Ascendis Pharma A/S (ASND) Earnings Call Transcript & Summary

Thank you for standing by, and welcome to the Ascendis Pharma Fourth Quarter 2025 Earnings Conference Call. [Operator Instructions] As a reminder, today's program is being recorded. And now I'd like to introduce your host for today's program, Chad Fugure, Vice President, Investor Relations. Please go ahead, sir.

Thank you, operator, and thank you, everyone, for joining our full year 2025 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; Jay Wu, Executive Vice President and President, Ascendis U.S.; and Aimee Shu, Chief Medical Officer. Before we begin, I'd like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act. Examples of such statements may include, but are not limited to, statements regarding our commercialization and continued development of SKYTROFA and YORVIPATH as well as 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 the result of regulatory decisions. 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 our forward-looking statements section in today's press release and the Risk Factors section of our most recent annual report on Form 20-F filed with the SEC on February 11, 2026. 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 then 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. Otherwise, please note that 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 agencies. None of the statements during this conference call regarding our product candidates shall be viewed as promotional. On the call today, we'll discuss our full year 2025 financial results, and we'll provide further business updates. Following some prepared remarks, we'll then open up the call for your questions. With that, let me turn the call over to Jan.

Thanks, Chad. Good afternoon, everyone. With strong execution across our business and continued progress toward delivering on our Vision 2030, Ascendis is transforming into a leading global biopharma company. We believe this progression demonstrates the power of our TransCon platform and our R&D capabilities to deliver a sustainable pipeline, while our global commercial infrastructure and financial profile continue to strengthen. We believe we are now at the base of a steep curve, where we expect to achieve operating cash flow of around EUR 500 million in 2026 and where we aspire to achieve at least EUR 5 billion in annual product revenue by 2030. And at the same time, we are building an expanded pipeline of blockbuster product opportunities. In the fourth quarter, we saw multiple achievements across the organization. Starting with YORVIPATH. The fourth quarter was another period of strong execution for the global launch of YORVIPATH. Revenue for the quarter was EUR 187 million, bringing full year 2025 YORVIPATH revenue to EUR 477 million. In the U.S., access continued to expand. Through year-end, more than 5,300 patients were prescribed YORVIPATH by nearly 2,400 unique health care providers, highlighting continued strong and steady demand. To date, less than 5% of U.S. patients are currently on YORVIPATH treatment, highlighting the significant long-term growth opportunity ahead. The overall insurance approval rate is about 70% of total enrollment, and we continue to see this figure moving higher over time. In addition, we continue to see a majority of approvals within 8 weeks. This provides a strong foundation for expected additional growth in 2026 and beyond, as more patients initiate YORVIPATH in line with treatment guidelines that support its use. Outside the U.S., we continue to reach more patients. As a reminder, YORVIPATH is now available commercially or through named patient programs in more than 30 countries. We have full commercial reimbursement in 4 countries in our Europe direct markets and 2 countries in our international markets. In Japan, our partner, Teijin, launched YORVIPATH commercially last November. In 2026, we expect full commercial launches in 10 additional new countries. We also advanced development activity to broaden YORVIPATH's label in a number of areas. In the U.S., we are working to expand the range of doses to our PaTHway60 trial. And globally, we continue to advance clinical trial to expand YORVIPATH to patients under the age of 18. Our work is progressing rapidly on once-weekly TransCon PTH for patients who have been titrated with daily YORVIPATH of conventional therapy and have achieved a stable daily dose for a well-defined period. Last month, at the annual JPMorgan Healthcare Conference, we shared preclinical data that support the target product profile for our once-weekly TransCon PTH candidate, matching the released PTH seen with daily YORVIPATH treatment over the entire week, thus providing a comparable efficacy and safety profile. Overall, we remain confident that YORVIPATH has the potential to be a durable long-term growth driver for Ascendis globally. Turning now to growth disorder, comprising of our once-weekly growth hormone SKYTROFA or TransCon Growth Hormone or once-weekly TransCon CNP. SKYTROFA delivered another solid quarter with Q4 revenue of EUR 53 million. bringing full year SKYTROFA revenue to EUR 206 million. This performance reflects the strength and value of the brand. As a reminder, SKYTROFA is now approved in pediatric growth hormone deficiency in the U.S. and adult growth hormone deficiency. Today, SKYTROFA has an overall market share of around 7% in the U.S. During the fourth quarter, we initiated our Phase III