know, then we'd be ready to do it. You know, no promises of exactly when, but, you know, obviously we're tracking this. We're seeing such great trends, such strong trends, and we're still early in launch. We want to make sure, as always, when we give guidance, we believe in the guidance and can stick by it. There is And I think we've been very clear, everything we're seeing reaffirms our conviction in this. One, the strength of the launch, and really the strength of the long-term opportunity here, for the product.
Yeah. You talked about long-term opportunities. I don't know what the current consensus estimate is for peak sales, but as you look at number of patients in the U.S. and abroad, how are you thinking about what the TAM worldwide could be on sales here?
Yeah. We've said that the market itself, we think is about 58,000. We've not guided to what that could translate into sales.
Yeah.
Obviously, you know, the price, there'll be some variation outside the U.S. We're working very hard early on to maintain, as always, that rigid pricing corridor. We shared that we've got pricing in Japan on par with the U.S. WAC that's fixed for 10 years, really good.
Making very good progress there. Similarly, we have the list price in Germany is on par with the U.S. Again, we see it 58,000. We've said about 17,000 in the U.S. We, again, just as we see this going, we've already through the first quarter, have over 1,200 patients on drug, and we see an ability just to continue to build that base. That's really the key with good adherence and steady ads and a ccelerating ads outside of the U.S., that's how you get to that large opportunity.
Yeah. What has early discontinuation rates looked like? I think I asked this on the earnings call, but maybe we can go into a little bit more color. What's been the reason for discontinuation?
Yeah. We said we're in about the low double-digit percentage.
Yeah.
Which is really strong at this point in the launch, especially when you consider what I said earlier, which is. A lot of the early prescriptions in the U.S. were for those who were therapy naive, classical PKU, the more challenging patients. If we're seeing really good adherence in the more challenging patients, knowing that a lot of the KUVAN switches, for example, are still to come, that gives us a lot of confidence in the long-term adherence rate.
Definitionally, if you've been on an oral therapy for years and proven whether it's branded or generic, and you're going to switch to a therapy that's also once a day, let's just say has equivalent tolerance, but superior efficacy, that bodes really well for the long-term adherence there. In terms of reasons for discontinuation, you know, we have about, you know, half of them have been for clinical, which could be not effective or tolerability, others patient preference. We've seen a number that are patient preference, which falls into any number of buckets.
Is there a particular profile of patient as this launch is progressing that you think would be particularly likely to respond, or is it too early to know?
Well, look, I think we've said what we're seeing is response across the full spectrum, which is what's really, really important. The fact that we keep hearing stories of prescribers who put their most challenging patients on and hearing about phenomenal responses in terms of not only phenylalanine lowering but diet liberalization. Of course, we know from our data that any individual who's had any response to KUVAN branded or generic will have a superior response to SEPHIENCE. That's very clear. Even if they were able to get to target Phe or some diet liberalization, one would fully expect that to be much better on SEPHIENCE.
The good news is the word out there in the real world experience is that we're having meaningful effect across the full spectrum of disease, which again, continues to give us confidence to continue to penetrate these markets, right? If you're a prescriber and you put your challenging patients on the drug and you're seeing responses, that just says, "I'm gonna keep going there." Also, I have got these other patients that I can switch at some point. You know, just when you look at that across the board, you say, "Okay, that's why this has really long legs and a really large opportunity potential.
In terms of, you know, treatment-naive patients who are experiencing SEPHIENCE for the first time versus switch patients from something else, or as you described it earlier, patients who were initially lost to therapy and are coming back in, what do you think is the current split of that?
Right now, we somewhere around 30% are treatment naive. Which is a nice number. The switches and the tried and failed, it's a little harder to ascertain the exact numbers, you know, because it's not always clear if you've tried before. If PSF doesn't.
Yeah.
Always distinguish between the two, but I think, you know, let's call it an even, Actually, I think we have more tried and failed than on current therapies, again, because what we've heard is this desire to try patients on it who aren't on an existing therapy, which is why we believe we still have a very long way to go in terms of KUVAN switches.
Okay. From the time a script is written to when a patient receives treatment, has that time period contracted as the launch has progressed?
Well, I think it started very strong. I think we were an average of about two to three weeks.
Yeah.
When we started. We're probably still in that average range.
Do you expect that to be the normal range?
