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

Ladies and gentlemen, thank you for standing by. Welcome to PTC Therapeutics Second Quarter 2026 Earnings Conference Call. [Operator Instructions] Today's conference is being recorded. I would now like to turn the conference over to Ellen Cavaleri, 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 Pauwels; 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 and 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 a position to potentially reach the milestone of being cash flow breakeven in 2026. I'll begin with an update on Sephience global launch. Momentum remained strong in the quarter with continued steady growth in the U.S. and accelerating growth internationally. Second quarter global Sephience 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 Sephience globally. We continue to see broad uptake across all patient segments and age groups worldwide. There remains strong underlying demand for Sephience, 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 diet liberalization, but also of Sephience's benefits on mood, cognition and quality of life. These dynamics of strong demand and reported patients benefit reinforce our confidence in Sephience's long-term commercial opportunity. In international markets, momentum for Sephience 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 Sephience recently received the highest classification for therapeutic benefit 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 for Sephience. Turning to the votoplam Huntington's disease program. In April, we reported positive top line results from the 24-month interim analysis of the PIVOT-HD long-term extension study. At month 24, votoplam 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 across doses and disease stages. These data support the potential for votoplam to provide long-term meaningful clinical benefit for individuals affected by Huntington's disease. We also shared that Novartis has initiated enrollment in the global Phase III INVEST-HD 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 votoplam 10 milligrams or placebo, and the study includes an interim analysis. While the Phase III study remains the base case for votoplam approval, the Novartis and PTC teams are finalizing a plan to engage with FDA in the second half of 2026 to discuss the 24-month results and potential accelerated path. For the vatiquinone Friedreich's ataxia program, based on discussions with FDA, we have finalized the study protocol for the open-label trial with the 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 mFARS from baseline to month 24. The study design reflects the key learnings from our prior development work and has understandably generated enthusiasm within the FA community, particularly because it offers patients the opportunity to access therapy without the uncertainty of receiving placebo. We believe the study design, coupled with our experience in FA therapy clinical development, meaningfully enhances the probability of success of the PROVE-FA study and the potential to deliver an important new therapy for children and adults affected by FA. Shifting to our other clinical pipeline programs. We have initiated the Phase I study of PTC612, our oral NLRP3 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 PK/PD effect. As we have previously shared, PTC612 is differentiated from other NLRP3 inhibitors in terms of potency, selectivity and chemical structure. Later in the third quarter of this year, we expect to initiate a Phase IIa study of PTC844, our next-generation DHODH inhibitor. PTC844 is highly selective for the DHODH enzyme and benchmarks favorably to other DHODH inhibitors in preclinical potency models. The PTC844 study will be a 12-week PK/PD study in which we will assess treatment effect on biomarkers related to T-cell and B-cell immunity. The results of this study will help inform the ultimate target indications for PTC844. We've also made a number of advances in our splicing platform. We recently selected a development candidate for our MSH3 splicing program, PTC303. MSH3 is increasingly recognized as an important target for triplet repeat expansion diseases, including Huntington's disease and myotonic dystrophy. As we have discussed, targeting MSH3 provides a complementary approach to HCT lowering in addressing the key pathological causes of Huntington's disease. The MSH3 program also further reinforces PTC's leadership in the discovery and development of oral small molecule splicing therapies. PTC303 is fully owned by PTC, and we expect it to be in the clinic in 2027. Overall, 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 to the stock's closing price at the time of the deal. We closed the quarter with over $2.2 billion in cash and remain in a position to achieve cash flow breakeven in 2026. 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 Sephience launch. Eric?

