管理層發言
Ladies and gentlemen, thank you for standing by. Welcome to the Second Quarter 2026 Ascendis Pharma Earnings Conference Call. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Chad Fugure, Vice President of Investor Relations. Please go ahead.
Thank you, operator, and thank you, everyone, for joining our second quarter 2026 financial results conference call. I'm Chad Fugure, Vice President, Investor Relations at Ascendis Pharma. Joining me on the call today are Jan Mikkelsen, President and Chief Executive Officer; Scott Smith, Chief Financial Officer; Sherrie Glass, Chief Business Officer; and Jay Wu, Executive Vice President and President, Ascendis U.S. Before we begin, I'd like to remind you that this conference call, including the Q&A session that follows our prepared remarks, will contain forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act. All statements made on this call other than the statements of historical fact are forward-looking statements. Examples of such statements may include, but are not limited to, statements regarding our commercialization and continued development of SKYTROFA, YORVIPATH and YUVIWEL, including label expansion and combination treatment, certain expectations regarding patient access and financial outcomes, our pipeline candidates and our expectations with respect to their continued progress and potential commercialization, our strategic plans, partnerships and investments, our goals regarding our clinical pipeline, including the timing of clinical results and trials, our ongoing and planned regulatory filings and our expectations regarding the timing and results of regulatory decisions and our financial outlook and Vision 2030 objectives. These statements are based on information that is available to us as of today. Actual results may differ materially from those in our forward-looking statements, and you should not place undue reliance on these statements. We assume no obligation to update these statements as circumstances change, except as required by law. For additional information concerning the factors that could cause actual results to differ materially, please see the forward-looking statements section of today's press release and the Risk Factors section of our annual report on Form 20-F filed with the SEC on February 11, 2026. In addition, during this call, we will refer to certain non-IFRS financial measures. These measures are not prepared in accordance with IFRS accounting standards and should not be considered in isolation from or as a substitute for our IFRS results. A reconciliation of each non-IFRS measure to the most directly comparable IFRS measure, together with an explanation of why management believes these measures are useful to investors, is included in today's press release. TransCon Growth Hormone, or TransCon hGH, is now approved in the U.S. by the FDA for the replacement of endogenous growth hormone in adults with growth hormone deficiency in addition to the treatment of pediatric growth hormone deficiency and in the EU has received MAA authorization from the European Commission for the treatment of pediatric growth hormone deficiency. TransCon PTH is approved in the U.S. by the FDA for the treatment of hypoparathyroidism in adults and the European Commission and the United Kingdom's Medicines and Healthcare Products Regulatory Agency have granted marketing authorization for TransCon PTH as a replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. TransCon CNP is approved in the U.S. by the FDA to increase linear growth in pediatric patients 2 years of age and older with achondroplasia with open epiphyses. Continued approval for this indication, which was based on an improvement of annualized growth velocity, may be contingent upon verification and description of clinical benefit in confirmatory trials. Other than the approved products I've just described, our product candidates are investigational and not approved for commercial use. As investigational products, the safety and effectiveness of product candidates have not been reviewed or approved by any regulatory agency. None of the statements during this conference call regarding product candidates shall be viewed as promotional. On the call today, we'll discuss our second quarter 2026 financial results, and we'll provide further business updates. Following some prepared remarks, we'll then open up the call for questions. With that, let me turn it over to Jan.
