Ascendis Pharma A/S Sponsored ADR Stock

Hello, everyone. I'm Max Skor, biotech analyst with Morgan Stanley. Welcome. And just to start off, for important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. And with that, I'd like to welcome Jan Mikkelsen, CEO; Scott Smith, CFO; Jay Wu, Head of U.S. Market. Thank you very much for joining us today, team.

And thanks a lot for inviting us.

Really appreciate it. So I think in regards to the Ascendis story, let's start with last night's announcement. You've recaptured full rights to the metabolic and cardiovascular franchise. How are you thinking about what comes next for Ascendis?

That is an open question where I can come with a lot of answers because a lot of things is happening at Ascendis. First of all, we also had a press release yesterday related to buying back shares for $400 million. And I think that is part of our integrated strategy that we lay out in our Vision 2030, how to be a leading biopharma. And before I start, I think Scott would like to say a few words related to our financial positioning, how we are generating a profitable company and how we will progress in the next years.

Thanks so much, Jan. As Jan mentioned, we announced a $400 million share repurchase agreement, and that's really on the back of the strength of the financial transformation that happened with Ascendis this year in 2026, going from historically R&D to having approval and launch of 3 highly differentiated products with YORVIPATH achieving blockbuster status this year.

As you know, we've guided to over EUR 500 million of operating cash flow. And with the strength of the launch as well as the new launch of YUVIWEL, we expect that, that could potentially double next year or even more. So it's a great time for Ascendis to buy back shares. And we still retain all the capital we need to continue to advance R&D. And in particular, I think with the other announcement we made, it gives us a lot of opportunity to basically ensure the growth of Ascendis beyond 2030 into the 2040s.

So when I see Ascendis, and it laid out really well in our Vision 2030 because I really like this framework where we go out and lay a 5-year plan and how we follow on and how we execute it. So there's 2 cornerstones in our 2030 plan. One is to hit EUR 5 billion in product revenue. That is EUR 5 billion coming from our 3 approved products SKYTROFA, YORVIPATH and YUVIWEL. That is the cornerstone in our revenue generation. And it's coming from U.S. and also coming from our key effort.

We have to be independent on the U.S. revenue, but building up a sustainable part of our revenue flow from the ex-U.S. I think we are one of the few biotech that really have this effort going on, where we're building up a global organization. We recognize revenue more than for 40 countries now. And it takes longer time in the ex-U.S. segment.

So when we come to '27, '28, we will see about 10 to 20 countries every year being full commercial with our product. Jay will say a few words about U.S. because U.S. is still a cornerstone in our revenue generation and also explain a little bit about the effort we're doing really so we can grow the revenue every year.

Sure. Thanks, Jan. As Jan mentioned, from a U.S. standpoint, we now have 3 approved products in the U.S. We're feeling encouraging about all 3 of them, right? So YORVIPATH, I know we spent a lot of time talking about, given from a pure scale standpoint, it represents tremendous opportunity as you think about not only what it's generating in the near term, but also the longer-term potential of the hypoparathyroidism space overall. Within that, we've been investing quite heavily in a few areas.

So one, we've talked a lot about prescriber education as being a key area. We launched during the time we're following that par. This is a differentiated product, and we're reshaping people's expectations for what patients that have hypoparathyroidism need and what the condition actually entails. I think the second area where we've been investing quite heavily in is patient activation. If you think about 70,000 to 90,000 patients in the U.S. having hypoparathyroidism, this is a space where many of those patients aren't actively either seeking care, have established care with their specialists and/or are searching for something more above and beyond the conventional therapy that they're on.

And that takes time, but we're seeing some really encouraging signs of some of those behaviors and beliefs changing. And then lastly, with the ever-evolving access landscape, patient experience, we know that this condition, in particular, these patients go through things like brain fog, they might go through fatigue and making sure that they have the requisite level of patient support both during their journey to get a prescription as well as post prescription is another area that we've been ensuring that we're supporting from a seamless experience standpoint.

YUVIWEL, we just recently launched this year. You've seen some of the numbers that we've shared previously, incredibly encouraged by what we're seeing with that new product launch to date. And again, really speaking to the fact that this is a clinically differentiated profile, we believe is best-in-class. And from a standpoint of offering something unique to this community, we're seeing really positive sentiment across providers, patients, patient advocacy groups and conversations with payers have all been going very well.

And then, of course, we mentioned the cornerstone of SKYTROFA. We're still seeing continued growth in that segment, tracking with what we see in prescriptions. And then because SKYTROFA is continually being developed in other areas as well, we do see SKYTROFA as a foundation to start with a very bright future ahead.

So what Jay has talked about how he implement an excellent center of commercialization in the U.S., we're doing the same ex-U.S., building up a global organization where we want to reach basically more than the 400,000 to 500,000 patients, for example, with hypopara. That is sitting ex-U.S., huge amount of patients. And this is one of the effort we will continue to doing. So when we talk about revenue in 2030, the EUR 5 billion, we have a strong fundament to achieve that just with our 3 current products. This is the fundament to hit the EUR 5 billion.

This is not peak sales of this portfolio. The peak sales comes years after that. We continue label expansion -- we have 5 to 10 trials ongoing now. Many of them are late stage, both in label expansion, combination therapy, really to build on further how to really reach the best kind of treatment to all the different patients. At the same time, and this is coming to the second part is in our Vision 2030, how to be sustainable with a continued new flow of new chemical entity like one like SKYTROFA, like one like YORVIPATH, like one like YUVIWEL.

And we have now a strategic strategy to take at least 1 new NCE in clinical development besides all the label expansion we continue to do with our current portfolio of products. And it's coming both in rare disease endocrine -- it will come in other indication outside. And part of our strategic post for 2030 is that we have built a new fundament for a new therapeutic areas beside our rare disease endocrine. And we are not limit ourselves to rare diseases more. We have the capacity as a company. We have the infrastructure to move outside rare diseases.

And when we see how we build up our rare disease endocrine, it was built on a product at least 3, where we add 1 product more after the time, really have the economy of scale and synergies, both in commercial organization, in manufacturing, regulatory expertise really to do it. And we will do the same thing in the new therapeutic area. We are not dependent on in-licensing. We are a company built on an R&D development on our strong technology platform with TransCon technology, which have given us 3 out of 3.

Scott is still calculating what is the chance to start with 3 preclinical and get 3 products approved. He still believes it's very, very, very low. And think about all 3 of them are highly differentiated. All 3 of them really showing best-in-class compared to anyone. All of them are extremely doable. They have IP up to the end of the '30s in the '40s. They are combination products. We don't have a patent cliff like a small tablet. They're just falling down the cliff 1 year after it basically are in a position where IP disappear.

We own the products. So we're not ending in like other company that the royalty suddenly disappeared the day after the IP disappeared, but the products stand for 10 years more. We will own the product because we do own commercialization. So when you look on the future of Ascendis Pharma, we're just in the beginning of the beginning. We're not even in the end of the beginning because the first therapeutic area, we're first starting to mature, first starting to grow.

So this is why I really believe when you ask me this question, this is a long answer because we have so many possibilities. We're doing so many things. But I'm so happy to the states we are coming. We are independent in the way that we wrote in our Vision 2030. And independent meant that we are developing everything in our -- from the TransCon technology and be financially independent, and we can give EUR 1 billion back potential every year to the shareholder if we want to do that.

Okay. Maybe if I can ask on the cardiometabolic effort or what it looks like going forward, capital expenditure. Does the base business fund the expansion? Should we think about any sort of equity raise? Trying to think about it through the lens of the share buyback also. I think...

Are there bankers in the meeting?

I think the bankers are a little bit disappointed. First of all, Scott is never getting right out to [ dinner ] here from bankers now because somewhere all of them have given up that we're going to raise capital. So we're not really interesting more. We say [indiscernible] still being invited here. We are not going to raise capital, I can guarantee. And when you see our company, how we are as a company, most people expand R&D expenses because they don't take product out. Hey, we take one product out all the time. And when it's out, they're not sitting in the pipeline more, we take new one.

So when I see the expenses on our basic research and development, we are pretty stable. We will have a growth every year will be dependent on inflation. It will be tended on a few other elements per we expanding a little bit more and other things like that, but it's not making a material difference. Scott gave me a simple algorithmic. If we grow revenue 100% year-by-year, and we only grow expenses by 10% to 15%, will that give a lot of profit? And Scott convinced me about that. And this is basically the story we are implementing for the time being. Should we not raising capital?

Should we -- next year...

I'm very happy you guys are here. In regards to the cardiometabolic opportunity, though, should we think about it as potential upside to the Vision 2030?

This is a major upside because I want to be independent. I have -- we have multiple collaborations. All of them have actually failed. But we've been extremely successful as a company. I don't think anyone should be dependent on a big pharma. That is really a big mistake. The first major collaboration we had with Sanofi, we made the first triple agonist once weekly, but then they got a new CEO and he didn't like metabolic diseases. If they had continued on that, they likely have been larger than Lilly today.

Then we basically made ophthalmology with Roche-Genentech and that went into a CMC problem, which we solved afterwards. But now we have Eyconis. Mark is sitting there with the CEO of Eyconis. Our major spin-off, extremely successful. So the product are still fantastic. And then we have now a collaboration with Novo Nordisk. And in every contract, there is a way how to live together, how to work together. And if one is not fast enough, the one likely have a chance to go out of it.

And I think we will get it back, which give us a lot of opportunities, not only to have the best-in-class once-monthly semaglutide, but also have the possibility to access rare diseases in obesity and other metabolic diseases, which we couldn't do before to the same degree. So it opened up an extremely positive for us to really expand our opportunities in this way.

I know it's early, but can you just talk about time lines and capital allocation towards this cardiometabolic effort?

The capital application, it's basically are going to be in a combined Phase I, Phase II trial, which we will give you time lines on when we come to the beginning of next year. And it's not changing any way material our expenses in any way. So it's not going to be a driver of a new raising capital because that is definitely not needed from our side.

Okay. Maybe pivoting a bit, let's talk about YORVIPATH, which really anchors your Vision 2030. What are you doing to continue the momentum, potentially accelerate growth? What should we expect over the next 6 to 12 months?

Jay, can take you us.

Sure. When you think about YORVIPATH, transformational change from where you are requires something beyond just prescriber education, classic reach frequency, et cetera, right? Because 70,000, 90,000 patients with the number that you're treating, you actually need to get patients to raise their hand and come out of the woodwork. So a lot of our investments and commercial focus has been around that piece specifically. So I'll give you a few examples.

We've been looking at direct-to-consumer education. You've probably seen some of that depending on the demographic and the shows that you watch or streaming online or however. But we are starting to see some preliminary positive signs from some of those investments that we've made from a digital standpoint. We've invested heavily in patient-facing roles. So we now have an entire infrastructure of roles that we call patient access liaisons.

They coordinate with patients directly. They support them in all aspects, whether it's field reimbursement, clinical education and essentially supporting them through their journey, both in terms of wanting information about the therapy, accessing therapy as well as supporting them once they're on therapy. And then lastly, when you're starting to think about digital infrastructure for more commercial stage organizations, how do you have channels increasingly embedded within one another, right?

So from diagnosis to field personnel to nonpersonnel digital channels, how do you have them all work together in a way where you're offering people a seamless experience so that they get the information they need at the right time and in the right way. So those are 3 examples for which we have been actively investing in activating patients more broadly. And again, we're seeing some encouraging signs, and it's really an investment in not just today, but in the future as well.

From the ex-U.S., on the top level is to make more and more countries fully commercial. Today, we have about 7, 8 countries ex-U.S. that is fully commercial. Next year, we will add between 10 to 15, '27, and we will do that again in '28. So the overall perspective, besides each country have their own, you can say, execution or commercial operational execution is on a high level to get as money as possible country full commercial where we still keep the value of our product because we believe the value we're providing with, for example, YORVIPATH providing creation not only for the patient, but also for the society. And this is why we not compromise really the value, what it really cost to basically implement such a treatment in each country.

Should we expect the investment in the YORVIPATH launch to increase over time? How does that look?

I think we've full-blown where we can basically be in this way, being in countries, we have a mixed model in ex-U.S. in countries, we are direct. We basically have built up all the legal entities that affiliate the basic people on ground in the countries where we have distribution agreement, we are basically not responsible for any further expenses in this. So out from that, you can say it's a mixed model where we basically have built up the infrastructure supporting a global launch in all the countries that is needed.

Great. And I know we've talked about the benefits of once daily being able to titrate with YORVIPATH. But can you give us any developmental time lines for the once-weekly TransCon PTH candidate?

First of all, the once-weekly product is not an LCM activity. It's providing a choice to patient that is stable on YORVIPATH. Meaning is that when you think about a patient journey, you come with a diagnosis of chronic hypopara. You are on conventional therapy, which consists of 2 compounds or 2 treatment active vitamin D and a lot of calcium supplement. When you come out from conventional therapy over to YORVIPATH, you actually go through a titration where you move first the active vitamin D and then you remove the calcium supplement and then you step up the YORVIPATH dose.

And when you are stable on that, you basically can be in a position that you have a lifestyle where you're not changing your activity level a lot, you basically have some of the same dietary components and other things like that. Compared to diabetes 1, if you -- everyone was somewhere had the same amount of carbohydrate every day exercise in the same amount, then you will be really well on a stable insulin level. But if you change your activity level, get an infection or a disease, change your dietary component, you need to be sure you can titrate up and down.

And there was a why -- I got asked once, you make SKYTROFA once weekly. You made TransCon CNP more than weekly. Why did you not make PTH once weekly from the beginning? Because we know the complication in the titration phase. And there is not an antagonist to high level of PTH. It's not like insulin where you can take glucagon. You don't do that. There's only one thing to go to emergency room. So from that perspective, if we know they're getting hypocalcemic, they just stop treatment in 1 or 2 days and then they're down slowly, slowly again.

And that is why we never wanted to start with a once-weekly product. But if a patient have a more stable lifestyle, on over a period, have a stable dose and they want to go over on a once-weekly product, we will develop a one weekly product, which we're doing now that basically will give them the same properties that you get with YORVIPATH. And endogenous replacement therapy because the other once weekly is not an endogenous replacement therapy, only have half of the effect that you get with normal PTH.

So it's not really a substitute for YORVIPATH. So forget that. So from that perspective, we want to have a once-weekly product building up exactly the same active mode of action that you have in YORVIPATH with basically the same level of PTH 24 hours, 7 days a week. So it basically is bioequivalent with a daily YORVIPATH treatment.

Great. Now let's pivot over to YUVIWEL. How is the launch going? What can we expect in regards to patient adds through year-end?

But see, Jay, he looks such a happy person and extremely pleased. I was -- she was always -- he's always negative, but when he saw all the numbers, he even -- Jay needed to be positive.

Yes.

Now you need to be positive.

Yes, we're very encouraged by what we're seeing. I think what we last showed, again, we last reported 220 enrollments, over 100 prescribers. If you even take that comparing it to previous analogs, that's quite outpacing, I think, what we've seen in the past as it relates to incumbent or older therapy. So that's corroborated by not just -- again, I said before, qualitatively beyond just what we're seeing in the numbers is there's just a high level of enthusiasm, right? A lot of patients that are on it. This is an ultra-rare community.

There's word of mouth. And I think you can measure a lot of leading indicators through being present, whether it's conversations with advocacy groups at congresses. And I think as you continue to see patients see their specialists throughout the year, knowing that this is an area where it's not like they just go in the next day, we do anticipate that we will see continued growth in an encouraging way from what we've seen to date. I also -- when you look at the space in achondroplasia specifically, it is very center of excellence based in terms of where the patient concentration is, which is very different when you look at it relative to like a hypopara where it's much more diffuse across a right tail of accounts.

So for achondroplasia, specifically, we've also been investing quite heavily in going on an account-by-account basis and understanding like what is the unique needs of each local regional account, which is a very different type of approach for an ultra-rare category versus something that you might see in PTH. So again, all these things, qualitatively, leading indicators, we're feeling really good about where we are and where we'll continue to be.

Any comment on the mix of patients? Is this -- I know we talk about it on the earnings calls, et cetera, but new starts, switches, patients who potentially discontinued VOXZOGO and testing? Any comments around that?

Yes. I mean I think what we've shared before, just to reiterate, we see patients anecdotally coming across 3 segments. We have patients coming across patients that are currently on vosoritide that have switched over. There's a second category of patients that were previously on vosoritide, but have since discontinued maybe because they weren't seeing the efficacy that they wanted, maybe that from an injection site reaction, they didn't feel it was tolerable and they decided to discontinue vosoritide, but then wanted to start YUVIWEL.

And then the third one, which is patients that have been holding out because they weren't convinced by the older therapy on market. Now that there's a new option, they're like raising their hands like, now, I'm willing to try and want to try. I think with any type of second product coming in, you naturally should expect that probably there's a greater number of patients that have been on existing therapy that are hand-raising to move over. So while we don't necessarily track that with specificity, I do anticipate that earlier on, we're going to get more of the patients that are previously on therapy. But anecdotally, we see it across all 3 segments.

Any comment on gross-to-net over time? How should we think about that for YUVIWEL?

Yes, I would say we don't usually disclose gross-to-net over time is probably the best way to think about it.

Clear answer.

And maybe if we could just touch on the recent agreement you signed with BioMarin. If you'd like to lay out any comments on that, I have a few follow-up questions, but we can go from there.

The content of the agreement is that we will pay royalties in a limited number of countries until May 2030. And it give us a global freedom for all IPs from BioMarin related to specific patents. And from my perspective is that we won the case in Europe. For me, it's not really what is right, what is wrong. I'm a pragmatic person there. Out of 2 things, I actually prefer to pay to BioMarin instead of paying to the lawyers. At least I feel a little bit better with that.

So from that perspective, it's a total win for both companies in the way that BioMarin get compensation for the loss of revenue that we get in specific countries. And we have a freedom really to go out and really come out to as many as possible patients immediately and be in a position that we're really building up the franchise to what we believe best-in-class opportunity. This is the only product YUVIWEL that has shown really benefit beyond linear growth in a placebo-controlled manner.

And also when we look on how we develop this franchise further on with the combination therapy where we combine it with SKYTROFA, we basically will provide a treatment option to this patient group, first achondroplasia, where we basically can avoid basic all elements of surgeries, everything from spinal stenosis to arm lengthening, leg lengthening, leg bowing, really key element that really have a major impact in a negative manner on this patient's life.

So out from that perspective, we feel that we're making a complete new standard on treatment, not only with YUVIWEL, but also what that really being created as a possibility treatment option with the combination therapy. We now have 18 months data in the combination therapy, never seen results like that. You basically generate 3 to 4 years treatment in 1 year, plus additional things that we don't see the same effect as with monotherapy like arm lengthening and other things like that.

We're coming out now with the newborn data, children -- down to newborn. And we have the first data cut with -- for the first 7 patients that came in. And it looked exactly as we had hoped for. But the key element is safety. Never forget that. And I think when we look on the safety perspective of the CNP-based therapy, it's really providing no safety signals. One of the safest treatment I ever have seen would give an obvious choice for the parents and the patients.

Great. The royalty agreement runs through 2030, as you said. How should we think about margins beyond that?

I mean, at least from my side, you'll see there will be some impact in the next quarterly report, and you won't even know where it is. It will be immaterial.

But also think the royalties you're talking about is not a weighted basis over the global situation. This is the countries where we pay royalties, there will be a lot of revenue generating outside. So if you really will try to calculate an effective royalty rate until May 2030, it will be likely down in the single-digit numbers and not impact us in any way.

Okay. And then over the next 6 to 12 months, what can we expect from Ascendis in regards to clinical readouts, clinical updates and just the story overall?

I think it's pretty well laid out what we expect -- I think from -- when I talk with investors, there's a lot of focus. Can we really build up the EUR 5 billion up to in 2030? And I think a lot of feedback I get how will be the next quarters. We came out with the perspective that we will have more than 1,000 patients every quarter going forward. And you will see that reflected in the revenue numbers. And I believe you will continue to see the launch. You will see YUVIWEL still continue to grow dramatically in this way.

And what you see, we will see the expansion in our label expansion that will come results that will come 2 years data from our combination trial end of the year. There will be other elements coming out from our portfolio. Next year, we will have 2 or 3 Phase III readout. And then you will see the new product opportunity coming in with the new chemical entities. So I think we are building up 2 things: continue the revenue generation at the same time, building on the sustainability on building new chemical entities that really providing the next level of support to our sustainable revenue generation for the next 20 years.

Great. So we have 2 minutes left. Anything you'd like to leave investors with after the updates from last night and the discussion today. I think that speaks volumes. I think we're good. Ascendis team, thank you very much for joining us today. Really appreciate it.

Thanks so much.

Ladies and gentlemen, thank you for standing by. Welcome to the Second Quarter 2026 Ascendis Pharma Earnings Conference Call. [Operator Instructions] 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 believe 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 continue 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 combination products, SKYTROFA, YORVIPATH and YUVIWEL. We believe these products will be the key driver 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 enable us to fulfill our plans to file at least 1 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 hypopara and growth disorder.

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 hypopara that addressed 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 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 standing standard of care in postsurgical and all subset of hypopara, including ultra-rare genetic causes like DiGeorge, ADS-1 and ADS-2. Results showed sustained response rate of 82% to 86% for the multicomponent endpoint with clinical benefit across multiple organ systems, CNS, kidney, small intestine and bone, plus meaningful improvement in quality of life.

Patient retention as high as 95% after 5 years of treatment, pretty unique. In parallel, we are working to further advance our leadership in hypopara with additional clinical trials that include expanding the label to include the age from 12 to 18 years and in the U.S., higher doses for patients and developing a once-weekly product for the patient that is on stable doses of YORVIPATH.

Turning now to YUVIWEL. We believe YUVIWEL is positioned to become the market leader 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 enrollment 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 background, those switches 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 will love to see when a highly differentiated product is introduced into an area where there still exists a high unmet medical need. Long-term data for the now completed pivotal ApproaCH trial showed durable and consistent improvement in growth like leg bowing, body proportionality along with a general 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 program using the U.S. FDA approval. Longer term, we are pursuing expansion opportunities for TransCon CNP to ongoing and planned trials. These include ongoing activities such as infants, 0 to less than 2 years of age, and we recently announced completion of this target enrollment faster than expected. Adults with achondroplasia, children with hypochondroplasia and still continue geographic expansions.

Turning now to combination therapy with TransCon CNP and TransCon Growth Hormone. The biological rationale for this combination treatment is clear and extremely well founded on science. TransCon CNP is removing the limitation caused by overactive FGFR3 pathway. So TransCon Growth Hormone can 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 have a negative IGF-1 SDS value as shown of the demographic in both our Phase II and Phase III trial.

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 this result, 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 #1 long-acting growth hormone by brand value in the U.S. We are extremely proud that SKYTROFA recently achieved more than 20,000 unique enrollment. This illustrates the strength of our capabilities from supply chain, commercial infrastructure and market support to benefit such a large number of patients -- rare disease patients. And 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 partnership. In metabolic disorders and obesity, our once-monthly TransCon semaglutide program with Novo Nordisk continue 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 patient first, Ascendis has delivered 3 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 '26, 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.

[Operator Instructions] 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. And I was just wondering if you're able to kind of update your cash flow expectations for the year. I know it's sort of like a greater than is unbounded. But curious, if 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 besides 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 -- I heard you say EUR 100 million, so greater than EUR 500 million. And at this time, we don't want to bound the upper side because we're initial into the launch of YUVIWEL. And that's Europe, by the way, EUR 500 million, 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 that we don't have really the insight in exactly the distribution of where the patients are coming from. And our general feeling and how we see it is that with such a strong demand, we have a really strong belief that it is not only coming from switches, it must also coming from either patients that have stopped therapy or new patients that basically are coming to a situation because of the highly differentiated nature of YUVIWEL that they want to start therapy. And I think this is where we have this strong belief that we see an expansion of the market.

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 just maybe walk us through what the potential outcomes are? This is for a patent that expires, obviously, in 2030. And so between now and then, can you just 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. And it's basically a question that is addressing the ongoing legal I would call it, battle between Ascendis and BioMarin. And let me just come back to some facts. The fact is that this patent that is in discussion got completely invalid in Europe. So we never really come to a discussion if we were infringing and anything like that. So when we see the situation outside U.S., we got the patent invalid immediately to the patent system in Europe.

In the U.S., we never managed to come into the patent system because BioMarin selected to go to the ITC case, which are a system which we can easily say traditional never have really dealt with a lot of cases that dealing with branded pharmaceutical. In the ITC case, there will be a first opinion from a single judge, and he will come with opinion here in August. And then there will be a -- next time will be in December, there will be an opinion from the ITC.

And then later on, there will be a potential confirmation of the ITC decision 2 to 3 months after to a presidential order. So you can see we are not guiding any clarification in August in one way or the other way, even if it's positive for one company and negative for the other one, it's not really any kind of decision where it's going to be ending.

And after the first initial opinion from a single judge because the ITC case will be taken to a decision for -- I cannot remember how many judges that will be part of that decision. There is a huge opportunity to provide what we call interest for this product. And when we see the public interest, meaning the element of how these product opportunities are really being serving an unmet medical need in the U.S. market with this rapid uptake of patients is really, really clear that is a huge public interest to keep that. And just recall, I cannot remember one single case in the U.S. where a branded product that provides a benefit to U.S. patients had been denied.

But you can see me just in a case where it's only -- it's a U.S., it has been cleared ex U.S. And so whatever has happened, it will not have any material impact on Ascendis pathway. I can guarantee that. It's some kind of -- people take it up as a life and death for Ascendis. This is a total not taken into the perspective what it means for Ascendis. And out from that, I see it's not really is a material element for our destiny to be a leading biopharma and hit the 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. So you noted in your prepared remarks that 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?

It was because I somewhat felt that the 2 product opportunities that we have developed through our partnership built on the TransCon technology will still consider as an NCE, the one that's now in clinic with Eyconis and the other one we expect to go into the clinic now with Novo Nordisk is still somewhere being developed to the TransCon technology funnel.

And again, perhaps I shouldn't have done that, but I still believe I feel some kind of a little bit of ownership on these 2 product opportunities. At least we have major upside in both of them. So from that perspective, I still consider the potential that have this year 2 new chemical entities being entered into clinical trials. And I think Kennett and his team and anyone else, they are working very hard on that there will be at least one of these new chemical entities coming into every year now.

And I'm really proud about that. But it's also addressing the sustainability of Ascendis independent of going out and buying something no one else want to have. And I think this is where we really feel extremely pleasant by the situation by being a fundamental company that's building on a strong, strong technology platform that provide both sustainability for ourselves, but also a continued flow of potential partner licensing.

And the next question will come from Yaron Werber with TD Cowen.

Great. A question on YUVI. Do you expect that there is some seasonality in terms of new patient starts in the summer as kind of kids are going on vacation. We're getting a lot of questions on sort of the 60 patient start forms kind of in April and now you're sort of at 220. It sounds like there's like 50 per month now. Is that sort of sustainable from now on?

And then it sounds like you're planning -- you think you could be the #1 brand by the end of the year. BioMarin, we think, has about 750 patients on drug you think in the U.S. Are you kind of referring to getting to a higher number than that by, let's say, late February?

Thanks for the question. I actually don't think Ascendis have really made some clear forward-looking statement related to how we see YUVIWEL being accelerating and expanding the market in a quantitative manner. I don't think we have come with any kind of indication related to that.

I have no doubt it will do it, but it's not the same thing that we're going to quantify it currently. I think after basic only 4 months in the market, I feel really not prepared to come with clear guidance to it before we have more quarters really into our, you can say, analytical system where we basically can look on trends and other things like that. But one person that really can give you a good feedback, now we talk about the U.S. market is Jay, and he's extremely enthusiastic about what he's seeing, and you can give the latest way what you see how the market will develop.

Thanks, Jan. As Jan mentioned before, 4 months in, we're not prepared to give longer-term guidance, but what we can say is we're incredibly encouraged by what we're seeing today. When you look at some of the fundamentals behind the YUVIWEL uptake, whether it's prescriber reach, we talk a lot a bit before around this space, there's quite a few centers of excellence. We're seeing 80% of them, nearly 80% already in a short 4-month period already prescribed YUVIWEL to their patients. So even in early days, we're seeing a lot of enthusiasm from providers around the clinical profile of this product.

I think even more importantly, when you look at the patient enthusiasm, I think you can see in early days we're seeing a very positive trajectory. While we don't explicitly collect information on what therapy or non-therapy, a patient is coming from. And again, that's driven largely by the fact that we have a broad label. So we don't need that information in order to ensure that this patient can get on therapy. This is rare disease.

