Ascendis Pharma A/S Price & Performance (ASND)

And thank you, everyone, for joining our full year twenty twenty four financial results conference call. I'm Scott Smith, Chief Financial Officer. At Ascendis Pharma Joining me on the call today are Jan Mikkelsen, President and Chief Executive Officer Sherry Glass, Chief Business Officer Jay Wu, President, U. S. Market and Amy Xu, Chief Medical Officer. Before we begin, I would like to remind you that this conference call will contain forward looking statements that are intended to covered under the Safe Harbor provided by the Private Securities Litigation Reform Act. Examples of such statements may include that are not limited to statements regarding our commercialization and continued development of SKYTROPA and YORVIPATH for The U. S, European and other markets. Well as certain financial expectations our pipeline visits and our expectations with respect to their continued progress and potential commercialization. Strategic plans, partnerships, and investments, our goals regarding our clinical pipeline, including the timing of clinical trials and results, our ongoing and planned regulatory filings and our expectations regarding the timing developments and our exploration of market opportunities and therapeutic areas outside of endocrinology rare disease. These statements are based on information that is available to us today Actual results may differ materially.

Could differ materially from those in our forward looking statements and you should not place undue reliance on statements We assume no obligation to update these statements as circumstances change except as required by law. For additional information concerning the factors that could cause actual results to differ materially. Please see our forward looking statements section of today's press release and the Risk Factors our most recent annual report on Form 20 F filed with the SEC today, 02/12/2025. TransCon Growth Hormone Or TransCon HGH Is Approved In The U. S. By FDA and in The EU has received MAA authorization the European Commission for the treatment of pediatric growth hormone deficiency TransCon PTH Is Approved In The U. S. By the FDA for treatment of hypoparathyroidism in adults and the European Commission and the United Kingdom's Medicine and Healthcare Products Regulatory Agency have granted marketing authorization for TransCon PTH as a replacement therapy indicated for the treatment of adults with 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 On the call today, we will discuss our full year 2024 financial results and we'll provide further business updates.

Following some prepared remarks, we will then open up the call for questions. With that, let me turn it over to Ian. Thanks, Scott, and good afternoon. [indiscernible] 2024 was a pivotal year for Ascendis. As we achieved key milestones. That set us up to deliver strong growth and value creation in 2025 and beyond. With Scudhoeffer firmly established. As a high value growth hormone brand, in 2024. Volume [indiscernible] reaching around €200,000,000 on a 6.5% market share of the total growth almond market in The U. S. And around 45% of the total U. S. Non acting growth hormone market based on third party prescription data. With further penetration in pediatric growth hormone deficiency. And a planned commercial launches across multiple indication and countries. We expect sustained value creation for the TrendKron growth hormone franchise in the coming year as outlined in our Vision 02/1930. Importantly, Europet, the only FDA approved treatment for Hypopair athyroidism in adults is now launched in The U. S. And has already begun to establish itself as the new standard of care. [indiscernible] Given the long standing need for a treatment option like UOPAT, We are seeing significant early demand.

In both the patient and physician communities.

And we are pleased with the PACE or payer approval so far. The large global population living with a significant hypoparent disease burden underscores the typical the potential for UOPAT to grow into a multibillion dollar product over time. Rounding our tower into Crime Rare Disease portfolio, TransCon CNP clinical data demonstrated it could be a highly differentiated product with an unique profile. That represent a major step forward in the treatment of acondylplasia and other growth disorder. We believe the once weekly transcon CMP data demonstrating superior linear growth and benefits beyond linear growth. Supporting our proposed label for treatment of achondroplasia. For this reason, following our NDA meeting with FDA we are track to submit an NDA to FDA this quarter followed by an MAA submission to the EMEA in the third quarter of this year. All three of these endocrine rare disease medicine demonstrate the value of our TransCon technology platform. And its potential to address major unmet medical needs with highly differentiated product. We are also bringing the TransCon technology platform beyond endocrine rare diseases. In last patient population, through our collaboration with Novo Nordisk, metabolic diseases such as obesity, type two, diabetes and cardiovascular diseases.

In ophthalmology, to the creation of Iconis. We have also expanded the TransCon technology platform incorporate protein digrators. A very promising area where we believe that new the new TransCon technology platform will expand our pipeline with additional potential blockbusters. We entered 2025 with a very strong financial position. With a cash of €665,000,000 on our balance sheet, including the $100,000,000 upfront payment that we will see from Novo Nordisk. Last month. As a result, we are in a strong position. To invest in commercial uptake and new product development to drive continued revenue growth. Let me review our key programs in rare endocrine disease in more detailed In The U. S, Skatova was launched just over three years ago. Today is the treatment of choice. And at the same time growing the growth hormone market. Importantly, Deficiency Indication Alone, We Are Currently Addressing Only Half Of The Existing U. S. Growth hormone market.