We think so. That's an average. Some can get on very quickly, and some may take a little longer depending on their specific circumstance. You know, we said we now have policies with over 2/3 of American lives. The policies have been consistent in being very, very flexible, with very few obstacles to getting on therapy. All of that, we think, is gonna continue to help.
Now, what are you hearing about the qualitative measures like, you know, the quality-of-life measures like, you know, diet liberalization. Things of that nature, which we had talked about pre-launch?
Yeah. We're hearing great things, and we're seeing great things. In fact, on social media, it's so fun to see stories of kids eating certain foods for the first time. We saw a photo of a kid eating a piece of steak off his parents' grill and never having been able to do that before, and hearing stories of families all being able to have the same meal for the first time.
We're also hearing a lot about benefits on cognition and mood, which is super interesting because if you talk to families affected by PKU or healthcare providers, they'll talk a lot about the burden of anxiety, brain fog, and cognitive difficulties. We, in our recent publication looking at the open-label extension from the phase III study, we're showing on the QOL measures that we're having a good impact, a very favorable impact on anxiety, mood, other aspects of mood, and cognition. These are things that go a long way for patients in feeling better. In fact, when we talk about the policies, the criteria for reauthorization include quantitative things like Phe lowering, potentially diet liberalization, but also overall medical benefit. We're hearing from a number of folks that, "I know my numbers are a little bit better, but I just feel so much better. My brain fog is gone".
That's, that's really important because that's, you know, talk about quality of life, being able to. You know, we had the story of [use to take] a woman who used to have to use GPS to get home from work, right? To be able to not have to do that, mood being better. All those are really important favorable effects of the drug.
As you talk to physicians, you know, is there one thing in particular that they are impressed by? Then I'm sort of trying to figure out sort of the depth of prescriptions. Are you still at the phase where doctors are trying it on a couple of patients and you keep getting new doctors that are adding a couple patients? Or are you seeing more trying to use it in a, in a more significant-
Yeah.
group?
I think, you know, again, we're in over 90% of the centers.
Yeah.
These are the larger centers, and we've been in contact with the other centers and fully expect to get them on board. Those are the late adopters as you typically would see in any launch. I think we've seen a variety. Definitely, the larger centers, what we're seeing is, you know, we're putting everyone on. Just like we said we would. We're gonna try all our patients on it. We've seen other centers that were maybe at first a little skeptical, said, "I'm gonna try one or two more difficult patients," and then they started to respond. Okay, now the floodgate's open. We're gonna try to put everyone on.
I think Those early, that early experience in the more severe patients was so important to reaffirm that, you know, all patients should have the right to try this drug. It becomes the first line therapy for PKU. That's where we're going. I mean, we're there in a lot of the major centers again, that's what gives us the confidence of the durability, I'll use the word sustained again the of the launch momentum.
Yeah. Okay. As it relates to Europe, do physicians there have a similar view of SEPHIENCE to how U.S. physicians think about it? I mean, you guys have been in an unusual position of being able to market drugs in Europe for longer than you have in the U.S., so you have that built-in expertise. Have you been able to capitalize on the infrastructure you had built out for Translarna for this launch in Europe?
Yeah, absolutely. you know, we have that playbook for Europe. We have it for LATAM. W Ith the approval in Brazil and we're using a similar playbook that we're writing for the first time in Japan, and the experience in Europe and Japan are actually quite similar to what we're seeing in the U.S. Great enthusiasm on the part of the KOLs and understanding of the potential of the drug to treat the full spectrum of patients. It may differ center by center who may try first and how that works, but a lot of excitement and we also, using that infrastructure we had in the Translarna playbook, we knew a lot about how to how do we leverage early access programs in a number of European countries, which we're doing while pricing and reimbursement goes on.
That gives us the ability to sell the drug at the price that's consistent with the, what we're maintaining for the narrow corridor, all while we're going through the period of formal pricing and reimbursement. To be clear, through these early access plans, you're not gonna get, you know, all the patients on. It's gonna be smaller numbers. Once we get final pricing and reimbursement set, then you'll expect the large numbers to come in. It allows us to, one, start getting revenue in the country, and two, building up the physician and patient experience in those countries in a very positive way so that once pricing and reimbursement are in place, again, it opens that floodgate and allows us to access the larger patient pools in all of these countries.
For Germany in particular, I think for some launches when they've gone particularly well, they've had to go back and take a price decrease. What is your expectation of that happening?