basket trial evaluating TransCon Growth Hormone in additional established growth hormone indications, including ISS, SHOX deficiency, Turner syndrome and SGA, which compromise up to half of the growth hormone market. Over the long term, this indication represents meaningful opportunity to expand the role of SKYTROFA as a treatment of choice in additional growth disorder. We also see an opportunity to potentially expand SKYTROFA's use to novel indications where growth hormone has not previously been approved for use, such as achondroplasia in combination with TransCon CNP. TransCon CNP is expected to be the first and only once-weekly treatment for children with achondroplasia, providing the full linear growth outcome that can be achieved with monotherapies addressing the overactive FGFR3 tyrosine kinase. In addition, in our pivotal trial, TransCon CNP achieved significant improvement in leg bowing compared to placebo, increasing spinal canal dimension and a similar safety and tolerability profile compared to placebo, with a very low rate of injection site reaction and no cases of symptomatic hypertension. In the U.S., our NDA for children with achondroplasia remains under review with a PDUFA date of February 28. In the EU, the MAA review is underway following our submission last October with a regulatory decision expected in the fourth quarter of 2026. Recruitment of our ongoing trial in infants with achondroplasia age 0-2 is going well, and we anticipate complete enrollment later this year. Turning to the combination therapy. Our 52-week COACH data in achondroplasia underscore the potential power of dual treatment with TransCon CNP and TransCon Growth Hormone, where continuous exposure to CNP enables the benefit of sustained exposure to unmodified growth hormone. In comparison, monotherapy trials of daily growth hormone in achondroplasia delivered only a limited effect on growth and no reported benefit on linear growth. Our 52-week data from the Phase II combination trial support our vision to significantly raise the bar for treatment of achondroplasia with linear growth improvements in achondroplasia-specific height score that were 3 to 4x what has been shown with CNP or daily growth hormone monotherapies in the same time period. In addition, the combination trial demonstrated accelerated improvements in body proportionality and for the first time, a meaningful improvement in arm span has been reported without compromising safety or tolerability. Importantly, this benefit beyond height are meaningful to the achondroplasia community and have been a core objective of our patient-focused development program in both our monotherapy and combination therapy programs. Importantly, all children completed 52 weeks of treatment and remain in the trial, reinforcing the benefit of treatment and acceptable treatment burden of the once-weekly regimen. These Phase II results demonstrate the effect of these complementary therapies, supporting that TransCon CNP acts in synergy with growth-promoting effect of TransCon Growth Hormone and has positive effect beyond linear growth. We believe, over time, the standard of care in achondroplasia and other growth disorder long term will include dual therapy as a treatment option, building on the potential role of TransCon CNP as an essential fundamental therapy. We recently held a successful end of Phase II FDA meeting and Scientific Advice meeting in EU in July on our Phase III trial for this novel combination approach for treatment children with achondroplasia. We also remain on track for additional COACH trial updates, including week 78 by midyear and week 104 by year-end and plan to explore further opportunity in other growth disorders. To sustain durable long-term growth for Ascendis, well into the next decade, we plan to continue to invest in label expansion of our current products in rare endocrine diseases. In addition, we have a strong focus on the development of new [ blockbuster ] product opportunities, both inside and outside rare endocrine diseases to fuel significant product revenue growth in the future. Looking at our partnerships. TransCon technologies support a continuous flow of highly differentiated product opportunity across multiple therapeutic areas, more than we can develop and commercialize ourselves. For this reason, our Vision 2030 includes a focus on creating additional value through partnership and collaboration. Our collaboration with Novo Nordisk for once-monthly TransCon semaglutide continue to advance towards the clinic. At Eyconis, TransCon anti-VEGF is on track to enter the clinic this year. In Japan, Teijin received approval for YORVIPATH in August 25 and commercially launch it in November 2025. In addition, recent approval of SKYTROFA in China in late January '26. In summary, 2025 was another positive and transformative year for Ascendis, with 2 commercial TransCon products [ continue ] to scale, the potential approval of the third high-value TransCon product in the coming weeks and a growing pipeline of highly differentiated programs, we believe we have the fundamentals in place to deliver durable long-term growth. A rapidly strengthening financial profile give us confidence to achieve an expected operating cash flow of around EUR 500 million in 2026. And our aspiration to achieve at least EUR 5 billion in annual product revenue by 2030, all consistent with our Vision 2030 strategy. I will now turn the call over to Scott.