Both are on path to expand Cretophus addressable market in multiple ways.

Near term, we expect U. S. Approval in adult growth hormone deficiency this year. Our PDUFA date on July 27. Longer term, we will investigate Skatova in additional therapeutic [indiscernible] In the third quarter of this year, we plan to submit NIND application for this basket trial to the U. S. FDA. Planned commercial launches across multiple countries. In 2024, Skytoffel volume increased 84% in The United States. With premium net pricing of 3x compared to once daily glaucoma. Skytober achieved revenue of around €200,000,000 in '20 supporting the potato for it to become. A blockbuster. Product over time. Moving to Europes. Twenty twenty four was a critical year for Europet. With Commercial Availability In Europe starting early in 2024 And then this past December in The U. S. With Europet, also available to name patient programs. [indiscernible] can begin to assess this long awaited treatment option. Hypoparatide Erasmus, represent a large global market of opportunity for Senes to address a major unmet medical for an effective and well tolerated treatment option. To create durable long term leadership for Europest. Are building this market by educating above the well documented limits on risk of conventional therapy and the clinical benefit seen with our PTH3.

In The U. S, [indiscernible] thousand to ninety thousand patients with chronic hyperparathyroidism.

Most of Vu.

Are currently using conventional therapy of oral calcium and active vitamin D. Our claims demonstrate that ten thousand to fifteen thousand of these U. S. Patients are uncontrolled. And thirty to thirty five thousand are partly controlled. We believe EuropeAD can sustain growth over a long time as the vast majority of patients, the hypopairatrial qualified for PTH treatment per the current international guidelines. Less than two months in The U. S. [indiscernible] Initial demand is strong with nine hundred and eight patient AS off Pirbrew twenty twenty five [indiscernible] five thirty nine unique prescribers in around 44 states. Nearly eighty percent of the enrollment are new to Europes. The majority of whom are switching from conventional therapy with the remaining being existing patients from the TransCon PTH clinical trial or expanded access program.

Discussion with peers are ongoing. And as expected, the novel specialty product we estimate the majority of insurance approval to eight weeks. We are pleased with the initial pace of insurance approved across commercial and government payers and have shipped reimbursed drug to patient in around 35 states. Our site U. S. B remain on track for decent commercial launches in what we call [indiscernible] where we expect to add five or more countries this year. We also expect launches in multiple international markets '25, further expanding our global exclusive distribution agreements covering 50 plus countries so far. European is a unique product. Our broad and extensive clinical data include three successful Phase III trials in The U. S, Europe, Japan and China, covering diverse disease groups. Including post surgical auto immune ADH1 idiopathic hyperpathyroidism, Last year, we presented three years data from our Phase two forward trial. And later this year, we plan to present four years. These are demonstrating excellent patient retention and sustained serum cancer control and bone health. Sustained reduction of calcium phosphate product independent from conventional therapy, and normalization of twenty four hour urinary calcium. The data also showed sustained improvement in kidney function. Switching to TransCon CNP.

Air Condorcet remained at the seas with high unmet medical And we believe TransCon CMP has the potential to be a highly differentiated treatment option. In the pivotal APPROSE trial, TransCon CMP demonstrated significant improvements in linear growth and body proportionality. Compared to Plasego. As well as benefit beyond linear growth. As one example of benefits beyond linear growth, we have shown data demonstrate significant improvement with Triscon CMP [indiscernible] That can result in pain, impaired physical functions need for corrected surgery and a negative impact on quality of life. CRP has shown a safety and tolerability profile comparable to placebo. With low frequency of injectant cyclohexane. All of which were mild, and no evidence of hypertension effect. So for porting TransCon CNP potential as a best in class treatment for echo and dolpation Following our productive pre NDA meeting with a we plan to submit an NDA for the treatment of Iconoclase during the first quarter of twenty twenty five And Sumit, and MAA for treatment at Chilupid Achondylation Tuba EMEA during the third quarter of twenty twenty five. We believe TransCon CF will be setting a new bar for treatment of [indiscernible] To further raise For linear growth, and other clinical benefits.

We are also working on a combination treatment of TransCon CMP and TransCon Growthonomo in echondoplasia. Zendesk is uniquely positioned to bring these two once weekly medicines together in a combination providing two different modes of action.

