Ascendis Pharma A/S (ASND) 2025 Q4 法說會逐字稿

Thank you for standing by and welcome to the Ascendis Pharma fourth-quarter 2025 earnings conference call. (Operator Instructions)

As a reminder, today's program is being recorded. And now I'd like to introduce your host for today's program, Chad Fugere, Vice President of Investor Relations. Please go ahead, sir.

Thank you, operator, and thank you, everyone, for joining our full year 2025 financial results conference call. I'm Chad Fugere, Vice President of Investor Relations at Ascendis Pharma. Joining me on the call today are Jan Mikkelsen, President and Chief Executive Officer; Scott Smith, Chief Financial Officer; Sherrie Glass, Chief Business Officer; Jay Wu, Executive Vice President and President Ascendis US; and Amy Xu, Chief Medical Officer.

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 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 US 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 US 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 EUR500 million in 2026 and where we aspire to achieve at least EUR5 billion in annual product revenue by 2030.

And at the same time, we are building an expanded pipeline of (inaudible) 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 EUR187 million, bringing full year 2025, YORVIPATH revenue to EUR477 million.

In the US, 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 US 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 eight 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 US, 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 (inaudible) in four countries, in our Europe direct markets and two countries in our international markets. In Japan, our partner (inaudible) 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 US, we are working to expand the range of doses to our PaTHway60 Trial. And globally, we continue to advance clinical trial to expand YORVIPATH to patients under the 8 of 18.

Our work is progressing rapidly on once-weekly TransCon PTH for patients who have been titrated with daily (inaudible) of conventional therapy and have achieved a stable daily dose for a well-defined period.

Last month, at the Annual JPMorgan Healthcare Conference, we shared preclinical data that support the target product profile for 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, (inaudible) or TransCon Growth Hormone or on weekly TransCon CNP. Sketch over delivered another solid quarter, with Q4 revenue of EUR53 million, bringing full year SKYTROFA revenue to EUR206 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 US and adult growth hormone deficiency. Today, SKYTROFA has an overall market share of around 7% in the US.

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 one 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 (inaudible) dimension and a similar safety and tolerability profile compared to placebo, with a very low rate of injection (inaudible) and no cases of symptomatic hypotension. In the US, 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 (inaudible) zero to two is going well, and we activate complete enrollment later this year. Turning to the combination therapy. Our 52 VCOs data in (inaudible) underscore the potential power of dual treatment with TransCon CNP and (inaudible). 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 (inaudible) 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 (inaudible) with linear growth improvements in (inaudible) place a specific (inaudible) that were 3 to 4 times. 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 (inaudible) 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 (inaudible), 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 (inaudible) continue to advance towards the clean. (inaudible) 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 two 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, (inaudible) confident to achieve an expected operating cash flow of around EUR500 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 EUR187 million, up from EUR140 million in Q3. Foreign currency had a negligible impact compared to the previous quarter. Total YORVIPATH revenue for 2025 was EUR477 million. For the full year, the weaker US dollar negatively impacted YORVIPATH revenue by approximately EUR27 million. SKYTROFA contributed EUR53 million in Q4, with negligible foreign currency impact compared to Q3 '25. Total SKYTROFA revenue for 2025 was EUR206 million. For the full year, the weaker US dollar negatively impacted SKYTROFA revenue by approximately EUR9 million. Including EUR7 million in collaboration revenue, total Q4 2025 revenue amounted to EUR248 million. and total revenue for full year 2025 was EUR720 million.

Continuing on to expenses. As previously announced, total operating expenses for Q4 were EUR214 million and total operating expenses for the full year 2025 were EUR761 million, as we previously noted. Operating profit for Q4 2025 was EUR10 million, with Q4 operating cash flow of EUR73 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 EUR106 million was EUR93 million net. Net cash financial expense, however, for the full year 2025 was about EUR8 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 EUR616 million in cash and cash equivalents, as previously reported, up from EUR560 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-US dollar exchange rate for any potential impact. And finally, we also look forward to the potential US 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)

Jess Fye, 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.