So qualitatively, we have heard confirmed anecdotes across all 3 categories for which our patients are coming from. And those 3 categories, again, are: one, patients that are switching from current therapy; two, patients that have previously discontinued pharmacological therapy and has now wanted to return pharmacological treatment. And then third, a group of patients that historically have set out and have said based on the clinical profile of YUVIWEL, they now want to try a therapeutic option for the first time.

So all that, again, to underscore there is existing unmet need here. And because of our profile, we're definitely seeing that patients are coming out of the woodwork from growing the market standpoint and we're just getting started.

Just to summary to add on to Jay's excellent comments. Ultimately, we have no doubt we will be #1 in the achondroplasia space. Ultimately, we will expand the market because of the unmet medical need. And that is just with the monotherapy. And when you look at how commitment we are after this era, where we now are making a complete new standard with the [indiscernible] treatment.

I believe we have dedicated to be not #1 in the first year, but continue to build for the next 5 to 10 years with monotherapy combination integrated treatment regimes. And I believe with our once-weekly TransCon product built on growth hormone and CNP we are extremely, extremely well positioned really 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 just wanted you 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. I guess which quarters are you referring? Because I think the quarter-over-quarter growth in 1Q was negatively impacted, saw some catch-up here in the second quarter. So maybe you could just clarify which quarters you are referring to?

Yes, Derek, thanks for the question. I think that 2 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 would be -- and you could refer to our prior quarters and maybe Chad can point to prior comments.

But I think that now that we've seen the full year, you know the various trends that will come into play related to Q3 and Q4 and then Q1 next year. So we think actually folks did a pretty good job modeling out Q2. And now you have all the information you need to model the rest of the year going forward until we update basically the KPIs.

Just to give you some kind of what is our value in this year. The value for us, we want to give you -- we want to give you not so you basic getting a lower number, so we look like heroes. We want to give you the number so you are right nearly every time. And I think this is the way we try to come up with our different mathematic algorithm, how we see it and give you all the information for you really to be right in this manner.

And I think this is a way we like to be extremely transparent with everything what we perform. So we're quite sure that you basically can go out and really somewhere feeling always comfort with the guidance we give you.

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, I wanted to ask how you're defining the enrolled population? And how do you -- how large do you see the diagnosed treatable pool of hypochondroplasia patients who are not already being treated in some cases, if they're at the more severe end versus achondroplasia?

Yes. This is from -- this is a very interesting question because it's actually some way going into the situation on how we basic are to genetic testing, taking a big patient group that was in old days, what called ISS idiopathic, meaning we have no clue what is the underlying disease is. And then you go out and do more and more and more genetic testing. And then when you find a mutation in the FGFR3 receptor and you find it in the right regions, and then you suddenly are not an ISS patient, but then you find hypochondroplasia patient, even if you don't have, you can say, the phenotype of looking like an achondroplasia patient or a hypochondroplasia patient that we saw for 10 years ago.

So therefore, you can see the ISS population is some way getting smaller and smaller because of the genetic testing is basically going out and giving them an underlying reason why you [indiscernible] will have a short status without potential have the other element that you see for the phenotype of that.

So this is where you can then -- when you go into ISS, are you defined it from a genetic perspective or you define it for a phenotype or anything like that. And we are in a situation where when you see the clinical trial, how we're doing it, you will basically see that it's one of the pathway we have selected.

And our next question will come from Daniel Bronder with Cantor.

Congrats on the quarter. On for Li Watsek. We were just wondering if you could give us a little more color on the quality of life metrics in the COACH trial. You already alluded to the body segment ratios, but how should we think about benefit on arm span and other metrics?

Just to recall, the COACH trial is the combination trial where we're combining the 2 TransCon based product, our TransCon Growth Hormone and TransCon CNP. And I have to say, when I look on elements like arm span, it's actually -- we already reported some of the data. We have reported the 52-week data. And if you cannot find that deck, I can send it to you or Scott can send it or Chad can send it or I don't know we have so many IR people I don't know all names now. So from that perspective, it is already came out.

And I have to say there was one of the -- I will say, extremely positive surprises I saw because when we look on monotherapy, but either a CNP-based one or a growth hormone based one, we did not see the expected hopeful development that we can hope for. But we definitely saw it when we look under combination therapy. And then you can ask me what is the scientific reason why you see it much more influenced benefit by the combination therapy. And I have to say, I don't know.

But what we saw was an arm span that was really -- give us this hope with the combination therapy, you basically will be in a position that you basically could avoid all kind of limb elongation surgeries in achondroplasia, both related to both legs and arms by that. And it's this Slide #5, as I remember it. And what we see, Scott, read up.

The unprecedented improvements in the arm span with combination were plus 9.4 centimeters with TransCon CNP naive cohort 7.9 centimeters with the TransCon CNP-treated cohort.

So it was really and...

Compared to limb lengthening surgery, 8 centimeter.

Exactly. Exactly. I have to say it was one of the days where I felt it was worth to go to a job and really can see the benefit 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 number for YORVIPATH in case I missed anything. And so I know that you said the patient demand remained robust in the quarter. So I wonder if there is any additional quantitative information that you can provide.

And going forward, are you going to provide that number in the coming quarters? And I think you had this question before at the beginning of the launch and when do you expect that you will feel comfortable providing a guidance in terms of the sales range on actual revenue?

You are right. And I think it's starting to be a little bit positive every quarter come out and saying that we have about more than 1,000 patients being unique enrolled per quarter. We have continued that measure that we see steady state, steady state and steady state. And we said in last year that we will stop coming with this because it was too repetitive. And then because people doubted for Q1. Then we also come up with the Q1, and it was the same number again.

And what we're writing is that we see a robust steady-state in enrollment of unique new patients. And here, we are referring to the U.S. with about 1,000 new patients every quarter, and we don't believe really. Now we went over to YUVIWEL. So now we're starting to give you a unique prescription enrollment of YUVIWEL instead. So we always -- we have one product opportunity where you will have something to play with numbers and everything like that.

Scott, do you have some comments to the last one?

Yes. I think our comments were directed to assume the metrics that we've given YUVIWEL are consistent because Jan wants to make our script shorter. So we're not -- don't want to repeat them more. And you should just assume that until we change it.

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. I guess as we think about potential scenarios here and again, acknowledging sort of this idea around the public interest of the product and unmet need. Do you see a settlement as a reasonable scenario to think about? Or is that really not something that you think is reasonable?

Alex, I think I'm a very flexible person. And one of the things I really want to do, I will always do 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 just wondering if dropouts are still mostly during the titration phase. And if you can comment at all on how reauthorizations are trending?

I think you're 100% correct. And when we see a patient being successful coming into a treatment with YORVIPATH coming over titration part on it and be into the treatment after that, we see extremely, extremely low dropout. And I think that illustrates one thing, the patient satisfaction with this treatment because now often being asked, what can we do more for these patients in the therapeutic treatment on it. And want to see the satisfaction that it is in this way, then I think that there is an extremely good precision, retention and everything would really show that.

We still develop once weekly for patients on stable doses. Just to give patients the choice if they want to do it in this way. We will look at other ways to improve their life, like, for example, at home, calcium monitoring and anything like that, we can help the patient like it's happening in type 1 diabetes and other things like that.

So now you're addressing the element where we're saying is we developed this year with a once-weekly profile, even if we could make it -- sorry, once daily because we wanted to do the titration most easily because it's really complex to take patient off of conventional therapy.

At the same time, you increase the PTH in replacement therapy. And this is why we made it as a once daily this really to facilitate the best possible titration but still, we know it can be problematic for some patients. And Jay can try to explain what we're now doing to basic and hold the patient in this period. So we also can make that extremely successful. So when you get a prescription, we know everything will be much more successful for the patient not just after they are really being stable in the titration.

So Jay, will you explain of the effort you're building in to really to get that to be as soft and as possible?

Absolutely. I can chat a little bit more about certainly, the investments that we're making and also to answer your questions around drop-off and re-auths. Yes, as we've shared before, the majority of the drop-off is during that titration period in terms of when patients experience the most amount of change and where additional education and a higher touch support model makes sense. .

And then for re-auth, that's actually pretty routine for us. So there really isn't much there in terms of it being a measurable effects on any kind of ongoing patient support, we have patients re-authing throughout the year, and it's just part of our day-to-day operations.

From an investment standpoint, we've invested heavily in patient-facing roles for which we've deemed our patient access liaisons, they support patients both pre prescription as well as through the prescription process and post. So essentially, we've seen a lot of success in early days with this field team being able to engage with this patient community. They have appreciated this high level of support and we, of course, support them throughout the journey to ensure that we're optimizing for patient experience.

One thing that's imminent. Now we focus more on U.S., but there is still a world outside U.S. Outside the U.S., we have not seen the same level of drop out in this phase. It looked like the interaction is pretty well established between the physician and the patients and support system, we need to see it without this kind of drop out. So it basically is a U.S. issue. And so therefore, we know we can get it to function. We just need to ensure that the support system also in U.S. is strong enough to be sure that it's not a problem.

And our next question will come from Eric Joseph with Citi.

As far as your named access named patient programs or your early access programs, can you elaborate a little bit on which markets you're active in whether eligibility might be determined by treatment status of a patient? And just generally, how we should think about whether name patient programs could be meaningful contributors to patient volumes this year for YUVIWEL in particular.

Okay. I just wanted to ask what product you were referring to.

YUVIWEL.

Yes. I can guarantee that as we basic in our prepared remarks, tried to put emphasis on. We have a global infrastructure in commercialization and patient support, product supply and everything like that. Just the number of SKYTROFA rare disease patients we have taken over to the system, more than 20,000 patients. We are having the system functional more than in 35 different countries. So we're not a company that just need to get started. We already have established all this infrastructure.

And what we're doing is that we are utilizing this established infrastructure basically that got established because of YORVIPATH because this is what we did with YORVIPATH. We're using exactly the same infrastructure also for YORVIPATH. So we will be where patient is, and we'll be quite sure we will also serve the patient outside U.S. and potentially the market is much larger outside U.S.

And I think we hope we also will see a large penetration in the U.S. where another short-acting product really failed to do it. And we believe because of the highly differentiated nature of YUVIWEL, we will see a complete different pickup in the U.S., but it's definitely -- we have a strong, strong, strong focus on the ex U.S. And we will give you some guidance when we come later in the year, so you can give also building up a model for the ex U.S.

And the next question will come from Luca Issi with RBC CM.

[indiscernible] for Luca. Circling back to YUVIWEL, and Jay the 3 categories that you very nicely touched on for the naive switch and discontinued patients that are not on script. BioMarin mentioned on their second quarter call that less than 100 patients have switched off of VOXZOGO. So the simple math that we're trying to do here is that it leaves you with about 70 patients in the second quarter who are naive or return to treatment.

So that's taken off the switch patients. But does that align with the numbers or impression that you have? And how does the dynamic look like between the truly naive patients and the patients who were once on VOXZOGO stopped treatment and are now returning to treatment but to YUVIWEL? And separately, very quickly, if you've commented or not on the ex U.S. strategy for YUVIWEL, given the decision is pending and the [indiscernible] coming very soon this year.

I like your way of doing all the calculation, anything like that. I cannot support it or I cannot deny it because I don't have the factual insight to some way to confirm anything of the numbers. I also saw the numbers that came out, but I cannot really support it because I don't have the insight from our own numbers to really come out and come with any statement that indicate if I'm aligned or not aligned with. Related to the ex U.S. for me to understand your question, was this reflecting what is the limitation in the ex U.S.? Or what was the question?

Thanks for asking to clarify it. More about are you committed to running the show by ourselves or you're considering partnering given that 70% of the VOXZOGO sales is historically coming from ex U.S. can be a quite heavy lifting?

Yes. But -- so basic in the ex U.S., we have our direct markets, which are, I think, 60, 70, 80 where we have our own commercial infrastructure, anything like that is pretty, pretty clear what we're doing there. Then we have our sales and distribution agreement. And this is, I think, it's 70 countries or something like it. Well, Scott it's...

80

80 countries that is covering this sales and distribution agreement. And the vast majority of all of them are all 3 products. So basic is already established infrastructure for the distribution. And then we have the 2 other. The third model where we have our partnerships, one in Japan, one in China, and they also have all the 3 products. So we don't need to go out and make any new agreements for anything -- everything is established. Everything is running on full speed. And we -- for some of the EU direct market, we're just waiting for our expected approval here in Q4 this year.

And our last question is going to come from Faisal Khurshid with Jefferies.

Just wanted to ask a little bit on the YORVIPATH life cycle strategy. Can you give us an update on the latest on getting the higher dose into the label for FDA? And then also any update on weekly YORVIPATH?

Yes. What we see today is that we are enrolling the trial in the U.S. where we're evaluating the 30 to 60 dose ranges in 2 different means that has been aligned with the FDA in their design, what they wanted to see. And we see that enrollment going extremely fast. So we expect very, very, very fast. And you can say, label expansion in the place where we don't have up to the 60. So we see that basic -- just on execution. And your second question was related to?

On weekly YORVIPATH, any update there?

Yes. I think there's no news in this way that we're just executing and getting it into the market as fast as possible from the expectation that we see that not as any kind of LCM activity, but more a patient support for patients that really are in the stable dosing which are not a lot after they have been in a situation where there have been stabilized with our daily treatment.

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.

Good day, and thank you for standing by. Welcome to the First Quarter Ascendis Pharma Earnings Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to hand the conference over to your first speaker today, Chad Fugure, Vice President of Investor Relations. Please go ahead.

Thank you, operator, and thank you, everyone, for joining our first 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, EVP and President, U.S. Market.

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 YORVIPATH, YUVIWEL and SKYTROFA, 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 planned regulatory filings and our expectations regarding 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. 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 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 for the treatment of hypochondroplasia in children aged 2 years and older. Continued approval for this indication, which is based on an improvement in annualized growth velocity may be contingent upon verification and description of clinical benefit and confirmatory trials. TransCon hGH is 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.

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 agency. 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 first quarter 2026 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 it over to Jan.

Thanks [indiscernible] Good day, everyone, here from Copenhagen. The first quarter of 2026 was [indiscernible] inflection point for Ascendis, with the FDA approval of our third [indiscernible] product, YUVIWEL. Our revenues are growing rapidly. We are profitable. We have a pipeline of high-value product opportunities to support long-term growth.

Three elements are cementing our position as a leading global biopharma company. First, our diversified product portfolio in one single therapeutic area. Following FDA approval of YUVIWEL, we have now achieved approval of 3 products in a row across 4 rare endocrine indications. Second, our rapid revenue growth from our existing endocrine rare disease portfolio, [indiscernible], YUVIWEL and SKYTROFA, each highly differentiated with long durability, we expect sustained revenue growth for many years to come.

Third, expanding our pipeline. We have proven our ability to create transformative medicines, addressing unmet medical needs using our TransCon technology platform. To date, we have more than 20 ongoing or planned clinical trials, aiming at label and market expansion, including 4 new clinical entities in preclinical development.

Turning now to YORVIPATH. Global YORVIPATH revenue in the first quarter reached EUR 197 million. YORVIPATH revenue for the first quarter was impacted by 2 onetime items. A temporary increase of U.S. patients supported by free drug caused by reimbursement disruption and onetime impact of Europe Direct related to expanded market. Scott will explain the financial impact of these two events in his remarks.

In the U.S., new patient enrollment in Q1 remained in line with the strong uptake we have seen in Q4 2025, with more than 1,000 new patients prescribed YORVIPATH during the quarter. Through the end of March 2026, more than 6,300 patients have been prescribed YORVIPATH by more than 2,700 unique health care providers. March was our last revenue month ever for YORVIPATH, supported by an increased number of new patients, as well as patients returning to reimbursement from free drug.

Importantly, the enrollment trend we saw in Q1 have continued through April, consistent with our guidance. Insurance approval rates and medium time to approval continue to improve. This strong support a strong foundation for revenue growth in 2026 and many years to come. Outside the U.S., YORVIPATH is available commercially or to [indiscernible] patient programs in 35 countries, including full commercial reimbursement in 6 of our Europe Direct markets, with additional launches expected through '26.

Looking [ forward ] ahead, we continue to pursue multiple expansion opportunities for YORVIPATH in new markets and indications. This includes doses up to 60 micrograms in the U.S., global expansion to patients 8, 12 to 18 and continued development of once-weekly TransCon PTH for patients on stable YORVIPATH [ process ]. With 70,000 to 90,000 patients living with chronic hypopara in the U.S., and 5 to 10x that number outside the U.S., we remain highly confident in YORVIPATH's long-term global potential.

I will now turn to our growth disorder [indiscernible]. With week our once-weekly growth hormone, SKYTROFA, we believe Ascendis is uniquely positioned to strengthen its leadership in those disorders. Our U.S. commercial infrastructure built and refined since SKYTROFA launched in 2021 has enabled a focused and high-impact launch for YUVIWEL, which became commercially available in early April. Since then, YUVIWEL has already been prescribed for more than 60 children by more than 35 unique health care providers.

With children approved for reimbursement as fast as a few days, YUVIWEL has shown compelling results compared to placebo across multiple clinical trials in addition to linear growth outcomes. These results include improvements in final [indiscernible] dimensions, body operationality, physical function and health-related quality of life compared to placebo, without compromising safety or tolerability. We believe this outcome reflects YUVIWEL's unique ability to provide continuous systemic [ CMP ] exposure throughout the body over the weekly dosing interval. Looking ahead, we plan to make YUVIWEL available in selected international markets through early access programs using the U.S. FDA approval. As a reminder, our global infrastructure covers over 70 countries and has already generated product revenue for us in more than 35 countries.

In EU, a regulatory decision on our marketing authorization application for YUVIWEL is expected in the fourth quarter of '26. We are also pursuing label expansion for YUVIWEL to ongoing trials. These include infants on the 2 years of age with hypochondroplasia and [ 7 with ] hypochondroplasia as well as geographic label expansion in clinical trials.

Turning now to SKYTROFA. In the U.S., SKYTROFA maintained consistent performance as a premium product with [ 7% ] share of the overall growth hormone market, reflecting steady demand across pediatric and adult patients as the only once-weekly product delivering on [indiscernible]. With the expected label expansion that could double the addressable patient population in the U.S. and geographic expansion outside the U.S., we believe SKYTROFA will remain a cornerstone product in our growth disorder portfolio.

Turning to our pipeline. This includes combination therapy with once-weekly TransCon CNP and TransCon Growth Hormone for children with hypochondroplasia. In our Phase II COACH trial, we have reported unprecedented results that exceeds the already compelling foundation established by YUVIWEL monotherapy. Week 52 data from COACH presented in January showed improvement in hypochondroplasia specific height score that indicates a triple of efficacy compared to TransCon CNP monotherapy, along with improvement in body proportionality.

More recently, we shared additional week 52 data that showed improvement in lower limb alignment, as well as an [indiscernible] improvement in spinal can dimensions and an improvement in arm strength, not previously demonstrated with pharmacotherapy within a single treatment. Based on this finding, we believe our unique combination therapy of TransCon CNP and TransCon Growth Hormone could potentially eliminate the need for highly invasive procedure such as [indiscernible] and leg straightening surgeries. We believe that this combination therapy could become the preferred treatment option for hypochondroplasia.

I will now briefly turn to oncology. In our Phase I/II [indiscernible] trial, we have elevated TransCon IL-2 beta gamma in combination with [indiscernible] in patients with late-stage [ platinum-resistant ] ovarian cancer or PRC. Median OS improved up to 10 months from 6 to 7 months from historical [indiscernible] with a general well-tolerated safety profile, validated the science on TransCon IL-2 [indiscernible]. As further internal oncology development does not align with our strategic focus, we have decided to discontinue internal development of TransCon IL-2 beta [ gamma ] in oncology and will explore other ways to maximize the value of these assets.

Turning now to our partnership. Our once-monthly TransCon semaglutide with Novo Nordisk continue to advance towards the clinic and [indiscernible] TransCon anti-VEGF also remain on track to enter the clinic this year. These programs further highlight the broader potential of our TransCon technology platform to address product opportunities in larger indications.

In closing, in the first quarter of 2023, we made significant progress across our business and our ability to make a meaningful difference for patients. We have 3 FDA-approved TransCon products across 4 indications, growing revenues, improving cash generation and a pipeline that supports long-term growth.

I will now turn the call over to Scott to review our financial results.

Thanks a lot, Jan, and good afternoon, everyone. I will touch on some key points surrounding our first quarter financial results, which reinforce our confidence for growing operating profit and cash flow into the future. For further details, please refer to our Form 6-K filed today.

YORVIPATH global revenue was EUR 197 million in Q1. The first quarter was characterized by steady global uptake and normal seasonality as well as 2 onetime items. Patients temporarily transitioned to free drug in the quarter in the U.S. and a onetime impact in Europe direct related to expanded market access. The combined impact of these 2 items was approximately EUR 15 million.

SKYTROFA contributed EUR 44 million in Q1. On a sequential basis, performance reflected consistent underlying demand with the expected drawdown in channel inventory built in Q4. Including EUR 6 million in collaboration revenue, total Q1 2026 revenue amounted to EUR 247 million.

Continuing to expenses. R&D expenses in Q1 were EUR 59 million, down from EUR 78 million in Q4 '25. R&D in Q1 was favorably impacted by a write-up of YUVIWEL inventory consisting of EUR 11 million due to U.S. FDA approval and lower clinical activity across the portfolio. SG&A expenses rose to EUR 145 million in Q1 2026, compared to EUR 136 million in Q4 2025, reflecting continued impact of global commercial expansion.

Total operating expenses for Q1 2026 were EUR 204 million and operating profit was EUR 25 million, reflecting a 10% operating margin. Non-IFRS operating profit was EUR 55 million and non-IFRS operating margin was 22%. As revenue scales, we expect meaningful improvement in our operating margin, which will be visible over the course of 2026 and beyond. Net finance expense for Q1 2026 was EUR 63 million, primarily driven by noncash items, including remeasurement loss of financial liabilities of EUR 34 million. Net cash financial expense for Q1 '26 was about EUR 1 million.

Net profit for Q1 2026 was EUR 629 million, which included recognition of a EUR 679 million deferred tax asset in the P&L. Refer to our 6-K for more detail. Non-IFRS net profit was EUR 18 million, or EUR 0.27 per share. We ended Q1 2026 with EUR 573 million in cash and cash equivalents, which includes the impact of EUR 60 million in Q1 from our previously announced share repurchase program and net settlement of certain RSUs.

In April, we successfully completed our transition to a direct listing of our ordinary shares on NASDAQ. We believe this will broaden access to global investment in the company, which has the potential to further enhance institutional ownership and trading liquidity for Ascendis shares. In May, we completed the full redemption of all of our outstanding convertible senior notes. Finally, today, we announced that we entered into an agreement to sell our PRV for USD 187.5 million in cash. The PRV was awarded by the U.S. FDA upon approval of YUVIWEL in February.

Turning to our commercial outlook. For YORVIPATH, we expect continued steady underlying increase in patients on therapy and the reversal of onetime factors seen in Q1 to drive strong growth sequentially in Q2. For SKYTROFA, we expect stable revenue throughout the year following a similar seasonal pattern to 2025. Regarding YUVIWEL, as Jan indicated earlier, we are encouraged by the early demand trends and look forward to sharing more with you on our Q2 call.

With that, operator, we are now ready to take questions.

[Operator Instructions] And our first question comes from the line of Jessica Fye of JPMorgan.

I was wondering if you could help us estimate what U.S. YORVIPATH sales were in the quarter. I think in the past, you had run through an algorithm to consider, but I know the press release noted some onetime impact to Europe Direct as well. So just trying to get a better sense of the U.S. versus ex U.S. split this time around.

I think that Scott will give you just a little bit more background on the financial element, specific onetime in Europe Direct. And it's actually happening when we sometime and specific for one single country because we had an early access program that was running for nearly 15 months, 16 months. And it gave us a onetime event where we needed to write down for this single case. It's not something that really happening in other countries, but it was a single country event, which basically impacted our YUVIWEL, you can say, Q1 results.

But Scott, you can give you a little bit more flavor on the financial numbers.

Yes. And just for modeling purposes, it's probably a little bit more of an impact. But I would say the best way to think about it is take the algorithm that we laid out where you add 4 to 5 a quarter. And for Q1, basically that addition was just shifted into Q2. And then from there, the algorithm continues.

But I think just one of the key element I will take into regard is basically the underlying patient demand. Because I think the key element is really that we continue the same successful, you can say, rollout of the launch, both in U.S. where we now -- as we have provided you the number of indicated new patients on treatment with YORVIPATH. And as we have given in our previous guidance, we're still 100% correct in that, where we really see the same stability. We see the same flow coming in. And Jay can comment about how he's already starting to improve both the time to reimbursement and the numbers.

I do not, Jay, will you comment about your effort in really improving what you call the reimbursement situation for the U.S.

Sure. When you think about our reimbursement, we're seeing improved metrics across the board. So first and foremost, we've talked a little bit about our upstream coverage now expanding to about 80% of patient lives, which we're feeling really good about given the time on market. And I think, again, a testament to the compelling clinical value proposition that we have.

We're also seeing continued rapidity as it relates to patients being approved for reimbursement upon entering the funnel. So again, over half approved within 8 weeks of enrollment. And we are seeing continued progress against patients moving through the funnel whether it's upstream as the enrollments are coming in, but also supporting patients as they're entering into the funnel.

Our next question comes from the line of Tazeen Ahmed of Bank of America.

Mine will also be on YORVI, and maybe this is for Jay. Can you talk about the reauthorization rates that you're seeing now that patients are starting to annualize at this time of year? Any things to point out about things that were maybe unexpected or taking a little bit longer?

And then can you talk about usage among physicians? So is there a way of providing a split between how much of use is coming from first-time physicians versus an increasing use among doctors who've tried your YORVIPATH before?

Okay. There was multiple questions. I hope you got everyone down. Will you start on some of them?

Sure. I think I heard a few questions. One, which maybe I'll start with towards the end, which is prescriber breadth and depth, I think, was the question.

We're seeing continued traction across both. So as Jan mentioned earlier in the script, we've had over 2,700 prescribers, which again is an addition of about 300-plus quarter-over-quarter, which we're feeling really good about. So that would answer your question around new prescribers.

And then within existing prescribers, we're also feeling really good because the average prescription per physician continues to increase as well. In fact, over -- about 10%-ish of prescribers have now over 5 enrollments for patients. Again, as you think about the provider landscape here, they all do have a different patient volume just given how diffuse the patient volume is. But generally speaking, we're seeing not only one additional prescriber sign on to YORVIPATH given the strong patient satisfaction scores that we're seeing. But then because of those positive patient experiences, we're also seeing providers expand their scope of who they deem to be eligible given that lab values alone are not the reason that patients should be treated.

Okay. And then reauthorization was the last one.

And reauthorization, yes, that was the first part of your question. We're not seeing any meaningful differences in terms of approval rates for re-auth versus necessarily a patient that's coming in at the top of the funnel. We typically, again, have shared that 4- to 8-week time frame. We've seen those numbers continue to increase in terms of speed, which I referenced earlier with the first analyst question, but we're not seeing any meaningful difference with the re-auth coming in versus a new patient coming in.

Generally, what you'll see is if it's a re-auth of an existing payer insurance where there hasn't been a change in insurance, you might see some faster time line there. But if it's a brand-new insurance, then you're obviously going to treat it as just a brand-new case, so to speak.

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

Great. Maybe a quick follow-up and then a question on YUVIWEL. A follow-up on YORVI. So of the [ $15 million ], should we roughly kind of split it like half in Europe and half in the U.S.? I don't know if you can give us any sort of view on that. And then for YUVIWEL, in the ITC case is progressing, the bridge document, the briefs are out kind of back and forth. And it looks like the court is kind of siding with both parties. What -- I know you've been importing drug in the meantime. Any view sort of on how much capacity you might be able to have in the system by the time a decision is rendered?

First of all, I believe when you see the uptick in the prescriptions of in the U.S. We have more than 60 children being prescribed YUVIWEL treatment in less than 4 or 5 weeks. I think it illustrates the unmet medical need that exists in the U.S. related to an improved treatment in hypochondroplasia. And I believe what we have seen of clinical data in our multiple trials with YUVIWEL just as a monotherapy is really describing the reason why we see this take up.

This is not just of having a once-weekly product. This is providing a tolerability profile and documentated effect on benefit beyond linear growth. And I think everyone is aligning with the unmet medical need, the public interest for this to have a product [indiscernible] in the market. We will continue to be in a position that we have such a strong belief that in this case here, too, like it was in Europe, we can prove that this IP case should never have existed and only is built on promises.

