Ascendis Pharma A/S

Thank you for standing by and welcome to the Ascendance Pharma 4th Quarter 2025 Earnings Conference Call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you'll need to press star 1-1 on your telephone. If your question has been answered and you'd like to remove yourself from the queue, simply press star 1-1 again. We ask that you please limit yourself to one question. 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, 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, Investor Relations at Ascendus Pharma. Joining me on the call today are Yen Mickelson, President and Chief Executive Officer, Scott Smith, Chief Financial Officer, Sherry Glass, Chief Business Officer, Jay Wu, Executive Vice President and President Ascendus U.S., and Amy Hsu, 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 Skytropha and YorbiPath, 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 statement section in today's press release, and the risk factor section of our most recent annual report on Form 20F, filed with the SEC on February 11, 2026. Transcon Growth Hormone, or Transcon HGH, is now approved in the U.S. by the FDA for the replacement of endogenous growth hormone in adults with growth hormone deficiency, in addition to the treatment of pediatric growth hormone deficiency. And then the EU has received MAA authorization from the European Commission for the Treatment of Pediatric Growth Hormone Deficiency. Transcon PTH is approved in the U.S. by the FDA for the treatment of hypoparathyroidism in adults, and the European Commission and the United Kingdom's Medicines and Healthcare Products Regulatory Agency have granted marketing authorization for Transcon PTH as a replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. Otherwise, please note that our product candidates are investigational and not approved for commercial use. As investigational products, the safety and effectiveness of product candidates have not been reviewed or approved by any regulatory agencies. None of the statements during this conference call regarding our product candidates shall be viewed as promotional. On the call today, we'll discuss our full year 2025 financial results and we'll provide further business updates. Following some prepared remarks, 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, Ascend 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 shrink, we believe we are now at the base of a steep 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. And at the same time, we are building an expanded pipeline of blockbuster product opportunities. In the fourth quarter, we saw multiple achievements across the organization, starting with EuroPATS. The fourth quarter was another period of strong execution for the global launch of EuroPATS. Revenue for the quarter was 187 million euros, bringing full year 2025 EuroPATS revenue to 477 million euros. In the U.S., access continues to expand. Two years in, more than 5,300 patients were prescribed UroPath by nearly 2,400 unique healthcare providers, highlighting continued strong and steady demand. To date, less than 5% of U.S. patients are currently on UroPath 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 patients initiate EUROPAT in line with treatment guidelines that support its use. Outside the US, we continue to reach more patients. As a reminder, EUROPAT is now available commercially or to name 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 Tachin launched Europass commercially last November. In 2026, we expect full commercial launches in 10 additional new countries. We also advance development activity to broaden UR-PATS label in a number of areas. In the U.S., we are working to expand the range of doses to our Partway 66 trial, and globally, we continue to advance clinical trials to expand UR-PATS 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 UroPaths 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 PTA candidate, matching the release PDAs seen with daily UoPath treatment over the entire week, thus providing a comparable efficacy and safety profile. Overall, we remain confident that UoPath has the potential to be a durable, long-term growth driver for Ascentis globally. Turning now to growth disorders. Combining of our once-weekly growth hormone Skytofa or Transcon growth hormone or once-weekly Transcon CMP. Skytofa delivered another solid quarter with Q4 revenue of €53 million, bringing full-year Skytofa revenue to €206 million. This performance reflects the strength and value of the brand. As a reminder, Skytofa is now approved in pediatric growth hormone deficiency in the US and adult growth hormone deficiency. Today, Skytofa has an overall market share of around 7% in the US. During the fourth quarter, we initiated our Phase III basket trial, evaluating transcontinent growth hormone in additional established growth hormone indications, including ISS, shock deficiency, Turner syndrome, and SDA, which compromised up to half of the growth hormone market. Over the long term, This indication represents a meaningful opportunity to expand the role of scartofa as a treatment of choice in additional growth disorder. We also see an opportunity to potentially expand scartofa's use to novel indications where Croftamone has not previously been approved for use, such as acondoplasia in combination with TranscontCMP. Transcon CAP is expected to be the first and only once-weekly treatment for children with achondroplasia, providing the full linear growth outcome that can be achieved with monotherapies addressing the overactive FDRF3 tyrosine kinase. In addition, In our pivotal trial, Transcon-CMP achieved significant improvement in leg bowing compared to placebo, increasing spinal and calen dimension, and a similar safety and solubility profile compared to placebo with a very low rate of injection site reaction and 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 trial in infants with achondroplasia 8 0 to 2 is going well, and we anticipate complete enrollment later this year. Turning to the combination therapy. Our 52-week coach data in acromtoplasia underscore the potential power of dual treatment with transcon-CMP and transcon-clotamol, where continuous exposure to CMP enables the benefit of sustained exposure to unmodified clotamol. In comparison, monotherapy trials of daily growth hormone in agonoplasia delivered only a limited effect on growth and no reported benefit beyond linear growth. Our 52-week data from the Phase II combination trial support our vision to significantly raise the bar for treatment of agonoplasia. with linear growth improvements in air contact pressure specific height score that were three to four times what has been shown with CMP 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 span has been reported without compromising safety or toolability. Importantly, these benefits beyond height are meaningful to the ACONTOPLACER 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 regime. These Phase II results demonstrate the effect of these complementary therapies, supporting that Transcon-CMP acts in synergy with the growth-promoting effect of Transcon-Growth Tremor. and has positive effect beyond linear growth. We believe over time the standard care in acromioplasia and other growth disorders long term will include dual therapy as a treatment option, building on the potential role of Transcon-CMP as an essential fundamental therapy. We recently held a successful end of phase 2 FDA meeting and scientific advice meeting in EU to align on our phase 3 trial fund. This novel combination approach for treatment children with acondyloplasia. We also remain on track for additional COATS trial updates including week 78 by mid-year and week 104 by year end. and plan to explore further opportunities in other growth disorders. To sustain durable long-term growth for ascendants 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 blockbusters product opportunities, both inside and outside rare endocrine diseases, to food significant product revenue growth in the future. Looking at our partnerships, Transcon Technologies support a continuous flow of highly differentiated product opportunity across multiple therapeutic areas, more than we can develop and commercialize ourselves. For this reason, our vision 2030 includes a focus on creating additional value through partnership and collaboration. Our collaboration with Novo Nordisk for once-monthly Transcon semi-glutide continues to advance towards the clinic. At Arconis, Transcon NGVDF is on track to enter the clinic this year. In Japan, Japan received approval for UiPath in August 2025 and commercial launched it in November 2025. In addition, recent approval of Skytrover in China in late January 26. In summary, 2025 was another positive and transformative year for Centis. With two commercial Transcon products, continue to scale the potential approval of the third high-value Transcon product in the coming weeks. and a growing pipeline of highly differentiated programs, we believe we have the fundamentals in place to deliver doable 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 2023. all consistent with our Vision 2030 strategy. I will now turn the call over to Scott.