Yeah, so.
For this launch?
Well, Germany now has, it's a six month free pricing period.
Yeah.
That came to an end for us in January. We launched in July. We're in the process now of going through the pricing negotiations. The initial assessments were quite favorable. A lot of that is because of the data we have, the fact that we had done a head-to-head study, our AMPLIFY study, which showed that on average, patients had a 70% greater lowering in phenylalanine versus KUVAN. You know, that head-to-head data was super valuable. We saw them, what they don't often do, but did in our case, was recognize the biomarker of Phe being meaningful and have meaningful therapy. That's going very well. We expect there'll be some discount. What it is, we'll know better as we play out-
Yeah.
in terms of the negotiation.
Okay. You mentioned phenylalanine. In the U.S., are doctors actually going back and measuring these levels in real time? I was just curious about that.
Yeah, I think, I think they do measure them.
Yeah.
I think it's, you know, patients want it. Well, the funny thing is that if an individual PKU will tell you that their brain is like a PKU a phenylalanine monitor. They know when their levels are high and levels are low. The physicians do look at it, and they do monitor.
Yeah.
Monitor it. The patients do it. I mean, we've seen on social media people posting their Phe results, you know, down 80%, which is really cool.
That's another motivator for patients to stay on therapy, do you think?
Absolutely. Well, the way it works typically is you need to get to a certain level before technically you should be liberalizing the diet.
Yeah.
One of the things we've done in this launch, again, our experience in working with centers and pre-launch, making sure we understood the dynamics at each of the centers of excellence is the important role of the dietitian, right? The last thing we want, you know, we're sitting here in Las Vegas, the last thing we want is someone to start on the drug and run to the buffet and start eating everything, right? You want it to be a very thoughtful, measured approach. We've been working a lot with the centers, and they've been working a lot with those who get on the drug to have a very measured approach to first establishing that you're having a certain amount of lowering of phenylalanine, then gradually increasing the diet so there's a setup for success.
We avoid, you know, that risk that there's this expectation that, oh my God, I'm gonna be able to eat everything in the first week on the drug, which probably is not realistic. That, that's just another thing we're doing to make sure that we're set up for success and that most importantly, that the patients are set up for success.
Okay. In terms of the competitive landscape, we talked about, you know, who you're currently competing against, how do you see this over the next, I don't know, five to seven years evolving?
Yeah, I think right now, the next therapies in the pipeline are ones targeting the SLC6A19, I think, transporter in the kidney. Very interesting approach that you think has the benefit that it's agnostic to mutation. Basically tells the kidney, "Stop reabsorbing phenylalanine, pee it out," that should lower the levels. Again, interesting approach. The early data are looking encouraging. Still a lot of open questions, right? That I think the current Otsuka trial is in adults only. There's a lot of questions about long-term safety of lowering the other amino acids 'cause this target is not specific to phenylalanine. It's all neutral amino acids. There is this risk that if you have a lot of lowering of phenylalanine, it's gonna be lowering a lot of other things as well.
Yeah.
What we've heard from a lot of the prescribers is they really would love to have this as an adjunctive therapy to SEPHIENCE, to be able to say, "Okay, SEPHIENCE is doing great. We can add something on and maybe even do even better." Of course, in a disease like PKU, the patient's already used to having cocktail approaches, right? They have cocktail supplements approach. We see this as something that could be on top of SEPHIENCE, especially given the head start that we have.
There's some programs that are earlier on, looking at specific mutations, but of course, there's like, I think, 10,000 different mutations in drugs. I think that that's, you know. We don't see that as a significant competitive threat. I would say, you know, this also show safety and efficacy of the kidney-directed drugs, and we would see that being something on top of SEPHIENCE.
Okay. Maybe let's, in the few minutes that we have left, talk a little bit about the pipeline. You just recently gave us an update on the Huntington's program. Can you just give us a quick recap of that?
Yeah.
What the next steps are there?
Yeah, absolutely. We shared the results of the 24-month long-term extension from the PIVOT-HD phase II study. Really great results. I think that the headline is that in the stage 2 patients, which is the group that we thought went along was the right clinical trial population, we had dose-dependent lowering of cUHDRS 52% at the higher dose of 10mg , 27% at the lower dose of 5mg . Good effect across three of the four subscales, slight numeric benefit on the fourth subscale. Continued safety and tolerability, NfL at both dose levels below baseline.