Thanks, Matt. In the second quarter, our commercial team continued the strong global launch of Sephience, 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 Sephience. In the second quarter, Sephience revenue was $151 million, representing 21% growth over the first quarter of 2026. In the U.S., launch execution remains strong with steady demand. As Matt noted, all U.S. centers of excellence are now prescribing Sephience 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 Sephience 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 Sephience 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 health care providers and the patient community to facilitate access to Sephience. 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 AMPLIPHY study, demonstrating the ability of Sephience to reduce blood Phe significantly more than BH4 as well as new data on patients switching to Sephience 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 Phe levels have also experienced significant improvement in their day-to-day quality of life on Sephience 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 named 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 Sephience'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 Sephience 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 Sephience's 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 Sephience has had on PKU patients in countries around the world, with lower Phe 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 Sephience's responders led to a substantial portion of participants achieving complete normalization of blood Phe levels of 120 micromoles per milliliter in a rapid time frame, including those PKU patients who are classical and BH4 nonresponsive. This impressive real-world data demonstrated that achieving Phe level normalization is an important key treatment goal for all potential PKU patients. Now turning to our mature brands. In the second quarter, we continued to generate meaningful revenue despite challenges in the DMD franchise. For Translarna, we had continued sales in Europe and Latin America as well as the government order from Russia. In the U.S., Emflaza 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 team. 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 Sephience 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. Pierre?

Thank you, Eric. I will now share the financial highlights of our second quarter of 2026. Beginning with top line results. Total product 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 Sephience net product revenue of $151 million and DMD franchise revenue of $67 million. Translarna net product revenue was $42 million, including a government purchase order from Russia and Emflaza net product revenue was $25 million. For Evrysdi, Roche achieved second quarter global revenue of approximately USD 628 million, 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 noncash stock-based compensation expense compared to $104 million for the second quarter of 2025, excluding $9 million in noncash stock-based compensation expense. Non-GAAP SG&A expense was $68 million for the second quarter of 2026, excluding $13 million in noncash stock-based compensation expense compared to $76 million for the second quarter of 2025, excluding $10 million in noncash stock-based compensation expense. Cash, cash equivalents and marketable 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 due in 2031 at 0% interest rate and a conversion price representing a 40% premium over the stock's closing price at the time of the issue. Our strong financial position gives us the flexibility to pursue business development opportunities that support future growth while advancing towards cash flow breakeven and future sustained profitability. And I will now turn the call over to the operator for Q&A. Operator?

Our first question comes from Kristen Kluska with Cantor.

Congrats on a really strong quarter. I have 2 Sephience 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 therapy. 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 a breadth of patients? What are the key goals you hope to learn?

Kristen, thanks so much for the question. So on the first question, look, I think the key take home that we see this early in launch is we're incredibly excited about the demand and the uptake 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% of the centers of excellence, that's really an incredible milestone this 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 task is to get deeper and deeper into those centers. In terms of overall patients who may try the therapy, I think, the number we had always had is about 70%, 7-0 percent of individuals tried Kuvan. And that again suggests we have a very, very large number of patients who are yet to try Sephience. And we already know that we've seen patients who are therapy naive, that never tried Kuvan that are in that other 30% bucket who are coming back to clinic. So again, it's hard to put an exact number on it other than to say 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 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-BH4 mutations. And you had in NPKUA, one of the care -- 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 AMPLIPHY and patients who are on Kuvan, for example, where the brands are generic and to hear that 100% of those patients in our data have a much better response to Sephience 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 with Sephience, so we can continue to get those trying numbers up to 70%, 80% or even higher.

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

Matt, you've been really clear about defining how this launch is proceeding as very steady and consistent. So you have in the past talked about 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 absolutely. So Tazeen, we've moved now towards just really highlighting revenue in patients on drug because at this stage in the launch that 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 million to $950 million 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, we continue to see very high compliance and very high adherence rates. Discontinuations now remain low at about 20%, 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%. 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 the long-term significant potential -- revenue potential for Sephience.

Our next question comes from Joseph Han with Barclays.

It's Ellie from Barclays. You mentioned several early access programs ex U.S. Just to clarify, are you recognizing revenues from these programs yet? I think you mentioned seeing accelerated demand in France, Italy, Spain, LatAm and 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?

Ellie, I'll give just some general comments, and I'll let Eric give a little bit more detail on early access. And so all those early access patients are contributing to revenue. And what's important to note is that this whole approach we're taking in a global launch is really a well-thought-out plan. First, we have the global commercial infrastructure in place and already been commercializing in 50 countries. And a lot of this is 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 experience with Sephience. 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 [ recent ] revenue contribution. Eric?

