PTC Therapeutics (PTCT) Q3 2026 Earnings Call Transcript

Beginning with Sephience, we are now 1 year into the global launch, which by all measures has been a great success and all signs point to Sephience being a blockbuster rare disease product. In the third quarter, worldwide Sephience revenue was $182 million, led by consistent growth in the U.S. and continued expansion internationally. And as of September 30, we have over 2,000 active patients on Sephience worldwide. In the U.S., we continue to see strong underlying demand across all patient segments. Over the course of the third quarter, we saw an uptick in branded and generic Kuvan switches with continued penetration into the therapy-naive and tried and failed patient segments.

Adherence remains strong, reinforcing the meaningful benefits patients are experiencing on therapy, including diet liberalization, cognitive function and mood improvements. Internationally, we also had continued growth in the quarter, led by the strong launch in Japan as well as new patients granted access through main patient programs across several regions. As we have discussed, we expect international revenue to continue to grow with acceleration points as we achieve access and reimbursement in additional countries over the course of 2027. In the first year of launch, we built a broad commercial patient base upon which we are well positioned to expand as we move forward into 2027 and beyond.

In the U.S., there remains a large number of patients still on branded or generic Kuvan who are candidates for switching as well as a large number of patients not on any therapy that could benefit from Sephience. Overall, the vast majority of the 17,000 patients in the U.S. have yet to try Sephience. We see strong underlying demand across all patient segments, fueled by the differentiated profile of Sephience and the growing real-world evidence of meaningful Sephience benefits. Thus, while we are proud of all we have accomplished over the past year, we believe there is still a long way to go in the launch.

Furthermore, our teams have implemented plans to address a number of the key launch learnings that will support continued success in the coming years. Internationally, we expect continued growth in 2027 as we expand into new markets in Europe, Latin America, the Middle East, Russia and the Commonwealth of Independent States, all geographies where we have experienced teams with a track record of success. Overall, we remain confident in the $2 billion-plus peak sales opportunity for Sephience. In the third quarter, we acquired the BLA-stage Fabry disease gene therapy asset, ST-920.

ST-920 is a onetime administered AAV gene therapy that provides a humanized copy of the GLA gene, enabling the body to produce sustained physiological levels of the alpha-Gal A enzyme deficient in the disease. The data collected to date demonstrate that ST-920 significantly increases alpha-Gal A activity, decreases the lyso-Gb3 substrate that causes organ damage and improves renal function and other aspects of disease. In addition, the safety profile has been demonstrated to be favorable with no serious adverse events related to hepatotoxicity or other immune reactions. We expect to complete the rolling BLA submission for accelerated approval in Q4 2026 with the potential for approval and commercial launch in 2027.

Given the size of the Fabry population, our existing commercial infrastructure and experience working in the Fabry community as well as the differentiated profile of ST-920, we believe this is a potential meaningful global commercial opportunity. Turning to the votoplam Huntington's disease program. Due to FDA scheduling, the Type C meeting to discuss the votoplam data package and a potential path to accelerated approval is now planned for the first quarter of 2027. Enrollment continues in the Phase III INVEST-HD trial of votoplam, which is planned to enroll approximately 770 early symptomatic patients. The primary endpoint of the study is change in cUHDRS from baseline up to 36 months with an interim analysis planned for efficacy and futility.

Excellent progress on enrollment has been made with sites now open across the globe. For the vatiquinone Friedreich's ataxia program, we initiated the global PROVE-FA trial in the third quarter as expected. PROVE-FA is a single-arm study with a well-matched natural history comparator arm intended to support NDA resubmission. The study design, protocol and statistical plan have all been reviewed by FDA ahead of a trial initiation. The study is expected to enroll approximately 120 individuals between 7 and 21 years of age with the primary endpoint being the mFARS disease rating scale. In the third quarter, we also made good progress on our other pipeline programs. We initiated a Phase IIa study of PTC844, our next-generation oral DHODH inhibitor.

As we shared at our R&D Day last December, PTC844 has a differentiated potency and selectivity profile that benchmarks very well against approved DHODH inhibitors. The Phase IIa trial is a 12-week PK/PD study being conducted in a cohort of adults with rheumatoid arthritis with the objective of confirming the relationship between dose, DHODH inhibition and favorable effects on markers of B-cell and T-cell immunity. We plan to use the results of this study to help finalize which rare inflammatory disorders we will pursue for PTC844 development. The Phase I study of PTC612, our oral NLRP3 inhibitor, is progressing well.

We have dosed several SAD and MAD cohorts, including a cohort with inflammation and cardiovascular disease that could provide early evidence of pharmacodynamic effect on a number of biomarkers. We believe PTC612's potency, selectivity and the potential for improved tolerability are all key points of differentiation. We plan to focus development efforts on rare pulmonary indications where NLRP3 pathology has been closely linked to disease. Finally, we continue to advance PTC303, our splicing development candidate targeting MSH3. PTC303 is our next candidate from our oral small-molecule RNA splicing platform and is an example of how we are extending the reach of the platform into new and highly innovative areas of biology.

By targeting somatic expansion, PTC303 has potential applications in a number of triplet repeat expansion disorders. As we have discussed, we plan to focus on DM1 as well as Huntington's disease, where we believe PTC303 can offer a complementary approach to HTT lowering. We remain on schedule for PTC303 to enter the clinic in 2027. In conclusion, I am proud of our team's continued strong execution as we move into the fourth quarter. I will now turn the call over to Eric for a commercial update. Eric?