To potentially improve outcome in echondylation and other growth disorder. We look forward to sharing top line week 26 results Phase two cohort trial of TransCon CMP in combination with TransCon Growth on Mode, which we expect in the second quarter of twenty twenty five. [indiscernible] during the fourth quarter of twenty twenty five, we plan to submit an IND for similar Investigate [indiscernible] or and in combination with TransCon Growth Remote. For the treatment of hypochondroplastia. Looking to how we are expanding our pipeline. In endocrine rare disease. We are expanding into additional product candidates beyond our first three successful as we disclosed in at the JPMorgan Conference. In addition, we continue to broaden the reach of our platform outside endocrine rare disease [indiscernible] much greater patient number. For oncology, our internal development continues to focus on TransCon IL-two, beta gamma aiming for accelerated approval in one or more indication. In early twenty four, We announced the formation of Conis to explore the development of Tungsten based therapies in ophthalmology In November, we announced a multiproductal ablation in Novo Nordisk Kawasaki and Cardiovascular Diseases lead program to develop once monthly tranqon semiglucide. This entire loss to escalating tiered mid single digit royalties on Globonixar of approved products.

Finally, as I mentioned earlier, have expected TransCon to incorporate protein degraders. A technology that bear promising potential within as well as outside rare endocrine diseases.

As Zendesk today, with approved commercial product, a strong pipeline, and guided by our values of patient, science and passion is positioned to continue driving rapid and sustained growth in the years ahead. I will now turn it over to Scott Smith. [indiscernible] The progress we made in 2024 enables us to head into 2025 with the financial and organizational strength to execute on our strategic priorities. Which are to successfully launch YorbaPAT on a global basis to build on SKYKRS' leadership position in pediatric GHD by expanding The U. S. Label to adults while maintaining its premium net pricing of 3x compared to daily growth hormone and to submit TransCon CNP for approval to treat a contrapation in children in The U. S. And the EU. I will touch on some key points surrounding our fourth quarter and full year financial results, but for further details, please refer to our 20 F filed today. Sciitrofa volume increased 37% in the fourth quarter of twenty twenty four compared to the fourth quarter last year. While reported revenue was €58,500,000 compared to €664,200,000.0 in the fourth quarter of twenty twenty three, In the fourth quarter this year, Skytropha revenue benefited from volume growth and a favorable sales adjustment of €4,600,000 attributable to periods prior to 01/01/2024, which was offset by higher sales deductions compared to the same period Backing out this favorable sales adjustment, Skytropha revenue was approximately €54,000,000 for the quarter.

Sequentially, Skytrophic volume increased 16% in Q4 compared to Q3, while pricing was stable. Expect revenue growth to continue to track closer to script growth unless payer mix changes substantially as there have been no major Shifting to Yorba Path, as previously reported, fourth quarter Yorba Path revenue increased to €13,600,000 bringing total 2024 revenue to €28,700,000 As Jan noted, the launch of Yolropath in Germany and Austria in 2024 together with the initial demand and progress with reimbursement in The U. S. So far in 2025 has been very encouraging. Expect that YORBA PATH will have a significant impact on our financial profile at 2025. While it is early in the launch, we look forward to sharing data on parameters like enrollments, prescribing HCPs, time to reimbursement, etcetera, to provide more detail on launch dynamics. More importantly, everything we are seeing in the early launch phase supports our view that over time, we expect ORVIPATH to be the standard of care for patients with hypoparathyroidism and to become a multibillion dollar product. Closing out the top line, total revenue for the fourth quarter was €173,900,000 including revenue rec [indiscernible] [indiscernible] well as other revenue from partners. To be clear, although we recognize the $100,000,000 from Novo in 2024 for accounting purposes, as Cash was received after year end.

In January. Total revenue for the full year 2024 was €363,600,000.0 Turning to expenses. For the fourth quarter, R and D costs totaled EUR79.3 million compared to EUR90.9 million during the fourth quarter of twenty twenty three. The 13% decline was largely due to lower external development costs for TransCon Growth Hormone and TransCon PTH well as the Iconis spin off. SG and A expenses in the fourth quarter of twenty twenty four totaled €80,200,000 compared to €64,000,000 during the fourth quarter of twenty twenty three. The €16,000,000 increase was due to higher employee costs including the impact of additional headcount supporting global commercial expansion, most of which came toward the end of the year. Similarly, we spent more on external commercial costs to support launch activities and plan to continue to do so in '20 the global launches of Yoga Pass. Total operating expenses were €159,500,000 for the fourth quarter of twenty twenty four a 3% increase compared to €154,900,000 during the fourth quarter of twenty twenty three. Total operating expenses for the full year 2024 were €598,000,000 Net cash financial expenses for the full year 2024 were less than €1,000,000 while net finance expenses for the full year were €74,400,000 driven primarily by non cash items.

We ended 2024 with cash cash equivalents and marketable securities totaling €560,000,000 compared to €399,000,000 as of December 31, including the $100,000,000 upfront payment from Novo Nordisk that was received in January 2025 cash at the end of 'twenty four would have totaled €655,000,000 Finally, as separately announced, we expect to use to preserve approximately 200,000 ADS that is held as treasury shares. With that operator, we are now ready to take questions.

