Ascendis Pharma A/S Q4 FY2025 Earnings Call

At this time, participants are in listen-only mode. Thank you for standing by, and welcome to the Ascendis Pharma A/S Fourth Quarter 2025 Earnings Conference Call. After the speakers’ presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press star 11 on your telephone. If your question has been answered and you would like to remove yourself from the queue, simply press star 11 again. As a reminder, today’s program is being recorded. And now I would like to introduce your host for today’s program, Chad Fugier, Vice President, Investor Relations.

Thank you, operator, and thank you, everyone, for joining our full-year 2025 financial results conference call. I am Chad Fugier, Vice President, Investor Relations at Ascendis Pharma A/S. Joining me on the call today are Jan Moller Mikkelsen, President and Chief Executive Officer; Scott T. Smith, Chief Financial Officer; Sherrie Glass, Chief Business Officer; Jay Donovan Wu, Executive Vice President and President, Ascendis US; and Aimee Shu, 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; our strategic plans, partnerships, and investments; potential commercialization; 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 of regulatory decisions and results. 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 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 02/11/2026. TransCon Growth Hormone or TransCon hGH 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 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 US by the FDA for 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 agency. None of the statements during this conference call regarding our product candidates shall be viewed as promotional. On the call today, we will discuss our full-year 2025 financial results and we will provide further business updates. Following some prepared remarks, we will then open up the call for your questions. With that, let me turn the call over to Jan.