Eric Pauwels:Thanks, Matt. Our commercial team delivered another quarter of record product revenue, highlighted by the continued strength of the Sephience global launch. Launch momentum remains robust, supported by steady growth in the U.S. and increasing contributions from international markets. In the third quarter, Sephience revenue was $182 million, representing over 20% growth from the second quarter of 2026. More than a year into the launch, we have built a strong foundation that reinforces our confidence in our ability to deliver sustained long-term growth for the brand. Importantly, as Matt mentioned, more than 2,000 PKU patients are actively benefiting from Sephience therapy today, providing a large growing base for future growth in 2027 and beyond.

In the U.S., underlying demand remains strong with a steady cadence of new patients and seamless reauthorizations each quarter since the launch. As a reminder, all U.S. centers of excellence are now prescribing Sephience, and our field-based teams are now focused on how to penetrate deeper into each center. The teams are leveraging claims data and their prescriber interactions to tailor a center-specific approach as we build our base of knowledge targeting key PKU patient segments and roll out key programs to health care providers and patients going forward.

We have recognized the value of organic peer-to-peer sharing of real-world experience and have built a framework, including a new Ambassador program, leveraging identified Sephience champions to share their positive experiences across multiple channels. The program is focused on the U.S. initially and we'll extend the concept globally where applicable. We continue to enhance our digital presence for both branded and unbranded activities, targeting messages across channels and media types to support and reengage the PKU community through the web, social media, programmatic targeting and live navigating PKU events. Internationally, we saw continued momentum from the launch in Japan and continued growth in new patient starts in the Middle East, North Africa, Latin America and Canada.

In Europe, we continue to actively negotiate pricing and reimbursement in Germany, Spain, Italy and France, with the objective of maintaining a narrow global pricing corridor. Our highly experienced market access teams are well positioned to accelerate the global rollout and continued expansion in 2027. As Matt mentioned, Sephience's first year on the market has been a success by every measure, and we are just getting started. Of the approximately 58,000 individuals with PKU in target markets worldwide, the vast majority have yet to try Sephience. Building on our first year learnings, we have 3 key priorities to expand the market, reach more patients and accelerate growth.

The first priority is to continue to unlock the substantial opportunity among therapy-naive adults. In Q3, more than 1/4 of patients actively treated with Sephience were therapy-naive adults, many returning to care after years without treatment. We now better understand their treatment goals and care journeys, enabling more targeted initiatives to reach this important patient segment. The second priority is to expand adoption among patients switching from branded or generic Kuvan. Early in the launch, prescribers prioritized untreated or poorly controlled patients, including those with more challenging PKU before broadening use among patients already on therapy. AMPLIPHY supports switching to Sephience. In the extension study, every responding patient achieved further Phe reductions and increased protein intake after switching.

Combined with favorable U.S. payer policies and positive international health technology assessments, these data support continued expansion in this segment. The third priority is to build the real-world evidence supporting Sephience's potential across the full spectrum of PKU severity. Physician-led studies show encouraging results in patients with classical PKU, including those with non-BH4-responsive mutations with Phe reductions and diet liberalization comparable to those seen in patients with less severe mutations. Together with the opportunity for early treatment in newborns and children as well as treatment-naive adults and patients switching from existing therapies, this growing body of evidence reinforces Sephience potential to address some of the most severe forms of PKU and patients with the greatest unmet need.

We are applying launch learnings and executing activities that support these 3 priorities to expand adoption, reach more patients across the PKU spectrum and drive sustained growth across all PKU patient segments. While our teams are focused on the continued success of Sephience, we are also excited about the potential launch of our next commercial product, the ST-920 Fabry disease asset. Many of our PTC leadership and customer-facing teams have significant experience in lysosomal storage disorders and especially Fabry disease. We are excited about the potential to deliver a onetime administered therapy that provides the body the ability to produce continuous physiological levels of humanized alpha-Gal to individuals living with Fabry disease.

We are advancing our U.S. commercial preparation, including mapping claims data with centers of excellence, and importantly, we believe the Fabry patient community will play a key role in the treatment adoption, and our initial meetings suggest strong support for this innovative approach. In parallel, we are developing the long-term durability value proposition for payers and leveraging our established U.S. market access capabilities. As we advance towards completing our FDA submission by year-end, in parallel, we are preparing to bring ST-920 to the Fabry community as quickly as possible, marking another potential significant milestone for PTC's continued growth in rare diseases. Now turning to our mature brands.

We continue to generate meaningful revenue in the third quarter from both Emflaza and Translarna. For Emflaza, we delivered $25 million of revenue and continue to see strong brand loyalty despite multiple generics in the market. And for Translarna, revenue in the quarter was driven by ongoing sales in Europe, Latin America, the Middle East and North Africa and another government order from Russia. In summary, our customer-facing teams delivered another strong quarter, including record product revenue performance, underscoring the strength of PTC's global rare disease commercial capabilities. We remain confident in our ability to grow and establish Sephience globally as the standard of care for PKU.

With that, I will now turn the call over to Pierre for a financial update. Pierre?

Pierre Gravier:Thank you, Eric. I will now share the financial highlights of our third quarter of 2026. Beginning with top line results. Total product and royalty revenue for the third quarter was $358 million. Total net product revenue across the commercial portfolio was $276 million compared to $131 million for the third quarter of 2025, representing over 100% growth. Third quarter 2026 product revenue includes Sephience net product revenue of $182 million and DMD franchise revenue of $74 million. Translarna net product revenue was $49 million, including a government purchase order from Russia and Emflaza net product revenue was $25 million. For Evrysdi, Roche achieved third quarter global revenue of approximately USD 607 million, resulting in royalty revenue of $82 million.