Thank you, Jan, and thank you, Chad, for a well-read FLS. The significant achievements we made in 2025 provide us with substantial financial strength to drive our strategic priorities and goals in 2026, which include achieve blockbuster status for YORVIPATH; solidify our leadership in hypoparathyroidism through rapid progress of our label expanding clinical trials of TransCon PTH, while advancing development of our once-weekly PTH candidate; successfully launch TransCon CNP, if approved in the U.S. and other countries around the world; and expand our leadership in growth disorders through clinical and regulatory progress with once-weekly SKYTROFA, including in combination with once-weekly TransCon CNP. With that, I will touch on some key points surrounding our fourth quarter and full year financial results, which we mostly already announced at JPMorgan. But for further details, please refer to our annual report on Form 20-F filed today. As previously announced in January, YORVIPATH delivered strong global performance in Q4 2025 with revenue increasing to EUR 187 million, up from EUR 140 million in Q3, foreign currency had a negligible impact compared to the previous quarter. Total YORVIPATH revenue for 2025 was EUR 477 million. For the full year, the weaker U.S. dollar negatively impacted YORVIPATH revenue by approximately EUR 27 million. SKYTROFA contributed EUR 53 million in Q4 with negligible foreign currency impact compared to Q3 '25. Total SKYTROFA revenue for 2025 was EUR 206 million. For the full year, the weaker U.S. dollar negatively impacted SKYTROFA revenue by approximately EUR 9 million. Including EUR 7 million in collaboration revenue, total Q4 2025 revenue amounted to EUR 248 million, and total revenue for full year 2025 was EUR 720 million. Continuing on to expenses. As previously announced, total operating expenses for Q4 were EUR 214 million and total operating expenses for the full year 2025 were EUR 761 million, as we previously noted. Operating profit for Q4 2025 was EUR 10 million with Q4 operating cash flow of EUR 73 million. As we have discussed for some time, below operating profit, the drivers include the noncash accounting related to our convertible notes. Net finance expense, which was primarily driven by noncash items, including remeasurement loss of financial liabilities of EUR 106 million was EUR 93 million net. Net cash financial expense, however, for the full year 2025 was about EUR 8 million. In future periods, we may introduce a non-IFRS EPS measure adjusting for the impact of certain items to increase the comparability of period-to-period results. We ended '25 with EUR 616 million in cash and cash equivalents as previously reported, up from EUR 560 million as of December 31, '24. Turning to our commercial outlook and to help inform your revenue modeling for the coming year. For YORVIPATH, we expect continued strong revenue growth in 2026 based on steady patient uptake with some expected seasonality in reported revenue throughout the year. For SKYTROFA, we expect to follow a similar seasonal pattern to 2025 with full year revenue growth expected to track growth in prescriptions. Longer-term SKYTROFA revenue is expected to come through geographic and label expansion. As always, we continue to watch the euro-U.S. dollar exchange rate for any potential impact. And finally, we also look forward to the potential U.S. approval of TransCon CNP later this month, which, as a reminder, has been excluded from this 2026 outlook. With that, operator, we are now ready to take questions.

[Operator Instructions] Our first question comes from the line of Jess Fye from JPMorgan.

What's your confidence level heading into the TransCon CNP PDUFA? Are you comfortable that the issue leading to the review extension has been resolved to the FDA's satisfaction?

Jess, can you remember -- you asked me a question one time and the JPM conference. And can you remember my answer?

I do remember the answer.

And what was your question? You can ask the same question.

I remember your answer, but it was about a different product, if I recall, but your answer was yes.

Yes. So this is the same. You asked me, will TransCon PTH be approved? And I said yes. And you can ask me the same question today. Will TransCon CNP be approved? And I will say, yes.

And our next question comes from the line of Tazeen Ahmad from Bank of America.

You mentioned a 70% insurance approval rate in the U.S. so far for YORVIPATH. Where is that relative to where you thought it would be at this stage of the launch? And what is it going to take to expand that to a higher number? Where do you think -- how long do you think it's going to be before you get to 100% basically?

I think it would be infinitive because I've never seen a product hitting 100%. So I think the highest bar I've seen is something like an 85% or something like that, perhaps up to 90%. The element of where we are today, I'm really highly satisfied with it because it's also a compromise about how aggressive you're going into contracting and other things like that. So I think it's a balance between the 2 things where in the end, the overall and ultimate goal is basically to provide most value back to our shareholders and others in this way and at the same time, help the patient to as fast as possible to come on treatment. I do not know, Jay, if you have additional comments to my, I would not say, preprepared remarks.