Thank you, Yen. And thank you, Chad, for a well-read FLS. The significant achievements we made in 2025 provide us with substantial financial strength to drive our strategic priorities and goals in 2026, which include achieve blockbuster status for YorvaPath, solidify our leadership and hypoparathyroidism through rapid progress of our label-expanding clinical trials of TransCon PTH while advancing development of our once-weekly PTH candidate, successfully launch TransCon C&P, 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 Skytropha, including in combination with once-weekly TransCon C&P. 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 20F filed today. As previously announced in January, EuroPath 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 EuroPath revenue for 2025 was €477 million. For the full year, the weaker US dollar negatively impacted EuroPath revenue by approximately €27 million. Skytropha contributed €53 million in Q4 with negligible foreign currency impact compared to Q3 2025. total Skytrofa revenue for 2025 was 206 million euro. For the full year, the weaker U.S. dollar negatively impacted Skytrofa revenue by approximately 9 million euro. Including 7 million euro in collaboration revenue, total Q4 2025 revenue amounted to 248 million euro, and total revenue for full year 2025 was 720 million euro. 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 non-cash accounting related to our convertible notes. Net finance expense, which was primarily driven by non-cash items, including remeasurement loss of financial liabilities of €106 million, was €93 million net. Net cash financial 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 25 with 616 million euro in cash and cash equivalents, as previously reported, up from 560 million euro 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 and reported revenue throughout the year. For Skytropha, we expect to follow a similar seasonal pattern to 2025 with full-year revenue growth expected to track growth in prescriptions. Longer-term Skytropha revenue is expected to come through geographic and label expansions. As always, we continue to watch the US dollar exchange rate for any potential impact. And finally, we also look forward to the potential US approval of Transcon CMP 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 just five from JP Morgan. Your question, please.

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

Yes. Can you remember? You asked me a question one time at the DAPM conference. And can you? Do 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 PJs be approved? And I said yes. And you can ask me the same question today. Will Transcon CMP be approved? And I will say yes.

Thank you.

Thank you. And our next question comes from the line of Tazine Abman from Bank of America. Your question, please.