For the third quarter of 2026, non-GAAP R&D expense was $95 million, excluding $11 million in noncash stock-based compensation expense compared to $91 million for the third quarter of 2025, excluding $9 million in noncash stock-based compensation expense. Non-GAAP SG&A expense was $67 million for the third quarter of 2026, excluding $13 million in noncash stock-based compensation expense compared to $74 million for the third quarter of 2025, excluding $10 million in noncash stock-based compensation expense. Cash, cash equivalents and marketable securities totaled $2.13 billion as of September 30, 2026, compared to $1.95 billion as of December 31, 2025.

In the third quarter of 2026, we acquired ST-920 for an upfront payment of $111 million and up to $100 million in contingent milestone payments tied to U.S. regulatory approval. We view the acquisition as an opportunistic business development transaction that adds a BLA-stage asset with meaningful near-term revenue potential while leveraging our current infrastructure and supporting our broader financial objectives. This value-accretive transaction also preserves significant financial flexibility to pursue additional business development opportunities and support our path to cash flow breakeven and long-term sustained profitability. And I will now turn the call over to the operator for Q&A. Operator?

Operator: [Operator Instructions] Our first question comes from Kristen Kluska with Cantor.

Kristen Kluska:Congrats on a strong quarter. I wanted to ask where you would characterize yourself in the stage of the launch of Sephience, both in the U.S. and ex U.S. and how we should be thinking about the growth in both regions, respectively?

Matthew Klein:Kristen, thanks for the question. So first, let me just say how incredibly excited we are about now being at the 1-year launch mark. And I think by everyone's expectations, one, we've delivered far more than was expected. And I think we've really redefined what the opportunity can be in PKU globally for a well-differentiated therapy. And we've done a really great job in the first year, but I think we very much believe we're still in the very early innings here. We have a very long way to go. We -- we talked about 200 patients -- 2,000 patients on therapy rather, out of 58,000 globally.

Take the U.S., we're thinking we probably have at least 85% of PKU patients not yet tried Sephience. And clearly, that number is much bigger outside the U.S. So in this first year, what we've really done is built a strong, broad patient base that has allowed us to really accelerate the launch delivering strong revenue numbers in the first year, but also set the stage as we now move deeper and deeper into each of the patient segments that are now well defined. And as Eric mentioned, have tailored programs to leverage what we see as a very significant opportunity. That's both in the U.S. and abroad.

And look, we see a lot of people externally trying to track prescription data and predict where this launch is going. When we look at the real data, what we see is strong underlying demand, consistent growth in the U.S., room for strong long-term durable growth in the U.S., the ability now to grow ex U.S. as we get into additional countries, and everything we see reaffirms our confidence that we're on that trajectory for the $2 billion-plus opportunity we've talked about.

Kristen Kluska:Okay. And last question for me. We've seen the FDA out with a lot of public webinars specifically focused on tailoring trials for rare disease therapies in particular. So I'm curious if you've thought about that and if you think there's any read either for programs that are currently in late-stage development and/or as you start to think about your own pipeline and platforms as you progress that into the clinic.

Matthew Klein:Yes, absolutely. I think we can all agree, it's a really exciting time with what's going on for rare disease at FDA. And I think this has gotten to the top of the agenda in every part of the FDA. I've personally been a part of a number of discussions and there's been the public discussions where we're hearing importance of CBER and CDER alignment for rare disease, showing appropriate flexibility that what's been the standard approach for diabetes and hypertension doesn't apply to rare disease, and we really need a bespoke approach for each therapy, and this is something that was clearly articulated again yesterday at the Rare Disease Framework Forum.

So I think not talking about anything specific, but for us, in general, I think this is really great with upcoming discussions on votoplam with the Fabry program and other important programs we have in the pipeline being able to take part in this evolution of uniform alignment, consistency, predictability and a true understanding of the rare disease challenges. So I think overall, it's a great thing and I'm hoping that it's a high tide that raises all rare disease boats, if you will.

Operator:Our next question comes from Tazeen Ahmad with Bank of America.

Tazeen Ahmad:On Sephience as it relates to the breakdown between U.S. and ex U.S., ex U.S., you do have far more patients in total than you do in the U.S., but the price point is much lower. So I think it would be helpful to get a sense from you, Matt, about how you're thinking about ultimately the split of contribution of sales coming from U.S. versus ex U.S.? And can you give us a little bit of color on -- it's only been 4 quarters or so, but is the U.S. launch slowing? I think that's what people want to know.

Matthew Klein:Yes, absolutely. Thanks, Tazeen. I think what we have currently is we said we have over 2,000 active patients now on therapy. The majority of those remain U.S. patients, the revenue, the majority of which still comes from the U.S. I think that's very clear in the numbers. And we believe as we continue to go in the launch that probably in the end the majority -- when we get to peak, the majority will come from the U.S., but with strong contributions ex U.S. And part of that is as we talked about, we've got -- you mentioned the differential price point, 17,000 patients in the U.S.

And as I just mentioned, probably over 85% of those haven't tried Sephience yet. And what we're seeing is very much what you had alluded to, I think, in your recent note and your recent survey about what the potential for durable sales momentum in the U.S. given the -- what a lot of the KOLs you spoke with see is the potential peak penetration in the centers as we move on. And so that's what we're seeing. So I think while we unquestionably had an acceleration phase in the first few months of the launch, we really see ourselves now in a steady, durable growth phase. And we see that quarter-over-quarter.

