Ascendis Pharma A/S (ASND) 2025 Q3 法說會逐字稿

(audio in progress) to the third quarter 2025 Ascendis Pharma earnings conference Call. (Operator Instructions)

I would now like to turn the call over to Chad Fugere, Vice President of Investor Relations at Ascendis Pharma. Please go ahead.

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

Before we begin, I'd like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act. Examples of such statements may include, but are not limited to, statements regarding our commercialization and continued development of SKYTROFA and YORVIPATH as well as certain expectations regarding patient access and financial outcomes, our pipeline candidates and expectations with respect to their continued progress and potential commercialization, our strategic plans, partnerships and investments, our goals regarding our clinical pipeline, including the timing of clinical results and trials, our ongoing and planned regulatory filings and our expectations regarding the timing and the result of regulatory decisions.

These statements are based on information that is available to us as of today. Actual results may differ materially from those in our forward-looking statements, and you should not place undue reliance on these statements. We assume no obligation to update these statements as circumstances change, except as required by law. For additional information concerning these factors that could cause actual results to differ materially, please see our forward-looking statements section in today's press release and the Risk Factors section of our most recent annual report on Form 20-F filed with the SEC on February 12, 2025.

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 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 agency. None of the statements during this conference call regarding our product candidates shall be viewed as promotional. On the call today, we'll discuss our third quarter 2025 financial results, and we'll provide further business updates. Following some prepared remarks, we'll then open up the call for questions.

With that, let me turn it over to Jan.

Thanks, Chad. Good afternoon, everyone. In the third quarter of 2025, we accelerated our momentum towards fulfilling our Vision 2030 with key achievements in three areas. First, the global launch of YORVIPATH continues to be strong with a steady increase in new unique patient prescription and prescribers as seen in Q1 and Q2, along with expansion in new geographic markets. Second, we made great advancement towards leadership in growth disorders during the quarter. We saw the US approval of SKYTROFA in adult growth hormone deficiency. And following our late cycle meeting with FDA, we are progressing towards expected approval of TransCon CNP in the US Third, our strong operating fundamentals led to positive operating profit, signaling the beginning of sustained revenue and earnings growth for Ascendis.

Now I will provide some specific comments on our commercial and late-stage portfolio. Starting with YORVIPATH. YORVIPATH continues its strong global launch with revenue of EUR143 million in the third quarter. 9 months in the launch in the biggest market, the US patient demand continues growing quarter-by-quarter. From launch to the end of September, more than 4,250 patients have been prescribed YORVIPATH in the US by over 2,000 unique healthcare providers, highlighting the strong steady demand for YORVIPATH even during the summer months. In October, the positive trend continued with YORVIPATH being prescribed for more than 400 new patients in the US alone.

Positive physician and patient experience are driving a high rate of compliance. And we expect most patients will be on lifelong PTH therapy. We are expanding our physician reach each quarter within the endocrinology community, and we are also expanding to other physician groups who manage hypopara patients. As an example, at last week's American Society of Nephrology meeting, we presented three years of kidney function data across our combined clinical trials, demonstrated sustained clinical meaningful improvement in kidney function in the YORVIPATH-treated patients. In addition, we continue working hard to expand patient access in the US. The overall insurance approval rate since the start of the launch is around 70% of total enrollment, and we believe this figure will continue to increase over time.

We currently see approvals across all payer types with a majority of approvals within 8 weeks. We are pleased by the robust uptake of YORVIPATH in our first three quarters of commercialization in the US. Today, less than 5% of US patients are currently on YORVIPATH treatment. We see significant room to grow with around 80,000 to 90,000 patients already diagnosed with chronic hypopara in the US and 3,000 to 4,000 new patients being diagnosed every year. Outside the US, YORVIPATH is now available commercially or through named patient program in more than 30 countries. In Germany, Austria and Spain, we have now full commercial reimbursement.

In Japan, our partner, Teijin, launched YORVIPATH commercially last week following approval in August. We are looking forward to the commercial launch of YORVIPATH in additional countries in the coming years. With a broad label covering hypoparathyroidism for all causes, international treatment guidelines that recommend PTH replacement therapy and YORVIPATH position as first-in-class therapy, we expect sustained patient growth and revenue growth for years to come. As we're building this global market, we're expanding our offerings to patients with hypopara. We are conducting the PaTHway60 trial to support doses up to 60 micrograms of YORVIPATH in the US.