So [indiscernible] I'm confident YUVIWEL is here to stay, and it will always be a treatment option for patients with hypochondroplasia in the U.S. I hope that answers your question related to that part.

The other part, I think you are somewhere in the right estimate when you think about it.

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

This is [indiscernible] on for Gavin. We have 2 quick questions. Number one is for the Phase III [indiscernible] and growth hormone combo trial, can you share any update on the enrollment speed? And secondly, what are you seeing in your discontinuation rates over time?

So when we talk about -- as I understood your question right, it was related to the combination trial, the Phase II trial we call [indiscernible] trial. And we basically are now -- I do not know how many years we are into the trial now, but I think we are 2 years in 1.5 years now. And I think we see basically an extremely high element of retention in this trial.

To my knowledge, last time, it was 100%. And I think it's really been harder to get more than 100% in a clinical trial to my knowledge. And I think that's a very, very few trial where you have 100% retention after nearly 18 months. So from that perspective, I think it's really illustrating and addressing the satisfaction with the benefit you see in the treatment compared to the burden of treatment. And I think that is really the key element that we are always looking in the fundamentals. We want to see benefit for patients. This is why we're working, and we will continue to focus on that.

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

I guess on new patient adds you mentioned, steady growth. Is it reasonable for us to assume 1,000 is sort of the number that we should be looking at for the coming quarters? And will you be sharing new script number going forward?

That's a great question. Now some going back to the last time I said I will not come up with more prescription data for YORVIPATH because I believe that the revenue progression was so clear. And when I said that there was a big, big, what I call element of some interesting funds that pushed back and saying, I didn't want to come out with numbers because it must be really, really bad. And now we have illustrated for 1 quarter more that they are not bad. They are extremely good and exactly as predictable as we have said in this way.

And I expect a steady state enrollment in all the quarters because that is what we expect. We are only touching a small amount of this patient group. We have some more patient that is coming new patients every, every, every year. So I'm somewhat giving up to say that I will not come out 1 quarter more because last time, I said we will not come out with one quarter and then I got basic press because I didn't want to listen to that, that we didn't want to come up with a number because they are bad.

I don't hide anything. I always want to be transparent. And this is why I come out with a number, then you can see it. So I think we will continue to be so transparent on everything what we're doing. So you always have the best possible opportunity to see how well we are performing in our fundamentals.

Our next question comes from the line of Alex Thompson of Stifel.

This is Patrick on for Alex. Could you guys just talk about the potential impact of the YORVI 60 micrograms being on the label? And maybe what percentage of those 6,300 patients in the U.S. is dose caps at 30 with, maybe less than ideal supplementation levels?

This is a question which are very difficult for us to answer today because we see different kind of [ up titration ] in both different situation in clinical trials and also sideration in what I call more real world. We are following it a lot. We are now open for enrollment in our trial where we are having 2 arms in our evaluation of dose titration 30 up to 60. And we will enroll that in a decent speed.

We only do that in the U.S. because it's the only place where we restricted down to 30 and not have 60. And we believe that even if you are coming up to 30 micrograms, you still have a major benefit to be still on 30 microgram compared to many of the positive effect that YORVIPATH is still providing to it. So I think you can say, yes, there is someone that will benefit to go higher. But today, we're still providing the benefit to the patient that need to stop on 30 micrograms.

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

So some physicians we've spoken with have suggested that they might not want to put their office staff through the reimbursement challenges of switching their hypochondroplasia patients to a once-weekly injection only to then later switch them to a once-daily pill in the not-too-distant future.

Is this a dynamic that you guys are aware of? And what can Ascendis do to help support the hypochondroplasia patient, or physician community rather and encourage uptake? And then have any -- my second question is, have any physicians prescribed YUVIWEL in combination with SKYTROFA since YUVIWEL was approved?

Answering your first part of the question, I think the number speaks for itself. When you think about it, more than 10 prescriptions per week [indiscernible] rare disease product. I think they talk about the unmet need and the willingness for basic physician in connection with the parents, in connection with the child to basically to have the desire to take them on a treatment with YUVIWEL. I think it says everything with numbers. You can go out and ask one physician. You can go out and ask one parents. I look at numbers from a statistic. The numbers talks for itself.

Related to the last question, I cannot some way discuss an element we cannot promote. We cannot promote anyway [indiscernible] combination therapy. We have disclosed the benefit of the combination therapy. And that is up to the physicians if they really want to prescribe it or not prescribe it. And to my knowledge, and I can be pretty open about it, yes, it happens, and I understand why. This is the only way you basically can be in a position where you basically can avoid any kind of surgeries. Which I think is just a positive element for any child with hypochondroplasia to avoid the invasive surgeries. And I think this is the reason why the physician do it. And sure, we're looking forward to finalize the Phase III trial. We're looking forward to have it on label. So we really also can go and promote it.

Our next question comes from the line of Ellie Merle of Barclays.

This is Jasmine on for Ellie. Just kind of a follow-up to the last question. For YUVIWEL, can you say how many of those 60 enrollments were new starts versus switches? And more generally, do you think the initial population is going to see more new starts or switches? And what kind of patients do you think are the most likely to initially want to switch?

The insight you're asking for is the insight we will develop in the coming months and quarter. After 5 weeks to try to come with a general statement about what kind of patient, what kind of preference they have to go on to YUVIWEL treatment. I think it's too early for us to come with a conclusion but it is such a topic.

The only thing I can say, and Jay, you can add on, what we see is basically coming from everywhere. It's not just naive patients. It's not just [ switch ] patients. It's coming everywhere from where we expect it also to come from. And one of the things we have done at Ascendis that Jay has [indiscernible] impact on to help the physician, the patient is really to have a part that can go out and really help the physician, the patients everywhere to get through this journey to be sure they can come on the right treatment.

Jay, do you have anything to add?

Yes. I think you summed it up well. The only 2 additional things I would add is, one, to Jan's point, we're seeing across all segments. And we've discussed before the 3 areas or types of patients that we envision coming are. One, patients currently on VOXZOGO that are switching over. Two, patients that were previously on VOXZOGO but since discontinued and were on no therapy. And then three, a patient that perhaps had never made the decision to start therapy at all. And we are seeing anecdotally that it's coming across all 3 of those groups.

And I think really what that underscores is the continued and existing unmet need that exists in hypochondroplasia today even with the existing therapy on market, which I think emphasizes the value of having YUVIWEL on the market and the compelling value proposition that it offers patients.

I think the second area that Jan was talking about is our continued investment in just making sure that everything we're doing is hand in glove with patients, both as it relates to partnerships with the patient advocacy groups, but also as it relates to our scaling up of our patient access liaison team, which is our patient-facing field group that invest in the support and the journey as they go through the continuum of prescription to ultimately being on therapy.

Our next question comes from the line of Yun Zhong of Wedbush.

My question is on the monotherapy for hypochondroplasia. I remember that there have been some changes in terms of approach for that program, whether you're going to pursue that indication at all and whether it's going to be mono or combo or maybe just -- wanted to know the -- are you able to share any information regarding the thought process behind the decision if this is the final decision that you are going to just using monotherapy to target hypochondroplasia?

Yes. I think the strategy that we have applied to [ achondroplasia ] where we started with monotherapy and the addition to combination therapy. I think you will see that there will be alignment between the strategic approach that we have used in [ achondroplasia ], we will likely also use in hypochondroplasia. I can basically tell you that we're using the same principle between the 2 indications.

The 2 indication is very much aligned in the fundamentals of the disease. There's only, you can say, different mutation, different severity and other things like that. And we will implement the same thinking in treatment regime between these 2 indications.

Our next question comes from the line of Luca Issi, RBC Capital.

Maybe Jay or Scott, can you educate us on the mechanics of the free drug for YORVIPATH? Who are the patients that got the free drug? For how long do they stay on free drug? And are you expecting any patients still on free drug in Q2? Or is this just a kind of Q1 phenomenon? Any color there, much appreciated.

And super quickly, I think AstraZeneca has presented their Phase III data for [indiscernible] this week in the European Congress on Endocrinology. So wondering if you can comment on what are your expectations for that data?

Yes. I can start from the last question, and then I can move it up and then Jay can take over in the end.

The compound we are talking about in the end is the amyloid compound. And we have discussed that on many earnings calls, the lack of information that was related to data. Now that is disclosed some kind of information of the data package 1 year after finalization of the Phase III trial. And for me, and I think the key question, do this data package provide an approvability of any way of this compound? And to my best judgment, I hope this product never will be approved, and I don't see really as possibility that it should be and going to be approved.

So I think when we look on the competitive landscape for treatment in hypopara, I see YORVIPATH, our once-weekly approach to stable patient on YORVIPATH is really providing the fundamentals for a 20, 30 years treatment regime where I don't see anything that really can give up to the benefit we will see in the treatment with YORVIPATH or any other product that is currently in clinical development from that perspective.

Related to the first part of your question, you're right. We started to take already December a group of patients over to free drug because the essential part of YORVIPATH is that you cannot stop we first have started taking over to basically the element on what we call the conventional therapy. This basically is a disaster for the patient. So if there was a hiccup in the reimbursement that was a hiccup and it's something we have done corrective action to ensure that we can handle it much better next year. We were in a position that we took, and Scott explained the impact of that here in Q1, to take already from December until March and series of patients on free drug, and they are now coming back to be fully reimbursed.

And we are in a position that -- and the organization in the U.S. some way have built up network or other things that can help it that we're not ending in the same situation on time. Jay, have you any comments too?

Again, I think you summarized the need for bridge program well. I think just to clarify the earlier question, there is 2 types of [indiscernible] programs. We have bridge program, which again is pretty standard across the industry for those that have experienced a temporary insurance lapse. But we also just have our patient assistance program for patients that are underinsured or uninsured. So I think that's an important point to note because there will always be some patients that qualify for the patient assistance program. So we don't anticipate that, that will ever go away completely knowing that there will always be a certain level of patients that qualify for that.

Yes. I think that is a clarification. That's great from Jay, where we talk about this number of patients is only what we exceeded as success compared to the base level of patients. We always will help and provide free drug if there is an element of something where there is a disruption of the normal way to have drug.

It's a drug for the patients that we are -- always will take our patient focus first. And if there's a patient that gets disrupted, we will do everything to help this patient. And that includes also to take them for a period of free drugs until the disruption getting solved, and we will always be there for the patients.

Our next question comes from the line of Maxwell Skor of Morgan Stanley.

This is [indiscernible] on for Max. Given the relatively low treatment penetration in [indiscernible] in the U.S. to date, what proportion of patients typically initiate treatment at age 2 years or older?

I think some way to roll it a little bit back because you can ask the question why you have under treatment in the U.S? And I think actually this is the key question to find out how can we really help this patient better.

And I think -- and we believe that the undertreatment is basically the cause of lack of the right efficacy to show real benefit beyond linear growth. Many of these parents, children don't see linear growth as a key element. They really want us to address all the [ comorbidity ], specific if you can avoid surgeries, or changing the pain [indiscernible] with leg bone. You can avoid [indiscernible]. And I believe by having this focus on these elements and here, I talk about the older children. If you go to the younger newborn, yes, if we can avoid any kind of spinal stenosis by having early intervention from newborn, yes, there will be a major benefit for treatment in the state.

So I believe our product profile that we have generated [indiscernible] a product, clear benefit compared to placebo. It needs always to be placebo controlled because there is a development to. So you cannot say, we also improve a [indiscernible] child with actually have a big increase in arm length. So you always need to really show it compared to a placebo-controlled trial. It's the only way you can really just the benefit of the medical treatment in it.

So the question and the answer to you is I believe will be appealing product to the vast majority of parents, children in the U.S. also because they provide a way to address the comorbidities. So important one, everything that you basically will see benefit for not only quality of life that's associated with it, but also the element of physical strength.

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

Congrats on the good start with YUVIWEL. I was just wondering if you could clarify in terms of the 60 -- more than 60 prescriptions you've seen to date, whether it's more driven by treatment-naive patients or switches? Any quantification there would be great.

And I'm also curious in terms of your early starts or through the quarter, if you're seeing potential utilization in the below 2 years of age population, even though that's not officially on label yet.

Yes. We need to come with a meaningful answer. We need longer time because we only have been there for 4 or 5 weeks now. And we want to be sure that what we see in the initial part of the launch is also being representative of what we'll see in the later stage of launch. So Paul, we can discuss it, as Jay said, in a perfect manner. We see patients coming in for all 3 different groups, which was in a new group, patients that have discontinued [indiscernible] and patients that come directly on switching for [indiscernible].

So out from that, we see it coming in for all 3 different groups in the initial launch, we will expect to see perhaps one mix and when we come a little bit longer into the launch, we will potentially see a switch in the different 3 classes. And this is why really to make it meaningful, we need to wait longer time before we can give you something you can do the right modeling on. But when I look at this number we're coming up more than 10 patients per week, it's an orphan drug indication. I'm extremely proud that our product profile is getting so well recognized in the society in this way. Under 2, I cannot comment on that currently.

For the 70% cumulative U.S. insurance approval rate that you previously cited, can you give us any more color on what that cumulative rate looks like today? And then second, the EUR 500 million operating cash flow target that you laid out previously, are you reaffirming that guidance given the Q1 trends that you're seeing? And how should we think about the contribution of [indiscernible] to that target?

[indiscernible] one, we would like to come back in Q2 because we have a lot of positive data coming in now. We have the selling of our PMV and launch of YUVIWEL going much, much stronger than even myself hope. So apart from that, we will come with that claims guidance, but we will prefer to do it after our Q2 call, and we will give you what will be reflected on '26. Scott is saying yes to me. And Jay, you can give the [indiscernible] number, how it's improving the overall numbers.

Sure. So the overall cumulative approval rate since launch has continued to creep up as well. I think we're now closer to mid-70%, which again is incredibly high for any rare disease asset, much less one that has been on the market for the amount of time that we have. A lot of that is just a function of time given the favorable access policies that we have. So even some enrollments that might be many months old are coming through on appeal online, which would affect the cumulative approval rate over time. But given that it is a lagging indicator, it will take quite a bit of time for that metric to mature.

And our last question comes from the line of [ Cecilia Hernandez ] of [indiscernible].

This [indiscernible] is on for [indiscernible]. So given the revenue now from commercial products, the redemption of the convertible notes and the sales of the [ PRP ], can you tell us anything on your capital allocation strategy? What is the order of priority for you guys?

I think Scott you want really to answer the last question for today. So Scott get this opportunity now.

Thanks a lot, Jan. Of course, as you've seen with our R&D success, a key component for us is to invest in R&D and allocate capital there to continue to sustain not only into the 2030s, but the 40s and beyond with the continuous flow of new products.

I think Jan highlighted new NCEs in his prepared remarks, and you'll learn about more of those in the coming future. And of course, I think after we give an update after Q2, as Jan mentioned, to our outlook for the rest of the year, you may get more color at that point as well.

Thank you. That's all the time we have for questions. Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

Well, welcome, everybody, to the 46th Annual TD Cowen Healthcare Conference. I'm Yaron Werber from the biotech team, and it's a great pleasure to moderate the literally virtual fireside chat with Ascendis on the heels of the YUVIWEL approval. We moved the participation to virtual, and we appreciate that we're able to do that. So thanks so much for joining us. We really appreciate it, and congrats on the approval.

Thanks a lot for inviting me. We are sorry we're not in Boston. We would love to be, but we also felt we needed to be here.

So the conference call, I think, literally ended about 2 hours ago. The label looks very clean. As you guys showed the slide and the AEs are minimal. The nice feature of the drug is that it's weekly. It can actually be kept at room temperature for up to 6 months and then can actually be put back in the fridge. That's a slight differentiator also from VOXZOGO. The label is 2 years old. You'll show us the long-term extension later on. And I think you mentioned you're going to launch in early Q2, and you'll give pricing, it sounds like perhaps even next week.

So maybe the first question, you also mentioned about 100 providers treat about 55% of patients, right? And there's about 2,600 patients in the U.S., about 30% of them are currently on drug. So I guess the first question is, maybe what do you need to do to launch in Q2? And why can't you launch a little faster?

First of all, the launch segment is now most dependent on the information we got from FDA in the end where we basically get the final primary secondary packaging. We also get the element related to the inlet. So what we were waiting for to get this information. And what we then need to do is to finalize the printing of the primary secondary package and then get ready to the market.

So you can say there is no practical elements that basically are some way we need to do except that when we had the information back from FDA, we were in a position to get ready and roll it up. And this is why we say early next quarter, we basically will be ready to deliver. But the commercial effort can already start now.

And what we're doing here is that from SMEs perspective, one of the main reasons for us to focus on one single therapeutic area was that we couldn't be utilizing that for all our product opportunities. We have SKYTROFA, pediatric growth disorder. We have our [indiscernible] in rare disease, endocrine. And now we have YUVIWEL also in rare disease endocrine, pediatric.

So what we have developed is sales effort where we basically have a dedicated effort related to hypopara and then we have the other one which is the SKYTROFA and YUVIWEL. And think about we already have treated more than 10,000 patients just here in the U.S. with SKYTROFA. So we have a complete step-up, which we will utilize exactly to YUVIWEL too. So we're utilizing the same structure. We are utilizing sometimes the overlap between physician where some physicians will prescribe both SKYTROFA and also YUVIWEL. We have expanded it and ready to go to the market, and that is exactly what is happening over the time.

And so as you think about usage, do you have a sense what percentage of the market are not adequately served currently on VOXZOGO and would be eligible to switch? And do you think you're going to be -- it's going to be a wholesale switches? Is it going to be switches in a subsegment? How would that work?

So when we look -- and I think with the U.S. approval, we have 2 segments where we can launch the product. We can launch the product as a full commercial here in the U.S. At the same time, in the international market, we can be utilizing the U.S. approval to go out and use early access programs where we also can launch it. So this is the 2 segments we are initiating the launch after the U.S. approval. And then later in the year, we expect the European approval.

When we come to the U.S. and why I'm saying that because we believe each single country have their own story. And when we look on the U.S. to our best estimate, there is less than 1/3 of the patients that have achondroplasia in the U.S. that really are under treatment. So you can say that the majority of patients is not on treatment today. But where will the patient come from?

I believe they will come from both segments. There will be switch patients. And we were very pleased with clear indication how -- if they indicate how to switch? When you just stop with the daily therapy and then the day after, you just start on YUVIWEL, clear indication how to switch. So that is one segment. And when I believe I cannot find any good reason why not to switch. When I go to the new patient group that is not on treatment today, and I believe when you look at our publication where we really show benefit beyond growth, how they really can address things like going, get much better alignment of the legs, avoid potential 1 year's really hard life to an operation trying to do that because of pain and other complication.

I feel that there will be a large portion of this patient group that didn't go into any treatment because there was no really data where you have clear data, placebo-controlled data that indicate compared to a placebo group, there is clear benefit compared to be in treatment on really some important comorbidity beyond growth. Then you have added benefit like element, like muscle strength and other things like that, which also was clear statistic in this way. And this is why I believe that there will be patients coming on YUVIWEL treatment from both group. I see the benefit for both group to transfer over.

Okay. Maybe a quick -- also when we look at the 2 labels, VOXZOGO, as we all know, does have a tangible blood pressure risk, and it calls the need for hydration, prehydration, almost like 300 cc or so. In your label, there's also, I think, a caution about the potential for blood pressure changes. But I think it refers in the clinic -- in the safety section to a once-a-day CNP drug and it mentions the need for the patient to be hydrated, right? So there is no need for pre IV hydration. Can you discuss that? And why is that even mentioned? It sounds like it's obviously mentioned via class effect.

Yes. I think it comes into where there is a warning and precaution risk of the product. And then they are basically explaining the reason to take it up. And the reason why they have taken this because that clearly state transition decrease in blood pressure have been reported with a once daily CNP analog. They're not saying it has been observed with YUVIWEL, but it has been observed with a once-daily CNP analog. And this is exactly how the [indiscernible] as you 100% right indicated some kind of class warning about.

But I think the key element, don't forget why are there such a big difference between the once-daily product and YUVIWEL. YUVIWEL is built on the TransCon technology platform. And when we went into the design of this molecule, there was 2 things we clearly wanted to achieve with the TransCon technology. First, to have a sustained release over 1 week. You can see, yes, we get the benefit on the 1 weekly dosing profile, but we also avoid the high Cmax that provide the risk of hypertension. It was how it got designed.

So we were far, far away to have any kind of vasodilation effect on near the Cmax. The other thing we did with the TransCon technology was to build it into a [indiscernible]. So when you inject YUVIWEL, the active ingredients is basically inactivated in the [indiscernible] and first when it's in the blood compartment, it get released the active ingredients. This is why we have 4.4 injection site. Meaning is that you only see injection site every second year compared to the once daily that have major injection site [indiscernible]. And this is because it's not really [indiscernible] when you inject it the once daily because -- and therefore, you see the high effect of vasodilation. All that is science. So that was how we designed it.

What perhaps the more surprising was that we saw all the benefit on linear growth. That was added benefit, and this is why I'm so proud of this compound. We are so proud of the compound that we really can go out and address the comorbidity because when we talk with the patient organization, that is what we really want to see. We address the comorbidity. We accept linear growth is the desire for some parents but some children, but everyone to see a huge benefit to really address and solve comorbidities, and that is what we've done. And when we combined it with SKYTROFA, we saw an acceleration of this benefit.

Okay. Maybe a question next for me. And if anybody has questions in the audience, maybe raise your hand, and I can relay this way. On the price, so the price, it sounds like you'll announce it over the next 2 weeks or so. VOXZOGO's currently priced on a gross basis is at around $330 or so. I think on a net basis, it's around $240. In the past and even with YORVI and certainly SKYTROFA early on, you weren't really contracting. I think in this situation, would you contract with payers more because it is more of a competitive dynamic, and it sounds like you'll price it at a premium because it's a premium product. Is this something that we should expect as sort of a modest premium or a more tangible premium?

I think when you look on both SKYTROFA and YORVIPATH, yes, both of them has been priced on a best price on with a premium. And clearly, it's reflecting the superior benefit it's providing to the patient, to the society for everyone. And we believe that we split it in a way where everyone is winner, the patient, the society, reimbursement system and everything like that. And they always have been our. And when we see on YUVIWEL, I think, yes, we will realize on the benefit that we see with YUVIWEL compared to established treatment from that perspective.

When we look on the element on contracting, we are not really so much dependent on that because we have a great system not to live and [indiscernible] with medical exception. We did that with SKYTROFA in the beginning. We did that with our YORVIPATH and still doing that with YORVIPATH. And this is where we are, as a company, extremely well built, well acquired, have all the knowledge experience how really to be sure that the patient journey will be so optimal as possible for the patient when the prescription is written that they can go out and pick up the drug by the pharmacist. And that is exactly the same system we are using from both the SKYTROFA, more than 10,000 patients to this system and YORVIPATH [indiscernible].

I think in Q3, you said you'll have the data from the under 2-year olds, if I remember correctly. And what portion of the market is under 2? Obviously, it's all a lot of the newly diagnosed market, but in the prevalence pool perhaps.

Yes. I think the key element, and I think we will separate it a little bit because I think there likely will be a difference in the leading between EMEA and U.S. because in the EMEA case, we can still be adding in all the new data we are getting from this trial. We have only efficacy data for a small portion of the patient that was dosed when it was not randomized, and we have seen all the benefit we expected. When we take the entire randomized that is blinded, we can see the safety is exactly as we have expected. And the benefit we're getting there is exactly how we expected it to be really addressing some of the comorbidities that need to be addressed there early, and it's basically the development I'm avoiding to get stenosis and other things like that in the [indiscernible] fusion of that. And I think that is what we hope we can see with also the x-ray when we are on it.

The benefit we have here is that I believe that patient when do they really start? Yes, everyone get borne and perhaps it will be necessary for them to start an early treatment to address some comorbidities. So this is why we want always to do it. But when you also see that the majority of patients are still aged 2 and older, because they basically will be in a treatment much, much longer. And sure, one thing we also disclosed when we start the trial for adult achondroplasia because we still believe there is a benefit for getting treatment after you have fused. And I believe this is where we look on the holistic way how we ensure we can get the best for every subject that is with achondroplasia to the benefit.

One of the things that I think we noticed is the quote from the Little People of America, the Society Group, the patient support group and the patient representation group in your press release was slightly different than it was when VOXZOGO got approved. And I think that's a little bit of an aperture into the relationship with the group. Can you maybe talk about how you engage with them perhaps a little differently than BioMarin and maybe some of the missteps BioMarin did initially and how that's provided an opportunity for you?

In general, and I can say our approach to every patient group, it's not only LPA, which I believe we have an extremely good working relation with also. We are there to listen. We're there to understand what we really need to get out for a treatment. And if we don't do that, how can we be patient focused. And when you look at our values, number one is the patient. And I believe always to continue to listen to patient group, to patients because in the end, it's really how you make a successful product that really provides the benefit. And that has been our focus for each single product and will continue to be.

So I will be very disappointed if I didn't have a positive interaction with all the patient group. And I like to come to this meeting because I always get extremely inspired by the benefit and really understand how much it mean for [indiscernible]. I was sitting with them and talk about the bone. I heard them talk about [indiscernible] I heard them talk about 1 year in high school need to be out. And they're saying, if we have known that basic treatment like YUVIWEL could change and they have really the data. When we look on the placebo arm, yes, there is changes because it change to [indiscernible]. But when they compare to what we saw on the treatment arm and compare the placebo treatment to that, it was clear you can solve this problem. And that was really something we are saying this is extremely meaningful for us. This is somewhere we want to focus, and this is why we continue to work with them to ensure we make a patient-focused treatment for everything what we're doing.

So one of the questions we get a lot is, and you mentioned only 30% of the 2,600 are you think are currently being treated. The 2,600, is that the total number of diagnosed patients with achondroplasia? Or is that the 2,600 is patients still with open bones that you can actually target? And then secondly, we do hear from clinicians that penetration is still low. Morphologically, these patients are fairly recognizable. Now of course, not every parent is going to want to get their child treated necessarily. But maybe give us a little bit of a sense, what can you do to really boost the treatment rates?

When you look at this 70% in the U.S. and then I can take another country, Italy, 70% are on treatment, and I believe that illustrate extremely well the issue in U.S. In Italy, there has been much, much more focus on linear growth, and that is why 70% of the patient [indiscernible]. If I look in the U.S., I believe 70% to 80% will be on treatment because the basic can see, yes, I'm really not -- the main focus for me is not linear growth, but the main focus for me is addressing comorbidity.

So I think you will see a tiny penetration happening in U.S. when you're really going out and telling the story there is clear data that's showing that you address comorbidities. And I believe that illustrates exactly when everyone see the benefit of the treatment and everyone have a diversified view about what the benefit of treatment should be. And that is illustrated between Italy and U.S. and you can really be in a position, yes, everyone should basically go on treatment and everyone will be on treatment.

I don't think any parents will ever believe to take a child out of high school for 1 year, go to suffering of all this pain just to try to align things if you can go into a treatment regime for that. And I think that is a comparable fashion. This is why I believe Italy in penetration will be the same in U.S. after some [indiscernible].

Okay. Let's maybe move to YORVI a little bit. And in Q4, gross to net increased a little bit as it's typically the case, right? And in Q1, typically, there's obviously a lot of patient support that still goes into it. And you're constantly thinking about what's the right level of contracting to maximize access as well. And I believe you also did a price increase as well. So can you talk about sort of the net-net effect on gross to net? Is the price increase going to allow, in many ways, neutralize any gross to net impact?

And then secondly, we did see a little seasonality in Q4. This is sort of the first year on the market now in the U.S. Is there sort of a little bit of pent-up demand that we should think about hitting Q1? And again, you need to offset that a little bit with typical seasonality. So it's a lot of questions about how to think about Q1.

Yes. And I think we will be much, much, much smarter when we are coming to end of March because then we have the realized numbers and seeing how our first -- real first quarter. Everyone knows that it's a seasonal factor for going from Q4 to Q1. There is a new way of patient group that need to go to a new reimbursement system, how fast is this system going? What we know, and I can continue to confirm that the demand is still there, and it's still the same kind of demand that we have seen every quarter. This product, we're first starting to have under 5% of the patient -- established patients under treatment. The benefit of that is the same thing, will you believe 5% of type 1 diabetes patients should only have insulin. No, you will say the majority of them should have. And this is where we see this linearity in quarter-by-quarter new patients coming in.

And don't forget that the day when we really also can tap into the 3,000 to 4,000 new patients that come in every year, we are much, much better off. And new patient today should that not be blamed to be on treatment? I believe, yes. So this is where we see the seasonal factor. I believe the key element for me, are we still on the launch projected thing where we see the continued demand for this product? Yes, we are. And I believe that is the key element.