Actually, despite seasonality and some trends and the headwinds in the summer, we still delivered steady growth, and we obviously see room for continued growth and increasing growth in some quarters, but overall steady growth in the U.S. And outside the U.S., as we talked about, there'll be periods of acceleration as we get into pricing and reimbursement and gain access in new markets. The story of Q2 and Q3 was driven by the strong Japan launch. And then as we move into 2027, bring more countries on board into '28 further, we see a lot more room for growth outside the U.S. So again, as we said, we still think we're very, very early in the U.S.

We got through an acceleration phase. That gave us a very strong base, I think far larger than anyone would have imagined at this stage in the launch. And we have strong adherence rates, and that's really the key foundation from which we're going to continue to grow this quarter-over-quarter, year-over-year and get to those numbers that we've talked about in terms of peak opportunity.

Tazeen Ahmad:Okay. And maybe just to get a little bit more granular on it. When you say the majority when you're at peak will be U.S., is the magnitude going to be closer to like, I don't know, 55-45? Or is it closer to 70-30?

Matthew Klein:I think -- so just to be -- let me be careful. So the majority of the revenue will be U.S. The number of patients we expect will be larger outside the U.S. just given because you're talking 17,000 versus 41,000 plus/minus in areas we think we can get access and pricing and reimbursement. It's hard to have an exact number right now, Tazeen. We believe it's going to be the majority. A little bit is going to determine what we get outside the U.S. in terms of access and what comes through pricing and negotiations. So it's -- the harder part for us to figure out is exactly what that amount is going to be outside the U.S.

But again, nonetheless, we remain confident in what we've talked about, the $2 billion-plus opportunity. We see ourselves on that trajectory to get there by our internal metrics. And again, we have a long way to go and look forward to continuing to deliver for patients.

Operator:Our next question comes from Ben Burnett with Wells Fargo.

Benjamin Burnett:Excellent. Great to see the guidance increase. Just want to know if you can maybe talk about sort of what the new top line guidance contemplates. I assume you're getting some conviction, additional conviction around Sephience, but how much -- what's contemplated with regards to like the DMD franchise and some of the other elements of the project revenue base?

Matthew Klein:Ben, thanks for the questions. So once again, we felt based on the performance to date and what we see going forward, comfortable raising the guidance. Clearly, a lot of that comes from our confidence in Sephience and the continued growth of Sephience as we move into the fourth quarter. The DMD franchise, as we've talked about throughout this year, has really been a story of it outperforming our expectations. And I think a lot of that credit goes to our teams around the world who have done an incredible job continuing to deliver for 2 very, let's just say, products with a lot of headwinds.

As we move into the fourth quarter, what we're seeing on -- first on the Emflaza side, we're now seeing a new generic entrant to the market that has brought down the price quite a bit. So we may very well now be getting closer to that, I won't say race to the bottom, but we're starting to see the impact of generics in the marketplace and generic pricing. So that's obviously impacted our expectations for Emflaza.

And on the Translarna side, again, in the third quarter, we had a Russian order, a Russian government order, which was a bit unexpected, but we don't -- we do not expect in Q4 to have any additional large government purchase orders from Brazil or Russia. So that's a lot to say that I think we are increasing guidance. The majority of that is driven by our enthusiasm for Sephience. Obviously, we'll have contributions from the other products, but we don't expect the DMD franchise to contribute as it has throughout the earlier parts of '26.

Benjamin Burnett:Okay. That's super helpful. And then I also wanted to ask, so I thought that the Fabry deal was super interesting. What is the appetite going forward for additional BD?

Matthew Klein:We have talked a lot about the fact that we're aware that we have over $2 billion in the bank and the capacity from a commercial standpoint to add products globally, and we see that as a priority for top line growth. Pierre, do you want to talk a little bit about how we're looking at BD opportunities in general?

Pierre Gravier:Yes, absolutely. I mean, look, we have a global infrastructure with capacity, and we demonstrated that we know how to commercialize rare disease drugs globally. And I think that's a key strength of ours and very unique and very rare. And we will apply the same philosophy we mentioned all along. We want to be very disciplined. We have the full flexibility to operate with the $2 billion cash balance, and we want to make sure that we create value for shareholders.

Operator:Our next question comes from Eliana Merle with Barclays.

Unknown Analyst:This is [ Tejas ] on for Ellie. Can you comment first just on any trends you're seeing in the U.S. and ex U.S. around summer seasonality and if that impacted [ 3Q ]? And maybe from what you're seeing in 4Q, could there be an acceleration into the fall? And then just a quick second question. What's the latest you're seeing from current patients on persistency and dropout rates?

Matthew Klein:Tejas, so on the first question, we did -- as I mentioned previously, we did see some summer seasonality. But again, this is the benefit of a global launch. So while we saw maybe one part of the summer vacations in certain regions, other times, we did. So I think overall, despite the various seasonality, we saw a strong quarter. And again, I think this is the benefit of a global launch. And I don't know, Eric, do you want to talk a little bit just about how we are seeing patterns over the summer as we move forward and the global contribution?

Eric Pauwels:Yes. In terms of global contribution, first of all, again, there was some seasonality, but we saw steady and sustained growth. We saw even in the quarter, new patient adds. And importantly, we also had a very strong patient base, as Matt mentioned, 2,000 -- more than 2,000 active patients with continuous refills and reauthorizations, and we're seeing sustained prescriptions. Now of course, seasonality is only an effect of having patients potentially on holidays and on doctors' offices. But we've seen that move back into a nice steady cadence. And seasonality also can play out in different geographies. We also saw some of our first prescriptions actually in Latin America, and we're very -- in the winter months.

And so a lot of this is really part of our whole global learning and global understanding of the launch to date.