We plan to begin a clinical trial for people under 18 this quarter, and we are advancing our new once-weekly TransCon PTH product candidate, which we believe would be an attractive option for patients on stable doses of YORVIPATH. In the new year, we will share more on our plans to maximize YORVIPATH value and reach even more patients. Let us now turn to growth disorder, which today comprise of our once-weekly growth hormone SKYTROFA approved for growth hormone deficiency and our once-weekly TransCon CNP currently under review by FDA in the US and by EMEA and EU for children with achondroplasia.

SKYTROFA is approved in the US and EU for treatment of pediatric growth hormone deficiency. With this single indication, SKYTROFA is established as a high-value brand and treatment of choice for pediatric growth hormone deficiency. Q3 revenue for SKYTROFA was EUR51 million. In July, we received our first label expansion with FDA approval for adult growth hormone deficiency, the first of multiple planned label expansion. In Q3, we initiated our Phase III basket trial of SKYTROFA with a range of established growth disorder, including ISS, SHOX deficiency, Turner syndrome and SGA.

Turning to TransCon CNP. We recently completed a late cycle meeting with the FDA and are in the final stage of the label discussion. TransCon CNP is under priority review in the US with a PDUFA date of November 30 and is also under review in the EU, where our MAA filing was validated. TransCon CNP once weekly is well positioned to become the leading treatment for children with achondroplasia with the full degree of linear growth outcome that can be achieved with monotherapies addressing the overactive tyrosine three kinase.

In addition, TransCon CNP achieved statistical improvement in leg bowing compared to placebo, increasing spinal canal dimension, a safety and tolerability profile compared to placebo with a very low rate of injection site reaction and no cases of symptomatic hypotension. We are confident in TransCon CNP's ability to be a leading therapy. While we believe TransCon CNP monotherapy is transformative by itself, we want to further enhance outcome for people living with achondroplasia. Earlier this year, we presented 26-week results from the Phase II COACH trial of TransCon CNP in combination with TransCon Growth Hormone, which showed around 3 times improved linear growth compared to what had been observed with monotherapies over the same time period.

This resulted in healthy linear growth in children with achondroplasia, higher than that observed with an average state of children, accommodated by improvement in body proportionality and beat out acceleration of bone age. This data has been recognized by key opinion leaders as groundbreaking. Based on this data, we believe over time, the standard of care in achondroplasia will include combination therapy as a treatment option, building on the potential role of TransCon CNP as the backbone therapy.

Following our recent FDA end of Phase II meeting related to our combination therapy, we plan to initiate a Phase III trial this quarter. We anticipate disclosing 52-week data from the COACH trial in early 2026. With once-weekly growth hormone and once-weekly CNP, 2 highly differentiated medicines, both as monotherapy and in combination, we believe Ascendis is well positioned to become the global leader in many different growth disorders. Our Vision 2030 also includes creating value through partnership.

And we see that being achieved through the rapid progress of Teijin in Japan, VISEN in China, Eyconis in ophthalmology and Novo Nordisk in metabolic and cardiovascular diseases, where the once-monthly semaglutide program is making fast progress towards the clinic. And finally, the commercial success of YORVIPATH and SKYTROFA has already transformed the financial profile of Ascendis. In the third quarter, we achieved positive operating income along with positive cash flow. For the near term, the building out of our commercial organization is largely completed in advance of future global launches.

For the medium term, label expansion, LCM activities have been initiated to maximize the value of our current products. At the same time, for long-term sustainability, our R&D organization continues to advance the TransCon technology platform to ensure a constant flow of new programs and potential new products. In summary, with TransCon CNP nearing potential approval, Ascendis is well positioned to get approval of its third TransCon-based product in a row. This highlights the uniqueness of Ascendis.

The continuous development of highly differentiated product created by the TransCon technology platform and our unique low-risk drug development algorithm. Importantly, our current three rare disease endocrine products position us for doable future growth and give us confidence in our aspiration to achieve EUR5 billion or more in annual product revenue in 2030.

I will now turn it over to Scott.