Hi, good afternoon. Thanks for taking my question. You mentioned a 70% insurance approval rate in the U.S. so far for Eurovipaths. 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? How long do you think it's going to be before you get to 100% basically? Thank you.

I think it would be infinity because I've never seen a product hitting 100%. So I think the highest bar I've seen is something like an 85% or something like that, perhaps up to 90%. The element of where we are today, I'm really highly satisfied with it because it's also a compromise about how aggressive you're going into contracting and other things like that. So I think it's a balance between the two things where in the end, the overall and ultimate goal is basically to provide most of the value back to our shareholder 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 pre-prepared remarks.

Yeah, I would say two things. One is that we're very happy with the overall approval rate that we're seeing. And I think the speed in which you're seeing this product be covered, again, is a testament to the strong clinical value proposition that we're seeing in hypoparathyroidism. It is the first and only approved therapy in this category. So again, this approval rating based on where we are today is something that we are very encouraged by. I think to your second part of the question, Dazeem, which is, you know, when might you get to 100%? I echo what Yan 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's 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.

But I think still we need to, 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 six months through it, you actually will get a much higher number on it. Just to clarify the 70%. percent 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 axiom approved so you can say the hundred percent yes is basic When you get a prescription outside U.S. in traditional countries, you will be 100% electable 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 Gardner from Evercore ISI. Your question, please.

Hey, guys. Thanks for taking the question. Just on YorvaPath pricing, so there's an 8% WAC 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 would 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 your path or maybe just focus more on revenue?

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

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

Great. Thanks so much. I have sort of two questions. not really related, but I'm going to try to link them to, to keep it as one question. Um, maybe the first one, can you give us a little bit of a sense for your V how it's being used, um, out there? I mean, it's almost like when you, when you look at this 2,400 unique prescribers and, and, um, 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 two meeting with FDA relating to CNP and growth hormone for chondroplasia, maybe just can you give us a little bit of an update? What was the outcome and when will you start the phase three? Thanks.

Okay, that's perfect. I think, Jay, you can give some about how we're both expanding the physician prescriber thing based, 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?

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

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

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

Absolutely no problem. Our next question comes from the line of Joseph Schwartz from Learing Partners. Your question, please.

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

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

Great, thanks.

Thank you. And our next question comes from the line of Derek Archila from Wells Fargo. Your question, please.

Hey, good afternoon. Thanks for taking the questions. Yeah, I just wanted to understand your confidence level around your repath growth ex-US. You know, obviously the launch in Germany and Austria, is that like a good proxy or is it going to be more depth in those types of countries and then just kind of expansion in, 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 heterogenic that we cannot really compare to what we, for example, seeing in Spain now, what we see in France, what we see in Germany, what we're seeing in Austria. It's really different things because we see different speed of penetration for example germany has less induce so the bottleneck is really more tight it takes longer longer longer time to get them on therapy because there is fewer into in the general population if we go to spain there is more, there is more in France and we also see therefore a faster uptake because we basically have a pipe that is really larger. When we get so many other, ten more additional countries based on full commercial, we will see Different uptake, but what we are doing is everything will be accumulated in the way where we now see from 30 to 35 countries named patient programs. And when we go full commercial, what we see every place, it's basically an acceleration of patient uptake. Because of the burdensome nature of a named patient program, it takes so much effort really to get every single patient on it. And every patient 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're basically taking one country off of our county, first going in and getting approval. And then we're going to full reimbursement.

Thank you. Our next question comes from the line of Lee Wacek from Cantor. Your question, please.

Hey, thank you so much for taking our question. It's Daniel Bronner on for Lee. Can you give us a little bit of color on how you expect your transplant CNT 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 CMP to what we can provide, not only related to when we look on tolerability injection size reaction, having 120 injection size reaction compared to one every second year, being in a position to look on no risk of hypertension, to the element of just having the improvement on the once-weekly product, and then show the data packet that we have generated with Transcon-CMP for first time ever shown in a well-controlled trial against placebo benefit beyond linear growth. For example, the leg bone, 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 U.S. to ensure that this always will happen.

Thank you. And our next question comes from the line of Ellie 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 Transcom CNP XUS. Just given the majority of sales are XUS, 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 Transcom CNP. In the U.S., 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? Thanks.

Yeah. 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 Europads. Now you see what we have done with Europass. We 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 product basic into all these different countries in already the setup we are establishing around your patch. 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 established that. So I feel really, really, really confident that all the success we see now with on a global scale, we would just take it in. Don't forget, for example, even in Japan, the collaboration we have with Tijen is for all three products, the same thing in China and other places. So when we make this agreement, we're not making single product, single country. We make it as basic as a pipeline product. And this is why we don't need to go out and make new agreements or anything. It's just going done extremely fast from that perspective.

