Earnings Call Transcript - ASND Q4 2024

Operator, Operator

Good day and thank you for standing by. Welcome to the Fourth Quarter and Full Year 2024 Ascendis Pharma Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker’s presentation, there will be a question-and-answer session. Please be advised that today’s conference is being recorded. I would now like to hand the conference over to Scott Smith, Chief Financial Officer.

Scott Smith, CFO

Thank you very much, Operator. And thank you everyone for joining our full year 2024 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; Sherrie Glass, Chief Business Officer; Jay Wu, President, U.S. Market; and Aimee Shu, Chief Medical Officer. Before we begin, I would like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the Safe Harbor provided by the Private Securities Litigation Reform Act. Examples of such statements may include, but are not limited to, statements regarding our commercialization and continued development of SKYTROFA and YORVIPATH for the U.S., European, and other markets, as well as certain financial expectations, our pipeline visits, and our expectations with respect to their continued progress in potential commercialization, our 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 and the results of regulatory decisions, expected market 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 these statements. We assume no obligation to update these statements as circumstances change, except as required by law. For additional information concerning the factors that could cause actual results to differ materially, please see our forward-looking statement section in today’s press release and the risk factors section of our most recent annual report on Form 20-F filed with the SEC today, February 12, 2025. TransCon Growth Hormone or TransCon hGH, is approved in the U.S. by the FDA and in the EU, has received MAA authorization from the European Commission for the treatment of pediatric growth hormone deficiency. TransCon PTH is approved in the U.S. by the FDA for the 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 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 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 Jan.