Yes. I would say 2 things. One is that we're very happy with the overall approval rate that we're seeing. And I think the speed in which you're seeing this product be covered, again, is a testament to the strong clinical value proposition that we're seeing in hypoparathyroidism. It is the first and only approved therapy in this category. So again, this approval rating based on where we are today is something that we are very encouraged by. I think to your second part of the question, Tazeen, which is when might you get to 100%. I echo what Jan said earlier as well, which is I don't know that many drug analogs will get to 100%. And that actually has less to do with coverage and also has just to do with every single enrollment that comes in, not every single one of them will be eligible relative to the label. So there is some element of just natural filtering that comes that way. But more importantly, what I would say is that there are state Medicaid plans, for example, that review things on a staggered cycle. So you will anticipate that some of this will creep up over time, but it will take some time before it continues to inch upwards.

Yes. But I think still we need to some way -- this is a U.S. discussion. The U.S. discussion is built on 70% of all approvals in enrollment are there. So when you go in and look on an old cohort that perhaps had been 6 months to it, you actually will get a much higher number on it. Just to clarify with 70% on it, that is when you take everyone accumulated. If you take an old cohort, it's much higher. And when you go ex-U.S., the system is quite different. When you get a prescription, you in -- nearly in every other country, you are actually approved. So you can say the 100%, yes, it's basic when you get a prescription outside U.S. in traditional countries you will be 100% eligible and already approved for reimbursement.

And our next question comes from the line of Gavin Clark-Gartner from Evercore ISI.

Just on YORVIPATH pricing, so there's an 8% WACC increase in January. Maybe you could just discuss how net pricing will trend this year, including how to kind of quantify the magnitude of the 1Q seasonality here?

I don't think we really are discussing net prices. We will love to do it, but we are never done it, and I don't think we ever will discuss net prices.

If I could just ask a follow-up, just on patient enrollment. Are you planning to still report those forms going forward for YORVIPATH or maybe just focus more on revenue?

I think in the end, Gavin, it's 100% right. We will focus on revenue because now we basically have been in the market now in the U.S. We are on the market for about 4 quarters now. When we come to hear the fifth quarter, I think you have seen a steady-state development from '25 where we basically got an increase in basic revenue from both U.S. and ex-U.S. about EUR 40 million to EUR 50 million net every quarter. I think you will somewhere see a stability in how we are executing in it. We still have ex-U.S., we will expect 10 additional countries being fully reimbursed next year. And sure that is always improving what we call the net revenue we will generate outside the U.S.

And our next question comes from the line of Yaron Werber from TD Cowen.

I have sort of two, not really related, but I'm going to try to link them to keep it as one question. Maybe the first one, can you give us a little bit of a sense for YORVI, how it's being used out there? I mean it's almost like when you look at there's 2,400 unique prescribers and 5,300 unique patient enrollments. So is it that each physician just has sort of 1 or 2 patients in the practice? Or are they prescribing it sort of there and then they're going deeper? And then secondly, just the end of Phase II meeting with FDA relating to CNP and growth hormone for achondroplasia. Maybe just can you give us a little bit of an update? What was the outcome? And when will you start the Phase III?

Okay. That's perfect. I think, Jay, you can give some about how we're both expanding the physician prescribing base, but also go in more in the deep of the different patients, but still are far away to reach the level where we want to be. Jay?

Yes. So in the U.S., I think the question is really around segmentation and what types of patients are being treated. So if you think about the prescriber base, which is where you first started your question from, we are seeing broad uptake across the entire range of prescribers, right? So to your point, there are some physicians that might only see a couple of patients, but there's also some physicians that might see upwards of 10 patients, right? So more importantly, because we are seeing broad uptake across both high decile and low decile providers, we're not seeing a major discrepancy as to the type of prescriber that would prescribe, but we are seeing that breadth continue to increase. As it relates to the number of patients per physician, we are also seeing the depth of prescribing per physician also increase over time, which again is encouraging. That's both a testament to positive experience that they have with YORVIPATH as well as increased awareness of the hypoparathyroidism condition and now there being an option for it amongst patients. I think the last thing I would say is when you think about the types of patients that come through, you can look at it in 2 ways, right? One, which is the vast majority of them are postsurgical, so about 70% the remaining 30%, perhaps due to other factors, whether it's genetic, autoimmune, et cetera. And we're seeing broad uptake across both of those segments. So that isn't a major driver. And I think really where you're seeing some of the earlier uptake is patients that are self-aware of the condition that they have are linking the symptoms that they have to the underlying condition that they have and therefore, a combination of them advocating for themselves as well as providers having conviction in the product as well. So all in all, we're seeing broad uptake across provider groups as well as patient segments as well.

And our next question comes from the line...