Our first question comes from Jessica Fye with JPMorgan. I have one question with a few parts. Mostly just confirming some stuff. First, can you confirm that the $9.00 8 figure is unique patients and not like cumulative scripts including refills for example? Second, you just confirm how many of the EAP and OLE patients are now included in that 908 number? I want to make sure I heard you. I think you said it was 84% new to Yorkie Path, 16% from the EAP and OLE, Lastly, I think you reiterated that you continue to expect the majority of insurance Can you just confirm that's actually what you're seeing now that you've been in The U. S. Market for coming up on eight weeks?

Thank you.

Thanks, Jess, a lot for the questions. I think we can confirm nearly all the answers. So Jay and Sherry, will you confirm all the numbers? As of each year?

Happy to. Jessica, thank you for the question.

First part of your question from an enrollment standpoint, we can confirm that is unique patient enrollments. So not cumulative repeat I think the second question you asked was the percentage of patients that are coming over from either the EAP or clinical trials. Versus those that are new to YORMIPATH. So about twenty percent of the nine zero eight is existing patients from TransCon, PTH, EAP or clinical trials and then eighty percent of patients are actually new to your orthopath. And then the third question that I think we heard you ask Jessica is more around the four to eight weeks. That is our estimate of what we think it should take But keep in mind too that based on the timeframe for which the drug has been on market, it is still a very nascent period of time where for many of the patients enrolled, that time period hasn't actually occurred yet. Right? So we'll need more time to get a better sense of that, but that is our initial estimate Thank you. For my follow-up Can you provide the Yovipass patient number outside The U. S?

We have not proven that not put down. It's still increasing as we expected to do.

We are still only in Europe direct countries full commercial in Germany and Austria, We have our AP2 program France the non promotional program that also is enrolling reimbursed patients. And then we have our international market in this way. And the patient number are increasing to exactly as we have expected, but we have not broken down the numbers.

Our next question comes from Tazeen Ahmad Bank of America. Hi, guys. Good afternoon and thanks for taking my questions. Yan, could you provide any color on how many of the nine zero eight scripts that have been written have now been converted to patients on actual therapy And can you give us also any color that you might have on what proportion of these patients experience with Napara. And then I have a follow-up.

Yes. The question are you are addressing is a question where we still lack a all the information to give you and cope really the concrete answer that you want to have. What we have done in our market research, we have looked a lot on claim And we have defined patient group which we call the 10,000 to 15,000 patient which we will call not controlled on standard therapy [indiscernible] therapy. And this patient group is basic seeing the physician at least four times And there also will have one thing more in common, they have at least one hospitalization related to [indiscernible] We also know the limitation in really as in seeing and into So from that perspective, just by the random process when you can see and do we actually believe that many of the patients that we see of the nine zero eight XL are coming from the group, which we define as more uncontrolled in this. We don't have a positive definition if that is true or not, but that is our expectation in this. The second question you raised about how many patients we have on therapy now is a number we are waiting to some way to come out with until we feeling we have sufficient good enough data to give you a solid number because we are now in the initial part of our you can see, journey of getting them 100% reimbursed.

We were extremely positive on the broadness of having reimbursed patient both from the commercial setup, but also for the government side. And the basic Arcadian reimbursed patients place from. And when you see the broadness on the state, we're covering with about 35 different states, we're really coming out in all different [indiscernible] We also feeling that we are in a very, very strong position. The vast majority of the patients are on label. And basic, they're also fulfilling exactly the criteria that justify for them to be on a PTH treatment. So we are really highly positive On the development, we have seen the reimbursement [indiscernible] Okay. Thanks, Tian. And then, I just want to to clarify, I think you had said that you were considering providing sales guidance for Euroview for the full year sometime in the middle of the year. Does that still the plan?

I think it's still I think we will like to give you guidance when we believe in the numbers. And I think that is the criteria we take up. So depending on how we see the loans going and how we see different regions, we will come up with what we call revenue guidance, exactly when we're feeling that we feel the confident. Scott always like to give up a lot of numbers So you can hear in his listen what he said in his prepared remarks that he will come up with a lot of elements that can give you the best possible fundament to build up a solid model.

In your own way. [indiscernible] Yes. We will as we said, we're excited to continue to share with you the underlying parameters driving the launch and we plan to do that in the quarters ahead.

Our next question comes from Gavin Clark Gartner with Evercore ISI. [indiscernible] on the very strong progress so far. Just had one question on YorbaPASS and one on CNP. [indiscernible] how have your discussions with payers gone so far? And what are your assumptions for how the some of the prior authorization criteria may read? Specifically wondering if you think it's going to [indiscernible] than the label. And kind of on that same line, maybe you could just remind us your contracting or gross to net assumptions That's the first one. On the CNP side, for the CNP plus growth hormone combo data coming in the second quarter, Can you just remind us your expectations, specifically on AGV? Thank you.