Thanks, Chad. Good day, everyone. During the second quarter, achievement of important milestones and strong demand for our TransCon products continued to drive the transformation of Ascendis into a leading global biopharma company. The uniqueness of the TransCon technology platform, our strong development and global commercialization capability and our values and vision are the fundamentals driving this transformation. We believe the same strength will continue to drive Ascendis' growth in the following years. Starting with the long-term durability of our highly differentiated approved protein- and peptide-based products, SKYTROFA, YORVIPATH and YUVIWEL. We believe these products will be the key drivers of our growth story for the next 10 to 15 years through global commercialization, potential for label expansion, including combination treatments, and investment in patient support offerings. The continued expansion of the TransCon technology platform enables us to fulfill our plans to file at least one IND or CTA yearly each based on a new NCE, laying the foundation for strong growth for many decades. This will also enable us to establish new therapeutic areas in addition to hypoparathyroidism and growth disorders. As a further upside, our established partners are advancing TransCon candidates in large indications. This is why we believe Ascendis is well positioned for self-sustained long-term growth. Let us begin with a more detailed look at YORVIPATH. YORVIPATH is the first and only approved treatment for adults with hypoparathyroidism that addresses the underlying disease by replacing the missing endogenous PTH throughout the body. Uptake of YORVIPATH has grown steadily since launch, both in the U.S. and in many other countries, reflecting the significant unmet medical need among the more than 800,000 patients living with this serious rare disease in the geographic regions covered by our global commercial infrastructure. Outside of the U.S., we see consistent new patient demand and continued expansion of global commercialization launches with full reimbursement. YORVIPATH is now available commercially or through named-patient programs in more than 35 countries. This illustrates the strength of our ability to execute a rapid, broad global launch of a rare disease product. In the U.S., new patient demand for YORVIPATH in the second quarter has remained robust, consistent with prior quarters. In addition, physician prescribing is broadening and deepening. Patients who have successfully initiated YORVIPATH treatment continue to stay on therapy, indicating a high level of satisfaction. We continue to be excited by the growth of YORVIPATH in the U.S. and outside the U.S. and to see its continued strong launch performance. Data from our long-term Phase II and Phase III trials of YORVIPATH presented in the second quarter highlight why YORVIPATH is becoming a standard of care in postsurgical and all subsets of hypoparathyroidism, including ultra-rare genetic causes like DiGeorge, ADHS-1 and ADHS-2. Results showed a sustained response rate of 82% to 86% for the multicomponent endpoint with clinical benefit across multiple organ systems — central nervous system, kidney, small intestine and bone — plus meaningful improvement in quality of life. Patient retention was as high as 95% after five years of treatment, which is pretty unique. In parallel, we are working to further advance our leadership in hypoparathyroidism with additional clinical trials that include expanding the label to include ages 12 to 18 years in the U.S., higher doses for patients, and developing a once-weekly product for patients who are on stable doses of YORVIPATH. Turning now to YUVIWEL. We believe YUVIWEL is positioned to become the market-leading therapy for achondroplasia. Rapid uptake of YUVIWEL is already transforming the U.S. market. Across the board, we see a highly favorable response among patients and physicians to YUVIWEL's differentiated profile. In the U.S. through June 30, we had more than 170 unique patients enrolled. Since then, uptake has continued with more than 220 enrollments and more than 65% approved for reimbursement in the U.S. through the end of July — really a unique launch. The rapid uptake is by patients of all kinds of backgrounds: those switching, returning to medical therapy, or starting therapy for achondroplasia for the first time. We believe YUVIWEL is really growing the U.S. market, which is exactly the pattern you want to see when a highly differentiated product is introduced into an area with high unmet medical need. Long-term data for the now-completed pivotal ApproaCH trial showed durable and consistent improvement in growth, leg bowing, body proportionality along with a generally well-tolerated safety profile compared to placebo, underscoring why the community is quickly adopting YUVIWEL. In the U.S. and the EU, a regulatory decision for YUVIWEL is expected in the fourth quarter of 2026. We are also making YUVIWEL available in select international markets through early access programs using the U.S. FDA approval. Longer term, we are pursuing expansion opportunities for TransCon CNP in ongoing and planned trials. These include ongoing activities such as infants 0 to less than 2 years of age, for which we recently announced completion of target enrollment faster than expected, adults with achondroplasia, children with hypochondroplasia, and continued geographic expansions. Turning now to combination therapy with TransCon CNP and TransCon Growth Hormone. The biological rationale for this combination treatment is clear and is very well founded on science. TransCon CNP is removing the limitation caused by an overactive FGFR3 pathway, enabling TransCon Growth Hormone to provide a strong complementary effect. In addition, it has been observed that in achondroplasia there is a partial impairment of the IGF-1 growth hormone axis. This is illustrated by children with achondroplasia having a negative IGF-1 SDS