Thank you, Jan. I would like to reiterate Jan's comments that the positive operating income development seen in Q3 signals the transformation of our financial profile with sustained revenue and cash flow growth. With that, I will touch on some key points surrounding our third quarter financial results and outlook. But for further details, please refer to our Form 6-K filed today. In Q3, YORVIPATH global revenue grew to EUR143.1 million, up from EUR103 million in Q2, with strong growth partially offset by a EUR3.6 million foreign currency headwind compared to the previous quarter.

In Q3 2025, SKYTROFA contributed EUR50.7 million with 3% growth in demand, offset by a EUR1.6 million foreign currency headwind compared to the previous quarter. Including EUR20 million in collaboration revenue driven by a EUR13 million milestone related to YORVIPATH and increased partner activity, total Q3 2025 revenue amounted to EUR214 million. Continuing on to expenses. R&D costs in Q3 were EUR66.9 million, down from EUR73.5 million in Q3 2024, primarily driven by completion of certain clinical trials and development activities.

SG&A expenses rose to EUR113.4 million in Q3 2025 compared to EUR69.8 million in the same period last year, reflecting continued impact of global commercial expansion. Total operating expenses for Q3 2025 were EUR180 million and operating profit for Q3 2025 was EUR11 million. Net finance expense for the third quarter of 2025 was EUR60.9 million, primarily driven by noncash items, including noncash remeasurement loss of financial liabilities of EUR47.2 million. Net cash financial income over this period amounted to EUR400,000. Note that in our 6-K filed this evening, we provide more detail on the components of finance income and expenses.

In future periods, we plan to introduce a non-IFRS EPS measure adjusting for the impact of certain noncash nonoperating items, including related to our convertible notes. This is intended to increase comparability of period-to-period results. Finally, we ended the third quarter of 2025 with EUR539 million in cash and cash equivalents, up from EUR494 million at the end of Q2. Turning to our commercial outlook, primarily driven by the ongoing global launch of YORVIPATH, we expect continued revenue growth in the fourth quarter.

For YORVIPATH specifically, we expect continued growth driven by new patients, stable pricing, payer mix and contracting in Q4. Longer term, we expect YORVIPATH to be driven by continued growth in new patients on therapy, including expansion into additional markets. For SKYTROFA, we believe that sequential revenue growth should continue to track growth in prescriptions with stable pricing, payer mix and no changes in contracting with offsets potentially driven by currency as we saw in Q3. Longer term, we expect growth for SKYTROFA to be driven by geographic and label expansion.

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

(Operator Instructions)

Jess Fye, JPMorgan.

Hey guys, good afternoon. Thanks so much for taking my question. I was hoping you could speak to your expectations for the rate of new patient enrollments on YORVIPATH in the US from here. I think you talked about more than 4,250 as of the end of 3Q, putting you at -- what is that, about 1,150 adds or maybe a little more relative to June 30. Can we think of that as kind of like a good number to work off of from here? Should it continue to kind of drift lower a little bit? Just hoping you can frame some expectations there.

Thanks, Jes. First of all, we see really a stable number of prescriptions being written in the US when we some way take away the bonus that we have from the ERP program about the 200-plus patients we have in the ERP program. When we think about Q3, I'm actually pretty surprised positively about Q3 because I was fair that prescription will be written in the three weeks any physician typically take out of their quarter in that time. And what I saw, we saw nearly the same number of prescriptions being written that we actually have seen in Q1 and Q2.

And it's also following up with what we said in the October month. We saw more than 400 prescriptions being written in October, unique prescriptions being written in October. So when I look at this launch, look in the US, I see a very, very stable launch. And what we're also doing, we're building a fundament like a strong, strong fundament because patients stay on lifelong treatment. And therefore, when you start a patient, it basically is continued quarter-by-quarter. So it's building a house where you have a strong fundament, taking one brick on around every quarter and the house getting taller and taller every, every quarter.

Tazeen Ahmad, Bank of America.

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

Let me take the last question. Thanks, Tazeen, first. But let me take the last question first because it's an easy one because that's no. Just no, no, no. So it's really simple. So going to the next one, it's to more of what Scott was looking, he didn't read the FLS this time, chat FLS this time. But when I'm looking forward in the future, yes, there is some holidays come up.

But when I look back, I was more worried about Q3 actually compared to the Q4 because I actually believe that there's a longer summer vacation than in Q3 compared to basically what you will see in Q4. So I see pretty positive on Q4. I see we actually increasing our prescription basis for physician writing prescription with more than 500 new prescribers, meaning is that having a broader, broader boat where there's more and more that can come in growing on the ship. And this is where I feel pretty confident about it. So no worry from my side, Tazeen.

