Ptc Therapeutics, Inc. (PTCT) Q2 2026 Earnings Call Transcript

Ladies and gentlemen, thank you for standing by. Welcome to PTC Therapeutics' second quarter 2026 earnings conference call. All participants are in listen-only mode. After the presentation, there will be a question and answer session. Today's conference is being recorded. I would like to turn the conference over to Ellen Cavallari, Head of Investor Relations.

Please go ahead. Good afternoon, and thank you for joining us to discuss PTC Therapeutics' second quarter 2026 corporate update and financial results. I'm joined today by our Chief Executive Officer, Dr. Matthew Klein, our Chief Business Officer, Eric Powells, and our Chief Financial Officer, Pierre Gravier. Today's call will include forward-looking statements based on our current expectations. These statements are subject to certain risks and uncertainties, and actual results may differ materially. Please review the slide posted on our Investor Relations website in conjunction with the call, which contains information about our forward-looking statements in our most recent quarterly report on Form 10-Q and annual report on Form 10-K filed with the SEC, as well as our other SEC filings, for a detailed description of applicable risks and uncertainties that could cause our actual performance and results to differ materially from those expressed or implied in these forward-looking statements. Additionally, we will disclose certain non-GAAP information during this call. Information regarding our use of GAAP to non-GAAP financial measures and reconciliation of GAAP to non-GAAP are available in today's earnings release. I will now pass the call over to our CEO, Dr. Matthew Klein.

Thank you all for joining today. I'm excited to share the results of another quarter of outstanding execution across the company. Starting with revenue, we achieved another record quarter with total revenue of $361 million, including $239 million of product revenue driven by continued strong global supply and sales. Based on this performance, we are raising our full year 2026 product revenue guidance to $850 million to $950 million, and now expect total revenue of $1.18 billion to $1.28 billion. In addition, with our continued effective management of expenses, we remain in position to potentially reach the milestone of being cash flow break-even in 2026. I'll begin with an update on Suffiance Global Launch. Momentum remains strong in the quarter, with continued steady growth in the U.S. and accelerating growth internationally. Second quarter global suffiance revenue was $151 million, up 21% quarter over quarter, with the majority coming from the U.S. and increasing contributions internationally. And as of June 30, we had 1,647 commercial patients on suffiance globally. We continue to see broad uptake across all patient segments and age groups worldwide. There remains strong underlying demand for suffiance, and our teams continue to effectively execute. In the U.S., we now have received prescriptions from 100% of the Centers of Excellence, as well as prescriptions from other centers not previously designated as Centers of Excellence. This breadth of penetration this early in the launch is impressive, and we will now work to continue to penetrate deeper into these centers. We continue to see demand across disease severities and treatment histories, including treatment-naive patients, prior therapy failures, and those switching from existing treatments. Adherence rates remain strong, and we continue to hear reports, not only of meaningful reductions in phenylalanine and increasing evidence of diabolization, but also of suffice benefits on mood, cognition, and quality of life. These dynamics of strong demand and reported patient's benefit reinforce our confidence in Sufiance's long-term commercial opportunity. In international markets, momentum for Sufiance continues to build. Commercial sales in Japan began to ramp in Q2 following our first commercial sale in late March. We started expanded access programs in a number of European countries and have seen positive progress towards future revenue in Latin America, including Brazil, where supply has recently received the highest classification for therapeutic benefits from the country's drug market regulation chamber. As we have previously shared, we expect international revenue to increasingly contribute in late 2026 and into 2027 as additional markets come on board. Overall, based on the continued strong launch momentum and the persistent strong underlying demand, we remain confident in the $2 billion-plus global commercial opportunity. Turning to the Vodaflame Huntington's disease program, in April, we reported positive top-line results from the 24-month interim analysis of the PivotHD long-term extension study. At month 24, Vodaflame demonstrated dose-dependent slowing of disease progression on CUHDRS, including an average slowing of 52% relative to natural history in the 10-milligram Stage 2 cohort. Importantly, we continue to observe a favorable safety profile and provide long-term meaningful clinical individuals a special share that Novartis has initiated enrollment in the Global Phase III and FHD study, which is being conducted and funded by Novartis. The study is expected to enroll approximately 770 individuals with early symptomatic disease, randomized 3 to 2 to receive Vodaflame 10 milligrams or placebo, and the study includes an interim analysis. While the Phase 3 study remains the base case for Vodaflame, the virus and PCC teams are finalizing a plan to engage with FDA in the second half of 2026 to discuss the 24-month results and potential accelerated paths.

For the particularly known free-dress attack state program, based on discussions with FDA, we have finalized the study protocol for the open-label trial with a natural history comparator arm to support NDA resubmission.