value, as shown in the demographics in both our Phase II and Phase III trials. In our COACH clinical trial of children with achondroplasia, this unique combination has demonstrated sustained, transformative annualized growth velocity and ACH height score, including improvement in body proportionality. Based on these results, we believe this unique combination of once-weekly TransCon-based therapies will transform the treatment of achondroplasia and other indications over time. Our recent week 78 COACH trial data show sustained efficacy over 78 weeks with no compromises to safety and tolerability. This points to the potential for this novel combination to establish a new treatment standard in achondroplasia. The Phase III combination trial in children with achondroplasia will begin enrolling later this year. Turning to SKYTROFA, the once-weekly growth hormone treatment built on the mode of action of unmodified somatropin, with indications for pediatric and adult growth hormone deficiency, we continue to be the number-one long-acting growth hormone by brand value in the U.S. We are extremely proud that SKYTROFA recently achieved more than 20,000 unique enrollments. This illustrates the strength of our capabilities from supply chain, commercial infrastructure and market support to benefit such a large number of rare disease patients. We are working to make TransCon Growth Hormone available to more patients through label and geographic expansions. To support label expansion, as described in our achondroplasia program, we are conducting the Phase III basket trial investigating TransCon Growth Hormone in ISS, SGA and Turner syndrome. As an integrated part of our global growth disorder strategy, we expect to launch TransCon Growth Hormone in the same countries where we also expect to launch TransCon CNP. Turning now to our partnerships. In metabolic disorders and obesity, our once-monthly TransCon semaglutide program with Novo Nordisk continues to advance. In ophthalmology, our partner Eyconis recently initiated a first-in-human clinical trial of the anti-VEGF treatment built on the TransCon technology in patients with wet AMD. In closing, by always putting patients first, Ascendis has delivered three highly differentiated leading TransCon-based products: YORVIPATH, YUVIWEL and SKYTROFA. We are on track to achieve our Vision 2030 objective of being a leading global biopharma, building on a strong foundation for the future. With that, I will turn the call over to Scott to review our financial results and some additional comments.
Thanks so much, Jan, and good afternoon, everyone. I will touch on some key points surrounding our second quarter financial results. For further details, please refer to our Form 6-K filed today. Total product revenue was EUR 315 million, more than doubling year-over-year. Total revenue for Q2 2026 was EUR 339 million which included nonproduct collaboration revenue of EUR 24 million, which further included a EUR 17 million milestone related to TransCon CNP. YORVIPATH revenue was EUR 252 million in Q2, reflecting consistent new patient demand in the U.S. and continued growth outside of the U.S., reaching blockbuster status on a run-rate basis in the second year of launch in the U.S. SKYTROFA contributed EUR 55 million in Q2 which reflects increased demand in the U.S. and includes product sales to a collaboration partner. YUVIWEL was commercially launched in the U.S. during Q2 and generated EUR 8 million in revenue in its first quarter on the market, reflecting strong demand and rapid conversion to paid therapy with limited stocking. Continuing to expenses. R&D expenses in Q2 were EUR 76 million, up from EUR 59 million in Q1, reflecting continued investment in our pipeline and innovation. Recall, Q1 included a favorable EUR 11 million reversal of prior period write-downs of TransCon CNP prelaunch inventories. SG&A expenses were EUR 173 million in Q2 compared to EUR 145 million in Q1, reflecting additional investments in the commercial launches of YORVIPATH and YUVIWEL to accelerate growth for the long term. Operating profit of EUR 220 million in Q2 included EUR 158 million of other operating income related to the sale of the PRV. Non-IFRS operating profit was EUR 92 million and non-IFRS operating margin was 27%; refer to our press release for details. For Q2 2026, net profit was EUR 207 million, and non-IFRS net profit was EUR 61 million. We ended Q2 2026 with EUR 812 million in cash and cash equivalents, which includes the use of EUR 56 million in Q2 for our previously announced share repurchase program including the net settlement of certain RSUs. Following the settlement of our convertible notes, we have no bank debt, no convertible debt and EUR 1.4 billion of equity. Turning to our outlook for the rest of 2026. For YORVIPATH, we expect growth and performance consistent with prior quarters. For SKYTROFA, we expect relatively stable revenue in the U.S. For YUVIWEL, we are encouraged by the early demand trends. We believe it is expanding the market and is on pace to be the leading achondroplasia therapy in the U.S., reflecting the large unmet medical need and the highly differentiated profile of YUVIWEL. Our Q2 performance reinforces our belief that we can achieve EUR 5 billion in revenues in 2030. With our existing portfolio and our TransCon technology as a strong foundation we believe we are well positioned to grow revenue to more than EUR 10 billion in the next decades while developing and launching new TransCon products with blockbuster potential. We expect significant operating leverage as revenue scales through the balance of the year, while maintaining new investments in global product launches and patient access to reach as many patients as possible and support our long-term revenue aspirations. Even with these investments, we expect to generate more than EUR 500 million in cash flow from operating activities this year. With that, operator, we are now ready to take questions.