Yes. Thanks, Ellie, for the question. As Matt said, the strategic plan is laid out 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, and Latin America, places where we could 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 they will be meaningful contributors. We've said that there's up to 30 markets that could potentially provide revenue. Keep in mind, as Matt said, over the last 10, 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 Sephience to as many of these markets and as quickly as effectively as possible.

Our next question comes from Eric Joseph with Citi.

Congrats on the progress. Maybe just to pick up on the ex U.S. outlook. Can you talk a little bit about sort of the 30 global markets that you're pursuing, which are likely to have their own HTA review processes versus referencing other geographies to arrive at a pricing decision and also what HTA review time line might look like? And if I could just squeeze in a pipeline question. I'd be curious to kind of get a sense of time lines as it relates to the NLRP3 inhibitor program and what kind of profile might support later-stage development as those data read out?

Eric, let me -- I'll take the second question first, make a comment on the first and then turn it over to Eric. So we're excited about the NLRP3 program as we've talked about. We've done a lot of work preclinically demonstrating that this molecule is highly differentiated in terms of potency and being able to benchmark it against others. It has specificity for the target, and we talked a bit about how it's chemical backbone is a bit different than others that have been in development at 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 safety 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 favorable 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 II. And so we're -- again, we're super excited about this program. We've talked about focusing on rare pulmonary disorders as a first set of indications, and that was based on the understood overlap between NLRP3 inflammasome and a 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 and that was just in 2026. I just want to make 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 addressable market. Eric, do you want to talk a little bit about the HTA processes?

Yes, Eric, thanks for the question again. 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 HTA 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 health care 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 are expecting that to conclude sometime in early 2027. And as you already know, Germany, the HTA 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.

Our next question comes from Ben Burnett with Wells Fargo.

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 Sephience confidence? Or is this from sort of broader confidence with other programs? And then just one clarification on the discontinuation rate. How is that defined?

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 Sephience launch. And we also, in terms of the Duchenne franchise, had significant headwinds with a significant number of generics now for Emflaza and headwinds in some of the larger countries where we get group purchase orders as well as the fact that we were -- we're still selling product in Europe without a license. Clearly, the Duchenne franchise has had a bit more durability than expected and the Sephience growth has been terrific. So as we went and looked at revising the guidance as we did after the first quarter and now again after second quarter, it's based in large part on our confidence of Sephience 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 Emflaza is able to withstand the continued generics, for example. But a lot of it's our confidence in Sephience 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 2 months with that prescription renewal.

Our next question comes from Brian Cheng with JPMorgan.

Congrats on the quarter. Maybe just first, heading into the discussion with the agency on votoplam later this year. Is the discussion going to enable you to talk about the ability to file for an accelerated approval based on the 24-month data? Is that one of the primary goals here? And then secondly, we're seeing new patient add accelerated this specific quarter, and the revenue is not catching up as fast. So I'm curious if you can help us -- how do we best reconcile these 2 numbers?

Yes. Brian, in terms of votoplam, as we had said after we shared the data that we -- that our team and the Novartis team discuss whether we would review those data with FDA. Clearly, the FDA's seeming agreement to accept a filing from -- for the gene therapy on cUHDRS as an intermediate clinical endpoint was an important data point in our consideration of whether to talk to the FDA. So -- and I think the belief is that it's important to go and talk to them and talk to them about the data. And obviously, one of the important topics is going to be if there is a precedent for applications based on ICE in HD. We believe our data compare quite favorably when you consider just the number of patients exposed, 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 in 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 is 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 could look for any chance we have to accelerate access to a potential disease-modifying therapy given the significant unmet need for Huntington's disease patients. In terms of patient adds, look, I think what we're seeing, again, is what we said is consistent demand and consistent adds 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, then 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 we saw 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 $2 billion plus multibillion-dollar opportunity.

Our next question comes from Judah Frommer with MS.