Thanks, Chad. Good afternoon, everyone. With strong execution across our business and continued progress toward delivering on our Vision 2030, Ascendis is transforming into a leading global biopharma company. We believe this progression demonstrates the power of our TransCon platform and our R&D capabilities to deliver a sustainable pipeline. While our global commercial infrastructure and financial profile continue to strengthen, we believe we are now at the base of a steep growth curve, where we expect to achieve operating cash flow of around €500 million in 2026 and where we aspire to achieve at least €5 billion in annual product revenue by 2030. At the same time, we are building an expanded pipeline of blockbuster product opportunities. In the fourth quarter, we saw multiple achievements across the organization, starting with Yorvipath. The fourth quarter was another period of strong execution for the global launch of Yorvipath. Revenue for the quarter was €187 million, bringing full-year 2025 Yorvipath revenue to €477 million. In the US, access continued to expand. To year end, more than 5,300 patients were prescribed Yorvipath by nearly 2,400 unique healthcare providers, highlighting continued strong and steady demand. To date, less than 5% of US patients are currently on Yorvipath treatment, highlighting the significant long-term growth opportunity ahead. The overall insurance approval rate is about 70% of total enrollment, and we continue to see this figure moving higher over time. In addition, we continue to see a majority of approvals within eight weeks. This provides a strong foundation for expected additional growth in 2026 and beyond as more patients initiate Yorvipath in line with treatment guidelines that support its use. Outside the US, we continue to reach more patients. As a reminder, Yorvipath is now available commercially or through named patient programs in more than 30 countries. We have full commercial reimbursement in four countries in our Europe direct markets and two countries in our international markets. In Japan, our partner Taisho launched Yorvipath commercially last November. In 2026, we expect full commercial launches in 10 additional new countries. We also advanced development activity to broaden Yorvipath’s label in a number of areas. In the US, we are working to expand the range of doses towards PATHway-6 trial, and globally we continue to advance clinical trials to expand Yorvipath to patients under the age of 18. Our work is progressing rapidly on once-weekly TransCon PTH for patients who have been titrated with daily Yorvipath or conventional therapy and have achieved a stable daily dose for a well-defined period. Last month, at the annual J.P. Morgan Healthcare Conference, we shared preclinical data that support the target product profile for a once-weekly TransCon PTH candidate matching the release PK/PD as seen with daily Yorvipath treatment over the entire week, thus providing a comparable efficacy and safety profile. Overall, we remain confident that Yorvipath has the potential to be a durable long-term growth driver for Ascendis globally. Turning now to growth disorders, comprising our once-weekly growth hormone Skytrofa, or TransCon Growth Hormone, and our once-weekly TransCon CNP. Skytrofa delivered another solid quarter with Q4 revenue of €53 million, bringing full-year Skytrofa revenue to €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 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 evaluating TransCon Growth Hormone in additional established growth hormone indications, including ISS, SHOX deficiency, Turner syndrome, and SGA, which comprise up to half of the growth hormone market. Over the long term, these indications represent meaningful opportunity to expand the role of Skytrofa as a treatment of choice in additional growth disorders. We also see an opportunity to potentially expand Skytrofa’s use to novel indications where growth hormone has not previously been approved for use, such as achondroplasia, in combination with TransCon CNP. TransCon CNP is expected to be the first and only once-weekly treatment with monotherapies addressing the overactive FGFR3 tyrosine kinase. In addition, in our pivotal trial, TransCon CNP achieved a significant improvement profile compared to placebo, with a very low rate of injection-site reaction, increased spinal canal dimensions, and a similar safety and tolerability profile, with no cases of symptomatic hypertension. In the US, our NDA for children with achondroplasia remains under review with a PDUFA date of February 28. In the EU, the MAA review is underway, following our submission last October with a regulatory decision expected in the fourth quarter of 2026. Recruitment of our ongoing trials in infants with achondroplasia ages 0 to 2 is going well, and we anticipate complete enrollment later this year. Turning to the combination therapy, our 52-week data in achondroplasia underscore the potential power of dual treatment with TransCon CNP and TransCon Growth Hormone. Continuous exposure to CNP enables the benefit of sustained exposure to unmodified growth hormone. In comparison, monotreatment trials of daily growth hormone in achondroplasia delivered only a limited effect on growth and no group-reported benefit on linear growth. Our 52-week data from the Phase II combination trial support our vision to significantly raise the bar for treatment of achondroplasia, with linear growth improvements in achondroplasia-specific height score that were three to four times what has been shown with CNP or daily growth hormone monotherapy in the same time period. Additionally, the combination trial demonstrated accelerated improvement in body proportionality, and for the first time, a meaningful improvement in arm span has been reported, without compromising safety or tolerability. Importantly, these benefits are meaningful to the achondroplasia community and have been a core objective of our patient-focused development program in both our monotherapy and combination therapy programs. Importantly, all children completed 52 weeks of treatment and remain in the trial, reinforcing the benefit of treatment and acceptable treatment burden of the once-weekly regimen. These Phase II results demonstrate the effect of these complementary therapies, supporting that TransCon CNP acts in synergy with the growth-promoting effect of TransCon Growth Hormone and has positive effects beyond linear growth. We believe over time the standard of care in achondroplasia and other growth disorders long term will include dual therapy as a treatment option. Building on the potential role of TransCon CNP as an essential fundamental therapy, we recently had a successful end-of-Phase II FDA Meeting and Scientific Advice Meeting in the EU to align on our Phase III trial for this novel combination approach for treating children with achondroplasia. We also remain on track for additional COACH trial updates including week 78 by midyear and week 104 by year end, and plan to explore further opportunity in other growth disorders. To sustain long-term growth for Ascendis well into the next decade, we plan to continue to invest in label expansion of our current products in rare endocrine diseases. In addition, we have a strong focus on the development of new blockbuster product opportunities, both inside and outside rare endocrine diseases, to fuel significant product revenue growth in the future. Looking at our partnerships, TransCon Technologies support a continuous flow of highly differentiated product opportunities across multiple therapeutic areas, more than we can develop and commercialize ourselves. For this reason, our Vision 2030 includes a focus on creating additional value through partnership and collaboration. Our collaboration with Novo Nordisk for once-monthly TransCon semaglutide continues to advance toward the clinic. Adarx’s TransCon anti-VEGF is on track to enter the clinic this year. In Japan, Taisho received approval for Yorvipath in August 2025 and launched it commercially in November 2025. In addition, VISEN received approval of Skytrofa in China in late January 2026. In summary, 2025 was another positive and transformative year for Ascendis, with two commercial TransCon products continuing to scale, the potential approval of the third high-value TransCon product in the coming weeks, and a growing pipeline of highly differentiated programs. We believe we have the fundamentals in place to deliver global long-term growth. A rapidly strengthening financial profile gives us confidence to achieve an expected operating cash flow of around €500 million in 2026 and our aspiration to achieve at least €5 billion in annual product revenue by 2030, all consistent with our Vision 2030 strategy. I will now turn the call over to Scott.