Before you start, perhaps I can answer the last part of the question related to the COACH trial. Yes, we had an extremely positive meetings both from U.S. side and from the EU side. It was really impressive feedback to the data. They have never seen data before that basically are providing this kind of benefit to an achondroplasia treatment in. I'm not only talking about the linear growth where we basically on a Z-score got 3 to fourfold more that you can see with monotherapies in the same time period, but also was a unique element like such an improvement in body proportionality. But what was really -- what really -- they have never really seen in such a meaningful manner, was really important element, the arm span, where we also saw in the combination trial and unique improvement in arm span. And Aimee is sitting here with the management, and she's really doing everything to get this trial recruited as fast, we're ready to go. Protocol is finished and everything -- we open sites. Just remember that our pivotal trial in monotherapy, we recruited just in 3 or 4 months just because of the interest of the patient. So therefore, the bar for Aimee is very, very high because she needs to do that faster. Sorry for coming in.

Our next question comes from the line of Joseph Schwartz from Leerink Partners.

This is Heidi Jacobson on for Joe Schwartz. So can you help us understand how the TransCon CNP launch could factor into your EUR 500 million operating cash flow target for 2026, particularly with respect to launch investment and early revenue contribution?

It's pretty, pretty simple. It's not incorporated. So when we're coming into the launch, we see the initial uptake, which we believe will be pretty high, not only in the U.S., but also outside U.S. because we can utilize the U.S. approval to go to countries outside U.S., specifically in the international market. So from that perspective, we will come and provide you a better guidance and improved guidance when we have seen that. Scott is smiling or you're counting money or...

Taxes and money.

So we will come back after that.

And our next question comes from the line of Derek Archila from Wells Fargo.

Yes, I just wanted to understand your confidence level around YORVIPATH growth ex-U.S. Obviously, the launch in Germany and Austria, is that like a good proxy? Or is it going to be more depth in those types of countries and then just kind of expansion in, I guess, I think you said 10 additional countries. So how will that be sequenced through the year?

That is an extremely complicated answer because the heterogenicity of ex-U.S. is so heterogenic that we cannot really compare to what we -- for example, seeing in Spain now, what we see in France, what we see in Germany, what we're seeing in Austria. It's really different things because we see different speed of penetration. For example, Germany has less endos. So the bottleneck is a little more tight. It takes longer, longer, longer time to get them on therapy because there is fewer endo in the general population. If we go to Spain, there is more, there's more in France, and we also see, therefore, a faster uptake because we basically have a pipe that really is larger. When we get so many other -- 10 more additional countries basically on full commercial, we will see different uptake, but what we are doing is everything will be accumulated in the way where we now see from 30 to 35 countries named patient programs. And when we go full commercial, what we see every place, it's basically an acceleration of patient uptake because of the burdensome nature of a named patient program, it takes so much effort really to get every single patient on it and every patient deserve to be on the treatment. So when we come to '26, we will see initial speeding up in all this country. And when we come to '27, '28, we will continue to do it because just the nature, we just got an approval now in Canada, and we're basically taking one country after country, first going in and getting approval, and then we're going to full reimbursement.

Our next question comes from the line of Li Watsek from Cantor.

It's Daniel Bronder on for Li. Can you give us a little bit of color on how you expect your TransCon CNP launch to go? It seems like there is a few patients who aren't currently on treatment. Where do you think you will capture the majority of patients initially?

Pretty clear. The improvement that we see with TransCon CNP to what we can provide, not only related to when we look on tolerability, injection site reaction, having 120 injection site reaction compared to 1 every [ second ] year. Being in a position to look on no risk of hypertension to the element of just having the improvement of the once-weekly product and then show the data [ target ] that we have generated with TransCon CNP for first time ever shown in a well-controlled trial against placebo benefit beyond linear growth. For example, the leg bowing, which we have shown multiple times, we have shown improvement in muscle strength. We have improved quality of life. I think this is obvious every patient that decide to be on treatment should have the opportunity to have the best possible treatment option. And I think there is a public interest in the U.S. to ensure that it always will happen.

And our next question comes from the line of Ellie Merle from Barclays.

Curious if you can elaborate on your strategy for commercializing TransCon CNP ex-U.S. just given the majority of VOXZOGO sales are ex-U.S. Could you elaborate on your strategy for the commercial launches globally and the degree of investment that, that will take? And then just a second question on TransCon CNP. In the U.S., just can you talk a little bit more about how you're thinking about the cadence of uptake and which segments do you expect the most uptake from between, say, treatment-naive versus switches?