We plan to initiate this study, Prove FA, in the third quarter of this year. The trial will enroll approximately 120 individuals, ages 7 to 21, and the study primary endpoint is the change in MPHARS from baseline to month 24. The study design reflects the key learnings from our prior development work and has understandably generated enthusiasm within the FAA community, particularly because it offers patients the opportunity to access therapy. The study design, coupled with our experience in FAA therapy clinical development, meaningfully enhances the probability of success of the PROVE-FA study for children and adults. According to our other clinical oral NLRP-3 inhibitor, and have completed several of the single and multiple ascending-dose treatment cohorts. Notably, this healthy volunteer study will enroll a cohort of individuals with obesity and cardiovascular disease, which we expect will provide an early view of PQC844. As we have previously shared, PQC3 inhibitors expect to initiate a Phase 2A study for the DHODH. Marks favorably to other DHODH inhibitors in preclinical potency models. PQC844 study will be a 12-week PKPD study in which we will assess treatment effect biomarkers related to T-cell and B-cell immunity. The results of this study will help inform the ultimate target indications. We've also made a number of advances in our splicing platform. We recently selected a development candidate for our MSH3 splicing program, recently recognized as an important target for triplet repeat expansion diseases, including Huntington's disease and myotonic dystrophy. The MSH3 provides a complementary approach to HCT lowering in addressing the key pathological causes of Huntington's disease. The MFHC program also further reinforces PTC's leadership in the discovery and development of oral slow-mo. PTC 303 is fully owned by PTC. The company remains in a very strong financial position. In June, we strategically managed the 2026 convertible note liability with the refinancing of the majority of the existing notes at a 0% coupon and 40% conversion premium. We closed the quarter with over $2.2 billion in cash and remain in position to achieve cash flow break-even. In summary, I'm proud of our team's outstanding performance in the first half of 2026 as we continue to make significant progress across the business. I will now turn the call over to Eric to provide a commercial update, including additional details on the Supplyans launch.

Thanks, Matt. In the second quarter, our commercial team continued the strong global launch of the finance, driving solid product revenue and reinforcing confidence in our growth trajectory through 2026 and beyond. Launch momentum remains strong, supported by sustained contributions in the U.S. and increasing contributions from international markets. And now we have 1,647 patients on commercial therapy globally on Supplyance. In the second quarter, Supplyance revenue was $151 million, representing 21% growth over the first quarter of 2026. In the U.S., launch execution remained strong with steady demand. as matt noted all u.s centers of excellence are now prescribing suffiance with adoption spanning the full spectrum of disease severity all ages including classical patients and a broad mix of treatment backgrounds including therapy naive adults prior treatment failures and an increasing proportion of switches from existing therapies we are pleased to see persistent strong demand and to hear reports of the meaningful impact suffiance is providing children and adults on diet liberalization as well as mood cognitive improvements and improvements in quality of life with our increasing base of commercial pku patients being treated with suffiance in the u.s our customer facing teams are focused on rapidly filling new prescriptions and successfully managing reauthorizations refills and providing exceptional patient support our customer facing teams are dedicated to work closely with healthcare providers and the patient community to facilitate access to suffiance these efforts will help support continued momentum and growth as we move further into the launch turning to our patient advocacy support We had a strong presence at the National PKU Association Conference in Chicago earlier this month, where we focused on connecting with patients and caregivers and understanding their unmet needs. At this meeting, we presented data from the Amplify study demonstrating the ability of suffiance to reduce blood fees significantly more than VH4, as well as new data on patients switching to suffiance in both pediatric and adult PKU populations. We also held several engagement events with patient advocacy groups, including a symposium emphasizing the extensive real-world data and examples of patients who, in addition to seeing important reductions in blood feed levels, have also experienced significant improvement in their day-to-day quality of life on Sophia's treatment. Internationally, launch momentum continues to build. In Japan, the early launch results are exceeding our internal expectations with rapid uptake across many Japanese centers of excellence. We have secured pricing in Japan on par with the U.S., and importantly, this price is locked in for 10 years. As we observed in the early stages of the U.S. launch, we are seeing broad uptake in Japan across disease severities and age groups, as well as treatment histories. In Germany, we continue to see strong momentum in the quarter, especially with an increase in newly prescribed adult and naive PKU patients, as our pricing and reimbursement discussions are continuing in the country. In other European markets, we are leveraging early access and name patient programs effectively and are seeing accelerated demand in France, Italy, and Spain. In other regions, including Latin America and the Middle East, we are similarly leveraging early access programs as we grow the Suffiant's global footprint and see important contributions to future commercial patients. While the U.S. remains an important near-term growth driver, we expect global revenue to become an increasingly meaningful contributor in the second half of this year and well into 2027. As we discussed, there is a large addressable PKU population globally in markets where innovative treatments are reimbursed, And we expect to bring suffiance to as many of these countries as quickly as possible, reinforcing our confidence in achieving a multibillion-dollar peak revenue potential. Looking ahead to our key event this summer, our team is preparing for a strong showing at the SSIEM meeting in Helsinki next month, this being the largest global metabolism meeting of the year. We have 17 oral and poster presentations planned that continue to showcase evidence of suffiance treatment benefit across the broad range of individuals with PKU based on new analyses of long-term trial data, as well as reports of real-world evidence. Many of these presentations will highlight the positive impact that suffiance has had on PKU patients in countries around the world, with lower feed levels leading to better diet, neurocognitive, and quality of life outcomes for these patients. Importantly, we plan to present new data demonstrating that treatment with suffiance responders led to a substantial portion of participants achieving complete normalization of blood feed levels of 120 micromoles per milliliter in a rapid time frame, including those PKU patients who are classical and VH4 non-responsive. This impressive real-world data demonstrated that achieving feed-level normalization is an important key treatment goal for all potential PKU patients. Now, turning to our mature brands, in the second quarter, we continue to generate meaningful revenue despite challenges in the DMD franchise. For TransVarna, we have continued sales in Europe and Latin America, as well as a government order from Russia. In the U.S., Implaza continues to see new prescriptions, and despite generic pressure, we see ongoing brand loyalty attributable in part to our programs and continued high-touch, white-glove services from our PTC Cares teams. In summary, our customer-facing teams delivered another strong quarter with another record revenue performance, once again demonstrating PTC's global rare disease commercial capabilities. We remain confident in our ability to grow and sustain our launch momentum of suppliers globally and firmly establish it as the standard of care for PKU patients. With that, I will now turn the call over to Pierre for a financial update.