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

Your question, please. Oh, great. Thank you for taking our question. I want to ask, again, as we look at the €5 billion number you've put out there for product sales by 2030, no, you're not getting 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 sum. Obviously, you've got much more expansion opportunity in hypoparathyroid. You've got Transcon TNP potentially launching soon and Skytropha perhaps getting additional indications in combination. So I'd love to just hear maybe just philosophically how your outlook adds up with those three parts. Thank you.

Yeah, that is an element where we always in our forecasting are operating under different assumptions where we're basically building up models for each single country and then we accumulate that on a global setup. And we first basically are taking the 26, 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 oven? 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 has a continued stable revenue flow for multiple years. And don't forget, these product opportunities we have, when I look on the pipeline for each of them, I definitely not have sleep last night. I can guarantee that. There is no doubt that when I see the profile and how we design it to be best in class, we also see that realizing. And from that perspective, it's a combination product with lifespan of IP extremely long. This is where you have the durability of it. And this is why we take the value perspective of each single product opportunity instead of fast revenue. This is not how we operate. We go for value. And because the element of that is this is the product really deserves this treatment because we're really providing not only a unique benefit for the patient, but also for the society and everyone.

Great. Thanks very much.

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 two reach-in study is scheduled to reach primary completion next month. And so will you be in a position to file an SNDA for the newborn incident population this year? And in terms of the newborn incident population, in your discussions with the FDA and EMA for your phase three 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 typical 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's much harder some way to be coming to a situation where they will accept and label expansion to the infant without having the data and hands. where in Europe it's much more flexible because you have a discussion with them and you can have a basically what I call a partly rolling addition of data that is being generated to our trial. So there will be likely a difference between the three geographic regions that I have simplified. Japan is perhaps the easiest way to get it down to infant immediately, but What we are doing now is to ensure we generate the right data, and we're doing that in a trial. It's a placebo-controlled trial. And what we see is everything what we hope for is living up to our expectation. Why I can say that? Because in the enrollment, we have six patients on what I call a feasible treatment on it. You take them in, and there is no randomization and you can follow them and Amy can tell a few words about the benefit we really have seen from that perspective.

So Jens is talking about the sentinel kits who are not part of the randomized piece of the study and 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 really are So, please, with the progress we're doing in helping patients with TAC contemplation, not only on linear growth, but also benefit beyond linear growth.

Thank you. And our next question comes from the line of Yunzong from Whitbush. Your question, please.

Hi. Good afternoon. Thank you very much for taking the question. My question is on the weekly Transcom 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 UroGPath available, what do you see as the most efficient clinical pathway to maybe take the weekly PTH to approval?

I think what you're addressing is 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 hyperpare, that over the entire week of treatment, you basically are bioequivalent to Neuropath. And that is the aspiration, how we designed it, that you basically will always be an equivalent PTH level compared to your pet's daily dose for the entire week. Then we know you basically will get the expected safety, the expected tolerability from that perspective. And this will make a much, much more simplified easy way to consult the clinical trial. And 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.

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

Thanks, Tom. I think I will liberate Jay for answering the last question. I think when I look on this discussion on accelerated approval, that Biomarine are filing for that has no impact on our regulatory pathway and approval and other things like that. Totally independent. It's not any way how you can build up any barrier or any way 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 a teenager growing up. And one of the things you, at least I have four children, I'm teaching them, when they're going to be 18, you need to be financially independent as the first element in their life. And I think that is a great thing to see a scientist farmer now moving away from being a teenager, but basically can go up to a more adult life because we have shown now we are complete independent on basic asking investors and others for any kind of revenue. And I think this is how we see independency.

Super helpful. Thank you.

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

Great. Thank you very much. My question was asked, but I'll just take a shot at this. Could you give any color on the once-monthly TransCon semi-glutide 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 really the idea behind Once Monty Semiclutide? And the idea was to be sure that you can get fast weight loss and at the same time have high level of tolerability. And so just think about, I can define it, you have a naked GPL1 molecule that basically, when you give it in a weekly or potentially want to use a weekly product in a once monthly, you need to add up much, much more compound to compensate for the half-life to have and last. By doing this, you add a high max dose. And because it's naked, you will have very short Tmax, meaning that you will have a steep curve from the lowest level just before you start to give a dose up to the maximum concentration. That is basically what often gives the tolerability issue, where you get the element that basically limits people to stay on treatment and what you can achieve. So this is what I call the naked product. This is like Metzera and everything. This is a naked proton. What we're doing now is defining and what we call packed in semiglutide. So even if you give it high dose, you liberate it slowly, slowly, slowly. So you're getting a very, very long Tmax. By doing that, you basically have a slope that is not as steep at all that you see with a naked molecule. Then you can see you still have a big AUC. because you basically provide so much 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 solubility profile. And that was how we designed it at that time.