Yes. I will dial a little bit back now because what we did when we said that we want to have a global commercial effort, we actually started all our infrastructure building to Path. And now you see what we have done with YORVIPATH. We recognized the fast revenue, commercial revenue for more than 30 countries. We are penetrating them exactly as we can do. We will reach 60 to 70 countries in less than 2 to 3 years. So what we have done, we already have built up the infrastructure to be ready that we can take our integrated pipeline of rare disease endocrine product basically into all these different countries in already the setup we are establishing around YORVIPATH. So this is a positive element that we are not -- and you can say, a company that need first to take up an infrastructure to support a globalization. We have already established that. So I feel really, really, really confident that all the success we're seeing now with YORVIPATH on a global scale, we will just take it in. Don't forget, for example, us, even in Japan, the collaboration we have with Teijin is for all 3 products. The same thing in China and other places. So when we make this agreement, we're not making a single product, single country. We make it as basic as a pipeline product. And this is why we don't need to go out and make new agreements or anything. It's just going -- done extremely fast from that perspective.

And our next question comes from the line Leland Gershell from Oppenheimer.

I want to ask, as we look at the EUR 5 billion number you've put out there for product sales by 2030. I know you're not giving specific product guidance here. But if you could share with us sort of how you think about the relative contributions of your presumably 3 products by that point in time in terms of how they'll weigh into that total sum. Obviously, you've got much more expansion opportunity in hypoparathyroid. You've got TransCon CNP potentially launching soon and SKYTROFA perhaps getting additional indications in combination. So I would love to just hear maybe just philosophically how your outlook adds up with those 3 parts?

Yes. That is an element where we always in our forecasting are operating under different assumption where we're basically building up model for each single country and then we accumulate that on a global setup. And we first -- basically are taking the '26, we're taking the '27, '28 and '29. And then what we're doing, you always will go in and look on the risk balance, where do we have potential -- extra upside that we can explore? What are we going to do with this -- on it. But I think what makes Ascendis unique today is that we are not a single product in a single region. We will have 3 approved products in perhaps 20 different indications in about 30, 40 countries. Meaning is that what we really want to do, we will not be dependent on one single product in one single region. This is how we build up a sustainable company that basically have a continued stable revenue flow for multiple years. And don't forget these product opportunities we have, when I look on the pipeline for each of them, I definitely not have sleepless night, I can guarantee that. There is no doubt that when I see the profile, and how we design it to be best-in-class, we also see that realizing. And from that perspective, it's a combination product with lifespan of IP extremely long. This is where you have the durability of it. And this is why we take the value perspective of a single product opportunity in just fast revenue. This is not how we operate. We go for value and because the element of that is this is the product really deserve this treatment, because we're really providing not only a unique benefit for the patient, but also for the society and everyone.

And our next question comes from the line of Paul Choi from Goldman Sachs.

I think your Phase II reACHin study is scheduled to reach primary completion next month. And so will you be in a position to file an sNDA for the newborn incident population this year? And in terms of the newborn incident population, in your discussions with the FDA and EMA for your Phase III combination study, does your study design allow for those newborn patients to be included in the study population? Or will that require a separate study?

I think when you discussed a label discussion that typically is difference between -- now I just take the 2 main regulatory areas because we can also take Japan into it. But if you take, for example, the U.S., it's much harder some way to be coming to a situation where they will accept a label expansion to the infant without having the data at hand. Where in Europe, it's much more flexible because you have a discussion with them and you can have basically what I call partly rolling addition of data that is being generated to our trial. So there will be likely a difference between the 3 geographic region now simplified. Japan is mostly perhaps the easiest way to get it down to infant immediately. But -- what we are doing now is to ensure we generate the right data, and we're doing that in a trial. It's a placebo-controlled trial. And what we see, it's everything what we hope for. It's living up to our expectations. Why I can say that because in the enrollment, we have 6 patients on what I call feasible treatment on it. You take them in and there is no randomization, and we can follow them. And Aimee can tell a few words about the benefit we really have seen from that perspective.

So Jan is talking about the [ sentinel ] kids who are not part of the randomized piece of the instant study, and they are doing well, tolerating the medicine as well as we would expect, growing and starting to see early signals of other benefits as well, particularly radiology.

Yes. So we really are -- so pleased with the progress we're doing in helping patients with achondroplasia, not only on linear growth, but also benefit beyond linear growth.

And our next question comes from the line of Yun Zhong from Wedbush.

My question is on the weekly TransCon PTH. Is it reasonable to expect that the program could potentially enter the clinic in 2026? Or do you think that there is no such need to rush? And also, you mentioned matching PK to the daily product. So with data from YORVIPATH available, what do you see as the most efficient clinical pathway to maybe take the weekly PTH to approval?