Matthew Klein:And then on your second question regarding adherence, we're still seeing very strong adherence. We had mentioned last quarter that we believe we're reaching steady state in terms of discontinuations. And again, this quarter, we've been around low 20% cumulative discontinuations to date.

Operator:Our next question comes from Brian Cheng with JPMorgan.

Lut Ming Cheng:Maybe just on pricing negotiations here in ex U.S. regions. Can you give us an update on the final pricing agreement that will come soon in Germany and also other countries like France and Spain?

Matthew Klein:Brian, let me let Eric give you an update on where we're at with pricing discussions.

Eric Pauwels:Yes, Brian, thanks for the question. We're continuing to have those kind of discussions. I wish we could tell you we have a final agreement. I think it's interesting because the summer months literally created a little bit of -- the holidays in the summer months created a little bit of the delays in the administration over at GBA. But there's nothing unexpected at this point. We're still in active negotiations with GBA on the pricing and reimbursement in Germany, and we expect the decision to come out actually fairly soon, fairly shortly. But we have nothing specific yet. The launch, however, in Germany just continues with great progress.

And we've seen centers of excellence right now, and they continue to see broad access. We've seen young patients and older patients. And we're also seeing switches, which is an important and high-value driver for the business. So Germany will continue to be a major contributor and with a narrow corridor that we're establishing right now. France, Italy, Spain and Southern Europe, I would say, first of all, in Southern Europe, we're very pleased with the ongoing early access programs. Patients have been enrolling very quickly in those programs. There's been high unmet needs. Pricing and negotiation in these areas, including HTA assessments, they take a little bit longer.

But we have engaged with pricing and reimbursement in all 3 countries, and we anticipate somewhere in the first half of 2027 for those to be finalized.

Lut Ming Cheng:And then if I can squeeze in one more. From a quarter-to-quarter dynamics, how should we think about the number that we should project for 4Q and 1Q? Are there potential holiday season impact and also insurance reset dynamics that we should account for?

Eric Pauwels:Well, I think in the U.S., our case managers and PTC Cares will be way ahead of that. During the enrollment process, we're already reaching out to make sure that every single patient, we understand what their insurance coverage is. We'll be able to start and begin to get ahead of any of the changes. And importantly, prepare all the programs in the U.S. for the reset, if you will, in January. For us, this is not something new. We went through that in January. There was already a big lesson that we learned from that.

And now that we have thousands of patients now that we're actively working with and new patients coming in, this is a relatively routine for our case management teams to handle. So simple message is we're way ahead of that.

Operator:Our next question comes from Eric Joseph with Citi.

Eric Joseph:Just one on ST-920, assuming approval next year. Can you orient us a little bit around how you expect that launch to go from the standpoint of facilitating market access and reimbursement as well as how we should -- we might be thinking about pricing? And I guess, also what -- maybe you can describe the type of patient who might be an early adopter here assuming approval.

Matthew Klein:Eric, we're obviously quite excited about the potential of bringing ST-920 to individuals with Fabry, not only in the U.S. but worldwide. As we talked about, we're just getting the final parts of the BLA together and look forward to the submission in Q4. As you can imagine, Eric and his team have already begun to start exploring a number of your questions. So let me turn it over to Eric and to give you a bit of detail on what we're doing now in terms of market preparation and access discussion.

Eric Pauwels:Yes, thanks for the question, Eric. We're very excited about this opportunity because it's a near-term opportunity, and we're leveraging that commercial infrastructure on our teams, including myself and many others. We all have gene therapy experience, lysosomal storage disease and a very significant amount of our teams actually have Fabry, direct Fabry experience. This market is incredibly large in the U.S. alone, and that's where our focus is immediately. With over 11,000 patients, what we've already learned is that the market itself is not well served. And I think there's a lot of patients that are still going untreated. We have a number of key work streams right now in the U.S. to prepare for that.

I'll get to the -- your question about market access, but we have to first really clearly understand the patient segment. Are they naive? Are they newly diagnosed? Or are they on enzyme replacement therapy? As we go through that, we have to leverage the information from the STAAR study, which shows stability, improvement in some cases, in renal and cardiac functions, durability and efficacy going years out, tolerability and the study even demonstrated quality of life benefits, which I think will drive what patients need. But in the end, I think the value proposition that you're looking at will be segmented towards the right patient.

If you actually look at the costs associated with enzyme replacement therapy and care and others, we see that there is a potential cost savings to the health care system, but more importantly, really enhanced quality of life improvement for patients. And I'll just say that we've had 2 meetings already with patients. And these are patient advocacy groups for Fabry and the community is incredibly excited about having a gene therapy that we can bring to the market. And we already have a significant engagement with that community right now to help support those efforts.

Operator:Our next question comes from Faisal Khurshid with Jefferies.

Faisal Khurshid:I just wanted to ask for the U.S. when you're kind of characterizing this like steady, consistent growth trajectory that you expect, are you -- what are the key levers for that? Like is the bigger lever therapy-naive? And what are the kind of major unlocks to achieve that? And then I have a follow-up as well.

Matthew Klein:So as we talked about, we are well positioned to continue to go deeper into all of the key segments. I think the early launches we've discussed, we had a larger number of patients come from the therapy-naive, which was really a pleasant surprise, reaffirming that's really a component of what we see as the addressable market as well as those who tried and failed previous therapies. And then as we moved into Q2 and into -- further into Q3, we're beginning to see now more and more of the switch dynamic come into play.