分析師問答
And our first question is going to come from Jessica Fye with JPMorgan.
On that outlook for at least EUR 500 million of operating cash flow this year, I think you gave that in the beginning of the year prior to the PRV sale. I was just wondering if you're able to update your cash flow expectations for the year. I know the phrase 'greater than' is unbounded, but curious if there is anything more you can add there? And then on that comment that YUVIWEL seems to be expanding the market, is it possible to estimate how much of these patient enrollments are coming from market expansion?
Thanks, Jess, for the questions. And I have a happy person beside me, Scott. So Scott got the opportunity to be the first one answering questions. So please, Scott.
Yes. With respect to our cash flow guidance, just to be clear, greater than EUR 500 million — I thought you said EUR 100 million, so greater than EUR 500 million. At this time, we don't want to bound the upper side because we're early into the launch of YUVIWEL. And that's in Europe, by the way, Jan likes to point out.
And just related to the question, and it comes back to what we communicated last time we had this call: we don't have exact insight into the precise distribution of where the patients are coming from. Our general feeling, and how we see it, is that with such strong demand we have a strong belief that it is not only coming from switches; it must also be coming from either patients who stopped therapy previously or new patients who are now starting therapy because of the highly differentiated nature of YUVIWEL. I think this is why we strongly believe we are seeing market expansion.
And the next question is going to come from Tazeen Ahmad with Bank of America.
So Jan, I wanted to get your thoughts about the IP challenge on YUVIWEL. We know obviously what the blue sky scenario is for Ascendis and most of the scenarios look positive. But can you walk us through what the potential outcomes are? This is for a patent that expires in 2030. Between now and then, can you tell us what could happen and what the potential for payments that Ascendis would need to make in the worst-case scenario could be?
Thanks, Tazeen, for the question. This is essentially addressing the ongoing legal dispute between Ascendis and BioMarin. Let me come back to some facts. The patent in question was invalidated in Europe, so we did not have a discussion there about infringement. Outside the U.S., the patent was invalidated by the European patent system. In the U.S., BioMarin elected to go to the ITC, which is a forum that traditionally has not handled many branded pharmaceutical cases. In the ITC case there will be a first opinion from a single judge expected in August. Following that, there will be a Commission opinion around December, and later there could be a presidential review. That means we should not expect final resolution in August one way or another. After the initial opinion from the single judge, the ITC case will be taken to a Commission decision by multiple commissioners. There is also a significant opportunity to consider public interest in this product. Given the product's role in serving an unmet medical need in the U.S. market and its rapid uptake, public-interest considerations are very strong to maintain patient access. I cannot recall a case in the U.S. where a branded product that provides benefit to U.S. patients was ultimately denied on public interest grounds. Regardless of how this proceeds administratively, I do not expect this to have any material impact on Ascendis' path. People may treat this as existential for Ascendis, but that perspective is not accurate. It will not be material to our ability to become a leading biopharma or to hit EUR 5 billion in 2030.