I got asked a lot why do you want to stop giving a new enrollment in Q1? And then I heard people coming back to me and say, Jan, there's a lot of shorts or anything like that you hear from the Wall Street of where they are on the short really meeting them. There are somebody coming in and saying is, Jan, I didn't want to come out with a new enrollment in Q1 because it's horrible. And I said, okay, I have no problem by giving Q1 new enrollment if that somebody can give you the comfort. And sure we will give it to you in Q1, too because they don't want to listen to all the short discussion about that enrollment is not going fine. And I said it's fine to give them a number, then at least I can be wrong one time more.

It keeps us in business on the sell side. We appreciate it. Sarah has a really nice figure. When you're thinking about now that it's been on the market for a year, what can you tell so far about potentially durability or maybe a little bit of dropouts? What kind of patients decide ultimately not to continue on therapy?

First of all, we have a global launch, and it's different from country to country. What in general, what we have seen in every country is that when you started on your path, you stay on it. And it's obvious in this way. But sure the patient because it's a chronic treatment, you will be treated until you come to the final part of your life. And sure, there will be patient that's stopping because it's part of the life -- cycle of life. But it's a chronic treatment for rest of your life. So there will be patients stopping at some time. Most of them will stop [indiscernible].

So on from that idea, you can see there will be some turnover. But from that perspective is we see a product that really are living up to all the aspect of the patient, want to see physician want to see, and you see that in the adherence. If we go to Germany, we can have different parameter how to look at that. The best one is, for example, [indiscernible], where we have more named patient program because then we can follow every single patient. And then you can say it's a named patient program and more artificial one. I don't think really in adherence and retention, no, and we see nearly all the patients, only few percentage are dropping up. And if we have drop up, it's mainly in the beginning of the titration phase, and this is where we're trying now to get the patient much more in the titration phase where they go out of conventional therapy and basically are in a position to start the [indiscernible].

Okay. Maybe in the last 45 seconds or so, on the weekly version of YORVI, is that something you can take right into a pivotal? Do you have to run -- or is the pivotal going to be a Phase I PK program, bioequivalence program?

So what we try to do with once weekly and why we designed it? We designed 2 or 3 time points. Because we wanted to take over the entire week. You have seen the complete flat profile on your [indiscernible]. So we said we want to have a bioequivalent solution. So every day on every time point, 24 hours, 7 days a week, you need to be bioequivalent. And we're liberating the same compound using the same system, we just changed the entire linker setup.

Would that qualify to a bioequivalent strategy so we can get approval on PK profile or we need to show a limit clinical data? That is what we're discussing with regulatory agencies, and it could be different between U.S. and Europe, but I believe this product will come out. But this is not a -- once-weekly product can never be life cycle management. It's only dedicated to patients that have been titrated on the daily product to a stable dose for some period of time and then you can transfer them over to a weekly product, how it only can function today.

Well, terrific. Jan, Scott, Chad, and I -- sadly I can't see the rest of the team right there. So thanks, everybody. Good to see you. We appreciate it, and congrats on the launch, and we'll be in touch.

Thank you so much.

Thanks, Yaron.

Thank you.

Bye-bye.

Good day, and thank you for standing by. Welcome to the YUVIWEL FDA-Approved Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker, Chad Fugure, Vice President, Investor Relations. Please go ahead.

Thank you, operator, and thank you, everyone, for joining our conference call this morning. I'm Chad Fugure, Vice President, Investor Relations of Ascendis Pharma. Joining me on the call today are Jan Mikkelsen, President and Chief Executive Officer; Scott Smith, EVP and Chief Financial Officer; Jay Wu, EVP, President, U.S. Market; Aimee Shu, Chief Medical Officer; and Sherrie Glass, Chief Business Officer.

Before we begin, I'd like to remind you that this conference call will contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 as amended and Section 21E of the Securities and Exchange Act of 1934 as amended. Examples of such statements may include, but are not limited to, statements regarding our expected timing of U.S. commercial launch and product shipments for YUVIWEL, our expectations regarding the potential benefits of YUVIWEL, the potential market size and size of the potential patient populations for YUVIWEL, our patient services for YUVIWEL, our Vision 2030 and our plans and objectives for future operations and commercialization activities.

These statements are based on information that is available to us today. Actual results and events could 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 these factors that could cause actual results to differ materially. Please see our forward-looking statements section in the press release filed on February 27, 2026, and the Risk Factors section of our most recent annual report on Form 20-F filed on February 11, 2026.

On the call today, we'll discuss the U.S. Food and Drug Administration's approval of YUVIWEL and our plans to commercially launch YUVIWEL. Following some prepared remarks, we'll then open up the call for your questions. With that, I'll now turn the call over to Jan.

Thank you so much. It's a pleasure here Monday morning, 5 p.m. or a.m., I'm not sure what time it is to be here in [ duration ] to talk about our third FDA approved drug. Before I dive into the details, I would like to thank the patients because that is part of our vision. This is our focus to be patient-focus. The caregivers, the physician and the Ascendis team for their commitment and dedication to get YUVIWEL approved here in the U.S.

I know, it's only the beginning. We have the European and many other countries where we also will go for approval. I would also like to thank the extremely productive interaction discussion we had with the advocacy groups. Discussing with this group, I understand the real need what is important for the patient has been the guidelines how we have dedicated our effort to design a patient-focused YUVIWEL. And we thank them a lot for this positive interaction.

YUVIWEL is the first and only once-weekly treatment for children with achondroplasia, where we use the TransCon technology as designed to really get the benefit out of a normal native wild-type CNP molecule. The CNP pathway have been known for many, many, many years, but how to really make it to a druggable product. This has always been the challenge. It's a peptide with very, very, very short half life. And when you think what we did with the TransCon technology, we took a peptide with a few minutes half-life up to 5 to 6 days. I've never seen it before, and I only believe is only that strong technology like TransCon technologies that really is a platform to make that available.

But not only that because by designing it in the TransCon technology, we also address some major issues to tolerability, ensure we had a compound that basically were as inactive, as you would like to have it in a product but also the element of providing a sustained release. So you never have a high Cmax and have a potential risk for hypertension. So when I see the fit between the CNP molecule and the TransCon technology is really fit in the most optimal manner to really to go out and get the best possible out of this molecule and it's really improvement in the patient care.

FDA approval was based on data for three randomized, double-blind, placebo-controlled trials, including the Pivotal ApproaCH trial. In addition, we also got a bonus. With the FDA approval, we were also granted a Granted Rare Pediatric Disease Review Voucher, which confirms priority review to a future drug application that will not otherwise qualify for priority review.

A key takeaway from this slide is the callout box. And I believe it's really a point of pride, not only for Ascendis, not only for the patient, but also for myself to be in a position to have the third FDA-approved in a row for three preclinical candidates that got designed. Scott is still calculating what is the chance of that. He still calculated what is 0.05 up to 1/3. What is that percentage. But I believe that is really, really low but we beat every box.

I will now like to go to Slide 4. which provide some selective highlights of the U.S. prescribing information. I get asked from investors here during the weekend here. What is your feeling about the label? Are you proud? And I said, yes, I'm extremely proud, because when I look on the labeling it's providing such a well description about the benefit you see with YUVIWEL compared to alternative treatment. It describes in a very, very direct manner, the positive effect that we wanted through solve to the TransCon technology, the hypertension. It described very, very well the low injection reaction, having a product with a chance for every second year to have one single injection. I believe this is why we see this extremely high retention in our clinical trial.

So I'm really proud about it. And when I look on the combination of what we have in our way to go out to the market, we have a strong label to part of the commercial team, and we have a strong publication to other part of the team, really providing all the benefits beyond the new growth we have observed. So when I look at the integrated package, I'm proud about it.

So YUVIWEL is indicated to increase linear growth in pediatric patients 2 years of age and older. So basically, no limitation upwards. From 2 years and younger, yes, we're finalizing here in this year, next quarter, must be this quarter, we're finalizing I have to say that is going exactly as we have thought. We can see efficacy in a small number of patients, but we had a good safety overview of what we see in the trial.

YUVIWEL should be administrated subcutaneous once weekly based on body weight and refer to Full Prescribing Information for complete dosage administration information. Contraindications none. And this sentence was really interesting for me. Risk of low blood pressure, transient decrease in blood pressure have been reported with a once daily CNP analog, not on once weekly but once daily analog. Patients are advised to contact health care provider if they experience symptoms of decreased blood pressure while being treated with YUVIWEL. And adverse reaction. Aimee will show you the table and I have to say, you don't need to spend a lot of time reading this short table.

Okay. Let me move to the next slide number. This is all key label takeaway. When we compare trial, when we look on efficacy related to linear group, the only way where you really can compare is to go in on LS mean treatment difference. This is the only way where you have a meaningful way to compare trial. I know other try to observe value as a way to compare it and other things. Yes, we'll not talk too much about that but at least if you want to make a scientific comparison, please use the LS mean treatment difference in that. And when we saw AGV of 1.5 cm per year at week 52 for YUVIWEL versus placebo in all children. And when we go in and look on the group where it's easy to compare because previous trial had been made in children from 5 and older, we get an LS mean of 1.8 centimeter per year.

And we also saw in our Phase II trial that was running now I think, 4 years. For the first 2 years, we saw we achieved the constant increase in annualized growth velocity. And also in the label it is clear that recognize that continuous exposure with low incidence of injection site 0.4 and would also surprise me, which was in a very positive way was switch guidance because we really didn't test children in this way. We actually have an exclusion on this kind of children. But still, I think because of the safety of this compound, we saw once weekly YUVIWEL start 1 day after completing the last day of the daily CNP therapy. And if you read all the small notes everything else, there is no indication of food or fluid intake required before administration of YUVIWEL.

So going to Slide # -- it must be 6, I think. There is our three approved products. Growth hormone deficiency, TransCon Growth Hormone, we are now doing a lot of label expansion for that. Yorvipath, we have them approved in Europe and the U.S. We're now expanding that label too. And now we have the third one, YUVIWEL. This is the beginning. It's definitely not there yet. We for the next 3 to 4 years, major label expansion of all these products also in combination with these all new entities is coming from our research and development groups.

All of that leads to Slide 7. This is our guiding for how Ascendis is going to be developed to the road map from '25 to 2030. And I will not go to our Vision 2030. But the key point is really one bullet point, be the leading endocrine rare disease company and I have no doubt we're going to. And we're really on a strong way to generate the EUR 5 billion in product revenue in 2030, building from the three product opportunity, TransCon PTH, TransCon growth hormone, and TransCon CNP, through worldwide commercialization. And I feel really, really strong on how we're also investing now in developing the next generation in pipeline in rare disease endocrine.

I have a hope they will be exactly as successful as the first three out of three, but we'll never see. At least we have proven it once and we can do it again. And we continue to create value in additional area to our different utilization of our strong TransCon technology in different therapeutic areas. So I will not leave it over now to Aimee who will go to the next series of slides before James will take over, and I have the pleasure to round it out with the last 2 slides.

Thank you, Jan. On Slide 9, we have a brief overview of achondroplasia. As this group knows, achondroplasia arises from genetic variants that caused gain of FGFR3, fibroblast growth factor receptor III function and affect multiple tissues. Notably, the constitutive overactivation of FGFR3 leads to impaired endochondral ossification that is impaired chondrocyte differentiation of the skeleton. The clinical and radiographic phenotype of achondroplasia has been well described over the years and the complications represent a variety of medical, functional and psychosocial challenges that may vary across different stages of life.

Distinctive phenotypic features include a long narrow trunk and short limbs especially in the proximal segment, large head, hyper extensibility of the joints and restricted extension and rotation of the elbow. Radiographically, the shapes, relative sizes and alignment of bones are also distinctive with, for instance, thoracolumbar kyphosis and exaggerated lordosis of the spine, a narrow spinal canal and leg bowing.

Medical complications are the result of these differently shaped bones and body cavities. For example, complications may include hydrocephalus which is accumulation of cerebrospinal fluid within the cavities of the brain, cervical cord compression, quite problematic and recurrent otitis media, recurrent middle ear infections. Thus, major treatment goals are to decrease the incidence and severity of achondroplasia related medical complications, promote healthy and proportionate bone growth and improved quality of life.

I'll now move to Slide 11, which explains the design of YUVIWEL. You've heard some of this already from Jan. It's a prodrug of CNP, C-type natriuretic peptide that acts through the NPR natriuretic peptide receptor 2 receptor. It is administered once weekly and is designed to provide continuous exposure to active CNP to tissues throughout the body. The CNP moiety represented in purple is transiently conjugated to the carrier represented in blue. The carrier extends the circulation time of CNP through a shielding effect that minimizes CNP receptor binding and clearance. CNP moiety is inactive when bound to the carrier. And YUVIWEL does releases CNP in a controlled manner and is designed to provide continuous exposure with a low peak to trough as heard before, avoiding high peak concentrations and thus avoiding the natriuretic and low blood pressure effects. It's been really nice to see this play out in the clinical trials.

Now moving on to Slide 12, which is about efficacy at week 52. In the pivotal ApproaCH trial, superiority of navepegritide over placebo was demonstrated for the primary efficacy endpoint, annualized growth velocity at week 52. Children treated with navepegritide achieved least squares, LS mean AGV of 5.9 centimeters per year which was statistically significantly greater than 4.4 centimeters per year for placebo with an LS mean treatment difference of 1.5 centimeters per year, confidence interval 1.0 to 1.9 centimeters per year with a p-value less than 0.0001. Navepegritide increased AGV in each of the age subgroups. For instance, in participants greater than or equal to 5 years old, the treatment difference was 1.8 centimeters per year.

Similarly, the change from baseline in height Z-scores calculated using reference data from untreated children with achondroplasia that's called the achondroplasia-specific height Z-score and using reference data from the population with average stature that's the CDC-based height Z-score, demonstrated statistically significant treatment benefits with navepegritide. For both achondroplasia-specific height Z-score and CDC height Z-score, the treatment difference for change from baseline height Z-score was 0.3. Overall, improvements in AGV and height Z-scores were observed across all predefined subgroups analyzed, including for age, sex and geographic region.

Now moving on to Slide 13, which Jan promised won't take you a long time to read and maybe you wouldn't even need to break out your glasses to see it. This is a cut and paste of Table 2 from the U.S. prescribing information that was derived from pediatric participants with achondroplasia who received navepegritide 0.1 milligrams per kilogram per week or placebo during the double-blind period of the pivotal approach and Phase II ACcomplisH trials. The adverse reactions listed in this table were reported in greater than or equal to 5% of participants treated with navepegritide 0.1 milligrams per kilogram per week and 2% higher than placebo during the placebo-controlled period. There are just four items in this relatively short table. We feel like this is a major point of differentiation. And as you can see, this drug is safe and tolerable and appropriate for chronic long-term use in children.

Moving on now to Slide 14, highlights from dosage and administration section and storage and handling sections from our U.S. PI. So I will read through these, and we're really proud of these. So for instance, this is administration once weekly,by subcutaneous injection with dosage based on body weight. Physicians are guided to periodically monitor growth and adjust dose according to the body weight as would be expected. Discontinuation criteria are when no further growth potential is seen as indicated by epiphyseal closure of the growth plate.

There is even switch guidance within this U.S. prescribing information. Start once-weekly YUVIWEL on the day after completing the last dose of daily CNP therapy. And we'd like to point out there is no guidance for food or 10 ounces of fluid intake when administering YUVIWEL noted within this USPI. Finally, YUVIWEL can be stored at room temperature up to 86 degrees Fahrenheit for up to 6 months and can be returned to refrigeration within these 6 months if desired. And with that, I will pass it along to Jay.

Thank you, Aimee. As you mentioned, this is an exciting milestone for the achondroplasia community, and we are looking forward to sharing our initial perspectives on how we were able to support this approval. So if we move to the next slide on 16. The main thing we wanted to start with is that our approach has always been hand in glove with the community, and we have really appreciated these groups, in particular, not only to help us learn more about the space but also inform some of the key activities that we have undertaken to support the development and the ultimate approval of YUVIWEL. We've been engaging with these groups since 2017 to gain patient family advocacy as well as health care provider perspectives, and they have supported us in our filing approach as well as strategy towards current and planned trials.

Moreover, working with this group, they've also given us a lot of perspective on the diverse treatment goals of this community and what they may be looking for in terms of support should members of the achondroplasia community seek treatment. And lastly, they've also helped inform some of the novel approaches beyond even our approval today, whether it's exploring multiple indications in the future and/or combination regimens to expand treatment options and patient reach in the future.

If we move to Slide 17. This gives you a sense of the achondroplasia U.S. landscape today. Based on available information and our best estimate, we anticipate the U.S. pediatric achondroplasia prevalence to be around 2,600 in the U.S., of which approximately 30%, we believe to be on current pharmacological treatment. As I mentioned before, in the U.S. market, those living with achondroplasia have diverse treatment goals. Some may be currently on a daily therapy, some perhaps have previously tried a daily therapy, but has since discontinued, whether it's due to tolerability, convenience or perceived lack of benefit. And there's also an ample subset of this community that is not on and have never been on pharmacological treatments. I think what this really underscores is the level of unmet need that still exists in the achondroplasia market today in the U.S. And we believe that with YUVIWEL's clinical value proposition and differentiated profile, we're expected to grow the therapeutic class from both treated and untreated patients.

If we move to Slide 18, we have a bit of a snapshot on some of the commercial activities that we'll be focused on as it relates to supporting the YUVIWEL approval and launch. We'll be engaging with centers of excellence, thought leaders as well as patient advocacy groups to educate key stakeholders on YUVIWEL's clinical value proposition. And we also recognize the important role that patients and caregivers have in this space, in particular, when determining what is right for them. So really, our focus will be meeting where that community is at, knowing that it is a very diverse and heterogeneous group. We'll be investing in multichannel education as well as support for those caregivers and patients directly.

Another big priority for us will be focusing on optimizing the patient experience itself. We know that there are opportunities. We know that is sometimes challenging, particularly for ultra-rare conditions and making sure that patients have choice is something that will be a high priority for us. And then lastly, we have a lot of experience in rare conditions with the products that we previously have approved. So we'll be leveraging our existing infrastructure, systems and teams, which have supported over 15,000 patients on SKYTROFA. All in, just to say we are prepared to support YUVIWEL commercial availability in the early part of Q2 2026, as Jan had mentioned earlier.

On the topic of focus, if we move on to Slide 19, this gives you a brief snapshot of the patient care concentration, which you can see, we believe more than half of them to be concentrated in these top 100 health care organizations or skeletal dysplasia clinics. So again, as I mentioned before, focus and high impact and patient support is going to be in areas of key focus for us.

If we move to Slide 20, this gives you a sense. We'll be really, again, leveraging the infrastructure and experience that we have supporting rare conditions to ensuring affordable and broad access in the U.S. With our Ascendis Signature Access program that encompasses reimbursement access support, out-of-pocket assistance as well as resources and training. And for patient affordability, we do anticipate that eligible commercially insured patients will pay as little as $0 a month with a co-pay card. Government will have -- government payers will have affordable out-of-pocket as well as patients screened for available assistance programs if they are uninsured or underinsured.

And with that, I'm going to actually transition it back to Jan to talk to us a little bit more about the 2026 milestones and to close this out.

Thanks so much, Jay. This is only the 2026 milestones. We were just focused to give you a few expect how we continue our progress in -- with YUVIWEL not only in one single indication, but also starting our label expansion effort. Here in Q2, we are in a very, very interesting situation, we will have our -- as Jay mentioned, our U.S. commercial availability. A little bit later, we will have also for our international market because we can be utilizing the U.S. approval also to start on the patient early access program in countries outside the U.S.

In Q2, we will have a follow-up on 1.5 years data of our combination therapy the TransCon growth hormone or TransCon CNP. Just recall you that this is a place where we saw that we basically could achieve in 1 year, the same outcome that is basically 3 to 4 years with monotherapy. Complete paradigm shift really an unbelievable benefit in treatment outcome I ever have seen before. But perhaps a more and more important is safety, safety, safety. Why ever compromise on any treatment, take any risk to safety if you have no kind of improvement in treatment outcome.

Going to Q3, we will complete the enrollment for the 0 to 2 children. As I said before, really promising data we have seen until now. And we really look forward to have that integrated in the U.S. approval, in the European approval is much more easier during the ongoing regulatory interaction to provide more data.

Going to Q3. We had a dream or it was basically Scott dream to start to do a trial and also give adults with achondroplasia, some benefit of CNP treatment. We are now analyzing all the benefit we can provide there and find out which one will be the most meaningful for the patients really to provide a treatment that really will mean that it means something for them in their daily life. And also in Q4, we will be in a position to have the expected European approval. And at the same time, we will also get the 2-year data from our combination trial. That was just '26.

So now I come to the last slide, 22, which sum up a few next steps. Yes, today, YUVIWEL the first and only FDA-approved once-weekly therapy for children with achondroplasia. We got Granted and Rare Pediatric disease, PRV. We will have product availability in the early part of the second quarter in '26. We expect the approval in Europe end of the year. We plan to make YUVIWEL available to our existing infrastructure.

And I think Jay made it really, really, really clear how we have taken 10,000 of children to the system, we also using right now for YUVIWEL. And that is really the power of focus on one single therapeutic area with multiple product because we can utilize it in a much, much stronger way to establish infrastructure. And when we come to the international market, we really are through our YORVIPATH effort now are recognizing revenue for more than 30 countries, and we have more than 70 countries now under distribution agreements. This is the same infrastructure we will be utilizing also for YUVIWEL.

But we are not stopping here as always. This is just the beginning of the beginning. Now we start on the second phase. We will continue to use YUVIWEL as a strong foundation therapy specific in combination, not only with SKYTROFA but potential other indications. We will also go to the expected planned label expansion, which we already have started with hypochondroplasia, and we will continue to do in other indication.

So I will end where I started, three preclinical candidates, three FDA approved products in a row. Scott is still calculating what's the chance of that. But I'm really proud of that. So thank you so much today. We are now open for questions.

[Operator Instructions] Our first question will come from the line of Yaron Werber with TD Cowen.

Congrats on the approval. This is really great news. And we just have 2 quick questions, both on the label. On a, I believe you were expecting enrollment for the reACH study in patients 0 to 2 to be completed in Q3 of this year. You just guided to that. Can you give us a sense of what the target enrollment is and when we might expect to see data? And then would you need to -- what would you need to see in order to file for a label extension in ages 2 and under? And then second, just on the administration for the injection device. I know right now, it's subcu vial reconstitution and a key difference between the 2 labels is the much lower rates of injection site-related reactions for YUVIWEL versus VOXZOGO? Do you attribute this to the weekly versus daily injections? Or are there other factors that support the lower rates of ISRs?

I will take the last one because then can Aimee prepare herself for the first question. So let me take the question between the other daily therapy and our YUVIWEL. It's nothing to do with anything else the technology. What we are doing with the TransCon technology we're making an inactive product, why I say a little bit with a smile because the product by itself in definition is inactive.

So what it merely means is that you inject it without any biological activity in the injection. So whatever you did daily, weekly, monthly, yearly it is still [ detrimental ] and then it diffuse into the blood compartment and then it liberate the unmodified native CNP peptide.

When you take a daily, it's not really protected. It's fully active when you inject it. This is why you see this kind of injection site reaction. And this is how we really design with the TransCon technology. So TransCon technology is not only providing the sustained release profile which provide no risk for hypertension, but also protect it in the injection site reaction. And this is why when you look at 0.4 injections per year, meaningless that this is why we see this positive results. Aimee, will you take the first question about our young children?

Yes. I think the question was how are things looking for the infant trial and the target enrollment. And so there, we have shared for us approximately 72 kids, including the sentinels who are open label and the blinded kids.

And this is why we -- you can say we have one part on blind and already there, we can go to do the data and see extremely positive effect as we expected on the, you can say, the blinded part, we can basically only look at safety, but if you don't see anything, you also have.

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

Yes, congratulations on getting your third drug approved. I just wanted to clarify, have you guys announced price yet? If you haven't, can you just let us know when to expect that?

And then secondly, how do you see the initial uptake as far as the market opportunity? You've talked a lot about it and the focus on these 10,000 patients. But initially, based on what you're hearing from physicians, do you expect uptake that come from switches from the currently approved product? Or do you think that there would be significant uptake from frontline or treatment-naive patients as well?

Thanks a lot for these questions. First of all, let me go, start with the price and then Jay can follow up on, what I call, the commercial strategy.

Price, we have not disclosed yet. But I can give you, Tazeen, some guidance. So when you look at our products, we always say that this is a product that we have provided benefit compared to any other standard that have been in the market.

Out from that, we always said we want to share this kind of upside for the patient, for the society, for the reimbursement system and other things like that. And doing that, we always come up with a premium pricing. I don't think we ever have made any product that had been in a situation where we have not been taking this approach because every product we have has been a product that really providing highly differentiated benefit to any kind of standard. So, Tazeen, from that perspective is I will expect a premium pricing strategy also in this case. Jay, will you talk a little bit about the idea of both groups related to uptake.

Yes. Happy to go to those questions. And just to follow-on Jan's pricing comment as well, and Tazeen, I think the latter part of your question, we do anticipate that we will make price available either later this week or potentially even next, so that information should be out there soon.

As Jan mentioned before, price should be commensurate with the clinical value proposition that we have. And we also believe in patient choice, so that will be something we will be prioritizing.

For the other areas that you had inquired about, we do anticipate broad appeal for YUVIWEL. And as I mentioned before, there are a couple of segments, right? There are segments of patients that are currently on pharmacological therapy, and we have heard even since the approval that there are patients asking about potentially the process to switch over and/or commercial availability.

But we also anticipate that this will bring additional members of the achondroplasia community out of the woodwork who will want to try something new that for whatever reason, did not choose or elect the current available therapy that exists today.

Again, as I mentioned before, some of the patients that previously were on therapy that discontinued, whether it's due to tolerability, due to convenience or perceived lack of benefit. We do anticipate that some of those patients will be potentially interested in YUVIWEL as well.

Our next question will come from the line of Gavin Clark-Gartner with Evercore ISI.

Congrats on getting the approval here. I actually just wanted to ask about current YUVIWEL consensus estimates. So if I just focus on the fourth quarter of this year, kind of breezing over the first couple of quarters, where establishing access, et cetera, will be going into place I'm seeing about USD 25 million, maybe USD 30 million in 4Q consensus estimates.

If I just flip over to BioMarin consensus, I'm seeing about $75 million in fourth quarter of VOXZOGO sales. So I guess the current consensus is implying a pretty big relative market share shift pretty quickly. Do you think that consensus number could be achievable? And how important is the switch versus naive dynamic within that time frame?

One of the elements which I always are impressed on when results doing some kind of projection of revenue and sales without knowing the price of the product. So because I actually think that gives some kind of uncertainties in it. So as Jay said, there is a few days before you will know the price. And I think it will be potentially more relevant when we have disclosed prices. We go back to this question and give us a discussion, and I'm quite sure that both Scott and Chad are really fit for fight to discuss the different modeling perspective with you related to this if you have specific input that you really would like to get.

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

This is Heidi Jacobson on for Joe Schwartz. I wanted to add our congratulations on the approval as well. So what feedback have you received from physicians regarding the lack of a predose food and fluid requirement? And do you view this as a meaningful point of differentiation in practice?

I believe you always need to take the holistic approach on any treatment element in it. And I will never isolate a single element in how you will select a treatment. You will take the overall perspective of a drug.

So we decided to design YUVIWEL in a way that we really try to address all now, you can say, downside for not to be the best-in-class into this era. And that was why we addressed both hypertension. And you can see this relevant element. I believe it's relevant when I read publication, for example, from Japan, if you not have seen that, case studies of severe hypertension in small children, when they give over, when they give the once daily product, which have the fast Cmax.

When I look on insecticide reaction and see tolerability, I believe, is a really, really important part. For the interaction between the child, if you really see big redness to that how frequent you see with a daily treatment.

Other effect, if caregivers are following really the label with the shot in every treatment, you basically need to ask the child to drink a lot before you basically take the administration. So when I see that I never pinpoint a single element, I always take a holistic view, what is the right best treatment benefit for every subject that need to get a treatment, and some parents, some children are more aligned with one element, some it's more aligned with another one. Someone I'm saying it's such a hard thing just to take a daily administration. We cannot live a life because we are so busy. We're working. We need to do it if the child is screaming and therefore, we cannot take a daily injection. So therefore, I always believe, address all the points and be sure you have the optimal treatment.

Our next question comes from the line of Alex Thompson with Stifel.