And as Eric highlighted in his comments, we've been able to look carefully at what we've done in the first year and now understand not only on a segment level, but on subsegment levels, center levels, what we need to do to continue to penetrate deeper and deeper into all of those segments. And when we talk about our enthusiasm and our conviction in the potential for significant growth over time in the U.S., it comes from the fact that we know there's still a large number of patients in each of these segments, including somewhere between 2,000 and 2,500 patients still on Kuvan branded and generic that we know are all candidates for Sephience.

We know that as our data continue to show all those who switch over to Sephience do better in terms of lowering or -- and/or protein diet liberalization and other benefits. But we've also made a number of key learnings about those who are in the therapy-naive segment and how they -- how can we access them? What's that patient journey like? And so what we're really now -- it is really a fun part of the launch. We take the learnings from the first year, develop targeted plans so that we can leverage the opportunity, the significant opportunity we still have across all of those patient segments as we move forward.

Faisal Khurshid:Got it. That's helpful. And then just one quick one. Is there any context you can provide on the FDA scheduling meeting for votoplam? Obviously, we've had a little bit of a history of prevalence at the FDA. Just trying to understand if this is like anything like that or if it's just like simply a calendar thing.

Matthew Klein:Yes, absolutely. Look, as everyone knows, there's PDUFA guidelines that say if you request a Type C meeting, it's typically granted within 75 days of request. Clearly, given that both Novartis and PTC guided to this meeting occurring in the second half of '26. You can imagine that the request for the meeting was submitted at a time that typically would have resulted in that meeting being in the second half of 2026. Then FDA gets the meeting requests. And sometimes on their end, Faisal, they have to coordinate a number of different people attending these meetings. They've clearly been quite busy at a number of rare disease initiatives.

So it's a long way of saying this is simply a matter of FDA scheduling. There's nothing to read in there. And we look -- we remain excited about the opportunity to share the votoplam data, why we believe we have a compelling package and hopefully leveraging the precedent of cUHDRS being the basis of an intermediate clinical endpoint accelerated approval application in HD.

Operator:Our next question comes from Joseph Thome with TD Cowen.

Joseph Thome:Maybe, Matt, on those patients that you mentioned that are still on Kuvan, maybe what's the largest reason as to why they're still on Kuvan and haven't switched over yet? Is it just touch points? Is insurance a barrier for these patients at all? Or kind of what's going to be the key learning to get them to flip? And then in that patient segment that maybe has tried something else and it didn't work for them, what proportion of those are still under care versus maybe having lost a follow-up and you have to do a little bit of extra digging to bring them back into the clinic?

Matthew Klein:Joe, okay, I'll take the first one first. And I think there's not a one-size-fits-all answer here. Part of the answer is fine. If -- these centers have a limited throughput. There's only so many individual patients that are going to see at any one time. And we've heard from a lot of the KOLs that a number of these individuals will come in maybe every 3 months, maybe every 6 months. So -- and in the early days, the focus was getting those who weren't on the therapy, on the therapy. I think now we're switching to a stage where there is more of an interest in getting the switches done.

And in each center and for each patient, it may be different in terms of the time. And that's -- and it may just be getting into the clinic. In some cases, clearly, there's additional payer discussions we need, but our teams have really been able to manage those situations really, really well. So access questions and payer questions become a when, not an if. And furthermore, I think what our teams are really working on are continuing to deliver the value proposition here. Do we have the -- the AMPLIPHY data, which again, really reinforces the benefits that individuals have when they switch from branded or generic Kuvan to Sephience in terms of significant improvements.

And I think one of the other take-home points here, too, is that even those who may be somewhat controlled or moderately well controlled on branded or generic Kuvan, when they switch over, they're finding significant increase in diet liberalization, significant natural protein intake, which all agree is a super important thing for patients. So again, the value proposition there is a matter of time we're working through this, and our teams, again, are developing targeted plans and making sure that we manage through that process of the switches, and it will take time. In terms of quantifying those who were in the tried and failed and are not currently under active care, it's a little bit difficult.

But what we're learning importantly is they may not be -- a lot of these folks may not be under active care in terms of seeing the physician or nurse practitioner. A lot of them are tied into dietitians in the centers. And we've also made a lot of important learnings that social media networks and how individuals -- PKU is very well connected to each other. And while they may not be coming to clinic, they talk to other members of the community. It's a well-aggregated community. And we've had the opportunity to talk to and understand from a lot of individuals how these networks work.

And that's why when folks post on social media, started Sephience, having steak for the first time, pizza for the first time, feeling so much better and brain fog, all those things that appear on social media have incredible, incredible impact in terms of continuing to generate the market pull and getting folks to come back to clinic on their own because they want to enjoy the benefits that their peers, friends and folks they've known for years of PKU are having. And so again, part of this is what we do, right? What do we do in terms -- and what our teams do in terms of a launch. We went through the first stage.

We take the learnings, understand these networks, who are the influencers, who are the key parts, what -- how do we support patients on the patient journey, all those different things that we can now bring to bear as we continue to grow throughout the next stage of the launch.

Operator:Our next question comes from Maxwell Skor with Morgan Stanley.

Maxwell Skor:Regarding votoplam, would an accelerated approval path change INVEST-HD, the Phase III design or enrollment given that patients may be less willing to accept placebo if a commercial drug is available? And also, is there any chance you receive priority review for ST-920?

Matthew Klein:Max, on your first question on votoplam, that Phase III study when it was set up was really set up to have the potential to serve as a confirmatory study in the context of an accelerated approval. It was also a very thoughtfully designed study, large study population to serve as a pivotal trial if needed. It was also designed to have an interim analysis so that if there was not an accelerated approval based on the PIVOT-HD data, there's the opportunity to have success on the trial at an earlier time point in a smaller number of patients. So all those different factors were built in. Also, I'll point out this is a global trial.