Jan Mikkelsen, CEO

Thanks, Scott, and good afternoon, everyone. 2024 was a pivotal year for Ascendis as we achieved key milestones that set us up to deliver strong growth and value creation in 2024 and beyond. With SKYTROFA firmly established as a high value growth hormone brand in 2024, volume grew sustainably with revenue reaching around €200 million on a 6.5% market share of the total growth hormone market in the U.S. and around 45% of the total U.S. long-acting growth hormone market based on third-party prescription data. With further penetration in pediatric growth hormone deficiency and a planned commercial launch across multiple indications and countries, we expect sustained value creation for the TransCon Growth Hormone branches in the coming year as outlined in our Vision 2030. Importantly, YORVIPATH, the only FDA approved treatment for hypothyroidism in adults, is now launched in the U.S. and has already begun to establish itself as the new standard-of-care. Given the longstanding need for a treatment option like YORVIPATH, we are seeing significant early demand in both the patient and physician communities, and we are pleased with the pace of payer approval so far. The large global population living with a significant hypopara disease burden underscores the potential for YORVIPATH to grow into a multi-billion-dollar product over time. Rounding out our endocrine rare disease portfolio, TransCon CNP clinical data demonstrated it could be a highly differentiated product with a unique profile that represents a major step forward in the treatment of achondroplasia and other growth disorders. We believe the once-weekly TransCon CNP data demonstrates superior linear growth and benefits beyond linear growth, supporting our proposed label for treatment of achondroplasia. For this reason, following our pre-NDA meeting with the FDA, we are on track to submit an NDA to the FDA this quarter, followed by an MAA submission to the EMEA in the third quarter this year. All three of these endocrine rare disease medicines demonstrate the value of our TransCon technology platform and its potential to address major medical needs with highly differentiated products. We are also bringing the TransCon technology platform beyond endocrine rare diseases. In large patient populations, through our collaboration with Novo Nordisk in metabolic diseases such as obesity, type 2 diabetes, and cardiovascular diseases, in ophthalmology to the creation of Eyconis. We have also expanded the TransCon technology platform to incorporate protein degraders, a very promising area where we believe that 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 million on our balance sheets, including the $100 million upfront payment that we received 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 continual revenue growth. Let me review our key programs in rare endocrine disease in more detail. In the U.S., SKYTROFA was launched just over three years ago. Today is the treatment of choice and at the same time growing the growth hormone market. Importantly, with the pediatric growth hormone deficiency indication alone, we are currently addressing only half of the existing U.S. growth hormone market, but are on the path to expand SKYTROFA’s addressable market in multiple ways. Near-term, we expect U.S. approval in adult growth hormone deficiency this year with our PDUFA date on July 27. Longer term, we will investigate SKYTROFA in additional therapeutic areas through a basket trial, including idiopathic short stature shock deficiencies, Turner syndrome and SDA. In the third quarter of this year, we plan to submit an IND application for this basket trial to the U.S. FDA. Plan commercial launches across multiple countries. In 2024, SKYTROFA volume increased 84% in the United States, with premium net pricing of 3x compared to daily growth hormone. SKYTROFA achieved revenue of around €200 million in 2024, supporting the potential for it to become a blockbuster product over time. Moving to YORVIPATH, 2024 was a critical year for YORVIPATH, with commercial availability in Europe starting early in 2024 and then this past December in the U.S. With YORVIPATH also available through named patient programs, patients in multiple countries living with hypoparathyroidism can begin to access this long-awaited treatment option. Hypoparathyroidism represents a large global market opportunity for scientists to address a major unmet need for an effective and well-tolerated treatment option. To create durable long-term leadership for YORVIPATH, we are building this market by educating physicians about the well-documented limits on the risk of conventional therapy and the clinical benefits seen with our PTH treatment. In the U.S., we estimate there are about 70,000 to 90,000 patients with chronic hypoparathyroidism, most of whom are currently using conventional therapy of oral calcium and active vitamin D. Our claims analysis demonstrates that 10,000 to 15,000 of these U.S. patients are uncontrolled and 30,000 to 35,000 are partly controlled. We believe YORVIPATH can sustain growth over a long time as the vast majority of patients with hypoparathyroidism qualify for PTH treatment per the current international guidelines. Less than two months after the U.S. YORVIPATH launch, initial demand is strong with 908 patients with prescriptions as of February 7, 2025. This includes prescriptions for 539 unique prescribers in around 44 states. Nearly 80% of enrollments are new to YORVIPATH, 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. Discussions with payers are ongoing, and as expected, with a novel specialty product, we estimate the majority of insurance approvals will take about four weeks to eight weeks. We are pleased with the initial pace of insurance approval across commercial and government payers and have shipped reimbursed drugs to patients in around 35 states. Outside the U.S., we remain on track for additional commercial launches in what we call European countries, where we expect to add five or more countries this year. We also expect launches in multiple international markets in 2025, further expanding our global reach where we have signed eight exclusive distribution agreements covering 50 plus countries so far. YORVIPATH is a unique product. Our broad and extensive clinical data includes three successful Phase 3 trials in the U.S., Europe, Japan, and China, covering diverse disease groups including post-surgery, autoimmune, ADH1, and idiopathic hypoparathyroidism. Last year, we presented three years of data from our Phase 2 PaTH Forward Trial, and later this year, we plan to present four years of data demonstrating excellent patient retention and sustained serum calcium control and bone health, sustained reduction of calcium phosphate product, independent from conventional therapy and normalization of 24-hour urinary calcium secretion. The data also shows sustained improvement in kidney function. Switching to TransCon CNP, achondroplasia remains a disease with high unmet medical need and we believe TransCon CNP has the potential to be a highly differentiated treatment option. In the pivotal ApproaCH Trial, TransCon CNP demonstrated significant improvements in linear growth and body proportionality compared to placebo, as well as benefits beyond linear growth. As one example of benefits beyond linear growth, we have shown data demonstrating significant improvement with TransCon CNP treatment on leg bone and common and devastating complications in achondroplasia that can result in pain, impaired physical function, need for corrective surgery and a negative impact on quality of life. TransCon CNP has shown a safety and tolerability profile comparable to placebo with low frequency of injection site reactions, all of which were mild, and no evidence of hypertension effect. Supporting TransCon CNP potential as a best-in-class treatment for achondroplasia. Following our productive pre-NDA meeting with the FDA, we plan to submit an NDA for the treatment of achondroplasia during the first quarter of 2025 and submit an MAA for treatment in children with achondroplasia to the EMEA during the third quarter of 2035. We believe TransCon CNP will be setting a new bar for the treatment of achondroplasia. To further raise this bar for linear growth and other clinical benefits, we are also working on a combination treatment of TransCon CNP and TransCon Growth Hormone in achondroplasia. Ascendis is uniquely positioned to bring these two once-weekly medicines together in a combination treatment, providing two different modes of action to potentially improve outcome in achondroplasia and other growth disorders. We look forward to sharing topline week 26 results from Phase 2 COACH Trial of TransCon CNP in combination with TransCon Growth Hormone, which we expect in the second quarter of 2025. Additionally, during the fourth quarter of 2025, we plan to submit an IND or similar to investigate TransCon CNP alone or in combination with TransCon Growth Hormone for the treatment of achondroplasia.