I think what you're addressing is 2 things that is interconnected because if you, for example, can show the PK profile and it can even be healthy volunteers or patients with hypopara that over the entire week of treatment, you basically are bioequivalent to YORVIPATH. And that is the aspiration how we designed it that we basically will always be in an equivalent PTH level compared to YORVIPATH's daily dose for the entire week. Then we know you basically will get the expected safety, the expected tolerability from that perspective. And this will make a much, much more simplified easy way to conduct the clinical trial. And that was why we designed it exactly in this manner.

And our next question comes from the line of Luca Issi from RBC.

Congrats on the progress. Maybe, Jan, kind of big picture, I think one of your goals for 2030, as you articulated at JPMorgan is to remain an independent and profitable biotech company, and we obviously have seen many successful examples of that in our industry recently. However, how are you thinking about maybe continuing that same vision under the broader umbrella of a larger pharmaceutical company? I guess the question is how are you thinking about strategic Path A versus strategic Path B at this point? So any color there, much appreciated. And then maybe, Jay, quickly, I think BioMarin has announced that they will file VOXZOGO for full approval versus, I believe you will initially get approved on an accelerated approval basis for TransCon CNP. How should we think about that difference? Will that have implications for formulary access and reimbursement? Or you don't view that difference as material for adoption given you obviously have a less frequent dosing versus...

I think I will liberate Jay for answering the last question. I think when I look on this discussion on accelerated approval that BioMarin are filing for that has no impact on our regulatory [ pathway ] and approval and other things like that. Totally independent. It's not any way how you can build up any barrier or anyway in this way. The second thing, yes, in our vision, that is independent. And I believe that is a great word because we want to be independent like a teenager growing up. And one of the things you -- at least I have 4 children, I'm teaching them. When they're going to be aging, you need to be financially independent as the first element in their life. And I think that is a great thing to see Ascendis Pharma now moving away from being a teenager, but basically can go up to a more adult life because we have shown now we are complete independent on basically asking investors and others for any kind of revenue. And I think this is how we see independency.

[Operator Instructions] Our next question comes from the line of Maxwell Skor from Morgan Stanley.

Great. My question was asked, but I'll just take a shot at this. Could you give any color on the once-monthly TransCon semaglutide program? Any gating factors when we should expect an update? Any additional color would be helpful.

Yes. Let me go back to all the element and all the IP we have done files and data and everything like that before we went into this extremely productive collaboration with our neighbor in Copenhagen, Novo Nordisk. What was really the idea behind once-monthly semaglutide? And the idea was to be sure that you can get fast weight loss at the same time, have high level of tolerability. And so just think about -- I can define it, you have a naked GPL-1 molecule that basically when you give it in a weekly or potentially want to use a weekly product in a once monthly, you need to add up much, much more compound to compensate for the half-life to have [ at last ]. But doing that, you add a high max dose. And because it's naked, you will have very short Tmax, meaning that you will have a steep curve from the lowest level just before you start to give a dose up to the maximum concentration. That is basically what often get the tolerability issue where you get the element that basically limit people to stay on treatment and what you can achieve. So this is what I call the naked product. This is like Metsera and everything. It's a naked profile. What we're doing now is defining and what we call packed in semaglutide. So even if you give it high dose, you liberate it slowly, slowly, slowly. So you're getting a very long Tmax. By doing that, you basically have a slope that is not as steep at all that you see with a naked molecule. Then you can see you still have a big AUC, because you basically provide some compound, give it over the entire month. And then at the same time, you don't have this steepness in the slope and by that, you don't have that. So it was designed to have maximal weight loss as fast as possible with the best tolerability profile. And that was how we designed it at that time.

And our next question comes from the line of Alex Thompson from Stifel.

I guess maybe for Scott, could you talk a little bit about OpEx trajectory in 2026 in the context of the CNP launch and then sort of the SKYTROFA label expansion, both with mono and the combo pivotal studies?

Yes, no problem. I think that -- so we talked a little bit about this. We talked about -- a little bit about this at the JPMorgan conference event. But I think using Q4 OpEx as a run rate for the full year is not a bad way to think about it. And if things change, we come in and update you. And I think overall, everything related to CNP, as we said before, we'll come out and discuss more following approval.