Okay thanks yeah.

Gavin Clark-Gartner, Evercore ISI.

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

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

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

Yeah. Thank you for the question. As mentioned before, we're really encouraged about the 70% approval rate that we're seeing now. It's actually about what we expected or guessed at the beginning of the year, just based on what we know about the clinical value proposition of the drug, which again is incredibly positive and has been resonating with a lot of the payer accounts for which we are speaking with.

To answer your question, Gavin, directly in terms of what that peak approval rate could be and at what time frame, that's really hard to say, right? When you look at some of the analogs for similar drugs, that could, in some instances, take multiple years. And the reality is once you get to a certain high percentage, the remaining becomes a little bit more difficult simply just given the heterogeneous landscape of the payers, right?

It becomes quite fragmented. A lot of the government payers might review it on different timetables. So we are meeting a lot of those timetables where they're at. And again, we're continuing to talk about the incredible positive clinical value proposition that we're seeing. And that alone is resonating with a lot of them, which is why we continue to see that approval rate go up over time.

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

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

Okay. Like the point I'm trying to get at is, for a lot of the start form -- like let's take this 3,100, you had at the end of June, maybe you've had close to 70% conversion, but the rest of the 30% is not really lost at this point. Some more still may come through as conversion. It's just a matter of time.

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

Very helpful, thanks so much.

Joseph Schwartz, Leerink Partners.

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

Let me take the last question. As I said in the prepared remarks, we are in the late-stage discussion about the labeling. And I cannot really comment about what will really be in the final labeling in this perspective. What is really the key element for me in my discussion with patients and my discussion with physician, Aimee Shu's discussion, our medical affair discussion with the teams is really to explain the benefit they see behind the growth. And it's clear, unique effect in leg bowing, unique effect in changing body proportionality.

And we will have peer-review publication really supporting all this claim that will come out, really give us an opportunity to take and talk with the patient, talk with the physician about this benefit in it. I think this is the key thing for me. We -- I saw and -- we saw an element once with hypopara where basic it was impossible for getting into the labeling our element of patient benefit related to cognitive function, other quality of life and everything like that and everyone recognize it. Everyone see it, anything see that is the best thing. I think that's the key thing from our labeling discussion is have no restrictions, have a really safe product, really show our efficacy and safety in the best possible manner in this way. Jay, will you take the first part of the question in this one to Joe?

Yeah, could we repeat -- can we repeat the first part of that question?

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

Yeah. So when you think about the 80,000, 90,000 patients that Jan had referenced earlier in the call, I think there's probably a group that we would describe as highly symptomatic, patients are well aware of their symptoms, articulating those symptoms to a physician and within those, I would say we're doing quite well, particularly since the patients themselves are likely the ones that are in the offices most frequently and are keeping the appointments on the books to be able to essentially get some of that information and also be on their way to actually get prescribed the products.

I think where we're continuing to work on are some of the patients for which maybe they're not either self-identifying some of their symptoms as being related to the underlying condition and/or perhaps they've gotten used to some elements of it and therefore, haven't been as motivated to establish care and retain established care with a specialist. And I think that's why as we think about how we can continue to transform this market, there will be an element of patient activation as well simply because there is going to be a certain level of disease education required, particularly for a space like this where it is about redefining what's possible and kind of the status quo for how to manage this type of condition.

Yeah. If I can add something, Jay. I see it from 2 different perspectives. How often you come into the endo. This is one way. It is how we target it and define something that is not defined on medical terms, but only on how often you see an endo related to being controlled, partly controlled or -- and what I'm also trying to look at -- I try to look on where are they coming? Are they coming from the post surgery? Are they coming from the genetic part? Are they coming from the immunological part? I see them coming from everywhere. So for example...

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

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

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

Yeah. I think, Jay, at least I heard Jay's response to it. And my additional comments was that when we did the targeting of our physician, we made it out from the claims database where we defined three groups: controlled, partly controlled and incontrolled. It's nothing to do with medical terms, but basic is a acceleration, how we basically are looking on the patients seeing a physician. So what I'm also looking is, do we see all patient group in our patient being coming on YORVIPATH's treatment.