Thank you, Eric. I will now share the financial highlights of our second quarter of 2026. Beginning with top-line results. Total products and royalty revenue for the second quarter was $310 million, and total net product revenue across the commercial portfolio was $239 million, compared to $118 million for the second quarter of 2025, representing over 100% growth. Second quarter 2026 product revenue includes Defiance net product revenue of $161 million and DMZ franchise revenue of $67 million. Translana net product revenue was $42 million, including a government purchase order from Russia, and MFlaza net product revenue was $25 million. For a RISD, Roche achieved second quarter global revenue of approximately 628 million US dollars, resulting in royalty revenue of 71 million. For the second quarter of 2026, non-GAAP R&D expense was $89 million, excluding $11 million in non-cash stock-based compensation expense, compared to $104 million for the second quarter of 2025, excluding $9 million in non-cash stock-based compensation expense. Non-GAAP SG&A expense was $68 million for the second quarter of 2026, excluding $13 million in non-cash stock-based compensation expense, compared to $76 million for the second quarter of 2025, excluding $10 million in non-cash stock-based compensation expense. Cash, cash equivalents and market-level securities totaled $2.23 billion as of June 30, 2026, compared to $1.95 billion as of December 31, 2025. In the second quarter of 2026, we repurchased the majority of our existing 2026 convertible notes and issued new convertible notes during 2031 at 0% interest rate and a conversion price representing a 40% premium over the stock's closing price at the time of the year. Our strong financial position gives us the flexibility to pursue business development opportunities that support future growth, while advancing toward cash flow break-even and future sustained profitability. And I will now turn the call over to the operator for Q&A. Operator?

Thank you. if you would like to ask a question please press star one one if your question has been answered and you'd like to remove yourself in the queue press star one one again our first question comes from Kristen Kluska with cancer your line is open hi good afternoon everybody and congrats on a really strong quarter I have to find questions the first is based on the patients on therapy and accounting for potential dropouts my math is getting to about 10% or so of the patient population on the U.S. has tried the P. Curious if that matches what you think and also what percent of patients you think may at least be open to trying a therapy, not saying we'll get on it and assume peak penetration there. And then second, just thinking about the conference circuit, you just came off the biggest one for the patients in the U.S. and now you have a big medical focus. What are really the key drivers there? Is it awareness? Is it proving that the therapy works across breadth of patients? What are the key goals you hope to learn? Thank you so much.

Hi, Kristin, thanks so much for the question. So on the first question, look, I think the key take home that we see this early launch is we're incredibly excited about the demand and the updates thus far, but as you highlight, we still have a very, very long way to go, given the size of the population in the U.S. of 17,000 and the 58,000 patients we see in addressable markets worldwide. I think when we look to metrics thus far and we see penetration into 100 percent of the centers of excellence, that's really an incredible milestone that's early, and it basically puts us in the position we want to be with a strong base of patients to now go deeper and deeper into those centers of excellence. Usually at this stage of a launch, you're usually trying to get to all the centers of excellence. We're there, and now it's the tactic to get deeper and deeper into those centers. In terms of overall patients who may try the therapy, I think, you know, the number we had always had is about 70%, 7-0% of individuals tried CUVAD. And, you know, that again suggests we have a very, very large number of patients who are yet to try suffiance, And we already know that we've seen patients who are therapy-naive that never tried Cougar, that are in that other 30% bucket, who are coming back to clinic. So, again, it's hard to put the exact number on it other than to say, you know, we're still very early in this launch. We've had strong momentum at the start, but we have a very, very long way to go in terms of continuing to get a much larger number of patients to try the therapy and, of course, to stay on the therapy and enjoy the benefits, which I think goes then into your second question about our goal at these conferences. It's multifold, right, manyfold. One is, look, there's a lot of patients and there's a limited number of clinics, and we know that means that it's going to be just a steady cadence over time given the strong underlying demand. What we do at these conferences is continue to promote awareness of the drug for those who may have been not on therapies or remote to care and are starting to come back or are curious about being on a therapy, and then also continuing to let people understand the benefits we're seeing, that we're seeing benefits in patients who have classical PKU and non-VH4 mutations. And you have it in NPKUA, one of the caregivers, I'm sorry, one of the prescribers told stories about patients, severe patients with classical PKU having significant responses. That's really important for patients to hear. that they can get an oral therapy that allows them to lower phenylalanine and liberalize diet. It's also really important to continue to reinforce the data and the messages around Amplify and patients who are on Cougan, for example, where the brands that are generic, and to hear that 100% of those patients in our data have a much better response to suffiants and are able to get even lower in phenylalanine and liberalize their diet even more. So I'd sum it up by saying we're early in the launch. The response has been strong. The demand is really strong. But our teams still have work to do in continuing to reinforce the message, continuing to engage with patients, family members, caregivers, prescribers, letting them understand the benefits that they could enjoy this time so we can continue to get those trying numbers up to 70%, 80%, or even higher.