Yes. I think Jay will come with some further flavor about the contracting situation, but also as I said before, I've been lucky to see both of the PRETTYS and have been aligning to the labeling but I believe Jay will come up with comments related to the Contracting landscape.

Yes. So thank you for the question. As you can expect for any new launch, we are still in the early stages of establishing policy with payers. So just as an example, most medical policies right now for our large national players haven't yet even published a policy yet.

Right? So our conversations have all been productive today, really focusing on the clinical value proposition of the drug. As you can see and based on our data array of clinical studies, we feel really positive about the benefit that we can convey to the patient community and we're having great conversation around that. Specifically, your question around prior offs and what that might look like, we're expecting and again as part of those negotiations and discussions wanting to ensure that the standard PA is consistent to label, both in terms of reauthorization timelines, tests that may need to be conducted to ensure that Ascendis is consistent with label. So while many of those plans and policies still need to take some time to come into fruition, we're feeling encouraged by those conversations.

So the CMP question is always looking in the crystal ball. Because you asked me, Jan, [indiscernible] And it's first time to my knowledge everyone have done a combination CMP and Growthomo. And why I think it's really, really our interest because it's two different compound. We very different physiological mode of action. And if I ever believe in science, which I always do a lot, It should be a great combination. Because its synergistic pathway And when I look on what you can do the HyperACT2 Tirosine kinase systems that you have in Akronoplasia, you can do that with either the tyrosine kinase inhibitors. You can do it by GMP. As short acting or you can say continuous exposure I think it's easier to saturate the analyzed high velocity in this part of the integrated effect you expect give as a treatment option in the acondylplasia, one of them that eases to hit is basic the analyzed high velocity. And when I look on all the data, [indiscernible] around 5.5 to six point zero on analyze high velocity. [indiscernible] what the science also will say. You are moving a brake and you restore normal growth. So out from that perspective.

And this is why I love the growth hormone. Because what is growth hormone This is like sitting in a car and then you suddenly get rid of the speeder. Some may take a little bit on the speeder, get the break off and then you really can move. And this is why I've seen this combination will give a good results. And I look forward to the results as much. I can ask you what would a good result be?

That's helpful.

We'll leave it there for now.

Our next question comes from the line of Lee Wasik with Cantor Fitzgerald.

Hey guys, wanted to add my congrats on the strong Your Repet launch as well.

Just curious for these 900 plus prescription more severe versus more moderate diseases? And if you can share any early trends of compliance in initial titration, whether it's consistent with your clinical trials?

Yes. It's a question we tried to address with before. But I think Cher, you're also sitting with a lot of [indiscernible] describe the limitation that we have in our data set really to answer that question today. Sure. And thanks for the question, Lee.

So what we don't actually have data in terms of the enrollments on patient severity. What we do know though is a couple of important things. One is that at the end said earlier, the most severe patients are going most frequently to the endocrinologists. So by that practical matter of them getting into the office to get the prescription, it's likely that we have severe patients initially getting some of the first prescriptions. And again also mentioned, there are a number of those uncontrolled patients in The U. S. There's 10,000 to fifteen thousand of them and then a number more people who are partially controlled. So to the extent that we are starting to see some of the first patients being the more uncontrolled and severe patients. We know there's still a tremendous amount of room for expansion. Beyond that.

Our next question comes from Derek Archila with Wells Fargo.

Hi, this is Yvonne for Derek. Thanks for taking our questions and congrats on the progress. A quick one from us on your behalf. So can you provide some color on what type of docs are prescribing Yurbi Path or just like high volume docs or are you starting to get some docs from the community? And as a follow-up, how long do you expect patients will take to convert from drug in the EAP over to paid drug?

Yes. Let me take the last question before I turn it over to to Jay or Sherry. What is happening in our ERP program, the last package I got was a three pack of basic three months and some of them got them in December to in January. So the 100 plus patient that we are converting from our ERP clinical trial over. We'd likely come into conversative drug starting in February and then majority in March. So that was the second question. And I think Shari or Jay, who will take the Sure. Happy to start. I think the question around prescriber breadth, I think as we mentioned before, five thirty nine across 44 states. We're seeing that pretty broadly across all different type of physicians, across all deciles. Naturally, you would expect directionally physicians that are treating perhaps a greater number of patients, right? You're We're naturally also focusing on them quite heavily. So from a field standpoint, we're actually over 50% reach for a lot of our priority physician. So I think naturally you're going to to see some directional lean in that direction, but more importantly, what you're seeing is a broad outreach and broad interest across the provider community agnostic of Dessa.

And maybe I'll just add that to that, what is really exciting is that we see that we're broadening a lot beyond the natpara prescriber. So of the five thirty nine physicians, only about 200, a little less than 200 had prescribed Natpara.

So we see that we're really broadening our reach.