And our next question will come from Gavin Clark-Gartner with Evercore.
I actually just wanted to ask on the earlier pipeline. You noted in your prepared remarks that the TransCon platform can fuel one IND for an NCE annually. I guess there hasn't been one yet this year. Should we expect one in the near term? And what exactly are the go-forward plans for the earlier pipeline?
I should clarify: the two product opportunities developed through our partnerships that are built on TransCon could still be considered NCEs. One is now in the clinic with Eyconis; the other we expect will go into the clinic with Novo Nordisk. I feel some ownership of both of these opportunities, and we see major upside in both. From that perspective, I still consider the potential for two NCEs entering clinical trials this year. Kennet and his team are working hard, and I expect at least one new chemical entity to enter clinical trials each year going forward. I'm proud of that. This provides sustainability for Ascendis independent of external large acquisitions, and it supports a continued flow of partner licensing opportunities.
And the next question will come from Yaron Werber with TD Cowen.
A question on YUVIWEL. Do you expect some seasonality in terms of new patient starts in the summer as kids go on vacation? We're getting a lot of questions on the roughly 60 patient starts in April and now you're at 220. It sounds like about 50 per month now — is that sustainable? And it sounds like you think you could be the number-one brand by the end of the year. BioMarin, we think, has about 750 patients on drug in the U.S. Are you referring to getting to a higher number than that by, say, late next year?
Thanks for the question. We have not given a quantitative forward-looking statement related to how YUVIWEL will accelerate and expand the market. After only four months on the market, I do not feel prepared to provide precise guidance until we have more quarters of data to analyze trends. Jay, who oversees the U.S. market, is enthusiastic about what he is seeing and can provide the latest perspective on market development.
Thanks, Jan. As Jan mentioned, four months in, we're not prepared to give longer-term guidance, but we are incredibly encouraged by what we're seeing today. When you look at the fundamentals behind YUVIWEL uptake — whether it's prescriber reach — there are quite a few centers of excellence, and nearly 80% of them have already prescribed YUVIWEL to their patients in a short four-month period. So even in early days we're seeing a lot of enthusiasm from providers around the clinical profile of this product. More importantly, on the patient side, we are seeing a very positive trajectory. We don't explicitly collect information on prior therapy or non-therapy status for each patient, largely because our label is broad and we don't require that information to support access. Qualitatively we have anecdotes across three categories of patients: one, patients switching from current therapy; two, patients who previously discontinued pharmacological therapy and now want to return to treatment; and three, patients who historically have not tried pharmacological therapy but now want to try based on YUVIWEL's clinical profile. All of this underscores the existing unmet need and that patients are coming forward; from a market-growth standpoint, we're just getting started.
To summarize Jay's comments: we have no doubt we will be number one in the achondroplasia space and that we will expand the market because of unmet medical need. That applies for monotherapy, and we are committed to building for the next five to ten years with monotherapy and combination integrated treatment regimens. With our once-weekly TransCon products, both growth hormone and CNP, we are extremely well positioned to be the leader in this segment.
And our next question will come from Derek Archila with Wells Fargo.
Congrats on the progress. Scott, I wanted to clarify a comment on YORVIPATH growth for the rest of the year. I think you said it's going to be like prior quarters. Which prior quarters are you referring to? The quarter-over-quarter growth in Q1 was negatively impacted, and we saw some catch-up in Q2.
Thanks, Derek. Two points: one is the consistent performance with the KPIs that we've given you, for example, with enrollments — we expect those to continue and be consistent. The other is that you can refer to our prior quarters; now that we've seen more of the full year, you know the various trends that will come into play related to Q3 and Q4 and then Q1 next year. We think folks did a pretty good job modeling out Q2, and now you have the information to model the rest of the year until we update those KPIs.
Just to give you some context: our goal is not to give a lower number to make ourselves look better. We want to give you numbers so you are right nearly every time. We try to be transparent with our modeling assumptions so you can feel comfortable with the guidance we give.