Congrats as well on the approval. I just wanted maybe some additional color on sort of the overlap between your current commercial infrastructure and how that being leveraged for the YUVIWEL launch. Have you added any additional sales force elements, et cetera?

Yes, Jay can go in. Yes, we have that and typically, we basically have to, you can say, arms in our sales force. One that is basically focused on hypopara and the other one is basic the arm that is focusing on SKYTROFA-APPROVED, the YUVIWEL products because our aspiration is also on a long-term perspective, when we get it on label, there will be a utilization, a lot of combination therapy. So this is why we have built it in this way. So you can say, as Jay said, we have already more than 10,000 patients in SKYTROFA treatment. So we really have what we call a high-capacity system to really to take the patient to it. But Jay, you can talk about how you have scaled up in the U.S., I can perhaps say in the European side, we're also scaling up, so all the different direct market and international market, we are ready to YUVIWEL-approved.

As Jan mentioned, we have scaled across the U.S. organization for a variety of reasons, right? Hypopara, that product obviously has had a very positive trajectory, and we have needed to support that. But even SKYTROFA, we also had a line extension last year as well into adult growth hormone deficiency. So I think to Jan's point, as an organization, we are growing overall, we don't comment on explicit field sizing, but generally speaking, the U.S. organization has been growing.

I think your second question was pertaining more to overlap, and we do have an overlap of certain prescribers given SKYTROFA is in the pediatric endocrine rare condition space, there is some natural overlap there for prescribers that are also interested or treat achondroplasia.

Our next question comes from the line of Derek Archila with Wells Fargo.

This is Simone on for Derek. Congrats on the approval. My first question is, what impact do you think YUVIWEL's approval has an ongoing ITC case given the win with the EU case and the citizen petition likely being drawn out?

It's always hard for me to comment on an ongoing trial. I would like to refer to more to the European case, which have been now resolved. From that perspective is that there is three steps that need to be fulfilled. First, that need to be a validation of the actual patents. Second time, there needs to be a discussion, do we actually do an infringement. And then in the third step, if we ever come so far, which we never came is are there a public interest to have this product in the market.

And in the European case, we only came to one single step. Was this pattern really should be issued or not. And clear, they got basically taken away immediately. So we never came into either if we basically had an infringement in any kind of the case.

This is what the European way. The U.S. we still have the same three different states. Except that compared to Europe and U.S., that's a much, much higher infancy on the element of public interest, which are not a strong part in Europe. So when I look at this product here, it comes from a priority review, from FDA meaning is that FDA as the regulatory agency are recognized that it is providing a benefit compared to standard treatment that is out in the market today. And that is also what we have seen now through the approval.

So I feel extremely confident that this case would never should have been the case, but at least, there's some legal people that earn a lot of money on it. And we also get damaged payback every time we win, that is also fine for us. At least, we can have some good parties from that. I feel that in some way, we should just let it go and not will interfere anything in this case. We will be in the market. There is no doubt of that.

Our next question comes from the line of Yun Zhong with Wedbush.

So Congratulations on the FDA approval. So I just want to confirm, do you still have a plan to explore hypochondroplasia with TransCon CNP. And also, I saw that she had included the adult subject with achondroplasia. So I wanted to see if you are able to comment on the size of the opportunity, or any special approach that you will need to take for the adult subject with achondroplasia.

We see a lot of opportunities in our product portfolio in the area of, we call it, growth disorder, but it's not really a right mean because it's really is much, much broader in this way. And when we look on indication like hypochondroplasia, we have to see a huge opportunity there for not only YUVIWEL, potential also SKYTROFA, potentially also the combination therapy. And this is where we are in the uniqueness because we can make both of them as a single monotherapy, but we can also make it as combination therapy.

Today, because of the more extensive genetic testing, so patient that came from the ISS group, many of them are basically being relocated into hypochondroplasia or when you find the mutation -- you'll find the mutation, it's not really longer. And ISS is not idiopathic because now we know it. And therefore, it's basically and patients that came from ISS, but now belonging to the hypochondroplasia and typical just will be treated with a growth hormone therapy.

And this is where Aimee, we really are designing a program. So every patient will get the best possible treatment. And I think we can do it as the only company because we have access to both SKYTROFA and TransCon CNP.

Our next question will come from the line of Ellie Merle with Barclays.

Congratulations on the approval. Curious when in early 2Q specifically, you anticipate launching. And if you could elaborate on what the gating factors are between now and before you launch? And I guess, in other words, why you're not launching sooner than 2Q?

And then in terms of reimbursement, just what are your expectations from your early discussions with payers and the work that you've done with pricing ahead of the launch in terms of like reimbursement timing and the time, I guess, from a script to potential reimbursement?

Yes. I think Jay would take the last part of the question and related to the U.S., I can take related to the international market.

Your first question is that when you're getting an approval in the last days, you get the final information that you need to have on your packaging information. And therefore, it's impossible to launch directly in the day after because you need to print both primary and secondary packaging, get the insert in the right format that get from FDA. And even if we have a product supply group headed up by Flemming, that is one of the best and fastest one in the world. We basically are in position, it takes some weeks before we can get the paper until we can print them, we can sit down and pack them and get them out to the patients. So all that is happening here in the U.S. So we just need to be quite sure we have the right information from FDA. And Jay, will you take the question related to the reimbursement?

Yes. The question pertaining to reimbursement. Those conversations are happening in an ongoing fashion. We are encouraged by all the initial conversations we're having in the sense that being able to talk through the clinical value proposition that we have, which we believe is very compelling for this community. We look forward to those opportunities to continue to educate on the label, and the data itself.

Right now, it's a bit premature to give you a bit more of a time line on when this, when that, primarily because a lot of these reviews can be staggered over time. So much like any product approval that are coming through in the early days, we do anticipate in the beginning, it will be primarily through formulary exception as these plans take the time to review the information and the data and label that we have. But we look forward to having those conversations and feel confident that the clinical value proposition will speak for itself.

Jay is exactly saying -- exactly what I was saying to that happened with YORVIPATH. And you can say, we really, really are prepared. I think pass, we're one of the best company prepared to run with medical exception because this is what we have done for basically all our product in the beginning. And you can see we basically continue launching product, new labeling and other things like that. So there is nothing.

Related to the international market, which we also can access now is basically on early access programs. And so therefore, there is clear rules, the regulation, how they are getting reimbursed in all the different countries.

Our next question comes from the line of Paul Choi with Goldman Sachs.

Let me add my congratulations as well. Can you comment on what the FDA has indicated is required for full approval of YUVIWEL here. Would you potentially be seeking label for the general treatment of achondroplasia or just maybe seeking to get additional data or clinical benefits on label and just sort of what is required there?

And my second question is on the label, there is some commentary on how to switch from the daily CMP drug. In terms of the prescribing information. Can you maybe comment on how you intend to potentially promote that among existing CNP patients -- patients on CNP therapy? Are you primarily looking to promote to data on label? Or are you thinking about any incentives for driving switches?

Yes, you can say it's really important for us to have a labeling because that is basically give us the opportunity to get our commercial effort really to promote it because it's on label. And I can say this is a huge benefit that we got that taking up in this expect. I do not know if you have further comments to that, Jay?

Yes. The only other comment I would say, echoing what you said earlier, the guidance is very clear, right? You can start it on the day after completing the last dose. So I guess I think about it less from a promotional standpoint. And again, I talked about before, it's meeting patients where they're at. We know there are many patients for which this will be a very interesting option for them, but it won't just be limited to patients currently on pharmacological treatment as well. There will be patients that are not on pharmacological treatment that may now be interested based on the value proposition that YUVIWEL has. So I think our approach will be much more holistic than solely looking at patients looking to switch.

Related to your first question, Paul, we have two -- basically two ways to progress from there. We can do out and getting what we call an approval on the linear growth, or we can go up and getting a treatment label. And we actually are finding out that we really have a lot of impressive data that really are showing benefit on linear growth, which can be utilized to basically move it over to a treatment.

And I think this is something we're now starting to have interaction with FDA about how really to be quite sure we can take that into label consideration and then potentially be taking into change to a treatment label. We hope that we have sufficient data already now with existing data to get a positive outcome of this discussion. If FDA some way propose and want to have more data, we are also willing to generate more clinical data to support this data system. So you can see we have an active approach how really to turn it into a treatment.

Our next question comes from the line of Luca Issi with RBC Capital Markets.

Congrats on the label. I'll just have a question on PRV and congrats on that as well. How should we think about the PRV? Would it be fair for us to assume that if you had gotten the approval back in November, you wouldn't have gotten the PRV given Congress just reauthorized the PRV in time for this approval. Also now that you have gotten the PRV, is it fair for us to assume that you likely is going to monetize it?

I think Scott looks so happy now because it looked like he got a question.

Yes, it doesn't make a difference. We were grandfathered in because we received a priority review designation -- or pediatric review designation years ago. Or will we sell it, yes. Well, most of the products we're developing are getting priority review. So I'm not sure that we actually need to keep it. So I think we can sell it if anyone's interested.

Our next question comes from the line of Maxwell Skor with Morgan Stanley.

Great. And congrats on the approval. Could you help us understand how the EU achondroplasia market breaks out? I know there's more patients on treatment, but kind of looking at Slide 17, thinking about specifically the proportion of patients on treatment and what proportion not on treatment are due to discontinuations or just treatment naive?

Yes. The problem in answering this question is that we talked about an extremely heterogenic market. There is many countries where daily CNP therapy is not even at reimbursed. So you can say all patients are male. Then there is areas or countries where it's approved, and you see a high level of penetration up to 70% to 80%.

So it's extremely heterogenic in all the different countries, and that is not only in Europe, but it's also in the international market segment. So what Jay said for the U.S. I actually believe it's the same that can be utilized both for the European market and international market for Asian and other things. It will come from everywhere.

There's a huge benefit switching for the daily CNP, there is a huge benefit going in for a treatment now. And there's also the possibility is that we believe, it can be possible to go to the country where it's not possible to have any kind of CNP therapy when we come with the combination data because it basically are providing so much higher efficacy benefit that in all their cost-efficient modeling, we can also get an acceptable reimbursement in these countries here.

But don't forget one thing. We also saw benefit beyond linear growth. And that was in a well-controlled trial compared to placebo. No one else has done it. It's also meaning that we can go out and do much better pharmacoeconomic modeling and also, hopefully, we can get a much better penetration in many countries where it was not possible to do it for the CNP.

Our next question comes from the line of Kalpit Patel with Wolfe Research.

Maybe just setting aside the ITC case, I guess how are you thinking about the District Court and Federal Circuit proceedings? And do these present any meaningful risk to your launch timing or commercialization in your view?

In my view, no. I believe this is a product that basically have priority review. It's a product where regulatory agencies are saying that it basically is providing a benefit compared to what is stated in the treatment landscape today. And if you can give me any case study in the U.S. where a product with priority review has got any kind of temporary injunction. I would like to see that because I cannot find one.

And our last question will come from the line of Li Watsek with Cantor Fitzgerald.

I wanted to add my congrats as well. Jay, you touched on different buckets of patients. Just curious what proportion of these patients may fall into this group of who might have tried daily but discontinued due to various reasons that could be perhaps low-hanging fruit for you guys. And wondering if you have already identified any of these patients.

Would you take? Okay, start Jay.

Yes. Li, thanks for the question. We have had inbound patient requests. And of course, we're very beholden into compliance. So from an approval standpoint, we won't have that responded to any of those inquiries until the actual approval. We, of course, recognize that there are patients coming from all segments that would be interested. I think from a pragmatic standpoint, what you can expect is for patients that have already made the decision that they want to be on pharmacological treatment. That is one fewer question that they may be considering when considering whether or not they want to start a new one, right? There are other patients that may not have been on treatment yet that are debating whether they want to start treatment for which this one might be their first intro into it.

So I do anticipate that we will have uptake across all segments, although some of them may be further along that journey than others. But again, some of this is just a matter of time as it relates to their comfort level with pharmacological treatment given the diverse treatment goals that they have, which we fully respect in the achondroplasia community.

Aimee, do you have anything to add more to?

We have certainly been hearing the side channels from patients and physicians about their enthusiasm for a weekly therapy.

If I can sum up here. We are extremely proud about the YUVIWEL approval. Three out of three is nearly like our vision, our last vision was 100% correct, and we fulfilled it 100% as we also will fulfill Vision 2030. But I think still, we should never remember our values, focus on the patient. And when we go to the pediatric segment, key element is safety and safety. No one should take risk in any kind of population that's going into any kind of treatment.

There can be benefit-risk balance. But what I really are proud about the YUVIWEL, we saw all the expected benefit related to linear growth, we saw effect beyond the linear growth that was much better than we ever had hoped and just with the -- like government providing that alignment and what we saw from the safety, which are also illustrated in the label, extremely, extremely safe product. And I think that is what I'm really proud of. Thank you so much for today.

This concludes today's conference call. Thank you for participating, and you may now disconnect. Everyone, have a great day.

[Audio Gap] 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 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 continued to strengthen. We believe we are now at a base of a steep growth 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 [indiscernible] product opportunities. In the fourth quarter, we saw multiple achievements across the organization. Starting with Europe. 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, to 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 European treatment, highlighting the significant long-term growth opportunity ahead. The overall insurance approval rate is about 70% of the 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 patient initiates UFS in like the 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 to name patient programs in more than third countries. We have full commercial [indiscernible] in 4 countries, in our Europe direct markets and 2 countries in our international markets. In Japan, our partner [indiscernible] launched YORVIPATH commercially last November. In 2026, we expect food commercial launches in 10 additional new countries.

We also advanced development activity to broaden YORVIPATH label in a number of areas. In the U.S., we are working to expand the range of doses to our partway 6 trial. And globally, we continue to advance clinical trial to expand YORVIPATH to patients under the 8 of 18. Our work is progressing rapidly on once-weekly TransCon PTH for patients who have been titrated with daily [indiscernible] of conventional therapy and have achieved a stable daily dose for a well-definedperiod.

Last month, at the Annual JPMorgan Healthcare Conference, we shared preclinical data that support the target product profile for a once-weekly TransCon. Candidate matching the released PDAs seen with daily YORVIPATH treatment or the entire week, thus providing a comparable efficacy and safety profile or we remain confident that Europe has the potential to be a doable long-term growth driver for Ascendis globally.

Turning now to growth disorder. Combining of our once-weekly growth hormone, [indiscernible] or TransCon Growth Hormone or on weekly TransCon CNP. Sketch over 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 relating, TransCon Growth Hormone in additional established got hormone indications, including ISS, shock deficiency, Turner syndrome and SDA we compromise up to half of the growth come market. Over the long term, this indication represent meaningful opportunity to expand the road of SKYTROFA as the treatment of choice in additional group disorder. We also see an opportunity to potentially expand SKYTROFA used to novel indication their growth hormone has not previously been approved for use, such as achondroplasia in combination with TransCon CNP. TransCon CAP is expected to be the first and only 1 weekly treatment for children with achondroplasia, providing the full linear growth outcome that can be achieved with monotherapies addressing the overactive FDR3 tyrosine kinase.

In addition, in our pivotal trial, TransCon CNP achieved significant improvement in lag Boeing compared to placebo, increasing [indiscernible] dimension and a similar safety and tolerability profile compared to placebo, with a very low rate of injection [indiscernible] and no cases of symptomatic hypotension. In the U.S., our NDA for children with economic 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 2020. Recruitment of our ongoing trial in infants with [indiscernible] 0 to 2 is going well, and we activate complete enrollment later this year. Turning to the combination therapy.

Our 52 VCOs data in [indiscernible] underscore the potential power of dual treatment with TransCon CNP and [indiscernible]. We have continuous exposure to CNP enables the benefit of sustained exposure to unmodified growth hormone. In comparison, monotherapy trials of daily growth hormone in [indiscernible] 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 [indiscernible] with linear growth improvements in [indiscernible] place a specific [indiscernible] 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 improvement in body proportionality and for the first time, and meaningful improvement in ARM spend has been reported without compromising safety or tolerability. Importantly, this benefit burn height are meaningful to the achondroplasia community and have been a core object 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 receive. These Phase II results demonstrate the effect of these complementary therapies, supporting that TransCon CNP at internet with growth-promoting effect of TransCon Growth Hormone and has positive effect beyond linear growth. We believe over time, the standard care in achondroplasia and order growth disorder long term will include dual therapy as a treatment option, building on the potential road 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 to align on our Phase III trial for this novel combination approach for treatment children with achondroplasia. We also remain on track for additional codes trial update including week 78 by midyear and week 104 by year-end and plan to explore further opportunity in other group disorders. -- to sustain dual 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 lot product opportunities, both inside and outside [indiscernible] product revenue growth in the future. Looking at our partnerships.

TransCon Technologies support a continuous flow of highly different sale product opportunity across multiple therapeutic [indiscernible], 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 [indiscernible] continue to advance towards the clean. [indiscernible] TransCon and TBTF is on track to enter the clinic this year. In Japan, Japan received approval in US in August '25 and commercial long in November 2025. In addition, been approval of SKYTROFA in China in late January '26.

In summary, was another positive and transforming to sales. With 2 commercial TransCon products continue to scale the potential approval of the 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 global long-term growth. a rapidly strengthening financial profile, [indiscernible] confident to achieve an expected operating cash flow of around EUR 500 million in 2026 and our aspiration to achieve a least in a product revenue by 2023, all consistent with our Vision 2030 strategy. I will now turn the call over to Scott.

Thank you, Jan, and thank you, Chad, for 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 and while advancing development of our once-weekly PTH candidate, successfully launched 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 a 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.

Yes, can you remember, you asked me a question, one time and the TPM 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 ask me, will TransCon PTAs 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 10%. So I think the highest bar 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 [indiscernible] 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 will not say preprepared remarks.

Yes. I would say 2 things. One is that we're very happy 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 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, [indiscernible] 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 it 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.

I think still we need to summary. 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 have been 6 months to it, you actually will get a much higher number on it. Just to clarify 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 [indiscernible] 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% electable and already approved for reimbursement.

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

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 have never done it, and I don't think we ever will discuss net prices. .

Maybe 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, is 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 quarters now. When we come to here the fifth quarter, I think you have seen the steady state development from '25 where we basically got to be increased in basic revenue from both U.S. and x about EUR 40 million to EUR 50 million net every quarter. I think you will always 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, I'm 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 Cowen.

I have sort of 2 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 your how it's being used out there? I mean it's almost like when you look at the 2,400 unique prescribers and 5,300 unique patient enrollment. 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 at 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 JV, you can give some about how we're both expanding the physician prescriber think 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?

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 [indiscernible] 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 [indiscernible] as well as increased awareness of the hypoparathyroidism condition, and now there are 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 or 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 [indiscernible]

Before you start, perhaps I can answer the last part of the question related to the COACH trial. Yes, we had extremely positive meetings both from U.S. side and from the AU 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 basic on [indiscernible] 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, but really important element, the AMP spend where we also saw in the combination trial and unique improvement in [indiscernible]. And Amy is sitting here with advertisement and she is really doing everything to get this trial erected as far as we're ready to go protocols finish and everything, be open sites. Just remember that our pivotal trial in monotherapy, we receded just in 3 or 4 months. just because of the interest of the patient. So therefore, the bar for AM is very, very, very hard if you need to do that faster. Sorry to coming in.

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

This is [indiscernible] on for Joe Schwartz. So can you help us understand how the TransCon CNP launch could factor into your $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 loans, we see the initial uptake we believe it will be pretty high, not only in the U.S. but also outside the U.S. because we can utilizing the U.S. approval to go to countries outside U.S., specific 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 mining, [indiscernible]

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 your bypath 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 and 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, seen 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 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 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 country basic on full commercial, we will see different uptake, but what we are doing is everything will be accommodated in the way where we now see from 30 to 35 countries named patient programs. And when we go full commercial, what we see are place, it's basically is an acceleration of patient uptake because of the burdensome nature of a named patient program, it takes [indiscernible] effort really to get every single patient on it and every patient deserves to be under treatment. So when you come to '26, we will see initial speeding up in all this country. And when we come to '27, '28 you will continue to do it because just in nature, we just got approval now in Canada, and we've basically taken 1 country after [indiscernible] first going in and getting approval, and then we go into full reimbursement.

Our next question comes from the line of [indiscernible] from Cantor.

It's [indiscernible] on for Lee. 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 [indiscernible] compared to 1 every second year, being in a position to look on no risk of hypotension to the element of just having the improvement on 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 [indiscernible], 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 is all this will happen.

And our next question comes from the line of [indiscernible] from Barclays.

Curious if you can elaborate on your strategy for commercializing TransCon CNP U.S. Just given the majority of [indiscernible] 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 dive 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 Europe. And now you see what we have done with we recognized very fast revenue -- commercial revenue for more than 30 countries. We are penetrating them exactly as we can do. We will reach 60 countries in less than 2 to 3 years. So what we have done, we already have built up for infrastructure to be ready that we can take our integrated pipeline of rare disease endocrine product basic into all these different countries in already the setup we are stabling around our pads. So this is the positive element that we are not, and you can say, a company that needs first to take up an infrastructure to support a globalization. We have already stated that. So I feel really, really, really confident that all the success we're seeing now with our path on a global scale we will just take it in. Don't forget, for example, even in Japan, the collaboration we have with [indiscernible] 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 over and make new agreements or anything. It's just going down extremely fast from that perspective.

Our next question comes from the line Leland Gershell from Oppenheimer.

I wanted to ask, [indiscernible] 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 some. 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 see in our forecasting are operating under different assumptions, where we basically building up model for each single country and then we accumulate that on a global setup. And we first basic are taking the we take 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 one. 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 1 single product in 1 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, 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 out from that perspective is 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 each single product opportunity in start 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 best society and everyone.

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

I think your Phase II [indiscernible] 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 that 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 will that require a separate study?

I think when you discussed a little discussion that's typical is different between -- now I'll 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 and hands where in Europe is much more flexible because you have a discussion with them, and you can have basically what I call [indiscernible] addition of data that is being generated to our trial. So there will be likely a difference between geographic region now simplified. Japan is most perhaps the easiest way to get it down to infant in Italy. 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 expectation. 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 Amy 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 that part of the randomized piece of 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 -- so pleased with the progress we're doing in helping patients with a contemplation, 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's no such need to rush? And also, you mentioned matching PK to the daily product. So with data from our path available, what do you see as the most efficient clinical pathway to maybe take the weekly PTH 2 approval.

I think what you're addressing is 2 things that is interconnected because if you, for example, can show the PK profile, and they can even be healthy volunteers or patients with [indiscernible] over the time week of treatment, you basic are bioequivalent to Europe. And that is the aspiration, how we designed it, that you basically will obviously be in excellent PTH level compared to Europe at daily dose for the entire week. Then we know you basically will get the expected safety expected tolerability from that perspective. And this will make a much, much more simplified way to in terms of the clinical trial. And it was why we designed it exactly in this manner.

And our next question comes from the line of [indiscernible] from RBC.

On the progress. Maybe a kind of big picture, I think one of the goals for 2030, as you articulated, JPMorgan is to remain an independent and profitable biotech company. And we obviously have seen many successful example 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 you're thinking about strategic past A versus strategic path B at this point. So any color there, much appreciated. And then maybe, Jay, quickly, I think [indiscernible] has announced that they will file [indiscernible] 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 a material for adoption in obviously have less frequent [indiscernible]

I think I will liberate [indiscernible], for answering the last question. I think -- when I look on this discussion on accelerated approval that biomarine filing for that has no impact on our regulatory pathway and approvals and other things like that, totally independent. It's not any way how you can build up any bar or anyway in this way. The second thing, yes, in our vision, there is independent. And I believe that is a great word because we want to be independent like teenage are growing up. And one of the things you -- at least I have 4 children, I'm teasing them, when they were going to be 18, you need to be financial independent as the first element in their life. And I think that is a great thing to see [ Ascendis Pharma ] now moving away for being a teenager, but basically can go up to a more adult life because we have shown now we are complete independent on basic 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.

My question was asked, but I'll just take a shot at this. Can 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. [indiscernible] to all the element and all the IP we have done, filed 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 month simile. And the idea was to be sure that you can get fast loans, at the same time, have high level of tolerability. And so just think about -- I can define it, you have a naked [indiscernible] molecule. That basic when you give it in and quickly or potentially want to use a weekly product in advance monthly, you need to add up much more compound to compensate for the half-life to have a large. But doing this, you add a high max dose. And because it's nice, you will have very short [indiscernible], 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 gives a 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 Mercer and everything [indiscernible]. What we're doing now is defining and what we call packed in smile. So even if you give it high dose, you liberate it slowly, slowly, slowed. So we're getting [indiscernible] doing that, you basically have a slope that is not as steep as all that you see with a nice molecule. Then you can see you still have a big because you basically provide some must 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 maximum weight loss as fast as possible with the best tolerability profile, and this 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 specific 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 era and scale that we have now.

And our next question comes from the line of [indiscernible] from Wolfe Research.

I had one of the competitive landscape. Wondering how you're thinking about this internally as other agents like [indiscernible] and Celera are looking to expand into the chronic hypoparathyroid in landscape? And then does your longer-term outlook for your betas include that potential impact from such emerging agents.

So I can be polite or it can be a straight tube. 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 at [indiscernible] and giving incurred is not increasing and providing any [indiscernible] to this. We're talking about a hormone replacement therapy where you're helping multiple organs, the brain, so you have greater cognitive effects. [indiscernible] to have the right metabolic system. The kidney needs to have the right phosphate illumination. We need to have the right catch-on absorption and I can continue on organ after the other alum. And then you believe you can take a compound [indiscernible] that basic are casusynthesizing 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 [indiscernible], but that is not any way coming in as a hormone replacement therapy. So no, we have not calculated that in. There has an idea in 'ADH1 patient, which have a mutation in the calcium sensitizer one. It makes sense for this small amount of patients that makes sense, but not for a person that [indiscernible]

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

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 [indiscernible] and also the earlier stage long-acting CNP from [indiscernible]?

Yes. I think that is an interesting aspect cost? We have seen the benefit of CNP therapy for multiple years now. We are seeing it in last patient population and one of the things, a 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 carve us and trying to develop a product that basic are providing and sustained liberation of CNP over 1 week because they have seen out from our data, how we highly differentiated compared to for the website. So that is a complete different case about do they really have a once-weekly product or not. You cannot just that out from you need to see the profile over 1 week and other things like that. So as I'm not seeing these data on anything on the long-acting product for BioMarin. I do not know if anyone can just that is a viable product opportunity in any way, then we need to see the PK fold, get the half-life and all the different things, then we can take a judgment about it. The element of [indiscernible] kinase are a complete different element for me because that is an element of using a nonspecific action of a compound that basic are addressing the tyrosine kinase. And if you go to the BridgeBio is a nonspecific tyrosine kinase that both inhibit the 3 different compound FDR1, FDR2 and FDI. This is why it's called nonspecific. And what I'm not worried about? I'm not a word that you will see a treatment effect because when you address the tyrosine kinase we basically see an improvement in linear growth because you basically are in a position that you are in [indiscernible] super active pathway. Will we 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 [indiscernible]? Can we see all the element of improved quality of life with that. But [indiscernible] is the nonspec thing. And I really don't care about phosphate. People say, oh, are you worried about it, they have elevated phosphate. First of all, innovative 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 a treatment on each single subject has and impact on the phosphate level. If it has impact on the phosphate level, we know is a nonspecific inhibition. [indiscernible] and when you have a nonspecific inhibition of FDA 1, you also have nonspecific inhibition of FDR 2. And when you know that [indiscernible] is one of the key receptor that is part of really the CNS development of the rain, I'm extremely worried because this is not something you really see easily in a preclinical model. You don't see it any way in the short-term clinic trial. You see it after 3 perhaps 4, 5 years per treatment. [indiscernible] our patient focus. How can you really except that any patient should take this risk without being extremely well informed about it.

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.

I'm Jess Fye, a biotech analyst at JPMorgan. We're so excited to be starting the 44th Annual JPMorgan Healthcare Conference this week with Ascendis. The company's CEO, Jan Mikkelsen, is going to give a presentation, that's going to be followed by some Q&A. But first, it looks like I'm going to pass it over to Scott Smith, the CFO, for a forward-looking statements.

Thanks a lot, Jess. It's my honor to read the first FLS of the year for Ascendis Pharma.

Before we begin, I would 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, continued development of SKYTROFA and YORVIPATH as well as certain revenue and growth expectations, our pipeline candidates and expectations with respect to their costs, continued progress, potential commercialization and success, our strategic partners, partnerships and investments, our goals regarding our clinical pipeline, including timing and results of our clinical trials and our ongoing and planned regulatory filings and expectations regarding the timing and results of regulatory decisions.