Our next question comes from Yaron Werber with TD I got maybe a couple of questions. Scott, for you and then I don't know, Jan, if you want to take the next one.

I think Scott, you said that toward the end of the year, you could be you could reach profitability on a cash basis.

Does that still sort of hold? And what would drive that?

Is it going to be your VIP pass is the biggest driver? And then secondly, as you think about reimbursement for your OrbiPath, are you expecting with time prior authorizations or are you expecting not to have any prior auths? Thank you.

Okay. I think Scott will like to say something.

Yes, I think you're exactly right. The Orem Pass will be a big a big driver of ability to cash breakeven. It's a strong launch in Europe for us. Obviously, we're off to the races here in The U. S. It's a very profitable [indiscernible] So I think we agree that that will be a strong driver of breakeven potential this year.

Yes. But I also believe you need to look that U. S. Is the numbers we're giving you today. But we basically have a global And we also someway seeing that end of this year, we're starting to take into a much, much higher gear our Europe direct countries. We will also see the international market is starting to really, really getting engaged. I accept that it will be a major event for 2026. Where all the countries will come in mainly with full year launches in for many of them. But the $25,000,000 will be where we start in both Europe Direct in at least five countries more but basic also our international market. So The U. S. Should is a fast market, is a fast penetration we can get.

Because it's so large single market. So sure, it will dominate in the big beginning of the year. But just remember the number of patients outside U. S. With Hypopair is so much, much, much larger, past four, five, fold than what you have in The U. S. The second one, Will, you take that. Yes, sure. I mean, from a prior auth standpoint, I think the question was what do we expect for ORVIPAP?

It is a specialty product and I anticipate there would be some basic questions even as it's simple as who's prescribing it.

Right? I think whether it's an endocrinologist, whether it's a nephrologist, etcetera, And I think secondly, what you're going to see and should expect is there's going to be wide heterogeneity across what you'll see across both national and regional plans.

Think as we alluded to before, we are seeing approvals across commercial payers, public payers and even absent of there being a formalized policy at some of the large national payers, we still submit generic prior offs to seek exception through that policy. So again, some of this will take time to evolve and some of it we would expect to change. But we will see probably a wide range across the various plans.

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

Hi.

I'm Julie Park dialing for Joe.

Thank you for taking our questions. I believe in the last earnings conference call, you mentioned that in Germany physicians are prescribing Urbihazt to one to two of their patients whereas in The U. S. You are expecting physicians to prescribe the drug to the three of their patients And based on the metrics that you provided today, it seems like on average, each physician is prescribing of a drug to a little over 1.5 of their patients. So I was just wondering if you're still expecting each physician in The U. S. Prescribe OraPath to about two to three other patients and where does it go from there?

Yes. I think in summary, I accept what I said and I stand by what I said before. And I think the pattern we see now is an early launch. I have seen and followed some of the physicians that was part of our ERP and clinical trial. And some of these physician have been already make prescription up to 20 patients. So I'm no doubt that broadness of that will come, but in some way, this is an early launch, one to two months in the launch. So I will expect that to see income in the future.

Okay, great. That's helpful. And then a clarifying question. Are there any of the nine zero eight the the Yorvipad sales from 2024 considering the drug was available mid to late December, Thank you so much.

Got it.

I mean strictly speaking, so we did ship a very small amount in December. It was basically immaterial to the total.

Yes.

So in practical, no.

Our next question comes from the line of Kelly Shee with Jefferies.

Congrats on the greater quarter and manufacturing front, how should we think about the capacity bypass throughout the year? Thank you.

Yes. I think one of the things we have been very, very proud of at Ascendis Ascendis really our robust supply chains. We have seen how we have managed to go up in high demand on the shortest of the daily growth mode and could fulfill all requirement for all Vicious for having [indiscernible] [indiscernible] And when I look on the [indiscernible] We're using the same solid supply chains the same infrastructure. We followed the same I personally get a weekly report on Avis compound in every region in every place where we are selling product, how many months there is on storage. And we someway are taking that as a really serious thing because we will never be in position that we will go short. And that is our vision and I hope we never come to this [indiscernible] Thank you.

Our next question comes from the line of Ellie Merl Hey guys, thanks so much for taking my question and congrats on the launch progress. Just in terms of how we should think about The U. S. YORBA PATH script cadence, I guess, sort of what's the latest that you're seeing in terms of cadence of new starts? Are you sort of seeing a steady number of ads each week? Was there a bolus upfront? How should we think about this going forward? And second, just a follow-up on reimbursement. I know you said you're seeing approvals across a number of plans, but could you characterize maybe sort of the number of scripts that have been covered so far and sort of any trends that you're seeing in terms of ease of reimbursement say between the moderate patients versus the severe patients and your expectations there? Thanks.