Thank you. And our next question comes from the line of Alex Thompson from Stifel. Your question, please.

Hey, great. Uh, thanks for taking our question. I guess maybe, maybe for Scott, could you talk a little bit about, you know, OpEx trajectory in 2026 in the context of the CMP launch and then sort of the SkyTropa label expansion, both with mono and the combo, uh, pivotal studies. Thanks.

Yeah, no problem. I think that, um, So we talked a little bit about this at the Morgan 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, you know, as we said before, we'll come out and discuss more, you know, following approval.

Yeah, 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 actually take 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, specifically the direct market, 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.

Thanks. Appreciate it.

Thank you. And our next question comes from the line of Kolpit Patel from Wolf Research. Your question, please.

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

Thank you. I can be polite, or I can be a straight shooter. I have seen a lot of idiotic ideas. This one is really one of the most idiotic ideas I heard about. You have a patient that is missing a hormone, PTH, and giving incalate is not increasing and providing any hormone to this. We're talking about a hormone replacement therapy where you're helping multiple organs, the brain, so you have better cognitive effects. The bone needs to have the right metabolic system. The kidney needs to have the right phosphate elimination. It needs to have the right calcium absorption. And I can continue one organ after the other organ. And then you believe you can take a compound, that basic calcium synthesizing compound, take it into a person that don't have the hormone, and then you think you have a treatment. It's really one of the most scientific, I would say, ideas where I cannot see any kind of meaningful effect that it will have the patient you can increase basic the element of one single thing absorption of calcium 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 AGH1 patients which have a mutation in the calcium synthesizer one. It makes sense for this small amount of patients. It makes sense, but not for a person that missed PTH.

Got it. Thank you.

Thank you. And our next question comes from the line of Faisal Khurshid from Jefferies. Your question, please.

Hey, guys. Thanks for the question. Just wanted to ask, Jan, maybe because you're giving some open thoughts on competitive landscape, can you discuss your latest thoughts on the CNP competitive landscape, including upcoming FGFR data from BridgeBio and also the earlier stage long-acting CNP from Bymeren? Yeah.

I think that is an interesting aspect because We have seen the benefit of CMP therapy for multiple years now. We have seen it in a large patient population. And one of the things I 100% align with Biomarinon is that the CMP 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 side rise if you're not really encapsulated and so when i see the cmp therapy i understand why biomarine are trying to copy us and trying to develop a product that basic are providing and sustained liberation of CMP over one week because they have seen from our data how we highly differentiate it compared to vasovatyte. So that is a completely different case about do they really have a once-weekly product or not. You cannot just that out from AOC. 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 biomarine. I do not know if anyone can judge that it's 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 tyrosine kinase, a completely different element for me, because that is an element of using a non specific action of a compound that basically are addressing the tyrosine kinase. And if you go to the Bridge Bio, it's a non-specific tyrosine kinase that both inhibit the three different compounds, FDR1, FDR2, and FDR3. This is why it's called non-specific. worried about. I'm not worried that you will see a treatment effect, because when you address the tyrosine kinase, you basically will see an improvement in linear growth, because you basically are in a position that you inhibit the 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 they see an improvement in muscle strength? Can they see an improvement in basic leg bone? Can they see all the elements of improved quality of life with that? But what worries me is the non-specific thing. And I really don't care about phosphate. People say, oh, Jan, are you worried about if they have elevated phosphate? First of all, elevated phosphate, you cannot go in and grade it one, two, or three, or four. You need to see on the patient what is the phosphate level before treatment and after treatment. Because then you see, do the treatment on each single subject have an impact on the phosphate level? If it has impact on the phosphate level, we know it's a nonspecific inhibition of FDR1. And when you have a nonspecific inhibition of FDR1, you also have nonspecific inhibition of FDR2. And when you know that FDR2 is one of the key receptor that is part of really the CNS development of the brain, I'm extremely worried because it's not something you really see easily in a preclinical model. You don't see it anyway in short-term clinic trials. You see it after three, perhaps four, five years of treatment. You know, that worried me from our patient focus. How can you really accept that any patient should take this risk without being extremely well-informed about it?

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.