Thank you. Our next question comes from Tazeen Ahmad with Bank of America. Your line is open.

Good afternoon. Thanks for taking my questions. Matt, you've been really clear about defining how this launch is proceeding as, you know, very steady and consistent. So you have in the past talked about, you know, roughly adding about 140 new scripts per month. Can you just talk about whether or not you expect that to continue to be the cadence for the rest of the year and if not, maybe just talk to us about anything that's changed. And then can you just give us a little bit more color about what you're seeing in discontinuation rates so far?

Yes, so we've moved now towards just really highlighting revenue in patients on drug because at this stage in the launch site, you're starting to hear the global contributions and the prescriptions mean different things in different locations. I'll characterize things this way. I think we're continuing to see consistent demand. We believe in the potential for there to be steady growth, continued growth in the U.S. based on that demand and continue to expect accelerated demand outside of the U.S. And a lot of that is what underpinned our confidence in raising guidance to 850 to 950, that we believe that we can continue to have steady growth in the U.S. and accelerating growth outside of the U.S. In terms of discontinuations, you know, we continue to see very high compliance and very high adherence rates. I think discontinuations now remain low at about 20 percent, which is really impressive at this point in the launch, given the fact that a lot of the early patients who came on drug were those more severe patients. And we also feel at this level that we're getting pretty close to steady state based on what we have seen from the clinical studies. Importantly, the renewal rates on prescriptions is super high. It's over 90 percent. So overall, all these metrics look really, really good. and, again, support our confidence, not only in our ability to raise guidance for this year, but in a long-term significant potential, revenue potential for supply.

Thank you. Our next question comes from Joseph Hand with Barclays. Your line is open.

Hey, it's Ellie from Barclays. Thanks for taking the question. You mentioned several early access programs ex-US. Just to clarify, are you recognizing revenues from these programs yet? But I think you mentioned seeing accelerated demand in France, Italy, Spain, Lafayette, and the Middle East. Can you maybe give some color or characterize the number of patients on all of these early access programs and how that might compare to the 1,600 patients on commercial therapy globally? And then lastly, I think you've mentioned being launched in about 30 countries by the end of this year. So how should we think about which countries and when will contribute to revenues over the course of 3Q and 4Q?

Hi, Ellie. I'll give just some general comments, and I'll let Eric give a little bit more detail on early access. So all those early access patients are contributing to revenue. And what's important to know is that this whole approach we're taking in the global launch is really a well-thought-out plan. First, we had global commercial infrastructure in place, had already been commercializing in 50 countries, and a lot of this was about understanding different markets, understanding sequencing of launch, understanding how we can maintain a rigid pricing corridor, which is more important now than ever. And also, with early access programs, it allows us to get drug into patients in countries. It also tends to be a lot of those prescribers who are the leading KOLs in certain countries. That's super important because this allows those physicians to have positive experiences with clients, and those are going to be the same physicians that will be called upon when HTAs are making assessments about access and pricing. They can go to these physicians who will have had firsthand positive experiences with the drug, which has obvious benefits in terms of access and reimbursement. I'll let Eric talk a little bit more about just overall number of countries and how we're thinking about sequence and launch and revenue contributions.

Yeah, thanks, Kelly, for the question. You know, as Matt said, the strategic findings laid out many, many years ago, actually, because we are leveraging this infrastructure, which had a portfolio of products for over 12 years. So when we mapped out the sequence of this, we knew exactly that the U.S., Germany, and Japan would be commercial launches. But we've also mapped out very carefully where early access programs would actually be implemented. we knew that there would be large addressable populations in Europe, in the Middle East, in Latin America, places where we can get innovative pricing and reimbursement and maintain, if you will, a price for that innovation and maintain a narrow pricing corridor. So we've actually implemented programs in France right now in key major markets. France has already given us an HTA assessment, and that's completed, and they've approved our early access program. and we've seen an accelerated demand rapidly in France. We've also seen accelerated demand both in Italy and Spain and a number of southern European markets as well as central and eastern European markets. We're just in that process of beginning and implementing those in Latin America and the Middle East where there will be meaningful contributors. We've said that there's up to 30 markets that potentially provide revenue. Keep in mind, as Matt said, over the last 10, 15, 12 years or so, we have actually been commercializing products in over 50 countries, and we have extensive experience. So we're going to bring suffice to as many of these markets and as quickly and effectively as possible.

Thank you. Our next question comes from Eric Joseph with Citi. Your line is open.

Oh, thanks for taking the questions, and congrats on all the progress. Maybe just to pick up on the XQS outlook, Can you talk a little bit about sort of of the 30 global markets that you're pursuing, which are likely to have their own HTA review processes versus referencing other geographies to a rather pricing decision and also what HTA review time timelines would look like? And if I could just squeeze in a pipeline question, I'd be curious to kind of get a sense of timeline as it relates to the NLRP-3 inhibitor program and what kind of profile might support later stage development as those data read out.