Thank you, Jan, and thank you, Chad, for a well-read FLS. The significant achievements we made in 2025 provide us with substantial financial strength to drive our strategic priorities and goals in 2026, which include achieving blockbuster status for Yorvipath, solidifying our leadership in hypoparathyroidism through rapid progress of our label clinical trials of TransCon PTH while advancing development of our once-weekly PTH candidate, successfully launching TransCon CNP if approved in the US and other countries around the world, and expanding 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 J.P. Morgan. For further details, please refer to our annual report on Form 20-F filed today. As previously announced in January, Yorvipath delivered strong global performance in Q4 2025, with revenue increasing to €187 million, up from €140 million in Q3. Foreign currency had a negligible impact compared to the previous quarter. Total Yorvipath revenue for 2025 was €477 million. For the full year, the weaker US dollar negatively impacted Yorvipath revenue by approximately €27 million. Skytrofa contributed €53 million in Q4 with negligible foreign currency impact compared to Q3 2025. Total Skytrofa revenue for 2025 was €206 million. For the full year, the weaker US dollar negatively impacted Skytrofa revenue by approximately €9 million. Including €7 million in collaboration revenue, total Q4 2025 revenue amounted to €248 million, and total revenue for full-year 2025 was €720 million. Continuing on to expenses, as previously announced, total operating expenses for Q4 were €214 million and total operating expenses for the full year 2025 were €761 million. As we previously noted, operating profit for Q4 2025 was €10 million, with Q4 operating cash flow of €73 million. As we have discussed for some time, below operating profit, the drivers include the noncash accounting related to our convertible notes. The noncash net finance expense, which was primarily driven by noncash items, including the remeasurement loss of financial liabilities of €106 million, was €93 million net. Net cash finance expense, however, for the full year 2025 was about €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 2025 with €616 million in cash and cash equivalents, as previously reported, up from €560 million as of December 31, 2024. Turning to our commercial outlook 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. 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.

Certainly. And once again, ladies and gentlemen, we ask that you please limit yourself to one question each. Our first question comes from the line of Jessica Macomber Fye from J.P. Morgan. Your question please.

Hey, guys. Good afternoon. Thanks so much for taking my question. What is 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? Thank you.

Yes. Can you remember you asked me a question one time, and the J.P. Morgan conference? Can you remember my answer?

I do remember the answer.

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

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

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

Okay. Thank you.

Thank you. And our next question comes from the line of Tazeen Ahmad from Bank of America. Your question please.

Hi. Good afternoon. Thanks for taking my question. You mentioned a 70% insurance approval rate in the US so far for Yorvipath. When might you get to 100%, basically?

I think it would be infinity, because I have never seen a product hitting 100%. I think the highest bar I have seen is something like 85%, perhaps up to 90.

Where we are today, I am highly satisfied because it is also a compromise about how aggressive you are going into contracting and other things. It is a balance between the two things where in the end, the overall and ultimate goal is to provide most value back to our shareholders and others, and at the same time help the patient to come on treatment as fast as possible. I do not know, Jay, if you have additional comments to my I would not say, pre-prepared remarks.