And our next question will come from Joseph Schwartz with Leerink.
Congrats on all the progress. As you embark on a Phase III in hypochondroplasia, how are you defining the enrolled population? How large do you see the diagnosed, treatable pool of hypochondroplasia patients who are not already being treated, especially given some patients are more severe than others versus achondroplasia?
That's an interesting question because it touches on genetic testing and diagnostic definitions. Historically, some patients were classified as ISS — idiopathic short stature — because the underlying cause was unknown. As genetic testing has become more comprehensive, some of those patients are now identified as having FGFR3 mutations in regions associated with hypochondroplasia. So the ISS population is shrinking as more patients receive genetic testing and are reclassified. The question then becomes whether you define the population by genetic criteria or by phenotype. In our clinical trial design we have chosen a defined pathway that reflects those considerations.
And our next question will come from Daniel Bronder with Cantor.
Congrats on the quarter. On behalf of Li Watsek, we were wondering if you could give us a little more color on the quality of life metrics in the COACH trial. You already alluded to body segment ratios, but how should we think about benefit on arm span and other metrics?
To recall, the COACH trial is the combination trial of TransCon Growth Hormone and TransCon CNP. We have reported the 52-week data — I can ensure the slide deck is available. One of the extremely positive surprises was the arm-span improvement with combination therapy. Monotherapy with either CNP or growth hormone alone did not produce the level of improvement we saw with combination therapy. The arm-span improvement gives us hope that, with combination therapy, we could reduce the need for limb-lengthening surgeries in achondroplasia for both legs and arms. It's presented on Slide 5 in our materials.
The unprecedented improvements in arm span with combination were +9.4 centimeters in the TransCon CNP-naive cohort and +7.9 centimeters in the TransCon CNP-treated cohort.
Compared to limb-lengthening surgery, which is roughly 8 centimeters, this is a meaningful clinical effect. It was one of the days where I felt it was worth coming to work and seeing the impact of what we're doing.
And our next question will come from Yun Zhong with Wedbush.
I wanted to confirm that you have not provided prescription numbers for YORVIPATH; correct me if I missed anything. You said patient demand remained robust in the quarter, so I wonder if there is any additional quantitative information you can provide. Going forward, will you provide that number in coming quarters? And when do you expect to feel comfortable providing guidance in terms of a sales range for actual revenue?
You are right. We have been reporting that we see about more than 1,000 unique new patient enrollments per quarter in the U.S. for YORVIPATH; we have continued to see that steady state. We initially said we would stop repeating this because it was repetitive, but we restated it in Q1 because people questioned it, and it remained the same. For clarity, we are referring to the U.S. when we say approximately 1,000 new patients every quarter. Now that YUVIWEL is launching, we have started to provide unique enrollment numbers for YUVIWEL as well. We will continue to provide the metrics we believe are useful until we change them.
I would just add that our comments are intended to be consistent with the metrics we've given. Jan wants to keep our prepared remarks concise, so we won't repeat metrics more than necessary. Assume the metrics we've given continue unless we change them.
And the next question comes from Alex Thompson with Stifel.
Jan, I appreciate the color you provided to Tazeen's question around the ongoing legal battle with BioMarin. As we think about potential scenarios, do you see a settlement as a reasonable scenario to consider, or is that unlikely?
Alex, I am a very flexible person, and one of the things I always want to do is what is best for patients.
And the next question will come from Maxwell Skor with Morgan Stanley.
Just a quick one on YORVIPATH durability. I was wondering if dropouts are still mostly during the titration phase, and if you can comment at all on how reauthorizations are trending?
You're 100% correct. Dropouts predominantly occur during the titration period. Once a patient successfully completes titration and is on stable treatment, we see extremely low dropout rates, which indicates high patient satisfaction. We are developing a once-weekly formulation for patients on stable doses to give them a choice and potentially improve convenience. We are also exploring ways to improve patient support, for example remote calcium monitoring and other tools similar to innovations in type 1 diabetes. We developed YORVIPATH as a once-daily product to facilitate titration, because switching patients from conventional therapy while increasing PTH replacement can be complex. We plan to continue improving support during titration to reduce dropout, and Jay can explain the operational efforts to smooth this period.