I think questions first, need a comment on the person, then turn it over to Eric. So we're excited that the NLRP-3 program has been talked about and done a lot of work preclinically demonstrating that this molecule is highly differentiated in terms of potency We've been able to benchmark it against others that have specificity for the target, and we talked a bit about how its chemical backbone is a bit different than others that have been in development that worse, and that others had some potential toxicity concerns that we don't think will apply here. We've designed the Phase I study to answer the typical Phase I pharmacology, biodistribution, and AC questions, but also we're including a cohort of patients with sort of metabolic syndrome phenotype and inflammatory biomarkers so that we can get early confidence that the exposures that we're able to get, exposures we can get safely, the level of inhibition we're seeing is associated with behavioral biomarker effects. And we could have those data as early as the end of this year into early next year, and that would really put us in place then to move quickly into phase two. And so Again, we're super excited about this program we've talked about, focusing on rare pulmonary disorders as a first set of indications. That was based on the understood overlap between NLRB-3 and flavosome and the number of pulmonary inflammation and fibrotic pathologies. And the first question, let me just make a general comment. That number of 30 countries, we had said between 20 and 30, that was just in 2026. That's something clear that we expect this to be as the launch moves forward into 27 and beyond. There's many more countries we seek to get to and target that 58,000 global adjustable market. Eric, do you want to talk a little bit about HTA processes?

Yeah, Eric, thanks for the question again. You know, HTA assessments are primarily in large Southern European markets, and I'll just give you a little color for that, because those are the markets that are referenced pretty much around the world in international markets. So for France, the HEA assessment is complete. We've completed that, and the Early Access Program has been approved in Q2. And as I mentioned, there's been a very accelerated demand by healthcare professionals for the Early Access Program, and we're recognizing revenue there. The price is actually the German price. But in terms of timing, pricing and reimbursement discussions are now ongoing, and we would expect that to conclude sometime next year in France. In Italy and Spain, again, key markets, HTA process is still ongoing, and that's going to be going on for probably into the third and fourth quarter. However, we do have early access programs, again, being leveraged. Those are priced at the German price at this point in time. And then pricing and reimbursement discussions will be conducted with the authorities, likely in the fourth quarter and should – we're expecting that to conclude sometime in early 2027. And as you already know, Germany, the AT&T assessment was completed at the beginning of the year. And right now, from a GKV discussion, this is still ongoing. Pricing and reimbursement should be finalized before the end of this year in Germany.

Excellent. Thanks for all the color. Sure.

Thank you. Our next question comes from Ben Burnett with Wells Fargo. Your line is open.

Hey, thanks very much. I was wondering if you could maybe just talk to the revenue guidance. Great to see that increase. Just want to know what's considered in the increase. Is this mostly suffiance confidence or is this from sort of broader confidence with other programs? And then just one clarification on the discontinuation rate.

How was that defined? Hi, Dan. So on your first question on the revenue guidance, look, when we came into this year, we said we had a lot of unknowns that we were dealing with. We were still very early in the supply arm's launch, and we also, in terms of the Duchenne franchise, had significant headwinds with a significant number of generics now from Flaza and headwinds in some of the larger countries where we get group purchase orders, as well as the fact that we were still selling product in Europe without a license. Clearly, the Duchenne franchise has had a bit more durability than expected, and the supply and its growth has been terrific. So, you know, as we went and looked at and revised the guidance as we did after the first quarter and now again after the second quarter, it's based in large part on our confidence of supply and the ability for it to continue to grow in the way that we have seen it growing and some of the widespread of the guidance range incorporates the fact that we could still see some contributions from the Duchenne franchise if Ben Plaza is able to withstand the continued generics, for example. But a lot of it's our confidence in suffice with some confidence that we may get still some more life out of the Duchenne franchise. In terms of the discontinuation numbers, we define that as going basically 60 days or two months with that prescription. Great, thank you.

Thank you. Our next question comes from Brian Chang with J.P. Morgan. Your line is open.

Hey, guys. Congrats on the quarter. First, heading into the discussion with the agency on Volta Plan later this year, is the discussion going to enable you to talk about the ability to file for an seller approval based on the 24-month data? Is that one of the primary goals here? And then secondly, we're seeing new patient ads accelerated this specific quarter, and the revenue is not catching up as fast. So I'm curious if you can help us, you know, how do we best reconcile these two numbers?