Yeah. I would say two things. One is that we are very happy with the overall approval rate that we are seeing. I think the speed in which you are seeing this product be covered, again, is a testament to the strong clinical value proposition that we are seeing in hypoparathyroidism. It is the first and only approved therapy in this category. So, again, this approval rating based on where we are today is something that we are very encouraged by. I think to your second part of the question, Tazeen, when might you get to 100%, I echo what Jan said earlier as well, which is I do not know that many drug analogs will get to 100%, and that actually has less to do with coverage and also has 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 natural filtering that comes that way. 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.

Yeah, okay. But I think the US discussion is built on 70% of all approvals in enrollment are there. When you look at an old cohort that perhaps has been six months through it, your actual will get an almost higher number on it. Just to clarify that 70%, that is when you take everyone accumulated. If you take an old cohort, it is much higher. When you go ex-US, the system is quite different. When you get a prescription, in nearly every other country, you are axiom approved. So you can say the 100% yes is basic. When you get a prescription outside US in traditional countries, you will be 100% eligible and already approved for reimbursement. Got it. Thank you for the color.

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

Hey, guys, thanks for taking the question. Just on your 8% WAC increase in January. Maybe you could discuss how net pricing will trend this year?

I do not think we really are discussing net prices. We would love to do it, but we have never done it, and I do not think we ever will discuss net prices.

Maybe if I could just ask a follow-up then. 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, Gavin, is 100% right. We will focus on revenue because now we basically have been in the market in the US for about four quarters now. When we come to the fifth quarter, I think you have seen a steady state development from 2025 where we basically got an increase in revenue from both US and ex-US of about €40 million to €50 million net every quarter. I think you will see a stability in how we are executing. We still have ex-US. We expect 10 additional countries being fully reimbursed next year. I am sure that is always improving what we call the net revenue we will generate outside the US.

Thank you. And our next question comes from the line of Yaron Benjamin Werber from TD Cowen. Your question please.

Great. Thanks so much. I have a sort of two not really related, but I am 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 Yorvipath? How it is being used out there? I mean, it is almost like when you look at this 2,400 unique prescribers and 5,300 unique patient enrollment, so is it that each physician just has one or two patients in the practice or are they prescribing it there and then they are going deeper? And then secondly, just at the end-of-Phase II meeting with FDA relating to CNP and growth hormone for achondroplasia, can you give us a little bit of an update, what was the outcome and when will you start the Phase III?

Okay. That is perfect. I think, Jay, you can give some about how we are both expanding the physician prescriber base, but also go in more in the deep of the different patient but still are far away to reach delivery where we want to be. Jay, yep. 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, this is where you first started your question from. We are seeing broad uptake across the entire range of prescribers. So to your point, there are some physicians that might only see a couple patients, but there are also some physicians that might see upwards of 10 patients. More importantly, because we are seeing broad uptake across both high-decile and low-decile providers, we are 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 is both a testament to positive experience that they have with Yorvipath as well as increased awareness of the hypoparathyroidism condition and 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. One, the vast majority of them are postsurgical, so about 70%. The remaining 30% perhaps due to other factors, whether it is genetic, autoimmune, etc. We are seeing broad uptake across both of those segments, so that is not a major driver. Really where you are seeing some of the earlier uptake is patients that are self-aware of the condition that they have, and therefore 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 are seeing broad uptake across provider groups as well as patient segments.

Thank you. And our next question comes from the line of Joseph Schwartz.

Hi, this is Heidi Jacobson on for Joe Schwartz. Thanks so much for taking our question. 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?

Thanks. It is pretty simple. It is not incorporated. When we are coming into the launch, we see the initial uptake, which we believe will be pretty high, not only in the US but also outside US because we can utilize the US approval to go to countries outside US, specifically in the international market. From that perspective, we will come and provide you a better guidance and improved guidance when we have seen that.

Scott is smiling, are you counting money or what are you doing?

If you will come back after that.