These statements are based on the information that is available to us today. Actual results could 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 our press release dated January 9, 2026, and the Risk Factors section of our most recent annual report on Form 20-F filed with the SEC on February 12, 2025. And with that, I'll hand it over to Jan.

Thanks Scott. There was the first 2 minutes. So this actually with extreme proudness I'm standing up here today. It started actually in December last year because we really had a celebration.

Ascendis Pharma turned out to be 18 years. At least in Denmark, it means one thing, you throw your children away and they are financially independent. That is the key thing. You don't fund them more. That was exactly what happened at that time for Ascendis.

After 18 years. We came to the states, building on our TransCon technology, build it on our R&D engine, building on our late stage clinical development, building on what we call the last states of the rocket, how really to do global commercialization. We came to the stage where we 2 quarter of profitable business.

I call it going over the black hole because so few companies managed to come to that. So when you think about we basically are the edge of growing up. We're on the edge really to be an come a leading biopharma company. Looking on the numbers, Q4 product revenue above EUR 240 million with the entire year of about EUR 683 million.

And Scott, which are really strong in numbers calculate that it really impact a major increase in the year of '25. And that will continue. This revenue base is built mainly on two products, YORVIPATH and SKYTROFA. This is like having two bullet being fired and you already see the benefit on it and now the last bullet in coming, where we basically have our PDUFA date for TransCon CNP here end of February.

But we're not stopping there because I think this is the key thing with Ascendis Pharma. We got built on a strong technology platform, the TransCon technology. And we will sustain leadership to new product development, LCM activity and other patient offering we can do.

But we also creating value outside where we're known from our rare disease. We have in ophthalmology, our spin-off company, Eyconis, in obesity and metabolic working with Novo Nordisk. And in oncology, we have our own internal development. I will come back to some of this later on.

So -- but I always like to take vision up because this is our guiding principle, where do we really want to come. And it gives us really the strategic road map for the next years until 2030. And you can see we basically have changed single bullet. Is the first bullet? Because we're now feeling confident that we can take and have a revenue of more than EUR 5 billion in 2030. It will be a global revenue where we aiming of having a split between U.S. and ex U.S., where we believe the majority will come from the U.S., but that will be a major, major contribution from ex U.S. We will be the leader in growth disorder in hyper power. We are already there, but we will continue to an investment in new chemical entities in our LCM activity and other element in it. And as Kennett will explain later on, we're now expanding our rare disease endocrine pipeline with two to three product opportunities.

Don't forget to the TransCon technology are in a unique position. The way we use our algorithm is that we basically have got basic now, expect to get three out of three, start with three preclinical candidates and get three products to approval. And they are highly differentiated and no one ever can really repeat and make them. And I think that is the value you see in Ascendis Pharma. This is a sustainability with durability because of our IP and other things and also this is combination product. We will still go through our areas of business model where we're still investing in other areas rare disease endocrinology. For example, in obesity with our collaboration with Novo Nordisk in ophthalmology, where we really see the applicability of the TransCon technology also making highly differentiated product.

But we will always be working on the fundamentals for us. [ Outcome ] outperformed industry drug development benchmark, try to be extremely successful and really live up towards values the patient signs and the passion. So this is what everything we're doing is built on. And that is a technology platform expanding year-by-year. We see being expanded again.

Now the latest one is for protein degraders, where we basically can take hormones other things away from the body in a continual manner. This is our late-stage pipeline. This is our current pipeline internally only in basic in from our rare disease endocrinology products.

Going to our R&D platform. Today, we have two products approved. We have three indications: two new launches, label expansion, partnerships, we have an aspiration for 2035, 8-plus new chem approved that all durable long IP, highly differentiated sale, plus 25 indication. And you can see the fundamentals there. There is some of the new product opportunity that are coming up. And you can also see there will be in larger indication being split into partnerships.

Going to TransCon PTH, our leading product in hypopara. This is just giving illustration about the, you can say, the size of this market here. In U.S., 70,000 to 90,000, which are what we call the lowest number. Some people actually believe this is 100% higher. Europe Direct 150,000 to 200,000 and international market, a huge market. And this is where we're building up a global commercialization.

So currently, we see the big driver of the revenue increase is mainly been from the U.S. side. But what we see by long-term basic that ex U.S. will take over more and more because it's much more fragmented, it takes a longer time to penetrate, but you will really see the high value because of the large patient population.

So this is what we call the global commercial update. So if you start on U.S. we have 5,300 a unique prescription. We have nearly 2,400 prescribers. So you can see we have a constant flow every quarter up nearly the same amount of prescriptions and we see the broaden above the prescription basis.

Still a unique opportunity with less than 5% basis on drug today. Your direct, we only launched in countries now Germany, Austria and Spain. And Spain only started in Q3. Here in '26, we expect to have up to plus 10 countries coming in.

So this is where we see that big span of country coming in Europe direct. This is where we have direct commercialization. International market, we only covered to named patient program and but we have distribution agreement 75+ country. And we're also seeing our partner, Teijin, got the approval, had been launched in Japan, which we're really looking forward to see also how we penetrate this market segment.

Going to the right, you can see the increase in global revenue. And it's pretty clear we're really increasing and accelerating the revenue EUR 40 million to EUR 50 million every quarter.

Why I call it to building a big house. This is like the YORVIPATH skyscraper in Manhattan because you're basically building one or two floor every quarter and it's getting to all because patients stay on treatment. They stay on treatment, this is why we see this acceleration in revenue, which we hope we will see the same thing in '26. And then we will see the biggest, biggest tower ever being built in the Manhattan.

So there's been a lot of discussion about how we look at once weekly product. And we had a once-weekly product. And we had also a clear way how we see the utilization of the [ once-weekly ] product. We cannot see any other reason that every patient needs to be [ titrated ] with a daily product. Out from the that you are taking a lot of convention therapy at the same time, you're adjusting the dose to be right for the patient, doing that with a weekly product, make no sense.

So when we see the utilization of a on-site product will basically when we have stable patients. We believe about 35% to 40% will be stable when they have been trade to a stable level of YORVIPATH. For them, we really believe it could be a benefit for them to move over on a once-weekly product. If they then feel that we are in a position that change for them. They need to change their life. They need to have more exercise. Sure, they can go back to the once-weekly product or add in one daily product.

So we develop one product, but we also No, we made a benchmark with YORVIPATH. And if you go to some of the FDA regulatory documents, it's quite sure when there is a benchmark on a daily product, you cannot compromise safety and efficacy. So what we did, we needed to develop a complete new product when we saw that and got that interaction. And we said, we need basically to be bioequivalent every day in the week with what we call a weekly product. And that is what we develop here.

If you see our -- to the left, this is in monkeys. And when we do the human prediction, which we always have been 110% spun on. We never had anyone to have been different. You see the profile over once weekly, and then you compare to your kind over 1 day.

Clearly, all the interval or this is basic is a bioequivalent. It's the same product, the same active ingredients, the same element, the only thing we're changing is building. So there's a really believe there can be fast condensed program and helping the patient that really want to move over to that.

So when I look on our TransCon PTH is now indicated in adults. We had Q4 revenue of nearly EUR 190 million. And we saw a full year revenue on EUR 40 million to EUR 70 million, EUR 480 million. When I see U.S. expect to see a estate increase in the U.S. If I go to ex U.S., we will see in '26, likely an increase we're getting more and more country on board. We're getting more and more full commercial, we move away from name patient program. So when I see the ex U.S. for the next 3, 4, 5 years, you will see much more growth there in what I call ratio.

Clinical program to expand the labeling in the U.S., we have our PaTHway60, where we have a program to move up to 60 micrograms per day. And we have pathway going on to younger children. Now we are in the state for 12 to 18. When we have gone through that, we will likely go down to the lower children. The once weekly, we have it, we believe in this. This is exactly built on technology, where we never, never have failed on a preclinical candidate. We go into our global commercialization, and we expect launches in 10 additional countries here in '26.

And this is a doable product. When I look at the competition, I see no competition. If I look on the lifespan of this product, that is a combination product. There will be there probably next 10, 20 years. And this is why I don't see any way where we know going for what we call value optimization in each country. We are not going for sprinting into the market. We are going for the value optimization.

Going to SKYTROFA, I really love this product. It's approved in U.S. and other countries in a single indication, pediatric growth hormone deficiency. In this year, we expanded into adult growth hormone deficiency in the U.S. It was our first label expansion. We now have a basket trial for basic additional indication that we are running now. So we can basically explain to all the established growth hormone indication. We are also going to a new era, combine it with, for example, TransCon CNP in achondroplasia and hypochondroplasia. And what we want really to do really make this to a growing, growing product. How do we do it? Growing the basic business.

And we have a strong belief that were happening, we see the consolidation of the daily growth hormone. We see also how SKYTROFA in a best-in-class properties really increasing the brand share. We expand the traditional growth hormone indication. We add no new novel growth hormone dedication, and we broaden the geographic reach. This is how we're building this up to a blockbuster product.

Going to TransCon CNP, we decided TransCon CNP to provide a sustainable exposure of CNP of wild-type CNP in the product technology to avoid any kind of injection site reaction. And this is what we saw in the peer-reviewed validation of it. Yes, the enhanced linear growth as much as ever, you can get out of the inhibition of the tyrosine kinase.

We give for first time, benefit beyond linear growth compared to placebo in a controlled trial. There was no evidence of hypertension, low hemogenic signal. And because we use the product technology, no injection site reaction and once weekly administration, so where are we? Yes, we achieved really the target product profile. We have now durable response for up to 3 years in our open-label extension, we have our PDUFA date here in end of February, and we have our EMEA submission where we expect a decision in Q4.

I have no doubt that TransCon CNP really are providing the benefit that is needed to this patient group really showing benefit beyond linear growth because that is the key element. But we also want to improve can we boost the response if you have a child that has not been treated just for being newborn. And that is what we have done in our combination therapy, which I will come to next one, so the idea is this basically is when you do have achondroplasia, you have a [ hyperactive ] tyrosine kinase.

This is basically putting a brake on the system. This is taking car sitting up on a hill here in San Francisco, and then you take a brake on. It stand there. And this is what you basically see in this situation. When you increased, let the brake go, start rolling and independent, how you let the brake go, if you take it on electronic, you take it by hand or other thing. They're basically moving up to the same growth velocity, about 5.5 to 6.0 in annualized growth. Depending on gender, you can see it much easier in set score about 0.3. This is what you get when you remove the break.

But the idea is that when you move the break you basically have a new opportunity to take a growth stimulation, and this is where growth hormone comes in. Because you can nearly see for this scheme, if you take the green one and basically move the break, then you really can get full potential of both hormone. So when people say, growth hormone is not functional achondroplasia. Yes, it's not functional when you don't have the brake off. If you have a brake off, you'll get perhaps 1 centimeter in 1 year.

I heard some people coming and explain to me, we're getting 8 centimeter. Then I said, if we're really getting 8 centimeter, then quite sure growth hormone will be utilized everywhere in the world and not only in Japan. It's pretty obvious, no one gets 8 centimeters. This makes no sense. So you get about 1 centimeter when you really give it and it's not really durable or 3, 4, 5, you still get some benefit. And there was a, why you can see addressing is tyrosine kinase come in. That is already by what we are doing.

So when we see here the safety because that is basic #1 in any pediatric indication safety, safety, safety. The risk of exposing a tie to something that can harm it can give late-stage complication or anything like that. So when we look at this one of the best safety I've ever seen in this indication. So this is really the key. If any one of you look at this year, it basically of this year and is focused on growth velocity. So if you take the gray, that is new patients. And you look on the gray curve or the gray scattering, what we you achondroplasia growth chart, you have 50%, which are a normal growth pattern of a child with achondroplasia. Then you have the 50% and 95%. This is how you can take it. average state child is what a normal child will go off. And this is the blue one. And there, you can see we have the 3% and the 97%.

So when we take naive patient into our combination trial, they are growing at 4.92 centimeter per year. And when you go up and look, oh, they're the 50% factor. Oh, they're growing exactly as you expect of a achondroplasia child?

And will they come into the combination, they're actually growing more than you see in a normal child in across growth bus. I have no belief that could happen.

Let me say what is then from the children that is already happening in CNP treatment for about more than 2 years. Okay, look at them. They are starting not under 50%. We're starting much more up on the 95% fracture, because they've got CNP therapy for 2 years, and therefore, we have a benefit on it. But when we give them growth hormone, the are moving.

So independent, if you have been on CNP or not on CNP, you basically can see that you basically move the children up to a growth spurt more than you see in a normal child. If anyone have seen that more than one [ phase ], I've never seen it. And I don't didn't believe the basic possible to do.

So what is really happening with the growth of the child? Are everything being built in a normalization of the child, [indiscernible] and body proportionality, never seen an improvement in body proportionality to that level before. And then something completely new.

We have never seen that to a level on monotherapy in any way, increasing the life arm span. And that is a key element for the commodity that really limits them a lot of physical activity, the short arm. And when you see that, you see the same pattern, the no patient moving up but also the patient that has been on CNP moving up over the 94% factor, never seen before. First time I ever seen an improvement in an important comorbidity as arm span.

So there has been a lot of talk about really winding off the signal. It's getting weaker and weaker. And there haven't been discussion on that, oh, there is negative growth in I do not know so much I hear some time. But when I look at this curve here and then look at just too well right, TransCon CNP monotherapy. And look on the 26 week and 52 weeks. And you see a small decrease 3%, 4%. When you go and see on the COACH trial, the same decrease 3% to 4%.

So what is really happening is you unblind a complete new biology where the binding effect of growth hormone that has been seen in achondroplasia is not existing. And if people don't believe it then look at the data, that is the same limited small decline that you see with CNP monotherapy.

Really, really unique data. I've never seen any time before. So when I look on this program here is why we really are going to be the leader in growth to because we exceed every historical benchmark for growth without compromising safety and tolerability. This is a new benchmark. Go out and ask anyone else get this same effect and see if you can get it. And the safety is really that's what you hope for.

CNP has proven to be one of the most safe therapies for years and years in patients. Growth hormone has been the same thing. So combining two safe, well-known things in a pediatric indication, yes, 100% of the children completed, still on treatment. The burden of two injections a week is far out for what the element of the benefit we see. And the bone age remain consistent with chronological age.

We had end of phase II meeting with FDA. We went in and started now the Phase III trial. We have signed the protocol and start enrolling patients in Q1. We will also come up with the week 78 COACH data here in Q2. They continue now in 2 years, it's an open-label extension for 1 year more, and we initiate new trials where we're also using company. This is the most powerful combination in the 20-plus growth disorder that exists today.

Collaboration partnership. Novo Nordisk, yes, we developed the first once-monthly product with the best profile ever seen. There was why Novo Nordisk signed agreement was and not other companies. And it's on track.

You will see the benefit of that. It's a unique product. Before Eyconis, where we took all our ophthalmology product in really moving forward. Also they're going in clinic this year. Teijin, they have our right in Japan, and they're excusing excellent, get the first product into the market now. And VISEN is doing the same in China.

Financial update. This is typical a slide that is dedicated to Scott, but Scott gave to me to take to go to it. And when I look on our product revenue, EUR 683 million, yes. We really were we moving up. When you just look at the number for [ EUR 200 million ] for '24, huge [indiscernible] [ statements ] and it continues.

YORVIPATH is the main driver of the acceleration EUR 477 million, SKYTROFA EUR 206 million, totaled full year, EUR 720 million. And what we always said, we invested in highly profit product. You don't pay bills with revenue, you pay bill with profit. And that is what we're also doing in SKYTROFA. We only taking really the revenue when it's highly profitable. So we even in '25 increase our profit range there.

Total full year operating expenses, EUR 762 million, really control it, really take it in the way we want to do it. Cash balance, [ EUR 616 million ], increasing quarter by quarter now. And we expect to have an operating cash flow of at least EUR 500 million.

This is the dedication and how fundamentals are, how we can accelerate revenue. At the same time, we can control expenses, but not compromising our investment in globalization, not compromising our investment in life cycle market not compromise any of our investment that's coming in further. We also plan to buy at least $120 million shares back this year because the board said to me, yes, you're not a bank, you basically need to do something with your cash.

So this is the R&D milestone for '26. And you can see, we expect the CNP approval here in the Q1. We will come up with a 78 weeks data here in Q2 from our combination trial. And as a little good, we will come out with our overall survival in platinum-resistant ovarian cancer, this is over cancer, where we enrolled 7 patients. We expected it to here in Q1, but it's actually really positive when you delay OS for 1 quarter in my view because it does meaning is that we're only in the 30s. So we still have a long to go before we can go up to the OS.

TransCon [indiscernible], complete enrollment of the achondroplasia infant trial. We then have Q4 pediatric EMA decision of CNP, initiate proof-of-concept study in adult. This is also where we move in. There is a lot of comorbidity in adults, and we really have a product that really can show this benefit. We will give you the 2 years update from our combination trial. We will complete recruitment in our basket trial, and we also will have complete enrollment in PaTHway60 trial.

So thank you a lot for listening to us today. The Ascendis team is really proud. We feel we are on the edge of really being a leading biopharma company, we had all the fundamentals before the TransCon Technology, our R&D engine, our commercialization. We really built it up in the last 2 years to be a global commercial organization, and now we see the revenue coming in. And this is where I said Ascendis Pharma edge to be a biopharma company. Thanks so much.

So we're going to go into Q&A here. And if you're in the room, feel free to raise your hand or can send me questions on the iPad up here through the portal. So YORVIPATH been off to a very rapid start. How should we think about the growth drivers in the U.S. and Europe in '26? And are there any like underappreciated factors that could meaningfully influence the ramp this year?

That's divided in U.S. and ex U.S. And I think, Jay, you would take U.S., how you really are ramping up and doing all different kind of effort to really expand in extra rates.

Sure. So I would say in the U.S., we probably have three primary focuses. One, as you saw earlier, the penetration in the U.S. is still quite low, right? So there's a lot of opportunity remaining particularly in a rare disease condition where there's still an evolving understanding of the condition itself.

So the three things specifically, I would say. One is we're still engaging heavily in increasing that provider education and base right? So there's still ample room for us to increase not only the number of prescribers that may be prescribing something for the first time beyond conventional therapy as well as expanding their perception of the eligible patient for hypoparathyroidism given that some of these patients historically have just primarily been treated with conventional therapy.

The second area I would say is patient activation is a big piece, right? So whenever you're looking at any kind of underpenetrated larger group of patients really thinking about how you reach a diffuse group of patients that may not have established care, thinking about how to reach them through digital channels. that's going to be a big focus for us in 2026 as well.

And then lastly, I would say the third is we're constantly investing in just how we approach access and patient support, recognizing that experience, particularly, again, in these rare conditions is incredibly important, not only because it's the right thing to do for the community, but also because it materially impacts that patient experience while being treated with YORVIPATH.

Ex U.S., we're using some of the same strategic element for discussion in Germany, for example, the most mature country from our European launch.

In the other countries, you can say it's really, really simple. Get full commercial launch, and this is where we expect to add at least 10 more countries.

In the U.S., there last year, there was a lot of focus on kind of the time from a patient getting their prescription to when it was reimbursed. How do you see that evolving as the launch goes on?

Jay?

So I would say that a lot of the evolution in itself is time, right? So when you think about Evolution, there's a difference between like are you doing anything materially different from an activity standpoint. And I would say the team is doing the things that you would expect to do. Because the clinical value proposition is so strong for YORVIPATH, it's important for us to be able to continue to tell that story.

But the time lag that you see for a lot of these rolling staggered reviews for a lot of the fragmented payer in the system in the U.S. simply requires that time, patience, discipline, continued engagement and education, so I don't think the strategy in and of itself will change because the value proposition is strong. But I do anticipate that the needle will continue to move upwards that you would expect with any launch trajectory. But we actually feel really good about where we are today. And I think the percent coverage and approval rates that you're seeing so quickly out of the gates is a testament to the strong clinical value proposition that we have.

Great. Getting audience questions in here. So for TransCon PTH over path, given the low level of penetration in the U.S., can we expect quarterly new patient adds stabilize at the level you saw in the fourth quarter?

I think what seeing now is steady additions of new patients. And I think next year, again, were the three areas that we talked about. We do anticipate continued growth throughout 2026. So we're optimistic that we'll see that continued growth.

I think yes, we also need to look on the penetration we down on perhaps 3%, 4% of the patient population. And when we look on the clinical benefit we have provided to our clinical trial there was no one single patient group or patient that didn't benefit on being on treatment.

So in a theoretical optimized positive world, 100% of the patients should be on. Think about having type 1 diabetes without insulin, having hypopara without PTH for me, it's the same thing.

And some other questions coming in on the weekly PTH product. Can you elaborate on what the differences are between this weekly PTH and the MBX product? And can you talk about the registrational path for the weekly? What could that look like? Could it just be of PK/PD bridging, do you need a separate Phase III efficacy trial?

Yes. I will start with one and Kennett will take over. I think the key element, how we designed our once-weekly product is to build on your part, the same mode of action, the same active ingredients, the same way to designing, just changing the linker. So we basically are taking the same benefit you have seen with YORVIPATH. We expect also to tie with our once-weekly trying to cope.

About MBX there's nothing to do with basic the benefit we see with YORVIPATH or anything like that. And Kennett, you can explain the mode of action because it's completely different design of this molecule.

So what we wanted to do is build on the success that we have with YORVIPATH and having the release of unmodified PTH second reach receptors in all of the target tissues. So when we wanted to design the once weekly, we wanted to be able to do exactly that.

As Jan was mentioning in the presentation, we actually made a first generation once weekly PTH. This molecule actually had a peak to trough of 1.7, and by the modeling that we also showed that we are doing for this compound, we could see that would probably be too much over the course of a week. So you would have periods where patients could hypercalcemic and times where they would be hypocalcemic over the course of a week because we have set that benchmark with YORVIPATH, where we have a peak to trough of 1.3.

So we knew what the outer bounds for peak to trough could be. So we actually had to come up with new technology or new TransCon linkers that would address that particular point. And this is what our scientists have been able to do. And this is why you can now see over the course of a week, we had exactly the same variation in plasma exposure as you're seeing with YORVIPATH. And this is why we're quite comfortable, I'm not comfortable, confidence. If I have been Jan, I would just continue talking nobody would have understood confident that we actually have the right PK profile to address the needs for patients over the course of a week.

Just to sum up, Jes. YORVIPATH, TransCon once-weekly TransCon PNT . It's extremely durable product. If I look on the competitive landscape, there's nothing, nothing that's living up to the benefit we see with YORVIPATH. So this is why when I look in the next 15, 20 years, I cannot see anything that can come in and basically in a position to substitute or just living up to the standard of benefit we're giving with YORVIPATH. MBX, a complete mode of action, not giving anything what I call in replacement therapy, totally different mode of and the lack of data, I think, also illustrate it.

All right. Last 30 seconds. Can you remind me what your peak sales expectations are for YORVIPATH?

In the U.S. or global basis? I think it will be at least EUR 5 billion to EUR 8 billion just for that problem.

Worldwide?

Yes. But I'm typical, I'm wrong because I'm very conservative from the country side. So likely it will be higher.

Great. Thank you.

Thanks very a lot.

Thank you for standing by, and welcome to Ascendis Pharma's Phase II COACH trial top line week 52 data Call. [Operator Instructions] I would now like to hand the call over to Scott Smith, Ascendis Pharma's CFO. Please go ahead.

Thank you so much, operator, and thank you, everyone, for joining us on today's call. Joining me are Jan Muller Mikkelsen, President and Chief Executive Officer; and Aimee Shu, Executive Vice President of Endocrine and Rare Disease Medical Sciences and Chief Medical Officer. Before we begin, I would like to remind you that this presentation 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 continued development of TransCon CNP and TransCon Growth Hormone combination treatment, our pipeline candidates and expectations with respect to their costs, continued progress, potential commercialization and success, our strategic plans and our goals regarding our clinical pipeline, including timing and results of clinical trials.

These statements are based on information that is available to us as of today. Actual results could 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 the 12th of February 2025.

Today, we are pleased to review top line week 52 data from the COACH trial, our first trial to investigate how the addition of TransCon HGH, our established once-weekly growth hormone, may increase the clinical benefit of TransCon CNP monotherapy in children with achondroplasia. On our website is a presentation that we will go over, and the speakers will refer to these slides as they go through them. With that, I'll turn it over to Jan.

Thank you, Scott. It's a pleasure to be here today. As I said before, and as Sandy has said multiple times, we always have been confident in TransCon CNP's ability to be a leading treatment for children with achondroplasia. As a monotherapy with full degree of linear growth outcome, where we are addressing the overactive FGFR3 receptor. Beyond linear growth, we also have seen a statistic improvement in leg bowing body proportionality compared to placebo. And when I look at the safety profile, the tolerability profile, we see all the benefit of the TransCon product technology, which are exactly compared to placebo. We see this very low rate of injection site reaction and no cases of symptomatic hypertension because we have a continued long-acting exposure of a constant level of CNP.

We believe TransCon CNP monotherapy can really be transformative by itself. But we also want to really work on how we can give choices, how we can improve treatment outcome, making a new benchmark for what can be achieved in achondroplasia. And I believe this data we have today is really providing the fundament for that. It started with the 26-week data. We showed them for about a half year ago. And now we have the full year data. At that time, we show an efficacy around 3x related to linear growth, which was observed compared to monotherapy when we consider the same time period. It was accommodated with what we wanted to see related to how we have improvement in body proportionality without the acceleration of bone.

No doubt, this is the first clinical trial to evaluate how really a once-weekly TransCon CNP, once-weekly growth hormone really are performing in 1-year data in achondroplasia. I would like to start on Slide 3 in the deck you can find. When I look on the growth data, they significantly exceed any historical benchmark I ever see in achondroplasia, creating a complete new bar for what a treatment can see in achondroplasia. In naive children, we saw an annualized growth velocity of 8.8 centimeters per year with an improvement in ACH height score of more than 1 plus, 1.02. Remember, monotherapy for all therapy I've seen addressing basically the overactive tyrosine kinase is around 0.3. So basic, in 1-year treatment, you basically get 3 to 4 years benefit in the combination. I think this is a new bar.

In TransCon CNP treated experiences, we got 8.4 centimeter per year with an improvement in HG score of 0.82. Still remember, they already have the benefit of TransCon CNP therapy. We do not -- besides that, we also demonstrate benefit beyond linear growth, which is always the aim for us. We really want to aim really addressing the comorbidities. And we saw it -- we saw already with the data we already have, we don't have all the data still top line. We saw an improvement in both body proportionality and for first time, which I've never seen before, a statistic significant increasing in arm span, and really an important element of addressing comorbidity. The positive of this, all what we saw were aligned with what we saw related to height. At the same time, the linear growth was consistent with what we saw in the chronic. So we basically don't see any acceleration.

And I have to say, for first time, I think we have broken records in both our trials with SKYTROFA, we broke record with our trials with YORVIPATH. Here, we broke a new record. This is the first time I have been part of a 1-year trial where we basically have 100% of all the patients staying on the treatment. I think that illustrates basically the element of what we want to see in a treatment that really providing benefit to the patient, the physician, the caregivers that everyone stayed on treatment. And I have to say, today, all of them are still on treatment. And safety and tolerability, I think this is inherent because they stay on treatment is really consistent with what we saw for each of the product. Our key takeaway is there is a once-weekly TransCon CNP once weekly is really raising a new bar for treatment in achondroplasia, not only related to efficacy, but also related to safety and tolerability.

I would now like to go to Slide 4. And I actually think this slide illustrates everything what we basically summarized related to height. We have many other slides that really addressing what we really want to achieve addressing comorbidities beyond linear growth. This slide is addressing height. So if you start with the gray curve, which are called achondroplasia growth charts. This is how a child with achondroplasia will develop through the different years. And you can see the annualized growth velocity is falling down. And then you have the 50% fractal then 95% fractal. The blue one is what we see from a normal child. And you can see that you have the 50% fractal again, and you have the third fractal and 97% fracture.

So when we start with the gray box, the gray box, which have the number of 4.92 centimeter per year, you can basically see that it's patient, meaning is that they have never seen really treatment before, either CMP growth hormone. And you can see they represent normal children with achondroplasia because they're precisely under 50% fracture. One year after treatment, they are basically growing much more than you see in an a status child, more than 97% after 1 year, 8.8 centimeter per year. This is what I call a child with a growth, really growing to a level that you not have seen before. or going to the yellow one with the TransCon CNP. They basically have been untreated. I think there was on average about 2.6 years. And you can see really the benefit of the TransCon CNP treatment. You can see how they have moved from the 50% nearly approaching the 95% fracture. -- really the benefit of TransCon CNP related to height. But when we give them growth hormone for 1 year, they are moving up to the same era that you see with patients. The benefit is independent of the background. Do you have CNP before or not, really the same benefit.