And when I see that, it's pretty clear that we are in a position we see the obvious post surgery. But when we look on different element of generic, genetic or immunological, we also see all different groups of patients, even patients from the ADH1, which really, really are less than 1% in the claim database. We already have about 15 patients on treatment with this symptom, which really gave us a hope that we basically will see the same penetration everywhere in all different types of the hypopara patients in this way.

Thank you.

Li Watsek, Cantor.

Thank you guys, thanks for taking our questions. I guess just on can you maybe just give us a little bit color on payer mix and potential contracting, not just in Q4, but also in 2026? And should we sort of expect still minimum contracting and sort of stable gross to net for the next few quarters?

I think Scott more or less addressed it in his prepared remarks. There will be no changes into Q4. If we look forward, will there be potential more contracting that we have seen now and Jay can comment on it, we are in a position where contracting will not any way change dramatically our GTN in any kind of financial modeling in this perspective. And we see YORVIPATH really have all the characteristic of a product. It's a first in class. There's only one treatment option. And we see it actually being -- not only being prescribed, but also being reimbursed to the level that we have hoped for. Jay, you have further comments to the long-term perspective of contracting?

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

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

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

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

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

Yaron Werber with TD Cowen.

Great, thanks so much. Maybe, Jan, I maybe a couple of questions. Number one, just on gross to net. When we're kind of -- we were at around just over 4,200 and we had like a 65% approval, but we were getting to higher numbers for the quarter. So I'm wondering whether -- and we had 18% gross to net. Is it possible that gross to net discounts are higher than that? That wouldn't make any sense. And I guess the question kind of like what am I missing?

And then maybe secondly, are you -- it sounds like you may be very subtly intimating to expect some impact from the holidays in Q4. Are we reading it correctly because we didn't see much seasonality in Q3. And then finally, U.S. versus European sales for YORVI in the quarter, was it like around EUR4 million or so in Europe this quarter as well?

Yeah. There was three questions. The element of what I will take -- what we said in the beginning of the year is still what we really have seen. We said we will expect ex-U.S. be around EUR4 million to EUR5 million increase every quarter because we have not really expanded it more to fully commercial countries, which we did now in here in Q3, but we first see the effect on that perspective in this way.

Related to the seasonality on it, I don't expect to see any seasonality in Q4. That is pretty clear. I expect it to potentially to have seen it in Q3 because I expected the physician to be gone for 3 weeks. And when we not really saw a major impact in Q3 I don't expect to see any impact in Q4. Scott, he's really the guy with the numbers and everything like that. So he really is good at that. So Scott, can you take the first question?

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

Martin Auster with Raymond James.

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

Thanks, Martin, for the question. The first one is really, really -- spend a lot of time on it, spend a lot on the analytical. And we are losing very, very, very few patients when they have initiated treatment. There are few percentage. And if we lose them, it's basically in the first 4 to 6 weeks, meaning is that we are now trying to go back how can we potentially help them in the titration phase. And I think that is always the element where you start on a syste,m, where you are on conventional therapy, you start to do it, you need to take it off. And I believe if there are not a good interaction between both the physician, the place where we get calcium monitoring and everything like that, it -- are a more difficult period for the time. This is why the titration.

This is why we started obviously one daily product because we know we could never get this titration to function with a once-weekly product. So that is where we see. When we see after 4 to 6 weeks when we're starting to be stable, exactly as I said here, we expect nearly all patients to be on lifelong treatment. This is like building the fundament stronger and stronger. And Martin, I agree with you. If you look on vosoritide, it's doing really poorly in the US. They're saying they're doing really good outside the U.S. I think they're doing really poorly in US. That should be much, much higher. And I believe that because they're not really addressing what they really should address are the comorbidities.

And I believe this is where we come in with a differentiated product. This is why when I talk with the different patient organization groups, and really, they asked me a simple question. Jan, will you have set the primary endpoint to be linear growth if you were the first product? And I said, no, we will never have done that. We will really have addressed how we're really addressing the comorbidities because we believe that is really why patients should take that treatment, help them to the comorbidities, really help them in this way. And this is where I believe we have an extremely positive dialogue with all the patients and the patient related to that topic.

And looking for November 30.

(Operator Instructions)

Paul Choi with Goldman Sachs.