Hey, good afternoon. Thanks for taking the questions. I wanted to understand your confidence level around Yorvipath growth ex-US. Obviously, the launch in Germany and Austria, is that a good proxy? Or is it going to be more depth in those types of countries than just kind of expansion in, you know, I guess, I think you said 10 additional countries. So how will that be sequenced through the year? Thanks.

That is an extremely complicated answer because the heterogeneity of the ex-US is so heterogeneous that we cannot really compare to what we, for example, see in Spain now, what we see in France, what we see in Germany, what we see in Austria. It is really different things because we see different speed of penetration. For example, Germany has less endos, so the bottleneck is tighter. It takes longer time to get them on therapy because there are fewer in the general population.

If we go to Spain, there are more, there are more in France, and we also see, therefore, a faster uptake because we basically have a pipe that is larger. When we get 10 more additional countries on full commercial, we will see different uptake, but what we are doing is everything will be accumulated in the way where we now see from 30 to 35 countries named patient programs. When we go full commercial, what we see every place is basically an acceleration of patient uptake, because of the burdensome nature of a named patient program. It takes so much effort to get every single patient on it, and every patient deserves to be under treatment. So when you come to 2026, we will see initial speeding up in all these countries. When we come to 2027, 2028, you will continue to do it because, just by nature, we just got approval now in Canada, and we are basically taking one country after the country, first going in and getting approval, and then we are going to put reimbursement. Thank you. Our next question comes from the line of Li Watsek from Cantor. Your question please.

Hey, thank you so much for taking our question. It is Daniel Brondo on for Li. Can you give us a little bit of color on how you expect your TransCon CNP launch to go? It seems like there are a few patients who are 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 tolerability, injection-site reaction, having one in 20 injection-site reaction compared to one every second year, being in a position to look at no risk of hypertension. The element of just having the improvement on the once-weekly product and then show the data package that we have generated with TransCon CNP, for the first time ever shown in a well-controlled trial against placebo, benefit beyond linear growth. For example, the leg bowing, which we have shown multiple times, we have shown improvement in muscle strength. We have improved quality of life. I think this is obvious. Every patient that decides 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 it always will happen. Thank you. And our next question comes from the line of Eliana Rachel Merle from Barclays. Your question please.

Hey, guys. Thanks so much for taking my question. Curious if you can elaborate on your strategy for commercializing TransCon CNP ex-US. Just given the majority of vosoritide sales are ex-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, can you talk a little bit more about how you are thinking about the cadence of uptake and which segments do you expect the most uptake from between, say, treatment naive versus switches? Thanks.

Yeah. I will dial a little bit back now because what we did when we said that we want to have global commercial efforts. We actually started all our infrastructure building to Yorvipath. And now you see what we have done with Yorvipath, recognized their fast revenue, commercial revenue for more than 30 countries. We are penetrating them exactly as we can do. We will reach 60 to 70 countries in less than two to three years. So what we have done, we already have built up the infrastructure to be ready that we can take our integrated pipeline of rare disease endocrine products into all these different countries in the setup via step links around Yorvipath. So this is the positive element that we are not, you can say, a company that needs first to build an infrastructure to support globalization. We have already established that. So I feel really confident that all the success we see now with Yorvipath on a global scale we will just take it in. Do not forget, for example, even in Japan, the collaboration we have with Taisho is for all three products, the same thing in China and other places. When we make this agreement, we are not making a single product for a single country. We make it as a pipeline product. And this is why we do not need to go out and make new agreements or anything. It is just going to be done extremely fast from that perspective. Thank you. And our next question comes from the line of Leland James Gershell from Oppenheimer. Your question please.

Great. I want to ask, as we look at the €5 billion number you have put out there for product sales by 2030. I know you are not giving specific product guidance here, but if you could share with us how you think about the relative contributions of your presumably three products by that point in time in terms of how they will weigh into that total sum. Obviously, you have much more expansion opportunity in hypoparathyroid, you have TransCon CNP potentially launching soon, and Skytrofa perhaps getting additional indications in combination. I would love to just hear maybe just philosophically how your outlook adds up with those three parts.