Brian, in terms of Vodafran, as you know, you had said after we shared the data that we and our team and the Navar's team had discussed, you know, whether we would review those data with FDA. Clearly, the FDA's seeming agreement to accept a filing for the gene therapy on COHDRS's intermediate clinical work point was an important data point in our consideration of whether to talk to the FDA. So I think the belief is that it's important to go and talk to them, talk to them about the data. And, you know, obviously one of the important topics is going to be, you know, If there is a precedent for applications based on ICE in HD, you know, we believe our data compare quite favorably when you consider just a number of patients exposed with the dose-dependent effect seen in the stage 2 patients, the fact that we have objective data of target engagement and mechanism of action with the dose-dependent durable lowering of blood-huntington protein, as well as safety exposure of a larger number of patients in a drug that's titratable, reversible, and we have a Phase III study that's up and going, and enrollment's underway. So we think all of those things allow for a really good discussion with FDA. And obviously, Novartis has made the comment that they're still operating under the assumption that Phase III is the base case. Importantly, that study has an interim analysis, but they have also commented, as we have, that we can look for any chance we have to accelerate access to a potential disease-modifying and therapy, given a significant unmet need for Huntington's disease patients. In terms of patient ads, look, I think what we're seeing, again, is what we said is consistent demand and consistent ads in the U.S. and increasing contributions now globally. Obviously, patient numbers come in different. Patient numbers and revenue may be different in terms of that. Patient weights may be different. There's a lot of variables that actually go into the amount of reimbursement, and obviously all patients don't enter in a quarter at one time. Some can come in a lot early, some can come in a bit later. So I think there's a lot of variables that go into it. I think importantly to your point, we see consistent demand, we see growth in patient numbers that, I think we saw in your early note, is more than folks expected, and we expect that to continue. And we expect the revenue also to continue to grow over time, as we said, given the large number of patients. And, again, what we've consistently said is a significant, you know, $2 billion plus multibillion-dollar opportunity.

Thank you, Matt.

Thank you. Our next question comes from Judah Frommer with MS. Your line is open.

Yeah. Congrats on the quarter, and thanks for taking the question. Are you able to add any guidance or detail on switching dynamics, patients that are switching from standard-of-care therapy to suffiance? Are there particular sales efforts that are generating success there? Is it word of mouth amongst patients? Anything anecdotal or tangible, that would be helpful. And then just on, you know, the peak sales opportunity for suffiance, any change in speed to peak as you're now through several quarters of the launch, or do you expect things to kind of be in line with the original expectations as of now? Thanks for the questions, Judah.

Let me take the second one first, and then I'll ask Eric to comment a little bit on what we're seeing in the switching dynamics and some of the data that's driving that and some of the dynamics of those patients. Look, I think we've talked just generally about this being, you know, call it $2 billion plus, multi-billion dollar, not in terms of specific guidance, but just to help people understand what we believe is the magnitude of this opportunity. Recalling that when we started the launch, we were getting ready for the launch, a lot of people were benchmarking this to previous therapies. I mean, I think we are now at a full-year run rate that exceeds where many people thought the initial opportunity was for this product. So we thought it's really important to really say that there's no precedent, there's no benchmarking this in terms of previous PKU therapies, but rather to benchmark in terms of what a differentiated rare disease therapy with a population of, you know, 17,000 U.S. and 58,000 in markets where we could access patients and get reimbursed for drug could bring. I think as we get closer, as we get further into this year and next year, you know, we'll be in a better position to talk more about formal guidance. But, again, we just have that number and stuck that number now just to hold out the fact that, one, it's a much larger opportunity than many of the initial imagined. Two, what we're seeing thus far in the launch does nothing but increase our confidence that this is the magnitude of this opportunity. Eric, do you want to talk a little bit about the switching dynamics, some of the data, and what that's looking like?

Yeah, Jim, thanks for the question again. I think the first thing is that we said we're really impressed after 12 months in the launch that we were able to see a lot of the dynamics of those patients who are actually failed or poorly controlled, and we also saw that adults and naive have been coming in. What we thought may have been the case was that patients and physicians who are the highest of them they need would be the first ones treated. Now we have all centers of excellence who are prescribing, And we're also seeing now a significant movement to change what patients are seeing in terms of fee reduction. And I think we have a number of key programs that our sales teams or medical teams are communicating about not just fee reduction, but how lower fee reduction is more important. And what we'll be showing at SSIM will be some very important data that talks about normalization. Patients at 120 micrometers per milliliter. And when you think about normalization, that's incredibly important because we know patients who already respond to BH4 will have a much better response to suffiance and are likely to not only reach goal, but to reach normalization. And that's going to be a very, very important part of our communication and messaging as we go forward. and that could be supported by data as soon as next month at SSIM. So we have tailored programs from the medical perspective, and we're working with these centers. And as we thought, you know, these patients who were the most severe were the first ones to come on to therapy, but now we're seeing more and more benefits from patients who are switching, and that dynamic will continue over time.

Thank you. Our next question comes from Joseph Tome with T.D. Callen. Your line is open.

Hi there. Good afternoon, and thank you for taking my questions. Maybe the first one, I guess, in that upside scenario that the FDA is amenable to a filing for Huntington's, can you talk a little bit about where you are from a CMC perspective with Vodaflame and your readiness there? And then second, maybe on the DHODH inhibitor program, I know it's been a while, but you also have PTC-299. Can you talk a little bit about the differences between that older agent and your next-gen compound? Thank you. Yeah, absolutely, Joe. So on the HD, look, I think this is the benefits of, one, it's a small molecule, and two, having a partner like Novartis who's well-equipped to move all of these things forward as quickly as needed. And I think when we did a partnership back in 24 and then went through the official handover in early 25, you know, it's very clear that their teams are all over every aspect of getting things exactly in order for FDA approval. So, if we were given the opportunities and the clinical data, I think we'd be very confident that that application could get there. And, of course, obviously, the confirmatory study is already up and running. In terms of DHVH, I think DTC299 was really a legacy product, And as one would expect, when you go from Gen 1.0 to, I would say, this is technically 2.0, but it's more like a 3.0 or 4.0 in terms of how much more potency-specific it really is. And I think we had a lot of conversations internally about bringing this molecule forward, but when we saw how differentiated it is and understanding that there have been other THRDH inhibitors that have been approved that have been viable commercial products, and to be able to benchmark PCA4 to those, and we showed those data at our research day, as well as 299 and showed the superiority in terms of in vitro potency as well as specificity for the VH-VH target, tells us that we're now able to target a mechanism known to be important and do so in a very selective, specific, and potent way. So we're going to look forward to the Phase 2A study. We're going to be doing that in a population of patients with significant inflammation with rheumatoid arthritis, but that's not our intended indication, but rather what we want to do is take a population in whom we knew would have a biomarker profile of inflammation that would allow us to establish the relationship between DHO levels and effects on biomarkers in T-cell and B-cell immunity that can then help us inform where we would go from there in terms of specific target population. Great. Thank you.