Tazeen Ahmad, Bank of America.

You mentioned a 70% insurance approval rate in the US 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 two things where in the end, the overall and (inaudible) 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 two 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, (inaudible) 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 US discussion. The US 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 six 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 US, the system is quite different. When you get a prescription, you in nearly in every other country, you are (inaudible) approved.

So you can say the 100%, yes, it's basic when you get a prescription outside US in traditional countries, you will be 100% electable and already approved for reimbursement.

Gavin Clark Gartner, 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 US, 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 US and x about EUR40 million to EUR50 million net every quarter. I think you will always see a stability in how we are executing in it.

We still have ex US, 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 US.

Yaron Werber, Cowen.

I have sort of two not really related, but I'm going to try to link them to keep it as one question. Maybe the first one, can you give us a little bit of a sense for 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 one or two 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 US, 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 (inaudible) 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 (inaudible) 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 two 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 (inaudible)

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 US 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 (inaudible) 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 (inaudible).

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 three or four 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.

[Joseph Schwartz, Leerink Partners].

This is (inaudible) 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 US but also outside the US because we can utilizing the US approval to go to countries outside US, 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, (inaudible)

Taxes and money.

So we will come back after that.

Derek Archila, Wells Fargo.

Yes, I just wanted to understand your confidence level around your bypath growth ex US. 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 US 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 (inaudible) 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 one country after (inaudible) first going in and getting approval, and then we go into full reimbursement.

(inaudible), Cantor.

It's (inaudible) 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 (inaudible) compared to one 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 (inaudible), 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 US to ensure that is all this will happen.

(inaudible), Barclays.

Curious if you can elaborate on your strategy for commercializing TransCon CNP US. Just given the majority of (inaudible) US. 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 US, 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 two to three 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 (inaudible) for all three 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.

Leland Gershell, Oppenheimer.

I wanted to ask, (inaudible) as we look at the EUR5 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 three 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 three 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 three approved products in perhaps 20 different indications in about 30, 40 countries, meaning is that what we really want to do we will not be dependent on one single product in one single region. This is how we build up a sustainable company. That basically have a continued stable revenue flow for multiple years.

And don't forget these product opportunities we have. When I look on the pipeline for each of them, 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.

Paul Choi, Goldman Sachs.

I think your Phase II (inaudible) 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 two main regulatory areas because we can also take Japan into it. But if you take, for example, the US, 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 (inaudible) 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 six 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 (inaudible) 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.

Yun Zhong, 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 two things that is interconnected because if you, for example, can show the PK profile, and they can even be healthy volunteers or patients with (inaudible) 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.

(inaudible), 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 (inaudible) has announced that they will file (inaudible) 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 (inaudible)

I think I will liberate (inaudible), 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 four 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)

Maxwell Skor, 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. (inaudible) 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 (inaudible) 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 (inaudible), 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 (inaudible). 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 (inaudible) 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 [AOC] 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.

Alex Thompson, 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 three or four 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 (inaudible) from Wolfe Research.

I had one of the competitive landscape. Wondering how you're thinking about this internally as other agents like (inaudible) 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 (inaudible) and giving [incurred] is not increasing and providing any (inaudible) to this. We're talking about a hormone replacement therapy where you're helping multiple organs, the brain, so you have greater cognitive effects.

The goal is 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 (inaudible) 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 (inaudible), 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 (inaudible)

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 (inaudible) and also the earlier stage long-acting CNP from (inaudible)?

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 one 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 one 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 (inaudible) 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 (inaudible) 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 (inaudible)? Can we see all the element of improved quality of life with that. But (inaudible) 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.

(inaudible) and when you have a nonspecific inhibition of FDA 1, you also have nonspecific inhibition of FDR 2. And when you know that (inaudible) 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 three perhaps four, five years per treatment. (inaudible) 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.