And I -- it's so impressive to see the Novartis team get this trial up and running and really do an incredible job, a machine of getting study sites up all around the globe. So even if you had an accelerated approval in the U.S., there's still going to be study sites all over the world that are going to be open and enrolling where there wouldn't be an accelerated approval. So cannibalizing potential enrollment really isn't a consideration in that matter.

In terms of the potential for priority review for ST-920, clearly, we requested, given several factors, given the fact that there really still is a significant unmet need and several, we think, relative benefits to the differentiated profile of ST-920 versus other available therapies. And furthermore, it also has RMAT designation. So the potential for priority review comes along with that RMAT designation.

Operator:Our next question comes from Asim Rana with UBS.

Asim Rana:Congrats on the quarter. This is Asim Rana on for Joon Lee. Just on Sephience, can you remind us if the average dose per patient has moved up since the launch? And then on the Fabry program, how should we be thinking about OpEx to support the launch?

Matthew Klein:Sure. On the first question, the -- we said at the beginning, we expected average weight. Since it's weight-based dosing, we expected the average weight to be somewhere in the 45 kilogram to 50 kilogram ballpark. It stayed there. It's been pretty stable, and that's how it's been. We get adults to come on, but we also actually recently just had a number of newborns come on, which is super exciting to see a newborn get screened for PKU positive and then be able to go on Sephience right away and have optimal protein intake in those critical early stages of neuro development.

And I think that the newborn segment, not only in the U.S. but globally is one that we can now also think about starting to penetrate this 300-plus incident individuals in the U.S. each year and a large number, of course, internationally. But overall, again, that average weight stays about even. In terms of OpEx, I think as we talked about since we have the commercial infrastructure built, all those key components are there. We also have a number of experienced people, as Eric mentioned, in every part of the customer-facing organization. For Fabry, it would really be an incremental spend and incremental build next year.

Asim Rana:And just a quick follow-up. And just a quick follow-up. How quickly do you expect the deal could become accretive for the Fabry program?

Matthew Klein:I'm sorry, could you repeat that?

Asim Rana:How quickly do you expect the ST-920 deal could become accretive?

Matthew Klein:Look, I think one thing that is particularly attractive here in this opportunity is that for $111 million asset acquisition, we believe this could be accretive in 2027.

Operator:Our next question comes from Brian Abrahams with RBC Capital Markets.

Kevin Meli:This is Kevin on for Brian. So maybe just back on Sephience. Can you talk about maybe some leading indicators that you can be looking at, in particular, in the U.S. to suggest that you would be likely to reach those additional target populations that you talked about at your expected rate? I know you mentioned potential social media interactions earlier. Are there any other potential leading indicators you could be monitoring that are quantifiable to some degree?

Matthew Klein:Yes, absolutely, Kevin. So as we talked about earlier, we know there's a lot of folks trying to look for external leading indicators and of course, being in the closed system that we're in, really, the real data are the ones that we are seeing in addition to what we see in terms of start forms coming in, our significant extensive interactions, not only with prescribers, but also with the patient community and all the different local and national patient communities, the feedback that we continue to get in terms of demand and interest in trying Sephience, folks that proactively work and reach out to us, talk to our PTC Cares team.

All of those are really important leading indicators to us as well as the overall population that we know is out there as well as some of our own internal center-by-center data. We know it centers how many individuals there might be in each of these different segments, either under care who've been previously in care. We understand what the time line might be to get them in. These are all the kinds of things that we follow very closely.

And as Eric mentioned, one of the important things we're doing right now is having bespoke center level and even sometimes prescriber level data within each center that can also help us understand what is the potential prescribing base for that individual or that center, what's there -- how much is penetrated, what's the long way we see that they still have to go. And those are all the kinds of things we look at. Eric, anything you want to add to that and what gives us the confidence in what we're seeing on the ground?

Eric Pauwels:No, I think you covered it really well. And I think our -- we're really highly focused on each one of these centers going deeper to understand what are the unmet needs with those therapy-naive adults and the switches. And I think the Ambassador program that we discussed is incredibly important because these are 3 very important pillars. We have champions, patients who have actually on all spectrums of the disease, been able to share in many ways and engage with the community about what's happening with their Phe reduction. And the consequence is not only a diet liberalization, but also cognitive improvements and daily life. And then we have obviously peer-to-peer connect and advisory panels.

So we are working right now with programs that are plugging into these centers of excellence to really identify the unmet needs and how to bring patients back into those centers and then very importantly, make sure they have all the information going back out for the long-term support. These programs that we talked about, both web, on web and face-to-face and all are actively working with these centers. And these are the ones that are really very important in defining as we penetrate further and further into this, what I think is still a very untapped market.

We have 17,000 patients in the U.S. that are eligible for this, for Sephience, and we have still quite a ways to go.

Operator:Our next question comes from Basma Radwan with Leerink Partners.

Basma Radwan Ibrahim:Congrats on the quarter. We have a question on Sephience in the ex U.S. markets. Do you see similar dynamics to the U.S. markets? Meaning do you see the treatment-naive segment and the prior treatment failures, they are the primary growth driver early in the launch that slowly shift to the switch segment afterwards or is it different? And we do have a follow-up, please.

Matthew Klein:Yes. So the first markets that we've been in, in terms of having full access have been Germany and Japan and most recently in Japan. And that pattern is very much the same. This desire early on to get those who haven't been on a therapy on Sephience, again, with very positive feedback, including for those who have classical PKU, more severe non-BH4 mutations. And then as we're moving further into the launch now a shift and starting to look at getting individuals who are on what's known as Biopten in Japan, there's Kuvan here on to Sephience.