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

Thanks for the question. Yes, we expect there to be a lot of switches. We enrolled patients in the places where vosoritide were commercially available free for the patient. We enrolled it where there was other treatment alternatives, if you call them treatment alternatives. We were in a position that we preferred it out from the perspective is that not only the once-weekly profile, but the lack of injection site reaction. Really to be in a position, you don't need to worry about any risk of hypotension and anything like that. That was really one of the key movement.

And also at that time, we not even have really the clarity of beyond linear growth, the benefit beyond linear growth. So when I look today, is it going to be a last portion on switch patients when you have therapy being implemented to a high level, which it is in some European countries. In some European countries, 60%, 70% of all patients will be treated today, and there will be switching. They are just waiting for it. We know they're waiting for it because they asked for it all the time, when will it be approved in Europe. If you go to U.S., because of not high penetration, there will be many more new patients coming in because there's not too many to switch off. So this is what we see and how we will build up the commercial strategy.

Okay, great, thank you.

Yun Zhong, Wedbush.

Hi, good afternoon. Thank you very much for taking the questions. So the first question on the label extension to the higher dose. I assume the pricing is going to be the same. So would you expect any direct impact on maybe the number of patients on treatment and reported revenue, please?

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

Yeah. So single arm is going to be 18 subjects who will be titrated as they need based on serum calcium using the higher doses.

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

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

We see an improvement month by month. And when we looked at the data today, with about the 50% and the eight weeks, that is the data we see today.

Okay great thank you.

Alex Thompson with Stifel.

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

This patient group is a quite different patient group to compare to the pool of the patients we talk today in US and other countries. Many of these young children are coming from more the genetic and immunological part and not so much from head and neck operation. Still there can be postsurgical patients at that stage, too. These patients are in a severe case because if you have hypopara in such a young age, a lot of developmental part is really affected not to have the right calcium hemostasis, phosphate hemostasis and bone hemostasis in the body today.

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

Luca Issi with RBC.

Thanks so much for taking my question. Maybe on the unique patient enrollment, is that a metric that you're committed to report going forward? Or are you planning to sunset that metric at some point? And if it is the latter, can you talk about whether that could be Q4 or would that be later than that? And then maybe if I can ask about Novo Nordisk, can you just talk about how that collaboration is going?

Obviously, lots going on at Novo, given again, new leadership in place. And obviously, we just lost the deal on Metsera. I'm wondering if you're seeing any disruption with that collaboration with them or maybe the opposite, actually an acceleration of that collaboration. So again, any thoughts there, much appreciated.

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

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

Enrollment as a metric?

Yeah. The enrollment as a metric is a question that we discussed a lot. And we won't comment on it. When you're feeling that we are in a position that revenue that we are reporting now really are coming to a level where you're feeling that it's really coming to a stage where the addition of new patients really are not changing so much of the overall. As I said, we're building a strong fundament quarter-by-quarter. The strong fundament is building a really tall house.

And we are now taking bricks by bricks, quarter-by-quarter, and we're building this revenue base up more and more. And you can really from just a mathematic modeling, think about it when we are much more further in the launch, the addition of new patients just are not giving the same impact on the overall actual revenue at that stage. And therefore, I believe at one time, the number of new prescription is not really meaningful for you. You will just see a quarterly revenue growth that basically are just reflecting the addition of new patients

Maxwell Skor, Morgan Stanley.

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

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

If he's talking the guidance on OUS?

Ex-US, what we said for this year here is EUR4 million to EUR5 million increase quarter-by-quarter. What we said, this will further be accelerated when we come into '26 because we will have an addition of more and more countries. When we come into January, we will give you the perspective of what countries we expect to add in to the being fully commercial in '26 and '27.

Clara Dong, Jefferies.

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

Okay. So we gave you an algorithm for basic in the beginning of the year. We said that when you look in Q4 '24, there was about EUR14 million in net revenue. All this net revenue was basic ex-US. And we expected to add EUR4 million to EUR5 million net revenue in '25 every quarter. So you can nearly add 14 to 5, plus 5, plus 5, plus 5 and then you have the Q4. What we saw in here in '25, we got Spain full commercial.

We are in a situation where we not compromise the value because we have a doable product that basically will be here for 20 years. So for us, it's more important to really have the value being created in the right manner. And what we will give you here in the beginning of the year, the perspective of what and how many new countries we expect to add on in '26.

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

Thanks a lot.