I think the question related to what we call control to partly controlled and patient we have somebody answered this to our best of knowledge. We have no clear data of the patients that is already have received a prescription. We have a gut feeling and the gut feeling is that we believe many of them belongs to the uncontrolled part because the C the endo in a much higher frequency than [indiscernible] Else.

Related to the pattern on prescription, we are not breaking it down in weeks. Or anything. This is something we are following where they are tied. And we would like to see pattern being developed. We don't believe there's really a huge bolus coming in because there is not a huge availability of the buyback into really to come in and say, oh, I just want to have an appointment run into an into and now I have a prescription It's not like life it is that like Amy is sitting here. If you want to see Amy, our CMO, stand for. Take many weeks now, Amy? Well. Twelve weeks to see. So it takes a little bit time to get an appointment. So we don't believe that is a lot of buildup demand. It's basic is patient that come in and have the the need to be in a treatment. And I think it's pretty obvious for me when I see the benefit that all the patients get. Yes, everyone should have a treatment option. And come on PTHs like every one on type one diabetes should have insulin This is a home replacement therapy.

In this perspective.

Related to the reimbursement system, I do not know, Jay, if you have further comments. Compared to that.

Yes. As we mentioned before, because this is such early days, I don't think we would able to draw a meaningful pattern or trend based on just a few weeks that we've been in here. I think I go back to the statement we made before. We are seeing approvals across all both commercial and public payers, but fully recognizing too that because many policies aren't in place, a lot of these cases are exception by exception basis. [indiscernible] we believe that after least a few more months, we'll have a better sense of how these policies shake out and what that more stable Great. Thanks.

Our next question comes from the line of David Lebowitz With Citi, Thank you for taking my question. First on [indiscernible] you had the PDUFA date coming up this summer for the adult growth hormone deficiency. I'm just curious how should we be thinking about that in terms of what that market opportunity actually presents [indiscernible] unmet medical need that really exists in adult growth hormone deficiency.

From my perspective, there's two key things I really some way First of all is here with extremely low penetration to our best knowledge is under 5%, 6%, 7%. So you can say there is a huge opportunity [indiscernible] And the other thing is that has been a huge burden basic to be the treatment with daily growth hormone.

But Amy, you can explain and tell about what is really the unmet medical need the burden of having adult cochlear hormone deficiency.

Sure. Happy to do so. So many people arrive at growth hormone deficiency in adulthood following something involving organically the brain, right? So a brain tumor or a brain cancer or its treatment, either surgery or radiation. That's the at least fifty percent or more So many of them because they are missing function of the pituitary gland are taking many hormone replacements and growth hormone is just one on that list. So they have oftentimes said if I if it's something we can make simpler, right, that the community could provide more simply to them, They would it is something they would [indiscernible] knowing that it adds to their metabolic health. And overall endocrine health, right? But of course, their first their first priority always are the two life saving hormones from the brain, is from the adrenal gland and the thyroid gland. So those you can't forget and those are pills. So after that, they are willing to think about injectable less frequent therapies, knowing it is good for their overall health. We could admit that growth hormone deficiency is not immediately life threatening, thyroid or adrenal replacement is.

So we think we're in a nice sweet spot here.

It the hormone that should be replaced and if it meets patient's expectations We think there would be Thank you for that. And just jump Jumping over to to your overpass, I'm just curious as to thoughts on potential competing pivotal data coming out this year and how you think the market ultimately might evolve?

Yes. If you reflect on pivotal data, I don't think there is anyone else than one compound [indiscernible] [indiscernible] and to our best knowledge, when we talk with centers, the last page in was in beginning of [indiscernible] So I'm still pivotal trial. It's a small trial with little bit more than 100 patients. So it shouldn't take too long time to clean the data and come up with a top line data. But have not seen anything else. When I go back to the signs and one of our key values This is not an hormone replacement therapy. This is substitution of the non acting effect where you basic are placing [indiscernible] into a fixed position and therefore have a long is not even reflecting the normal biology where you are basic activating both the TGF1 receptor and the TGF2 receptor. And by doing the different mode of action, you already are from the data can see that it can be substituted as an hormone replacement therapy element on where you see is not restored normal function, for example, in the kidney both for example, related to phosphate [indiscernible] See, for example, it cannot lower a key element like calcium phosphate complex.

You also see the unnatural activation to the activating system in the bone and other organs. And then I'm not talking about the immunogenic potential that is in the compound. So we are looking forward to see the data. We would like to see the data and we hope one day that will come out, where should be out there now because it's so long time since that patient came into the visit.

Our next question comes from Paul Choi Goldman Sachs.