I am really impressed by this data. It was much more than I ever have seen. And I think when Aimee come and give her presentation, you can see the durability of this treatment. it's not winding off. It's continue and continue. I believe that is one of the big surprises we saw in this trial. There is no winding of effect. When we look on what you see between 26 weeks and 52 weeks of CNP treatment and what you see on the combination treatment, the same percentage winding off, meaning is that we basically unblock the potential of growth hormone treatment in this year. So let me go to why I really were extremely excited about this and why we made a lot of IP on this year for a long time. And it was because we have our values, the patient, the science and not the least our passion for what we do. And what we really went in and looked at what is really the synergistic effect of different ways. And we know what the hyperactive tyrosine kinase is really doing when we look just on the growth plate because there's a lot of synergies outside the growth plates.

In the growth plates, if you have a hyperactive tyrosine3 kinase, you basically are in a position that you put a break on the proliferation inside the growth plate, meaning take a break on really limited -- and when you then think about growth hormone, this is basically an accelerator for many other process inside the growth plate. But you know if you have a brake on a car and then express on the speeder, it's not moving a lot. And this is why growth hormone never, never, never really have been successful except a few places in the world as a monotherapy. When then think about you move the brake and you potentially move the brake more than you see in a normal child. And then you have the speeder on with growth hormone. This is why it's illustrated in the simplified form. So when I think about this treatment paradigm, it can be used to everything. I believe a normal child, if you get that here, that will grow to a complete different -- so from my perspective is this is a new treatment paradigm, a complete new way to look and how you really can get an integrated treatment for basic nearly every growth disorder. You don't need to find out which is the break, what is accelerator, just give them the combination. And I think this is why I'm so enthusiastic of the data we have seen, which are really groundbreaking, complete new way to think it and open up really to give choices to patients, to physicians and their parents, what do you want really to see. That was my short introduction, and now we go over to the facts, which Aimee will do.

Thank you, Jan. I'm going to start on Slide 6, showing the design of the COACH trial. We enrolled a total of 21 patients, and that included 12 subjects who represented in purple had not been previously treated with TransCon CNP, and these patients received both TransCon CNP and TransCon Growth Hormone from the outset. Then we also included 9 subjects who were already receiving TransCon CNP monotherapy through their enrollment in a previous Ascendis clinical trial. For these patients, TransCon Growth Hormone was added on top of TransCon CNP. The primary efficacy endpoint is annualized growth velocity at week 52, which we are reporting today, and you saw already in Jan's introduction, in addition to some secondary endpoints, including change in achondroplasia-specific height Z scores and annualized growth velocity at different time points over the course of the trial and some measures of body proportionality, including upper to lower body segment ratios.

Slide 7 starts to show the demographics and baseline characteristics of the patient population enrolled in COACH. The TransCon CNP cohort in the purple column was on average, younger as expected -- excuse me, that's the TransCon naive -- the TransCon CNP treatment-naive cohort in purple was younger as expected compared to the treatment experienced cohort. 4.7 years old versus 7.9 years old. Overall, the children enrolled were representative of the achondroplasia population and consistent with the demographics we have enrolled in prior studies. On Slide 8, we continue to show some more demographic information. As expected, you can see that the TransCon CNP treated children in the green column have now reached an achondroplasia-specific height Z score of 1.28 after an average of 2.6 years on the treatment dose of TransCon CNP. We also see at the bottom of the table, IGF-1 SDS levels, also called IGF-1B scores. And what you can see here is that in both cohorts, their SDS scores are below 0, indicating below average for healthy children. This may reflect an impact on the growth hormone and IGF-1 access in this achondroplasia population.

On Slide 9, we're showing the safety profile for the combination therapies used in this trial. I should say that the dose for TransCon CNP was 100 micrograms per kilogram per week and the starting dose of TransCon Growth Hormone was 0.30 milligrams per kilogram per week. So here, the table with safety shows that we've seen an excellent safety profile for the 2 drugs together through week 52. In fact, the safety and tolerability looks similar to what was observed with each agent individually and the adverse events were generally mild and unrelated. As you see there, 85% were grade 1 and mild. Importantly, we saw no symptomatic hypotension, so no symptomatic low blood pressure, no fractures. These are in particular of interest given that this is a bone active drug, and we are working on the naturetic peptide receptor. So this is reassuring. There was one subject, as you see here, who reported 2 serious adverse events, and these were both determined not to be related to study drugs.

On Slide 10, we show here reassuringly, bone age remained consistent with chronologic age at week 52 and injection tolerability was consistent with that observed for TransCon CNP alone and TransCon Growth Hormone alone and all events were adjudicated as mild. Now the fun part, we'll move over to a few slides about efficacy. What we see here in terms of efficacy at week 52 clearly raises the bar. We see an inflection in growth that is sustained and consistent across multiple ways of looking at growth. In the treatment-naive cohort on this slide, the purple, who are on average a little over 4.5 years old, with the primary endpoint of AEV, we saw at week 52 that they were growing at a rate of 8.8 centimeters per year on average. This represents an increase of 3.9 centimeters per year compared to their baseline and was statistically significant with a very low p-value.

The substantial improvement in growth velocity was commensurate with an improvement in achondroplasia-specific type Z score shown on the right-hand panel. The achondroplasia-specific Z score in treatment-naive patients increased to 1.47 from originally from being 0.46, representing a change from baseline of 1.02 standard deviation, and that represents roughly 3x the 0.3 standard deviation change we saw with vosoritide monotherapy in our Phase III trial. Again, this was statistically significant. On Slide 2, we move to the cohort that was experienced with TransCon CNP from being in the other TransCon CNP trials before coming into COACH. These results are similar. At week 52, these children, as shown in the last panel, who on average were almost 8 years old, had an annualized growth velocity of 8.42 centimeters, representing an increase of 3.28 centimeters per year compared to their baseline. This was significant.

On the right-hand panel, achondroplasia-specific height Z score reached positive 2.15 at week 52 and an increase of positive 0.86 compared to the TransCon CNP treated baseline. And this was also statistically significant. So from these 2 slides and data, we can see that the addition of TransCon Growth Hormone demonstrated a boosted growth in those children who are treated also with TransCon CNP. Now moving on to Slide 13, which Jan already walked you through earlier in this call. We're looking at growth velocity charts for average stature boys in blue there and for children with achondroplasia in gray. And this helps to contextualize the efficacy data that we saw at the week 52 primary analysis. So what we're seeing here in the COACH trial is a sustained healthy growth at a rate never seen before in children with achondroplasia. -- whether they are naive or experienced CNP monotherapy, the combination of TransCon CNP and TransCon Growth Hormone results in annualized growth velocities on average that are above the 97th percentile of growth rates for children of average stature.

Now I'll move over to some benefits beyond linear growth. So on Slide 14, we're showing here improvements in upper to lower body segment ratio, a measure of body proportionality in both treatment-naive kids in triple and previously treated kids in green. This is a strong indicator of the breadth of the effect of the combination and the fact that we are achieving healthy growth. The change from baseline in upper to lower body segment ratio is shown on the y-axis. So a reduction indicates the desired lengthening of the lower body segment of the waist and down compared to the upper, the torso body segment. For both cohorts, change from baseline over 52 weeks reaches a greater reduction than was seen with TransCon CNP monotherapy.

Now moving on to Slide 15. I have a figure here showing arm span from left fingertips to right fingertips, so the arm scan across the 2 arms of too. This is another way to look at clinical benefit in achondroplasia and something that has been of interest to people living with achondroplasia too. Here, we see an inflection in the growth of the arm span that is catalyzed by the use of the dual agents. The effect is seen in both the treatment-naive and the TransCon CNP treated cohorts. What you can see here is that over the course of the year, these children are cutting across IsoPlex. They're cutting across the lines where they would be growing without therapy. And in this case, they're approaching the 84th percentile of arm span compared to natural history in achondroplasia. What's important about arm span getting longer, it's something that we know has been of interest to regulators and to patients. But for example, it perhaps makes it safer to cook on a range or to reach into an oven, perhaps easier to drive the things that -- with a car that doesn't need to be modified.

On Slide 16, we show the durable efficacy across the achondroplasia trial. On the right panel, the gold bars, we show that TransCon CNP monotherapy, which is awaiting approval by the U.S. FDA, has established itself as a durable driver of consistent growth in achondroplasia patients in that -- in the Phase III trial. So you see there the 5.95 centimeters per year at the end of -- at week 52. In the left panel, shown in purple bars, TransCon Growth Hormone on top of TransCon CNP adds meaningfully to the benchmark set by TransCon CNP monotherapy and again shows durability between week 26 and week 52. So with that, I'll be happy to turn it back over to Jan.

Thanks, Aimee, for going through the data. When I look on the -- take the holistic view of the data, I've never seen data in achondroplasia like this here. The efficacy is out of any benchmark I ever have seen. And that is not only related to linear growth. That is important element how to really improve body disproportionality. For first time, I ever have seen data where there is a meaningful impact on arm span, one of the elements that really have been part of the treatment goal. We're still analyzing the data, getting more and more and more information. But when I see the integrated effect also related to safety, tolerability, I really see that we're building up a new treatment regime with an expectation of an outcome that is really to the benefit of the patient, the physician and caregivers where it's really highly meaningful for them.

We're moving forward at what we're doing now. We started already in Q4 to prepare for a Phase III trial. We see the benefit that we basically are boosting the effect at 3x. And we really are working as fast as possible to be in a position that we really were finalizing the Phase III, get it on labeling and see the CB implemented as a standard treatment in achondroplasia and other growth disorder. Ascendis is now waiting for getting TransCon CNP as the first country here in the U.S., we're confident that is happening in the near future. With our integrated pipeline, starting with SKYTROFA, EAP and a continued investment in R&D from our platform technologies to our R&D engine really to make a sustainable biopharma. I believe here when I look just on growth disorder with both TransCon Growth Hormone, TransCon CNP in our portfolio, both of them really showing some of the most unique properties, each of them, I feel really confident that we're building up the leadership in growth disorder. Thanks so much for today, and we now will take questions.

[Operator Instructions] Our first question comes from the line of Tazeen Ahmad of Bank of America.

Congrats on the high-quality data, the 3.89 centimeters over that 52-week period is impressive. I wanted to get your thoughts, Jan, on how you're thinking about expectations for longer-term efficacy. Is there any risk that this number could potentially lower meaningfully from where it is? And how would you think about the applicability of making sure that you have this longer-term data in hand as part of the label?

Yes. What we are doing now is that we continue our COACH trial, as Aimee described, in an open-label fashion. So we will get 2 years data. When we see the safety profile, it looks exactly as we had hoped for. From that perspective, we don't see any limitation in the treatment from that perspective. When I go back and look on all my 4 children and see them growing and see when they have the grow birth and they are growing so much, is always associated with pain or always associated, we are really a little bit surprised we don't see that. But we also want not really to be in a position that we see this growth that is much more than you see in a normal child continue forever. So we believe how we potentially see a regime, which always will be a decision from the physician, a decision from the patient, decision of the caregivers. But we can see a regime that you basically always as a background, we have TransCon CNP and unique product as a background therapy and then potential for 2 years, you will boost it with SKYTROFA. -- perhaps you will take a break 1 to 2 years. And then if you feel that you really need more boosting of the outcome, you will take basic perhaps 1 year to year more. So make this long answer short, we have not seen any safety concern and limit the use of it. I believe from a practical perspective, you shouldn't some way have this extremely high, you can say, efficacy for year after year after year, but in the end, there will be a decision for the physicians.

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

Congrats on the data as well. I was wondering if you can talk a little bit about Phase III design. Was there certain insights from the 52-week results that you were waiting on in order to guide that Phase III design? And can you talk a little bit about the device for TransCon CNP, both monotherapy and when used together with SKYTROFA?

Yes. Thanks, Joe. Let me take the last question, and Aimee can help me with the first question. Currently, what we have now is -- and this is how we are also conducting the clinical trial. We give them 2 injections every week. We have not got any complaints. We have not got any feedback related to that is a height burden or anything. I think it's totally overshadowing the benefit they see in the treatment on it. On an LCM perspective, yes, our vision is to integrate everything in a single injection. And -- but it will take some time, and we need exactly find out how is the optimal way to have the best patient care really to do this in the most best manner for them. So this is more what you can say, the way of building up the treatment regime on it. Related to the Phase III trial is pretty standard, I have to say. Everyone is a 1-year trial as everyone expects to be. We cannot change the primary endpoint in any way, it got established by FDA to be linear growth. We cannot change it, but we will put a lot of empathy on showing benefit beyond linear growth. And is everything what we see today, everything from body proportionality improvement, leg bone, arm span that we now have seen for first time. Other thing is quality of life, which we really integrated in a best way, so we really can see that also get the benefit out from the treatment. So it's a very, very simple design. There is basically only 2 arms in it, and this is basic monotherapy and combination therapy.

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

Congrats on the great data. Just maybe curious about the impact on comorbidities. Obviously, you've seen very nice improvement on body proportionality and on span. Just curious, have you observed or measure benefits on quality of life metrics or muscle function and what comorbidities do you plan to measure in the Phase III?

That is an element that we're still analyzing. We're still getting more and more information from our 52 weeks data -- and we are still analyzing the radiological elements on it. But as I said before, Li, clearly, element that is extremely important for the patients, disproportionality, leg bowing, arm span, that can be element related to radiological measuring on the spiral core, how it's getting developed. There can be other things that we don't know yet. But I think, Aimee, if you have anything to add, I think I got most of them today.

Yes. Quality of life will be part of it. Good physical functioning.

Yes. Perhaps muscle strength, too. So there is a lot of things we're measuring into this. So we just need to find out what is the statisticarity we will use them and to be sure that we can also have it filled into the entire packet in a statistic way.

Our next question comes from the line of Yaron Werber of TD...

On the really impressive data. This is Sarah on for Yaron. So we wanted to ask about a little bit more about the Phase III trial design. You noted that there's only going to be 2 arms, the mono versus combo therapy. So just to clarify, you're not going to contemplate a SKYTROFA alone arm. And then just one more question from us, if you don't mind. So given that the CNP monotherapy is under priority review with the PDUFA date of February 28, how do you foresee the labeling and market positioning for the combination regimen once the Phase III data is out?

Yes. You can -- you are 100% right. There is an interest from regulatory agencies and there's also from physicians really to see what is really the effect on a product like SKYTROFA with its unique properties patients. And we are analyzing exactly how we really are doing that, but we will do that. It will be a limit single-arm trial that basically will show that just to illustrate the benefit of the combination too. So I think this is an element that we're feeling we want to do because we always want to be sure we're giving the best possible treatment regime for every patient. Related to your question about the labeling, I think the labeling for our TransCon CNP has been more or less finalized. So we cannot expect any change in any kind of the labeling of TransCon CNP being impacted with this data here. We're using the TransCon CNP IND as a continuation of this year. So we are not filing a new IND. So basically, the combination therapy will build into the CNP filing.

Our next question comes from the line of Maxwell Skor of Morgan Stanley.

Congrats on the positive update. I was just wondering, how do you anticipate payers will view the value proposition of the combination therapy, especially given the potential for higher efficacy, but also increased cost versus monotherapy?

Payer for me is a very, very broad discussion. Are you talking about U.S.? Are you talking about Italy, Germany, South Korea, Japan and everything like that because I think there will be different views from different places. We are building a global company with a global commercialization. And I think there will be a lot of different consideration in each single geographic region. For example, we see a daily CNP not being available in many, many countries today out of the never can live up to the pharmacoeconomic modeling in it. And when we see the combination therapy on a global perspective, we are 100% sure that the benefit is so unique with the combination therapy and the cost structure by adding the SKYTROFA into is not really impacting that in a highly impactful manner. So what we see here, it's opened up for a global commercialization in many countries where basic therapies addressing the achondroplasia are not available today. When we go to a specific country like U.S. I think for first time, there will be a therapy available that's really addressing what the patient want to have, addressing the comorbidities, addressing arm span, addressing leg bowing, everything what we really want to see. And I think this is why it's going to be a completely new way to think about how to treat achondroplasia.

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

Let me also offer my congratulations on the data. With regard to the Phase III, can you comment on whether you plan to still allow patients who are treatment experienced either with growth hormone or potentially vosoritide still to enroll? And would you also potentially allow patients on background therapies such as FGFR3 inhibitors to enroll in the Phase III? Any color there would be helpful.

Why I'm a little bit stalling here because, first of all, we just are in a position where typical, you will not include other experimental drug in any kind of protocol. So when you think about what is approved for achondroplasia today, it basically is only one product. So from a logistic point, you cannot have patients coming over for this kind of trial in this way. And as you saw, we didn't see any difference really if they were CNP naive or were on basic and CNP therapy. So we will be the most flexible to adapt. What we really some way need to consider, which I'm still struggling with on a lot of different level is we need to be sure that the experimental treatment are safe enough for us to take them into a trial. We don't want to contaminate our extremely proven safety profile with potential agents that could give a safety profile that we don't want ever to see in our trials.

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

Congrats on the great data. On hypochondroplasia, are you still planning to do a monotherapy and a combination study? I also wanted to confirm if you submitted the IND in the fourth quarter. And as part of that, if you confirmed that you could do a single registrational study in hypochondroplasia?

Yes. Now we start to go down in technical details. And from a technical perspective, you can say it's 2 independent trials because it's on 2 different way we do the statistic analysis, but it's built in the same way in hypochondroplasia that we see in achondroplasia. But you're right, we are doing an active clinical development also in hypochondroplasia. There's a big difference between achondroplasia and hypochondroplasia, -- and this is basic from the genetic mutation you have. Many of them are not in the same severity impacted by comorbidities. And currently today, I believe many hypochondroplasia are successfully treated with just growth hormone therapy. And this is why we always want to give choices and we're designing the trial that we really will give the choices for that. But you're right, how we do it in hypochondroplasia, Aimee, you need to correct me. It's basically 2 independent trials.

That's correct.

So for hypochondroplasia, is it going to be like a combination study versus CNP like you're planning in achondroplasia? Or is there also going to be a placebo arm included there?

Between the 2 trials, there will be some placebo, some mono and some dual therapy.

So you can say it's basic expansion of the monotherapy at the same time, there was a placebo and a combination. So when you take the integrated value of the 3 trials, you will have 2 monotherapy, combination and placebo.

Our next question comes from the line of Yun Zhong of Wedbush.

Congratulations on the positive data. A follow-up question on the Phase III design. I wanted to confirm that you are still going to aim to show statistical superiority of combo versus mono? Or do you think a numerical difference could still be acceptable so that you don't have to run such a large study so that you can bring combo to approval maybe more quickly? And if you do show superiority in the long term, eventually, do you foresee both combo and mono to coexist? Or would you expect maybe combo will replace mono over time?

When we talk about specific achondroplasia, when you look at the number, I think with 12 patients, we can show statistic superiority in that. So we're not limited by the efficacy measuring. We limit more or less by the safety part and how we also have statistic power to show benefit beyond linear growth, which are the key thing for us to do. And this is, for example, arm length. This is body proportionality. This is quality of life and many of these other things like that. And I think we need to rephrase it. The rephrasing is to say TransCon CNP is the background therapy for everyone we do. And then you add in TransCon Growth Hormone if you really want to boost it. This is like when you're flying the rocket up, then you take the booster on and then it really leaves the earth and really fly high up in the sky. And then when you're up, you remove the booster it's falling off. And I think that is the way we see it and perhaps you need many boosters to come back to the earth too. But I think that is basically how we see the treatment regime.

Our next question comes from the line of Alex Thompson of...

Congrats on the data. I was just wondering, as you envision kind of the next 12 months or so, with this strong Phase II data, potentially a publication in a journal, et cetera, whether or not you think that it would support in the U.S., for instance, utilization of this combination by physicians that might choose to do it.

That is a question I cannot comment on because I'm not deciding what a physician are using in the treatment. That is a physician choice together with the patient and other things like that. Aimee, team are getting ready with publication, and we'll do that as fast as possible.

Our next question comes from the line of Luca Issi of RBC.

Congrats on the great data. Maybe if I can circle back on a prior question. Again, I totally appreciate this is still kind of early days, but how are you thinking about pricing specifically in the United States? Should we simply think about the price of the 2 individual drugs combined? Or is that more complex than that? And then maybe if I can kind of check your temperature on the upcoming PDUFA date, how confident are you that TransCon CNP does get approved by the end of next month and it does not get delayed again? Any context there, much appreciated.

Let me take the last question -- last part of the question. And we have answered everything to FDA even before this year started. So we have not got any request back for them. So we're just sitting and waiting and getting the approval, we hope, as fast as possible. Related to the presentations, as I some explained before, for years until the basic 2 LCM building into a one single injection, it basic will be likely a TransCon CNP presentation, and there will be a SKYTROFA presentation. And the patient will be taking and combination therapy, which are so common in so many other indications, for example, in the area of cardiovascular, just one thing where you have a lot of drugs being taken to benefit diabetes too and other things like that. And typically, when you look on price structure for this, it's the sum of the 2 that basically are driving the price.

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

Congrats on the updates here. Jan, I was just wondering, can you expand on your comments, I guess, on the timing of when you think like the combo will actually be used in the disease course. You talk about these periods of growth spurts. But I guess, do you presume that like long-term monotherapy will be used? Or will it be combo? Like I guess, how do you kind of envision the overall kind of treatment with the combo evolving from, I guess, early age to age 16, 18 years old?

I think what we're giving here, we're giving a patient office and physician possibility a society possibility. If I go to some countries, I can be quite sure there will only be one therapy available. It will be the combination therapy. And you will potentially take the combination therapy for 2 years, then make a break, see, do you need it more and other things and then potentially have a cycle of perhaps 3 or 4 cycles in that because it will be the most cost-efficient way to do it. In other societies, potentially there will be a consistent, which I think will be the optimal treatment way of having a consistent background therapy of TransCon CNP, not perhaps not only in the pediatric area, but also in the adult area because there's benefit also at that stage. And then you will boost it perhaps with 3 or 4 cycles of SKYTROFA TransCon Growth Hormone dependent on how much the physician, the patients and everyone and the caregivers feel that is their desire to do it.

Got it. And just a follow-up. So I guess, do you think the physicians -- will they be looking at some sort of just the growth curve, like where they are on it or some sort of biomarker? I guess like you're talking about different cycles, but when -- like I know it's at your discretion, but like give me an example of like when they might want to do that? Because I guess when we try to think about the modeling, like how many cycles they may get of combo, that's what we're trying to understand.

Yes. I think there's a different way. First of all, this is a part why we believe TransCon CNP without doubt will be the leading product in achondroplasia treatment because as a monotherapy, providing the best outcome safety, tolerability for the patient. And now we're adding on a new dimension, unprecedented outcome with combining with a second Ascendis product, SKYTROFA TransCon Growth Hormone. And I think this is what we are providing. We are providing the menu list of how you really have an option to treat the patient in this way. So you can see it from a modeling perspective is that this is just boosting the penetration of TransCon CNP throughout the entire achondroplasia treatment regime.

One way to think about it, Derek, would be when the child starts on medical therapy. If they start early on TransCon CNP, we know that, that brings up to the growth rates of average stature helps straighten the legs, enlarge the spinal canal, that may be enough. So if you start early and you continue it through your growing career and after that might be enough. And if there is a time when they want to get an extra boost, that could be very short term versus you could consider another patient who might decide to come to medical therapy late. And so they have a shorter amount of time before they would close their growth place. Potentially, for a patient like that, it is more urgent to treat with both for a longer time.

Don't just limit your thinking to achondroplasia here because this is how we will approach every growth disorder, so many different elements of growth disorder, 20 to 25 different diseases, and we will continue to do that. This is the way we're developing the leadership in growth disorder in rare disease endocrine.

At this time, I'd like to turn the call back over to management for closing remarks.

I would like to turn it over to Scott Smith that will have the final remarks.

Thanks so much, Jan, and thank you, everyone, for joining us this afternoon and this evening. Have a great day. Bye.

This concludes today's conference call. Thank you for participating. You may now disconnect.

Good day, and welcome to the Third Quarter 2025 Ascendis Pharma Earnings Conference Call.[Operator Instructions]. I would now like to turn the call over to Chad Fugure, Vice President of Investor Relations at Ascendis Pharma. Please go ahead.

Thank you, operator, and thank you, everyone, for joining our third quarter 2025 financial results conference call. I'm Chad Fugure, Vice President of Investor Relations at Ascendis Pharma. Joining me on the call today are Jan Mikkelsen, President and Chief Executive Officer; Scott Smith, Executive Vice President and Chief Financial Officer; Sherrie Glass, Chief Business Officer; Jay Wu, EVP and President, U.S. Market; and Aimee Shu, EVP and 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 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 these 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 12, 2025. We TransCon Growth Hormone or TransCon HTH 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 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 and adults and European Commission in the United Kingdom's Medicines and Healthcare Products Regulatory Agency of 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 unit effectiveness of product candidates have not been reviewed or approved by any regulatory agency. 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 third quarter 2025 financial results and will 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 afternoon, everyone. In the third quarter of 2025, we accelerated our momentum towards fulfilling our Vision 2030 with key achievements in 3 areas. First, the global launch of YORVIPATH continues to be strong, with a steady increase in new unique patient prescription and prescribers as seen in Q1 and Q2. along with expansion in new geographic markets. Second, we made great advancement towards leadership in growth disorders during the quarter. We saw the U.S. approval of SKYTROFA in adult growth hormone deficiency. And following our late cycle meeting with FDA we are progressing toward expected approval of TransCon CNP in the U.S. Third, our strong operating fundamentals led to positive operating profit, signaling the beginning of sustained revenue and earnings growth for Ascendis.

Now I will provide some specific comments on our commercial and late-stage portfolio. Starting with YORVIPATH. YORVIPATH has continued its strong global launch with revenue of EUR 143 million in the third quarter. Nine months in the launch in the biggest markets, the U.S. Patient demand continues growing quarter by quarter. From long to the end of September, more than 4,250 patients have been prescribed YORVIPATH in the U.S. by over 2,000 unique health care providers, highlighting the strong steady domain for Europe, even during the summer months. In October, the positive trend continue with Europe. Being prescribed for more than 400 new patients in the U.S. alone, positive position and patient experience. are driving a high rate of compliance, and we expect most patients will be on lifelong PTH therapy. We are expanding our physician reads each quarter within the endocrinology community.

And we are also expanding to other physician groups who manage hypopara patients. As an example, at last week's American Society of Nephrology meeting, we presented 3 years of kidney function data across our combined clinical trials demonstrated through state clinical meaningful improvement in kidney function in the UPAT treated patient. In addition, we continue working hard to expand patient access in the U.S. The insurance approval rate since the start of the launch is around 70% of total enrollment. And we believe this figure will continue to increase over time. We currently see approval across all payer types with a majority of approvals within 8 weeks. We are pleased by the robust uptake of YORVIPATH in our first 3 quarters of commercialization in the U.S. Today, less than 5% of U.S. patients are currently on YORVIPATH trade.

We see significant room to grow with around 80,000 to 90,000 patients already diagnosed with chronic hypopara in the U.S. and 3 to 4 new patients being diagnosed every year. Outside the U.S., Europe is now available commercially all to named patient program in more than 30 countries. In Germany, Austria and Spain, we have now full commercial reimbursement. In Japan, our partner, [ Caijing ] launched YORVIPATH commercially last week following approval in August. We are looking forward to the commercial launch of Europe in additional countries in the coming years. With a broad label covering hypoparathyroidism for all courses. International treatment guideline that recommend PTH replacement therapy and YORVIPATH precision as a first-in-class therapy, we expect sustained patient growth and revenue growth for years to come.

As we're building this global market, we're expanding our offerings to patients with hypopara. We are conducting the pathway to support doses up to 60 micrograms of Europe in the U.S. We plan to begin a clinical trial for people under this quarter, and we are advancing our new on TransCon PTH product candidate, which we believe would be an attractive option for patients on stable doses of Europe. In the new year, we will share more on our plans to maximize YORVIPATH's value and reach even more patient. Let's now turn to growth disorder, which to date combined of our [indiscernible] SKYTROFA approved for growth hormone deficiency, and our once weekly TransCon CP currently under review by FDA in the U.S. and by EMEA in AU for children with achondroplasia.