And I would also comment that I think there's probably in terms of proportion of population on Kuvan or BH4, I think it's one of the largest proportions in Japan anywhere else internationally. So that gives us a lot of confidence as well that we have a long way to go over time in the Japan launch.

Basma Radwan Ibrahim:Great. Our follow-up is about votoplam. Have you disclosed whether you're planning to disclose the 30-month -- 36-month data from the PIVOT-HD trial of votoplam in Huntington's along with your partner, Novartis? Or is that not announced yet?

Matthew Klein:Yes, I think that's going to be Novartis' call. We've not had any discussions. Clearly, all efforts right now are on getting ready for the FDA discussion on the existing data and of course, getting the INVEST-HD study up and running -- up and running, but getting it fully enrolled. And as we mentioned in the script, the Novartis team is doing a really, really great job of getting that -- getting sites up and getting folks into that study.

Operator:Our next question comes from Luke Herrmann with Baird.

Luke Herrmann:So just a follow-up on Sephience discontinuations and adherence dynamics. I think you said it was 90% renewal rate with last quarter's update. And today, I think you said 20% cumulative discontinuations again, similar to last quarter. So is renewal rate holding up around 90%? And I guess building on that, is there any reason to think discontinuation rate can actually come down as you pick up more switching patients who have reliably been on another drug for years maybe?

Matthew Klein:Yes, Luke, so the numbers are, as you said, we're seeing very high prescription rates. And as we commented on discontinuations, we're getting close to that steady state in the low 20% now. And as you alluded to and we've talked about, what makes that number so impressive is that early in the launch, we had folks coming in who are the therapy-naive, more severe patients and to be able to have the success rate that we've had in those individuals is incredibly encouraging.

And also, as you highlighted, since all of our data show and it makes sense from basic scientific biochemical principles that if you had a response to getting BH4, Kuvan branded or generic, you should have a better response to Sephience. And obviously, someone who's switching from branded or generic, Kuvan has already demonstrated his or herself to be adherent to that therapy. So that's a long way of saying we expect the adherence rate in the switch patients to be much higher than what we've observed to date. Eric, any additional color you want to give on prescription patterns and...

Eric Pauwels:Yes. And I think you covered it really well. And I think what's really driving this at an individual center level and individual patient level is the switching and the switching is very, very important because we're trying to change the paradigm from just getting to a theoretical goal or an established goal to now normalization. And the data with -- that Matt just described is that patients who respond to generic Kuvan or Kuvan will have x amount of response, 70% greater response and many of them can potentially actually get to normalized levels.

So part of our goal is to really tailor some of that data and show that to many of the health care providers and patients that the goal isn't to stay on medical foods and stay on Kuvan or anything else, but the goal is actually normalization below 120.

Operator:Our next question comes from Alex Nackenoff with Truist Securities.

Alexander Nackenoff:Just wondering if you could expand a bit more on your experience with the Kuvan switchers thus far. Just looking for some color that could give us some confidence that the trends you're seeing are sustainable. Just curious if these patients are coming from prescribers writing their first prescription for Sephience or perhaps from prescribers who wanted to have more experience in the more difficult-to-treat patients, for example, before prescribing to stable Kuvan population.

Matthew Klein:Yes. Alex, I think the success stories of the switch patients are many and are continuing to fuel patient demand to switch and physicians' and other prescribers' strong interest in switching. As Eric alluded to, this is really an enriched population, if you will. They are definitely going to be Sephience responders and going to respond really well if they have been on BH4 and even served a small amount. We're seeing significantly greater lower phenylalanine reduction. We saw that in the head-to-head AMPLIPHY study. That's really compelling data for any prescriber, right, to be able to have actual well-designed head-to-head intra-subject data showing the significant greater reduction.

The significant increase in protein intake that we're seeing, I think some of our latest numbers are on the order of 100% greater increase in natural protein on average for those who switch, that translates to significant, significant benefits for individuals in quality of life, flexibility of diet as well as just feeling better and getting the benefits of natural protein. And not only are our field teams out there talking about that, there's patient-to-patient communication on social media. We've got presentations at every local, national, international, global meeting that continue to reinforce this message. And so it's not a matter of a prescriber's first Sephience prescription, their 50th Sephience prescription or their 100th.

These are folks who very much understand the biochemical basis of the fact that their patients are quite simply going to do better as the data are continuing to show, and there's a great deal of enthusiasm to do this. And as you can imagine, if you're on a once-a-day therapy, whether you're a prescriber, a patient, a parent, if you could switch to another once-a-day therapy that could have greater benefits, well, that's a pretty strong motivating factor for everyone.

Operator:And I'm not showing any further questions at this time. I'd like to turn the call back over to CEO, Dr. Matthew Klein, for any further remarks.

Matthew Klein:Thank you all again for joining the call this evening. I'm incredibly proud of our team's outstanding performance again this quarter with record product revenue, continued strong momentum in the Sephience launch. And as we've alluded to, we see as being quite durable and feel we have a very, very long way to go as we continue on this trajectory to the $2 billion-plus opportunity. We also look forward to continuing to advancing our other programs that are in the pipeline and look forward to giving an update on those in January. Thank you, all.

Operator:Thank you. Ladies and gentlemen, this does conclude today's presentation. Thank you for your participation. You may now disconnect, and have a wonderful day.

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PTC Therapeutics (PTCT) Q3 2026 Earnings Call Transcript was originally published by The Motley Fool