Yeah. That is an element where we are always in our forecasting are operating under different assumptions, where we are basically building up models for each single country and then we accumulate that on a global setup. We first take 2026, we take 2027, 2028, and 2029. Then what we are 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 fountainhead? But I think what makes Ascendis unique 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 to 40 countries. Meaning 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 has a continued stable revenue flow for multiple years. Do not forget these product opportunities we have. When I look at the pipeline for each of them, I definitely do not have sleepless nights. 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 realized. This is why we take the value perspective of each single product opportunity instead of fast revenue. This is not how we operate. We go for value, and because that is the product really to serve this treatment because we are providing not only a unique benefit for the patient, but also for the society and everyone.

Thank you. And our next question comes from the line of Paul Choi from Goldman Sachs. Your question please.

Hi, good afternoon. Thanks for taking our question. I think your Phase II REACH IN study is scheduled to reach primary completion next month. Will you be in a position to file an sNDA for the newborn infant population this year? And in terms of the newborn infant 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 this study population, or will that require a separate study? Thank you.

I think when you discuss a label discussion, that typically is different between, now I just take the two main regulatory areas because we can also take Japan into it, but if you take, for example, US, it is much harder to come to a situation where they will accept a label expansion to the infant without having the data in hand. In Europe, it is much more flexible because you have a discussion with them, and you can have what I call partly rolling of data that is being generated to our trial. So there will likely be a difference between the three geographic regions. Now simplified, Japan is mostly perhaps the easiest way to get it down to infant immediately. What we are doing now is to ensure we generate the right data and we are doing that in a trial. It is a placebo-controlled trial, and what we see is everything we hoped for. It is living up to our expectation. Why I can say that? Because in the enrollment we have six patients on a, what I call, physical treatment on it. You take them in, and there is no randomization. You can follow them, and Aimee can tell a few words about the benefit we have seen from that perspective.

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

Yeah. So we are really so pleased with the progress we are doing in helping patients with achondroplasia, not only on linear growth but also benefiting beyond linear growth. Thank you. Our next question comes from the line of Yun Zhong from Wedbush. Your question please.

Hi, good afternoon. Thank you very much for taking the question. My question is on the weekly TransCon PTH. Is it reasonable to expect that the program could potentially enter the clinic in 2026, or do you think that there is no need to rush? Also, you mentioned matching PK to the daily product. With data from Yorvipath available, what do you see as the most efficient clinical pathway to maybe take the weekly PTH to approval?

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

Okay. Thank you very much.

Thank you. And our next question comes from the line of Luca Issi from RBC. Your question please.

Great. Thanks so much for taking my question. Congrats on the progress. Maybe, Jan, big picture, one of the goals for 2030, as you articulated at J.P. Morgan, is to remain an independent and profitable biotech company, and we have seen many examples of that in our industry recently. However, how are you thinking about maybe continuing that same vision under the broader umbrella of a larger pharmaceutical company? I guess the question is how are you thinking about strategic path A versus strategic path B at this point? Any color there is much appreciated.

And then maybe, Jay, quickly, I think BioMarin has announced that they will file vosoritide 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? Do you not view that difference as material for adoption given you obviously have a less frequent dosing versus—

I think I will liberate Jay for answering the last question.

I think when I look at this discussion on accelerated approval that BioMarin is filing for, that has no impact on our regulatory pathway and approval and other things like that. Totally independent. It is not in any way how you can build up any barrier. The second thing, yes, in our vision there is independence, and I believe that is a great word because we want to be independent like a teenager growing up. One of the things, at least I have four children, I am teaching them when they are going to be aging, you need to be financially independent as the first element in their life. I think this is a great thing to see Ascendis Pharma now moving away from being a teenager but basically can go up to a more adult life. We have shown now we are completely independent on asking investors and others for any kind of revenue, and I think this is how we see independence.

Super helpful. Thank you.