Hi, thanks. Good afternoon and congrats on the early launch success with UroverPath in The U. S. My first question is on OrbitPath and as we look at consensus numbers, The Street is modeling less than 900 pay patients in The U. S. For this year and you've already exceeded that in terms of scripts. So I was just wondering recognizing that you're not giving guidance and and the reimbursement is a work in progress, just your level of comfort with The Street revenue number for for the full year possibly or any color around that would be great. My second question is regarding CMP and the hypochondriplasia program that you plan to file an IND for later this year. Are you planning to do any run-in activities ahead of that possibly at some of the centers just to potentially help accelerate the timing of that study and enrollment? Any color there would be Yes. Let me take the first part together with because we are really [indiscernible] to be the leader in growth to solve. And when we see the two cornerstone we have, TransCon and Tantacount to CMP We really will do the best for the patient in eight cases.

How can we design and Optimum [indiscernible] In this way. [indiscernible] what we're doing now in hypercontemplation is defined What is really the pathway forward for us is then just a transcom CMP treatment or will it be a combination treatment between TransCon CNP and TransCon Procurume? And we are now in a position that we are starting with a Vector Toy agencies But I think Amy can give you [indiscernible] [indiscernible] Think that when we moving into hypercontemplation, one of many growth disorder we actually would like to focus on. And the actual design can also be a different state. [indiscernible] So exactly, we are taking the time to give hypochondriplasia the opportunity it deserves. While some of hypochondriplasia overlaps highly, with achondroplasia, and the genetic variant arises on the same FGFR3 receptor, [indiscernible] gene changes are very different along that whole receptor And we are understanding that hypochondriplasia has a unique phenotype. It's a broader phenotype and very unique. So along those lines, we are still figuring out it's an active process. What's the population of interest to us?

Where we can benefit from them and therefore the different ways to find a regulatory path forward, which I think gets to your question about how how much time do we put in into the run-in. So I couldn't tell you now as we are still figuring a lot of this out. But I think the the condition and other conditions of short stature especially on the skeletal dysplasia genetics side, right? Deserve a very good thorough understanding to find the best way [indiscernible] We are in this position that potentially we will start both trials at the same time.

And CMP in a combination trial. And then regulatory data and final that potentially we will go for an approval for both and then they can choose the optimal treatment from the position, how purpose can the patient needs in this way. If they really want to have an much more extensive linear growth likely the combination therapy will be the preferred option. Related to your last first question, I think we said Ascendis discussed prepared remark that we are not giving any guidance, as you correctly said. We would like to give you as much as possible what we can call elements we are using in our own modeling and giving that as fast as we can give it with all the different goals to ensuring that you have the best possible modeling that you can do. And I think Scott is always open for discussion. He's extremely extroverted. Like to talk with people. So I think if there is any element of model discussion, I think he likely will Our next question comes from the line of Alex Thompson Hey, great. Thanks for taking my questions. I guess GourmetPath, I wonder if you could talk a little bit about how titration is working in the real world with patients, whether that requires additional with their HCP, etcetera, if this is done at home?

And then maybe you talk a little about your expectations around growth to net stability in 2025 for Sky Trofa?

Thanks. Amy, would you take that first?

Sure. The first question was about titrations with YORBEPATH. From what we've heard so far, right, this is in in the domain, this is the sweet spot for endocrinologists. They know how to titrate medicine.

So we are but that being said, I'm not sitting on the shoulder of each person. To be straightforward to follow. They have gotten the guidance that they wanted. And the only times we may have touch points with them will be as we go further along and one switches from the medium dose pen to a high dose pen or a low dose pen. But we don't have that insight yet. But from what we're hearing just anecdotally, it's what endocrinologists know how to do.

At least what we have seen now being in market in Germany for one year now We are not seeing any issues to the saturation and patient physician field that is not complicated and easy element to do it and the getting out on conventional therapy exactly at the same speed that we saw in our clinical trials which surprised me a little that they were doing in the same speed. As we do when we have much more rigid framework for a patient to come into and talk the physician It's same thing having in REALife. They're out of conventional therapy extremely fast.

Our next question comes from the line of Yoon Zhong Wedbush Securities, Good afternoon. Thank you very much for taking the questions.

The first one on Yolipas. So when you report first quarter earnings, are you going to break down sales to tell us how much is coming from Europe, how much is That's a good question. We will decide when we come to that state exactly how we report the data.

Okay. Then follow-up question on the Sky Trofa. I believe what I heard was that the adjustment has largely been over for twenty twenty four, but you haven't really given any guidance unlike in January, you put out the guidance for 2024. And are there any uncertainties surrounding the SKY-twelve? Is that related to the daup launch or more related to the pediatric marketplace?

Yes.

Thanks for the question. So So we expect revenue growth to continue to track closer to script growth going forward, unless of course there's payer mix changes substantial payer mix changes. And this is primarily because there's been no major contracting changes [indiscernible] Q4 last year.

This concludes today's conference call. Thank you for participating. You may now disconnect. Two, [indiscernible] [indiscernible]