Thank you. Our next question comes from Faisal Kershitz with Jeffries. Your line is open.

Hey, guys. Thanks for taking the question. I'm just going to ask a couple of nitty-gritty commercial things, if you don't mind. Could you comment if there were any inventory effects for Cepiants in the second quarter? And then can you also comment on how we should be thinking about and modeling things like gross-to-net and net pricing and average patient weight, heavier assumptions that are changed at all. Yeah, I would thank you for the questions. I was simply positive. We've had no inventory effects to think about. Things have been fairly constant in that regard, I would say, as well, in terms of patient weight, patient age, gross-to-net, all those things that have been consistent. We haven't seen any real changes there.

Thank you.

Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is open.

Hi, everyone. This is Nevin on for Brian.

Thank you so much for taking our questions. Just one more on the fines. How are you kind of thinking about the split of revenues over the long term, especially just given that the ex-US is progressing so well and you seem to be getting pretty good reimbursement in pricing there, and just given that there's kind of a larger population outside the U.S. as well? And then I'm also wondering if you could talk about your updated thoughts on BD and if your kind of appetite has changed there, if you're looking at any specific programs or therapeutic areas, and what's the size of any potential deals that you might be able to deal with? Sure. First on the split, look, I think it may be a little early to give an exact breakdown. I think we think that international can be a significant contributor here, It's still the best – the majority will likely always be driven by the U.S., but I think there could be a significant contribution next to us when you start looking at that number of patients and what we believe we're going to be able to achieve in terms of reimbursement. But it's only for us to give an exact breakdown there. You know, I'd say, for example, what we're seeing thus far in Japan has been really impressive. You know, there's maybe 1,000 or 100 patients there at PKU, but we're seeing a lot like the U.S. There's early demand. There's patients not on therapy who are coming back in and getting on therapy. There's centers of excellence. And as Eric mentioned in the prepared comments, you know, there we have a price on par with the U.S. Price is set for 10 years. It's very easy for patients to get on drugs. So, you know, again, there's a lot of these kinds of stories out there where we're seeing international markets to be able to start to make an impact that we expect will continue to grow in the latter part of 26 into 27 and beyond. Pierre, do you want to talk a little bit about how we've been thinking about VD?

Yes, happy to. So first of all, I would say we closed the quarter with very strong cash position of $2.2 billion. We worked really hard to get there. And as we said, our team has demonstrated their ability to launch products globally. that's a key strength of ours they have capacity so we're looking at BD in a number of ways one obviously we're still laser focused on safe science we don't distract the momentum at all are there ways to complement that very strong franchise for us that's one bucket we're also looking at you know other areas in a rare disease space late stage or commercial again to leverage that global infrastructure that we have so that's how we're thinking about it again we want to make sure we're very disciplined in any potential transaction to make sure that we create value for shareholders. You mentioned size. Again, we're not going to do anything where we will lever up and use, you know, all our cash in one go. So that's how we think about it. Thank you so much.

Thank you. Our next question comes from Luke Herman with Baird. Your line is open.

Okay. Thanks for the question, team. So now that you're established in all the Centers of Excellence for Suppliants, has there been any shift in the proportion of new starts stemming from sort of a proactive visit as compared to a more typical checkup schedule? And sorry if you've already covered this, but to the extent you're able to qualify, how have new starts tracked into July? Thanks. Thanks for the questions, Luke.

I would say that we, what we've been hearing from a lot of the KOLs is that most of the prescriptions are coming now as part of regular visits. So, you know, early on, we said in the first couple months at launch, there were a lot of folks coming in waiting lists and a lot of attention in the first part. But most of the KOLs and prescribers have told us that somewhere late November or so, we saw a shift in feeling as patients are coming in. and they're looking to either start them on therapy or switch them, for example. Now, that being said, we still note that, you know, one of the questions earlier asked about what the effects of us going to conferences and the team work that our customer-facing teams do in the field and our patient support and patient engagement work does. We know that the more messages, the more patients hear about this, there still is a lot of patient pull and market pull to get into clinics and get on the drug. So in terms of starts into July, what we said is that overall, you know, we continue to see strong underlying demand. We expect it to be consistent growth in the U.S., accelerating growth outside of the U.S., and a lot of that is what underpin or prompted our confidence and our ability to raise guys in state 50 to 950.