And as a reminder, ladies and gentlemen, we ask you to please limit yourselves to one question. You may get back in queue as time allows. Our next question comes from the line of Maxwell Nathan Skor from Morgan Stanley. Your question please.

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

Yeah. Let me go back to all the elements and all the IP we have done, files and data and everything like that before we went into this extremely productive collaboration with our neighbor in Copenhagen, Novo Nordisk. What was the idea behind once-monthly semaglutide? The idea was to be sure that you can get fast weight loss and at the same time have a high level of tolerability. Just think about, I can define it, you have a naked GLP-1 molecule that when you give it weekly or potentially want to use a weekly product in a once-monthly, you need to add much more compound to compensate for the half-life to have a large AUC. By doing this, you add a high Cmax. Because it is naked, you will have a very short Tmax, meaning that you will have a steep curve from the lowest level just before you start to give a dose up to the maximum concentration. That is basically what often gives the tolerability issue where you get the element that basically limits people to stay on treatment and what you can achieve. This is what I call the naked product. This is like metacresol and everything. This is a naked protein. What we are doing now is defining what we call packed-in semaglutide. Even if you give it a high dose, you liberate it slowly, slowly, slowly, so you are getting a very long Tmax. By doing that, you basically have a slope that is not as steep at all as you see with a naked molecule, then you can see you still have a big AUC because you provide so much compound, give it over the entire month, and at the same time, you do not have this steepness in the slope.

By doing this, we designed it to have maximal weight loss as fast as possible with the best tolerability profile, and it was how we designed it at that time. Thank you. And our next question comes from the line of Alexander Thompson from Stifel. Your question please.

Hey, great. Thanks for taking our question. Maybe for Scott, could you talk a little bit about OpEx trajectory in 2026 in the context of the CNP launch and then the schedule of the label expansion both with mono and the combo pivotal studies? Thanks.

No problem. We talked a little bit about this at the J.P. Morgan conference event. Using Q4 OpEx as a run rate for the full year is not a bad way to think about it. If things change, we will come in and update you. Overall, everything related to CNP, as we said before, we will come out and discuss more following approval. Yeah. But that is mainly related to the revenue, because what we have now, we have a really mature company. It is not like we take something in a pipeline, we actually take product out of the pipeline all the time. So R&D is basically constant for the last three or four years. Our global commercialization, specifically the direct markets that we have built up already now, adding a few more people there, not major impact on anything like that. This is the benefit of a pipeline in the same therapeutic area and scale that we have now.

Thank you. And our next question comes from the line of Joori Park from Wolfe Research. Your question please.

Yeah. Thanks for taking the question. I have one on the competitive landscape. Wondering how you are thinking about this internally as other agents like encaleret are looking to expand into the chronic hypoparathyroidism landscape, and then does your longer-term outlook for Yorvipath include that potential impact from such emerging agents? Thank you.

I could be polite, or I can be a straight shooter. I have seen a lot of idiotic ideas. This one is really one of the most idiotic ideas I heard about. You have patient that is missing a hormone, PTH, and giving encaleret is not increasing and providing any hormone to this. We are talking about a hormone replacement therapy where you are helping multiple organs, the brain so you have greater cognitive effects. The bone needs to have the right metabolic system. The kidney needs to have the right phosphate elimination. It needs to have the right calcium absorption. I can continue one organ after the other organ. Then you believe you can take a compound incubator that basically is a calcium sensitizing compound, take it into a person that does not have the hormone, and then you think you have a treatment. It is really one of the most unscientific ideas where I cannot see any meaningful effect that it will help the patient. You can increase the element of one single thing, absorption of calcium, but that is not in any way coming in as a hormone replacement therapy. So no. We have not calculated that in. There is an idea in the ADH1 patient, which has a mutation in the calcium sensitizer 1, it makes sense for this small amount of patients. It makes sense but not for a person that misses PTH.

Got it. Thank you for your insight.

Thank you.

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