When you take now the whole phase II experience, what we've been able to show is that the drug's doing what it's supposed to do in terms of splicing, and having dose-dependent lowering of the disease causing huntingtin protein. It gets into the brain. We actually had higher exposure in the CSF than the plasma. We're seeing now a 24-month sign of dose-dependent clinical benefit on the disease rating scale. It's safe, it's well-tolerated, and we also learned about the right population for phase III. In neurodegenerative disease drug development, we have ticked every box and now have a phase III trial that's up and running that's really been de-risked. It's really well supported by everything that's been done so far in phase II. We mentioned Novartis, our partner, is running that study.
They're gonna have about 770 patients, early symptomatic patients, one dose level of 10mg versus placebo through phase II with cUHDRS as the endpoint, with a planned interim analysis for efficacy and futility.
When do you think that interim could happen?
Yeah, I think Novartis has said they expect the full trial to go till the end of 2029.
Yeah.
Obviously, the intent of the interim was to get a read sooner.
Yep.
On a smaller number of patients. They haven't given the specifics yet of that. I'd simply say that they've been quite clear that if they can get this drug to patients faster, they absolutely wanna do that.
That would be by an accelerated path to approval?
Well, the interim could be either full-
Enough to-
Yeah.
to stop the study. Okay.
Keep going but get approval while it's finishing up.
Yeah. Right. If you think about the mechanism of this, Huntington's is an area of high unmet need, but for whatever reason, it's also been difficult to drug.
Yep.
You know, based on where this program has reached, how are you thinking about, you know, what's your confidence that this is something that could make it to the finish line?
Look, we said all along the playbook here followed the Evrysdi playbook. The first molecule that came from our splicing platform where we early on tried to use the blood effects of, in case of, SMA, increasing SMA protein, then being able to use that to inform the dose, figure out then the clinical study to establish efficacy. Clearly, Huntington's is a bit more complicated just in terms of being a neurodegenerative disease with heterogeneity. I, again, I think what we've been able to do thus far in a very thoughtful, systematic approach is tick all the boxes we need to along the way to inform the next step.
To be able to enter phase III knowing that we've got a very high degree of confidence we have the right patient population, we have the endpoint, we have a dose that has the desired biochemical effect as well as signs of the clinical effect, you know, I think in neurodegenerative diseases, that's about as good as you can do. We know the drug's working on something that means something, right? It's not like we're going to some protein deposits that maybe affect, not cause. We're going to the underlying cause of the disease. When you put all that together, it gives us a lot of as much confidence as you can have in a neurodegenerative disease program, and we've got a partner in Novartis who's built to do these long study.
Right.
Long, large studies quickly, and in a high-quality way.
Before we let you go, just what is the status in Europe?
Of the?
Of how EMA will want you.
Oh, yes.
Will want Novartis to study this? Are they in alignment on that too?
Yeah. They've been working on global alignment for the clinical study.
Okay.
It's gonna be a global study with sites.
Then just remind us about the economics between you and Novartis.
Yep. This is, you know, again, this was a really good partnership deal for us. We got a billion up front.
Novartis is now responsible for all of the development costs going forward. We have a 40% profit share in the U.S., double-digit tiered royalties ex-U.S., and about $1.85 billion left in development and sales milestones.
Okay. Pierre, what is the strength of the balance sheet, just based on what Matt just mentioned to us?
Very strong balance sheet. I mean, you saw the evolution of PTC, some things obviously hold true, patient-centric, global footprint, et cetera. Also we brought financial discipline, right? We worked very hard for that strong balance sheet.
Yeah.
We closed the quarter with $1.89 billion cash. That allows us to develop all our programs, a highly differentiated platform on both the splicing and the ferroptosis inflammation, and also gives us capacity to add potential products through business development in a very disciplined manner, number one, and two, what we saw, highly creative transactions.
What types of products do you think would be what you would look for?
Rare disease is our DNA, right? We have a global infrastructure with capacity that demonstrated that we know how to sell drug. We know how to launch globally, in all geographies, obviously U.S., Europe, LATAM, and Japan. Rare will be core and rare metabolic, rare CNS DNA, but you know, we're looking at other adjacent therapeutics as well.
Okay, cool. With that, we are out of time. Thanks, guys.