Yes. But that's mainly related to the revenue because what we have now, we have a really mature company. It's not like we take something in, in a pipeline. We're actually taking product out of the pipeline all the time. So R&D are basically constant for the last 3 or 4 years. Sure, our global commercialization specifically the direct market that we have built up already now, adding a few more people there, not major impact on anything like that. This is the benefit of a pipeline in the same therapeutic area and scale that we have now.

And our next question comes from the line of Kalpit Patel from Wolfe Research.

I had one on the competitive landscape. Wondering how you're thinking about this internally as other agents like encaleret are looking to expand into the chronic hypoparathyroidism landscape? And then does your longer-term outlook for YORVIPATH include that potential impact from such emerging agents?

So I could be polite or I can be a straight shooter. I have seen a lot of idiotic ideas. This one is really one of the most idiotic ideas I heard about. You have a patient that is missing a hormone, PTH and giving encaleret is not increasing and providing any hormone to this. We're talking about a hormone replacement therapy where you're helping multiple organs. The brain, so you have better cognitive effects. The bone need to have the right metabolic system. The kidney needs to have the right phosphate elimination. You need to have the right calcium absorption. And I can continue one organ after the other organ. And then you believe you can take a compound encaleret, that basically are a calcium synthesizing compound, take it into a person that don't have the hormone and then you think you have a treatment. It's really one of the most scientific, I will say, ideas where I cannot see any kind of meaningful effect that it will help the patient. You can increase basically the element of one single thing, absorption of calcium, but that is not in any way coming in as a hormone replacement therapy. So no, we have not calculated that. There has an idea in ADH1 patients, which have a mutation in the calcium synthesizer one, it makes sense for this small amount of patients, it makes sense, but not for a person that miss PTH.

And our next question comes from the line of Faisal Khurshid from Jefferies.

I just wanted to ask, Jan, maybe because you're giving some open thoughts on competitive landscape. Can you discuss your latest thoughts on the CNP competitive landscape, including upcoming FGFR data from BridgeBio and also the earlier-stage long-acting CNP from BioMarin?

Yes. I think that is an interesting aspect because -- we have seen the benefit of CNP therapy for multiple years now. We are seeing it in a large patient population. And one of the things, I 100% aligned with BioMarin on is that the CNP therapy has shown to be extremely safe and well tolerated, except that you have elements like if you take too high concentration, you can get hypotension, you can get injection site [ right ] if you're not really encapsulated. And so when I see the CNP therapy, I understand why BioMarin are trying to copy us and trying to develop a product that basically are providing a sustained liberation of CNP over 1 week, because they have seen out from our data how we are highly differentiated compared to vosoritide. So that is a complete different case about do they really have a once-weekly product or not. You cannot judge that out from AUC. You need to see the profile over 1 week and other things like that. So as I've not seen this data on anything on the long-acting product for BioMarin, I do not know if anyone can judge that it is a viable product opportunity in any way, then we need to see the PK profile, get the half-life and all the different things, then we can take a judgment about it. The element of tyrosine kinase, a complete different element for me, because that is an element of using a nonspecific action of a compound that basically are addressing the tyrosine kinase. And if you go to the BridgeBio, it's a nonspecific tyrosine kinase that both inhibit the 3 different compounds, FGFR1, FGFR2 and FGFR2. This is why it's called nonspecific. And what I'm not worried about, I'm not a worried that you will see any treatment effect because when you address the tyrosine kinase, you basically will see an improvement in linear growth because you basically are in a position that you are inhibit the super active pathway. Will they see the same kind of benefit that we see beyond linear growth? That is up to them to show, can we see an improvement in muscle strength? Can we see an improvement in basic leg bowing? Can we see all the element of improved quality of life with that. But what worry me is the nonspecific thing. And I really don't care about phosphate. People say, Jan, are you worried about that they have elevated phosphate? First of all, elevated phosphate, you cannot go in and grade it 1, 2 or 3, 4. You need to see on the patient what is the phosphate level before treatment and after treatment. Because then you see do the treatment on each single subject have an impact on the phosphate level. If it has impact on the phosphate level, we know it's a nonspecific inhibition of FGFR1. And when you have a nonspecific inhibition of FGFR1, you also have nonspecific inhibition of FGFR2. And when you know that FGFR2 is one of the key receptor that is part of really the CNS development of the brain, I'm extremely worried because it's not something you really see easily in a preclinical model. You don't see it anyway in short-term clinical trials. You see it after 3 past 4, 5 years of treatment. You know that worried me up from our patient focus. How can you really accept that any patient should take this risk without being extremely well informed about it.

Thank you. This does conclude the question-and-answer session as well as today's program. Thank you, ladies and gentlemen, for your participation. You may now disconnect. Good day.