SKYTROFA is approved in the U.S. and EU for treatment of pediatric growth hormone deficiency. With this single indication, SKYTROFA is established as a high-value brand and treatment of choice for pediatric growth hormone deficiency. Q2 revenue for SKYTROFA was EUR 51 million. In July, we received our first label expansion with FDA approval for adult growth hormone deficiency, the first of multiple planned label expansion. In Q3, we initiated our Phase II basket trial of SKYTROFA with a range of established growth disorder, including ISS, shop deficiency, Turner syndrome and SDA. Turning to TransCon CNP. We recently completed a late-cycle meeting with the FDA and are in the final states of the label discussion. TransCon CNP is under priority review in the U.S., a bit of PDUFA date of November 30 and is also under review in the EU where our MAA filing was well validated.

TransCon CNP once weekly is well positioned to become the leading treatment for [indiscernible] achondroplasia with a full degree of linear growth outcome that can be achieved with monotherapies addressing the overactive [indiscernible]. In addition, TransCon CMP achieved statistical improvement in [indiscernible] compared to Placebo increasing [indiscernible] dimension as safety and tolerability profile compared to Placebo. With a very low rate of injectocide rarity and no cases of symptomatic hypotension. We are confident in TransCon CMB's ability to be a leading therapy. While we believe TransCon CNP monotherapy is transformative by itself. We want to further enhance outcomes for people living with achondroplasia. Earlier this year, we presented 26-week results from the Phase II Code trial of TransCon CNP in combination with TransCon growth hormone, which showed around 3x improved linear growth compared to what had been observed with monotherapies or the same time period.

This resulted in healthy linear growth in children with achondroplasia higher than that observed with an average state of children. Accommodated by improvement in body populationality and bid out acceleration of bonds. This data has been recognized by key opinion leaders as groundbreaking. Based on this data, we believe over time, the standard for care in achondroplasia will include combination therapy as a treatment option. Building on the potential role of TransCon CP [indiscernible] therapy. Following our recent FDA end of Phase II meeting related to our combination therapy. We plan to initiate a Phase III trial this quarter.

We anticipate disclosing 52 REIT data from the COAST trial in early 2026. With 1 weekly growth hormone and once-weekly CNP, 2 highly differentiated medicine both as monotherapy and in combination, we believe Ascendis is well positioned to become the global leader in many different growth disorders. Our Vision 2030 also includes creating value to partnership. And we see that being achieved to the rapid progress of [ Taigen ] in Japan. Recent in China icons in ophthalmology and novonordis in metabolic and cardiovascular diseases, where the once-monthly semaglutide program is making fast progress towards the clinic. And finally, the commercial success of YORVIPATH and SKYTROFA has already transformed the financial profile of Ascendis. In the third quarter, we achieved positive operating income along with positive cash flow. For the near time, the building out of our commercial organization is largely completed in bands of future global launches.

For the medium term, label expansion, LCM activities have been indicated to maximize the value of our current products. At the same time, for long-term sustainability, our R&D organization continues to advance the TransCon technology platform to ensure a constant flow of new programs and potential new products. In summary, with TransCon nearing potential approval Ascendis is well positioned to get approval of its third TransCon phase product in a row. This highlights the uniques of Ascendis, that continues to develop a highly differentiated product created by the TransCon technology platform and our unique low-risk drug development and commitment. Importantly, our current 3 rare disease endocrine product, positioning us for durable future growth and give us confidence in our aspiration to achieve or more in annual profit revenue in 2030. I will now turn it over to Scott.

Thank you, Jan. I would like to reiterate Jan's comments that the positive operating income development seen in Q3 signals the transformation of our financial profile with sustained revenue and cash flow growth. With that, I will touch on some key points surrounding our third quarter financial results and outlook. But for further details, please refer to our Form 6-K filed today. In Q3, YORVIPATH global revenue grew to EUR 143.1 million, up from EUR 103 million in Q2, with strong growth partially offset by a EUR 3.6 million foreign currency headwind compared to the previous quarter. In Q3 2025, SKYTROFA contributed EUR 50.7 million with 3% growth in demand, offset by a EUR 1.6 million foreign currency headwind compared to the previous quarter. Including EUR 20 million in collaboration revenue driven by a EUR 13 million milestone related to YORVIPATH and increased partner activity, total Q3 2025 revenue amounted to EUR 214 million.

Continuing on to expenses. R&D costs in Q3 were EUR 66.9 million, down from EUR 73.5 million in Q3 2024. And primarily driven by completion of certain clinical trials and development activities. SG&A expenses rose to EUR 113.4 million in Q3 2025 compared to EUR 69.8 million in the same period last year, reflecting continued impact of global commercial expansion. Total operating expenses for Q3 2025 were EUR 180 million and operating profit for Q3 2025 was EUR 11 million. Net finance expense for the third quarter of 2025 was EUR 60.9 million, primarily driven by noncash items, including noncash remeasurement loss of financial liabilities of EUR 47.2 million. Net cash financial income over this period amounted to EUR 400,000. Note that in our 6-K filed this evening, we provide more detail on the components of finance income and expenses.

In future periods, we plan to introduce a non-IFRS EPS measure adjusting for the impact of certain noncash nonoperating items, including related to our convertible notes. This is intended to increase comparability of period-to-period results. Finally, we ended the third quarter of 2025 with EUR 539 million in cash and cash equivalents, up from EUR 494 million at the end of Q2. Turning to our commercial outlook, primarily driven by the ongoing global launch of YORVIPATH, we expect continued revenue growth in the fourth quarter. For your the past specifically, we expect continued growth driven by new patients, stable pricing, payer mix and contracting in Q4. Longer term, we expect YORVIPATH to be driven by continued growth in new patients on therapy, including expansion into additional markets.

For SkYTROFA, we believe that sequential revenue growth should continue to track growth in prescriptions with stable pricing, payer mix and no changes in contracting with offsets potentially driven by currency as we saw in Q3. Longer term, we expect growth for SKYTROFA to be driven by geographic and label expansion. With that, operator, we are now ready to take questions.

[Operator Instructions]. Our first question comes from Jeff Fye with JPMorgan.

I was hoping you could speak to your expectations for the rate of new patient enrollments on our path in the U.S. from here? I think you talked about more than 4,250 as of the end of 3Q putting you at what is that about 1,150 ads or maybe a little more relative to June 30. Can we think of that as kind of like a good number to work off of from here? Should it continue to kind of drift lower a little bit? Just hoping you can frame some expectations there.

Thanks, yes. First of all, we see really a stable number of prescriptions being written in the U.S. when we some way take away the bonus that we have from the EAP program about plus patients we have in the ERP program. When we think about Q3, I'm actually pretty surprised positively about Q3 because I was fire that prescription not will be written in the 3 weeks, any physician typically take out of their quarter in that time. What I saw, we saw nearly the same number of prescription being written that we actually have seen in Q1 and Q2. And it's also following up with what we said in the October month we sold more than 400 prescriptions being written in October, unique prescribing being written in October.

So when I look at this long look at the U.S. I see a very, very [indiscernible]. And what we're also doing the building and fundamental like a strong, strong fundament because patients stay on lifelong treatment. And therefore, when you start a patient, it basically is continued quarter-by-quarter. So it's building out a house where you have a strong fundament taking one break on around every quarter and the house getting taller and taller every quarter.

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

I just wanted to get a sense of how you're thinking about the rest of this quarter. Are you expecting to see impact from seasonality, I guess, we can call it just because of the upcoming holidays, Thanksgiving, Christmas into New Year's. And do you think that the script trends for December would be directionally lower, let's say, than what you're seeing -- what you saw for October? And then if I could ask about the TransCon CNP review, you said you're in final labeling discussions, which is good to hear. Can you just confirm whether or not you've had any requests for any type of data from the agency in the review cycle?

Let me take the last question. Thanks, Tazeen, first. But let me take the last question first because it's an easy one because that's a no. Just no, no, no. So it's really simple. So going to the next one. Is it more was Scott [indiscernible], he didn't read the FLS this time IFRS this time. When I'm looking forward in the future, yes, there, some holidays come up. But when I look back, I was more worried about Q3 actually compared to the Q4 because I actually believe that there's a longer subapplication in Q3 compared to basic what you will see in Q4. So I see pretty positive on Q4? I see we actually increasing our prescription basis for physician biting prescription with more than 500 new prescribers, meaning that having a broader, broader boat where there's more and more that can come in growing on the ship. And this is where I feel pretty confident about it. So no worry from my side.

Our next question comes from Gavin Clarke Gardner with Evercore ISI.

I wanted to focus in on the conversion rate for YORVIPATH. I'm wondering why it's only 70%. And you noted that you expect it to be higher over time. how much higher do you expect it to be? And when do you think it will be higher? Just had a follow-up on this, too.

Yes. This is a question we have gotten multiple time every quarter. And what we have said in the previous quarter, we expect that it's going to be maturing over time, and it will go higher than that. And that is typical what we have seen in launches. And I still had a long discussion with Jay about it today. And what is when we see a mature brand? Is that 85%? Or is it 90%? Or what is really for the mature brand that you basic some way are ending up at that time. And I think from a modeling perspective is that we feel extremely well where we are today, we still have block taken into situation, we gating the patients, we're getting not only the prescription done, we're also getting the approvals done and we're getting it done in speed.

And as Scott also put emphasis on this, we don't expect anything changing in the contracting environment in Q4. So we -- some expect the same detail for this product that we are seeing in both Q1, Q2 and here in Q3 and no changes to it. But Jay, you can also take a little bit of our discussion about the future about what is really for an mature brand is that where we are today. And also we see a much higher number for SKYTROFA after it got matured.

Yes. Thank you for the question. As mentioned before, we're really encouraged about the 70% approval rate that we're seeing now. It's actually about what we expected or guessed at the beginning of the year just based on what we know about the clinical value proposition of the drug, which again is incredibly positive and has been resonating with a lot of the payer accounts for which we are speaking with. To answer your question, Gavin, directly in terms of what that peak approval rate could be and at what time frame. That's really hard to say, right? When you look at some of the analogs for similar drugs, that could, in some instances, take multiple years.

And the reality is once you get to a certain high percentage, the remaining becomes a little bit more difficult simply just given the heterogeneous landscape of the payers, right? It becomes quite fragmented. A lot of the government payers might review it on different time tables. So we are meeting a lot of those timetables where they're at. And again, we're continuing to talk about the incredible positive clinical value proposition that we're seeing. And that alone is resonating with a lot of them, which is why we continue to see that approval rate go up over time.

That is super helpful. And if I could just ask a like specific follow-up on that. Like for the 4,250 forms, reported through the end of this quarter. Are you guys basically saying you expect the conversion on this to be 70% and then trending higher for everything you just laid out after that?

No, that's not what we're saying. Because if we go back and look on the early cohort, meaning it's cohort for March, April, it's much, much higher than the 70%. So this is what you see. Your longer time, it takes you more and more be getting approved. And that is basically the element. And this is the question we have, can be really take this tail and shorten down the tail. So we're basically getting the higher percentage that we see from the cohort we had in the beginning of the year, which are much higher than the 70% can be started to get it in a shorter time frame.

Okay. Like the point I'm trying to get at is for a lot of the start -- like let's take the 3100, you had the end of June. Maybe you've had close to 70% conversion, but the rest of the 30% is not really lost at this point. Some more still may come through as conversion. It's just a matter of time.

Exactly. So if you take, for example, going to the cohort from March, April, much higher. If you take the earlier state cohort now that is near this month, we have is lower than that. So this is how you see it. It's the only question about timing.

Our next question comes from Joe Schwartz with Leerink Partners.

A question on YORVIPATH and then on TransCon CNP. Can you give us your latest views on how YORVIPATH has been penetrating the different segments of the hypo power market as you see it? Where is it beginning the most traction? And where could it do better? And then you previously emphasized the desire to do more than enhanced linear growth in achondroplasia. So I'm wondering, to what extent do you think you can obtain differentiated label claims on the TransCon CNP label?

Let me take the last question. As I said in the prepared remarks, we are in the late stage disruption about that. And I cannot really comment about what will really be in the financial labeling in this perspective. What is really the key element for me in my discussion with patients my discussion with physicians, misuse discussion or media discussion with their teams, it's really to explain that benefit be behind the growth. And it's clear unique effect in [indiscernible], unique effect a changing body proportionality, and we will have peer-review publication really supporting all this claims that will come up, really give us an opportunity to take and talk with the patient talk with the physician about this benefit in it.

I think this is the key thing for me. We -- I saw [indiscernible] saw an element once with hypopara, where pacing it was impossible for get into lately our element of patient benefit related to [indiscernible] function, quality of life and everything like that. And everyone recognizes it. Everyone sees anything see that is the best thing. I think this is the key thing from our leasing discussion is have no restrictions, have a really safe product, really show our efficacy and safety in the best possible manner in this way. Jay, will you take the first part of the question in this point to Joe?

Yes. Can we repeat the first part of that question?

Yes, sure. I was just wondering, you've outlined the different segments of the market based on how controlled the patients are. So I was wondering how are you making inroads into those segments lately? Where are you getting the most traction and where could you do better?

Yes. So when you think about the 80,000 - 90,000 patients that Jan had referenced earlier in the call, I think there's probably a group that we would describe as highly symptomatic, patients are well aware of their symptoms articulating those symptoms to a physician. And within those, I would say we're doing quite well, particularly since the patients themselves are likely the ones that are in the offices most frequently and are keeping the appointments on the books to be able to essentially get some of that information and also be on their way to actually get prescribed the product. I think where we're continuing to work on are some of the patients for which maybe they're not either self-identifying some of their symptoms as being related to the underlying condition and/or perhaps they've gotten used to some elements of it and therefore, having been as motivated to establish care and retain established care with a specialist.

And I think that's why as we think about how we can continue to transform this market, there will be an element of patient activation as well simply because there is going to be a certain level of disease education required, particularly for a space like this where it is about redefining what's possible and kind of the status quo for how to manage this type of condition.

Yes. If I can add something, Jay. I see it from two different perspective, how often you come into the -- is this one way [indiscernible] how we target it and define something that is not defined on medical terms. But only on [indiscernible] you see an [indiscernible] related to being controlled, partly controlled and what I'm also trying to look at -- I try to look on where are they coming from the [indiscernible]. Are they coming from the genetic part? Are they coming from the hemological part. I see them coming from everywhere. So for example...

Again, please stand by the conference call. We'll begin to resume momentarily. Please continue.

Where did you last hear I said? I think this was Joe, your question about the...

Yes. welcome back. So I guess, I was wondering about your progress within the different levels of control and where you can do better and just how you've been able to penetrate patients in each of these segments.

Yes. I think, Jay, at least I heard Jay response to it. And my additional comments was that when we did the targeting of our physician, we made it out from the claims database where we define 3 group controlled partly controlled and in control. It's nothing to do with medical terms. But basic is acceleration, how we basically are looking on the patients seeing and physician. So what I'm also looking is, do we see all patient group in our patient being coming on YORVIPATH treatment. And when I see that, it's pretty clear that we are in a position, we see the obvious [indiscernible]. But when we look at different element of genetic or hemological. We also see all different groups of patients, even patients on the ATH1 which are really, really are less than 1% in the claim database. We already have about patients on treatment with this symptom would really give us a hope that we basically will see the same penetration everywhere in all different of the hypopara patients in this way.

Our next question comes from Li Watsek with Cantor.

I guess just on BaaS, can you maybe just give us a little bit of color on payer mix and potential contracting, not just in Q4, but I'll think 2026, should we sort of expect still minimum contracting and sort of stable gross to net for the next few quarters?

I think, Scott, more or less addressed it in his prepared remark. There would be no changes in -- if we look forward, will there be potentially more contracting that we have seen now. And Jay can comes on, we are in a position where contracting would not anyway, change dramatically our GTN in any kind of financial modeling in this perspective. And we see European really have all the characteristics of a product is the first in class has only one treatment option. And we see it actually being not only being prescribed, but also being reimbursed to the level that we have hoped for. Jay, you have further comments to the long-term perspective of contracting?

Yes. I would just reaffirm what you shared consistent contracting strategy in Q4, as previously discussed given the first and only nature of what we have and the fact that the clinical value proposition speaks for itself, we don't anticipate any major contracting that's going to deviate above and beyond what we've shared before, which is more minor contracting around ensuring a frictionless patient experience. So again, nothing substantial or anything meaningful above and beyond what we've discussed to date. Any changes will be minor.

And when we look at the book, we can say the competitive landscape. We don't believe any of the -- what we see in the competitive landscape will really make us to move into a much more highly contracted product. As we see really the best-in-class properties compared to everything what we see.

And then just curious about the TransCon CNP and the Phase II meeting. In terms of the Phase III trial design, should we assume that the FDA would require a 1-year data on analyzed growth velocity? And anything that you can share on the powering assumptions?

Yes. That's an interesting question because I basically have never seen anything longer than 1-year clinical trial in any growth disorder. I've seen a lot of perception about something that could be taken up as 2 years, but I've never seen any regulatory packet that have more than 1-year controlled treatment in this. We have already what we call long-term data that will be generated from our Phase II trial. So I think that is basically the element of what I never have seen for in this way. And Aimee Shu went to the FDA meeting, so she can basically just give you the view about what she basically got a feedback from that perspective.

Yes. So Li, happy to say that we found our reviewers at FDA to be appropriately open-minded about appropriately clinically open-minded about duration here, but there's obviously a regulatory pathway, and that's usually 1 year of data.

Our next question comes from Yaron Werber with TD Cowen.

Great. Maybe, Jan, maybe a couple of questions. Number one, just on gross to net, when we're kind of -- we were at around just over 4,200 and we had like a 65% approval, but we were getting to higher numbers for the quarter. So I'm wondering whether -- and we had 18% gross to net. Is it possible that gross to net discounts are higher than that. That wouldn't make any sense. I guess the question kind of like what am I missing? And then maybe secondly, are you -- it sounds like you may be very suddenly intimating to expect some impact from the holidays in Q4. Are we reading it correctly because you didn't see much seasonality in Q3. And then finally, U.S. versus European sales for YORVI in the quarter? Was it like around 4 million or so in Europe this quarter as well.

Yes, that was three questions. The element of what I will take -- what we said in the beginning of the year is still what we really have seen. We said we will expect ex U.S. to be around EUR 4 million to EUR 5 million Europe increase every quarter because we have not really expanded it more to fully commercial countries, which we did now in here in Q3, but we first see the effect on that perspective in this way. Related to the seasonality on it, I don't expect any to see any seasonality in Q4. That is pretty clear. I expect it to potentially to have seen it in Q3 because I expected a physician to be gone for 3 weeks. And when we not really saw a major impact in three, I don't expect to see any impact in Q4. Scott, he's really the guide with the numbers and a return like that. So he really is good at that. So Scott, can you take the first question?

Yes. So I think your question was the 70% approvals and the time to revenue, we could probably follow up offline on how you're thinking about things. But just remember also when there's an approval, this isn't the exact same thing as patient on drug, right? They get approved and then sometimes it's soon, sometimes it takes a while. But that's probably the only thing to keep in mind.

Our next question comes from Martin Auster with Raymond James.

I'll try not to be too greedy, and just keep it to a couple. First, on YORVIPATH, and I was wondering if you could comment if you've got any sense on early data on what patient retention looks like from folks who started up on drug this year? And then second, on TransCon CNP. I guess from a commercial perspective, when you look at this market, it looks a little underpenetrated for a rare disease market compared to some other comps. Curious if you guys have a sense as to sort of why that's the case. And if you think TransCon CNP is sort of coming to market, improve upon that and improve overall penetration rates of treated folks at [indiscernible]?

Thanks, Martin, for the question. The first one is really, really spend a lot of time on it, spending a lot on the analytical. And we are losing a very, very few patients when they have initiated treatment. There are a few percentage. And if we lose them, it's basic in the first 4 to 6 weeks, meaning is that we are now trying to go back, how can we potentially help them in the titrating phase. And I think that is always the element where you start on a system where you are on convention therapy, you start to do it, you need to take it off. And I believe if there are not is a good interaction between both the physician, the place where we get [indiscernible] monitoring and everything like that. It a more difficult period for the time. This is where the time is until is why we started obviously on daily product because we know we could never get this titration to function with a one [indiscernible] medroduct.

So that is where we see. When we see after 4 to 6 weeks when we're starting to be stable, exactly as I said here, we expect nearly all patient to be on lifelong treatment. This is like building the fundamental stronger and stronger. And Martin, I agree with you on sort it's doing really poorly in the U.S. They're saying we're doing really good outside U.S., I think they're doing really poorly in U.S. That should be much, much higher. And I believe that because they're not really addressing what we really should address the comorbidities. -- and I believe this is where we come in with a differentiated product. This is why when I talk with the different patient organization group, and really ask me a simple question: Jan, will you have take the primary endpoint to be a linear growth if you were the first product? And I said, no, we will never have done that.

We will really have addressed how we're really addressing the co-mode because we believe that is really why patients should take that treatment. Help them to the comorbidities really help them in this way. And this is where I believe we have an extremely positive dialogue with all the patients and the patient related to that topic.

Our next question comes from Paul Choi with Goldman Sachs.

I also want to stay on TransCon CMP and maybe ask on the commercial strategy as you launch it and particularly for next year. Are you primarily going to target de novo patients? Or are you expecting a good portion of the revenue mix to be from PMP daily injection experience patients? And if you are expecting a decent size contribution from the latter. Can you maybe speak to what your market research suggests the appetite is on potential switch strategies? And just sort of what percentage of the existing treated patient base you might think, ultimately convert.

Thanks so much for the question. Yes, we expect that to be a lot of switches. We enrolled patients in the places where [indiscernible] were commercially available free for the patient. We enrolled it where there was other treatment alternatives, if you call the treatment alternatives. We were in a position that e preferred it. Out from their perspective is that not only the 1 weekly profile, but the lack of injection site reaction, really to be in a position, you don't need to worry about any risk of hypertension and anything like that. That was really one of the key movement. And also, at that time, we even have really the clarity of beyond linear growth, the benefit beyond linear growth. So when I look, today, it is going to be a last portion on switch patients when you have therapy being implemented to a high level, which it is in some European countries.

In some European countries, 70% of all patients will be treated today, and there will be. They are just waiting for it. We know they are waiting for it because they are asked for it all the time when it will be approved in Europe. If you go to U.S. because of not high penetration, there will be many more new patients coming in because there's not so many to switch off. So this is what we see and how we will build up the commercial strategy.

Our next question comes from Yun Zhong with Wedbush.

So the first question on the label extension to the higher dose. I assume the pricing is going to be the same. So do you expect any direct impact on maybe the number of patients on treatment and reported revenue, please?

First of all, when we look on treatment in the dose [indiscernible] the 30 dose is only restricted to the U.S. And currently, when we see in many countries, there is few percentage of patients that really need in a commercial setting. We accept some patients that really needed. And there in many cases already on treatment in the U.S. By having this trial, the patient at basic will need more than 30 in the U.S., we now have availability because they can join us in the clinical trial. The clinical trial, as Aimee can explain, it is a very simple single-arm study. You can explain how many patients we have is basically is a safety [indiscernible].

Yes. So single arm 18 subjects who will be titrated up as they need based on serum calcium using the higher doses.

So it's basically an 18-patient 6-month trial for safety perspective. and that will be the triggering point to also in the U.S. have it. I don't think it will have a material impact in any way on our revenue.

I see. Then a follow-up question on the payer discussion. I believe that initially, you said roughly it takes about 8 weeks to get payer approval and I think last quarter, you said 3 months and then this quarter, just now you probably said a month. Was that just a random maybe fluctuation or was there any meaningful change in terms of how long it takes for payers to approve coverage, please?

We see an improvement month by month. And when we look at the data today with above the 50% and the 8 weeks, that is the data we see today.

Our next question comes from Alex Thompson with Stifel.

This is Charles on for Alex. Maybe a bit of a different question, but in terms of the sort of adolescent buckets of hypopara patients you're looking at, I guess, like what kind of patient size this is represented in the U.S.? And what kind of growth do you expect to see from here, assuming there's successful label expansion?

This patient group is quite different patient group to compare to the pool of the patient we talked today in U.S. and other countries. Many of these young children are coming from more the genetic and hemological part and not some head and neck operations still that can be cost surge patient at that stage 2. These patients are in a severe case because if you have hypopara in such a young at lot of developmental part is really affected not to have the right calcium hemostasis, phosphate hemostasis and bone hemostasis in the body today.

So I see it as really a high level of severity of disease to have it also in this extremely young age. I even have seen young people that had it from young that already have kidney transplantation in the 20s because of the high burden of the treatment that has been available today with conventional therapy. And when we look on the number, there will not be a number ever can come up to the level that you see in the adult population, but it's not changing the severity of really making a treatment available for this patient group.

Our next question comes from Luca Issi with RBC.

Maybe on the unique patient enrollment. Is that a metric that you're committed to report going forward? Or are you playing a sunset a metric at some point? And if -- it is the latter. Can you talk about whether that could be Q4? Or would that be later than that? And then maybe if I can ask about Novo Nordisk, can you just talk about how that collaboration is going? Obviously, lots going on in Novo, given again, new leadership in place. And obviously, you just lost the deal on [indiscernible] wondering if you're seeing any disruption with that collaboration with them? Or maybe the opposite actually an acceleration of that collaboration. So any thoughts there? I much appreciate it.

Yes. Let me take the last question first about our collaboration. And when I look on the collaboration and we look on that once monthly semaglutide, which I believe have a unique profile because of the slowly release from the product system to a level where the [ TMAX ] is were late, and therefore, you don't have a high slope. So likely pitolerability, as we have seen in animal model really can also be established in the clinical to in humans in this way. As we are responsible for last element of the collaboration, they have definitely not been any disruption, and that has definitely not been any lack of interest in this program. And this is not one single program.

As I said in our press release is a series of programs that we are working on. So we definitely have not seen any kind of lack of interest and is progressing with speed, which we can do it to in this really positive collaboration as fast as we can do we believe that when they come to the late stage, sure, the muscle of a company like Novo Nordics to make a large Phase III trial in multiple waste is really unique because they really have the capacity and unique level of expertise to do it. I forgot the first question.

Enrollment as a metric.

Yes. The enrollment as a metric, is a question that we discussed a lot. And we won't comment on it when you're feeling that we are in a position that revenue that we are reporting. Now we are coming to a level where you're feeling that it's really coming to a state where the addition of new patients really are not changing summer of the overall. As I said, we're building a strong fundamental quarter-by-quarter. The strong fundament is building a really tall house. And we are now taking brick-by-brick quarter-by-quarter and we're building this radio base up more and more. And you can nearly form just a mathematic modeling, think about it when we are much more further in the launch, the addition of new patients just are not giving the same impact on the overall actual revenue at that stage. And therefore, I believe at one time, the number of due prescription is not really meaningful for you, you would just see a quarterly revenue growth. That basically just reflected at the addition of new patients.

Our next question comes from Maxwell Skor with Morgan Stanley.

I was just wondering when we can expect preclinical data supporting overpass potential for weekly dosing? And also, could you share your outlook on your past trajectory in Europe? How should we think about a potential ramp next year?

Typically, what we're doing is that, we will like in the beginning of the year, there is a conference and likely there, we typically will come up with and status on our new product opportunities and we expect to repeat the same element year-by-year. So a good time to expect to see data will be at the beginning of this year.

He's talking the guidance on OUS.

[ Ex U.S. ] what we said for this year here is a EUR 4 million to EUR 5 million increase quarter-by-quarter. With what we said, this will further be accelerated when we come into '26 because we will have an addition of more and more countries. When we come into January, we will give you the perspective of what countries we expect to add in to the being fully commercial in '26 and '27.

Thank you. And we'll take our last question from Clara Dong with Jefferies.

And just to follow up on the previous question, and I apologize if you've mentioned already, but it will be great if you can confer U.S. and ex U.S. revenue split for YORVIPATH and then in terms of DAUs launch momentum. So is there any specific time line for any upcoming reimbursement decision in any market and any pricing dynamics we should keep in mind as you expand internationally?

Okay. So we gave you an algorithm basic in the beginning of the year. We said that when you look at Q4 '24, there was about EUR 14 million in net revenue all this net revenue was basic ex U.S. And we expect it to add 4 million to 5 million net revenue in '25 every quarter. So you can nearly add 14 to plus 5 plus 5 plus 5 and then you have the Q4. What we saw in here in '25. We got Spain full commercial. We are in a sideration where we not compromise the value because we have a doable product that basically will be here for 20 years. So for us, it's more important to really have the value being created in the right manner. And what we will give you here at the beginning of the year, the perspective of what and how many new countries we expect to add on in '26.

Thank you. And that's all the time we have. Thank you for joining. You may now disconnect. Good day.

Thanks a lot.