Absolutely. I can provide more color on investments and on drop-off and reauthorizations. Yes, the majority of drop-offs occur during titration when patients experience the most change and when additional education and a higher-touch support model helps. Reauthorizations are routine for us and do not have a measurable effect on ongoing patient support; patients reauthorize throughout the year as part of our operations. From an investment standpoint, we've invested heavily in patient-facing roles, including patient access liaisons who support patients pre-prescription, during the prescription process, and post-prescription. We've seen early success with this field team engaging the patient community. Patients have appreciated the high level of support, and we support them throughout the journey to optimize patient experience.
One important note: outside the U.S., we have not seen the same level of dropout in titration. The interaction between physicians and patients and the support systems outside the U.S. appear to be well established, so the higher dropout in the U.S. is an execution issue we can improve with the right support model.
And our next question will come from Eric Joseph with Citi.
Regarding your named-patient programs and early access programs, can you elaborate on which markets you're active in, whether eligibility might be determined by treatment status of a patient, and generally how we should think about whether named-patient programs could be meaningful contributors to patient volumes this year for YUVIWEL in particular?
We have an established global commercialization infrastructure, patient support, and product supply that was built to support our existing products, including SKYTROFA and YORVIPATH. We are leveraging that infrastructure for YUVIWEL. We already serve patients in more than 35 countries and have capabilities in more than 80 countries through our distribution agreements and direct markets. We will use our existing systems to make YUVIWEL available where patients are, and we expect significant focus ex-U.S., where the market opportunity is large. We will provide more guidance later in the year to help you build models for ex-U.S. uptake.
And the next question is from Luca Issi with RBC Capital Markets.
Question for Luca: Circling back to YUVIWEL and the three patient categories you touched on — naive, switch, and return-to-treatment — BioMarin mentioned on their second-quarter call that fewer than 100 patients have switched off VOXZOGO. By simple math, that leaves about 70 patients in the second quarter who are naive or returning to treatment. Does that align with the numbers or impressions you have? And how does the dynamic look between truly naive patients and patients who were once on VOXZOGO, stopped treatment, and are now returning to YUVIWEL? Separately, very quickly, have you commented on the ex-U.S. strategy for YUVIWEL, given the regulatory decision is pending in some markets this year?
I appreciate the math you've done, but I cannot confirm or deny those specific numbers because I don't have sightlines into BioMarin's numbers nor do I have the factual detail to corroborate that calculation from our side. I have seen their numbers publically, but I cannot validate them against our data. Regarding ex-U.S. strategy: for ex-U.S. we have several models. We have direct markets — I think in the range of dozens — where we operate our own commercial infrastructure. We have sales and distribution agreements covering approximately 80 countries. The vast majority of those agreements cover all three of our products. In addition, we have partners in Japan and China who cover all three products as well. So we already have established infrastructure and distribution for ex-U.S. commercialization and are prepared to execute on that. For some EU direct markets we are awaiting expected approvals in Q4 this year.
To confirm, the sales and distribution agreements cover 80 countries.
And our next question will come from Faisal Khurshid with Jefferies.
Just wanted to ask a little bit on the YORVIPATH lifecycle strategy. Can you give us an update on the latest on getting the higher dose into the label with the FDA? And any update on weekly YORVIPATH?
We are enrolling the U.S. trial evaluating the 30 to 60 microgram dose ranges, in two cohorts aligned with the FDA on the study design. Enrollment is going extremely fast, so we expect very rapid progress toward label expansion to include higher doses up to 60 micrograms. Regarding once-weekly YORVIPATH, there is no new update beyond our statement that we are executing on development. Our priority is improving patient support for those on stable dosing, and we are progressing that program consistent with its intended role to provide choice to stable patients.
This is all the time that we have for questions today. This does conclude today's conference call, and thank you for participating. You may now disconnect.
Thanks a lot, everyone.