Our next question comes from Joe Schwartz with Lyric Partners. Your line is open.

Great. Thanks very much. I guess I have a question on Germany first. I think the pricing and reimbursement for suffiance was previously expected to be finalized this summer, with other European negotiations advancing behind that. Why is it seeming to take longer? Are you getting the traction you expected? and will it hold up any of the discussions with other European countries in any way?

Eric, do you want to talk a little bit about the negotiations globally and particularly Germany?

Yeah, and in fact, keep in mind, thanks for the question, keep in mind that we've launched in Germany and it has been just barely on the 12-month cycle. We have a number of what we call mandatory negotiation sessions, and then there are informal ones with GKV. Clearly, those discussions have been productive. They've been cordial. We've been working on that. We've just now hit the summer months. So those discussions will continue throughout the summer. It's likely that our pricing and reimbursement will be finalized sometime in the third quarter, but it could go into the fourth quarter. The list price right now that we have listed in the lower tax is very similar to the U.S. price. It has not affected any of the other markets. And, in fact, Brazil, which CMED has referenced in terms of innovation status, the current Brazilian price is linked to the German price. So, essentially, everything is going according to schedule, and we anticipate to have the final decisions sometime in the second half of this year.

Thank you.

Thank you. Our next question comes from Paul Toy with Goldman Sachs. Your line is open.

Hi. Congratulations on the progress, and thanks for taking the questions. I have two on Huntington's. Matt, I was wondering if you maybe offer your preliminary thoughts on development of PTC-303 as a monotherapy in Huntington's versus potential combination use with the photo plan. Any early thoughts there would be great. And my second one is, Roche recently discontinued its commonersion studies in Huntington's and, you know, caveating for the usual cross-trial and cross-drug differences. Any thoughts there just on the, you know, implications just given, you know, what was early, you know, and promising biomarker changes versus what looks like, you know, less success on clinical endpoints and just, you know, any thoughts on potential read-throughs there. Thank you very much.

Yeah, absolutely. So, first, look, we're super excited about PTC303. We talked about it at R&D Day, and I think, again, this shows PTC's ability to leverage splicing to bring forward potentially valuable and impactful therapies. And PTC303 is one that can target, you know, several diseases characterized by somatic expansion. This is one that I think from conception to getting to a development candidate took our team, you know, probably a little less than three years, which is phenomenal. And really, I think it was an example of how we were getting smarter and using the tools we have to facilitate and accelerate small molecule splicing development. As you pointed out, Paul, and we talked about it on the call, HD is a disease of somatic expansion. Targeting NFH3 is probably now the hottest target in Huntington's disease, drug development. We're very excited about Vodapam. We think they could work together. And also, it could serve as a monotherapy, particularly in, for example, juvenile HD, which in a juvenile HD is a setting where there's a large number of triplet repeats and it's characterized by rapid progression. What does that mean? There's rapid somatic expansion. So you would think that's something targeting somatic expansion. we could see a signal sooner and maybe louder in a short amount of time in, say, a juvenile IHD population. But, you know, we're very excited to be able to have this as a potential therapeutic option. We look forward to getting all of the IND-navaling studies done and getting this into the clinic as quickly as we can in 2027. In terms of trauma nurse, and I think it's been quite clear for a bit of time now, probably ever since the Generation HD1 data were presented, and probably even before that, when some of the earlier stage data were presented, that a lot of the challenges of tominursin were not really a mandate or a reflection of the potential of HGT lowering, but a lot of it was associated with the limitations of the ASO modality here. As was noted in earlier studies of tominursin, particularly when it was a four-week dosing arm, it had to be discontinued because of the significant amount of inflammation created in the CSF by the ASO. And, in fact, in the doses used in Generation HD1 as well as Generation HD2, you still saw white blood cells and protein markers of immunoinflammatory response in a CSF of patients who received it. That's been noted. That's something that has always been a concern. If you think about it, you're taking eight Huntington's of these patients, and a lot of those patients were later stage patients. So these are individuals who had brain inflammation and oxidative stress for decades, and you are dropping an inflammatory stimulus into your CFS. And so what ends up happening is you can't actually, I think, readily or easily detect a favorable hunting-to-lowering response because it's confounded by a significant inflammatory response in that population. And, again, that's corroborated by the protein and white blood cells in the CFS as well as by some of the other issues with the CFS that were observed in that study. and, of course, the association of certain points of NFL spikes following treatment. All of that put together is really where I think a lot of people are, you, the Tolman-Urston experience, is really a reflection of that drug and not HTT lower. And, you know, we think that the RISD pattern is probably a better way to think about Vodaflame, right? Oral small-offed splicing agent gets full-brain biodistribution, allow for titratability, allow to use the peripheral blood cells as a marker for target engagement, and change of protein of interest and then really allow you then to identify a therapeutic window so that you can deliver benefit along with safety. So that's how we think about it.

Thank you. I'm showing no further questions. I'd like to turn the call over to Dr. Matthew Klein for closing remarks.

Thank you again for joining the call this afternoon. We are incredibly excited about our performance so far in 2026, and we look forward to continued outstanding performance not only with Suffiance but across the entire company. Thank you all again for joining the call.

Thank you for your participation. You may now disconnect. Everyone, enjoy the rest of your day.