Scott Smith, CFO

Thanks, Jan Mikkelsen. 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 YORVIPATH on a global basis, to build on SKYTROFA’s 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 achondroplasia 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. SKYTROFA volume increased 37% in the fourth quarter of 2024 compared to the quarter last year, while reported revenue was €58.5 million, compared to €64.2 million reported in the fourth quarter of 2023. In the fourth quarter this year, SKYTROFA revenue benefited from volume growth and a favorable sales adjustment of €4.6 million attributable to periods prior to January 1, 2024, which was offset by higher sales deductions compared to the same period the prior year. Backing out this favorable sales adjustment, SKYTROFA revenue was approximately €54 million for the quarter. Sequentially, SKYTROFA volume increased 16% in Q4 compared to Q3, while pricing was stable. We expect revenue growth to continue to track closer to script growth unless payer mix changes substantially, as there have been no major contracting changes compared to Q4 last year. Shifting to YORVIPATH, as previously reported, fourth quarter YORVIPATH revenue increased to €13.6 million, bringing total 2024 revenue to €28.7 million. As Jan noted, the launch of YORVIPATH 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. We expect that YORVIPATH will have a significant impact on our financial profile in 2025. While it is early in the launch, we look forward to sharing data on parameters like enrollments, prescribing HCPs, time to reimbursement, etc., 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 YORVIPATH to be the standard-of-care for patients with hypoparathyroidism and to become a multi-billion-dollar product. Closing out the topline, total revenue for the fourth quarter was €173.9 million, including revenue recognition of the $100 million upfront fee related to our collaboration with Novo Nordisk, as well as other revenue from partners. To be clear, although we recognize the $100 million from Novo in 2024 for accounting purposes, cash was received after year-end in January. Total revenue for the full year 2024 was €363.6 million. Turning to expenses, for the fourth quarter, R&D costs totaled €79.3 million, compared to €90.9 million during the fourth quarter of 2023. The 13% decline was largely due to lower external development costs for TransCon Growth Hormone and TransCon PTH, as well as the Eyconis spin-off. SG&A expenses in the fourth quarter of 2024 totaled €80.2 million, compared to €64 million during the fourth quarter of 2023. The €16 million 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 2025 with the global launches of YORVIPATH. Total operating expenses were €159.5 million for the fourth quarter of 2024, a 3% increase compared to €154.9 million during the fourth quarter of 2023. Total operating expenses for the full year 2024 were €598 million. Net cash financial expenses for the full year 2024 were less than €1 million, while net finance expenses for the full year were €74.4 million, driven primarily by non-cash items. We ended 2024 with cash, cash equivalents and marketable securities totaling €560 million, compared to €399 million as of December 31, 2023. Including the $100 million upfront payment from Novo Nordisk that was received in January 2025, cash at the end of 2024 would have totaled €655 million. Finally, as separately announced, we expect to use approximately $25 million in the first quarter of 2025 to preserve approximately 200,000 ADSs held as treasury shares. With that, Operator, we are now ready to take questions.

Operator, Operator

Operator instructions. Our first question comes from Jessica Fye with JPMorgan.

Jessica Fye, Analyst

Hey, guys. Good afternoon. Thanks for taking my question and congrats on the strong YORVIPATH script number and breadth of subscribers. I have one question with a few parts, mostly just confirming some stuff. First, can you confirm that the 908 figure is unique patients and not like cumulative scripts, including refills, for example? Second, can you just confirm how many of the EAP and OLE rollover 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 YORVIPATH, 16% from the EAP and OLE. Lastly, I think you reiterated that you continue to expect the majority of insurance approvals will take four weeks to eight weeks. 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.

Jay Wu, President, U.S. Market

Happy to. Jessica, thank you for the question. The 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 YORVIPATH. So about 20% of the 908 is existing patients from TransCon PTH, EAP or clinical trials. And then 80% of patients are actually new to YORVIPATH. And then the third question that I think we heard you ask, Jessica, is more around the four weeks 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 today.

Jessica Fye, Analyst

Thank you. For my follow-up, can you provide the YORVIPATH patient number outside the U.S.?

Jan Mikkelsen, CEO

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

Operator, Operator

Our next question comes from Tazeen Ahmad with Bank of America.

Tazeen Ahmad, Analyst

Hi, guys. Good afternoon and thanks for taking my questions. Jan, could you provide any color on how many of the 908 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 may have had previous experience with NATPARA? And then I have a follow-up.

Jan Mikkelsen, CEO

Yeah. The question you are addressing is a question where we still lack all the information to give you really the concrete answer that you want to have. What we have done in our market research, we have looked a lot on claim data and we have defined a patient group, which we call the 10,000 to 15,000 patients, which we will call uncontrolled on standard therapy or conventional therapy. And this patient group is basically seeing the physician at least four times a year. And they also will have one thing more in common. They have at least one hospitalization related to the disease. And we also know the limitation in really that is in seeing an endo. So often that perspective, just by the random process, when you can see an endo, we actually believe that many of the patients that we see of the 908 actually 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 feel we have sufficient, good enough data to give you a solid number, because we are now in the initial part of our, you can say, journey of getting them 100% reimbursed. We were extremely positive on the broadness of having reimbursed patients, both from the commercial set up, but also for the government side. And we basically are getting reimbursed patients every 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 states. We’re also feeling that we are in a very, very strong position. The vast majority of the patients are unlabeled and basically 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 in the reimbursement spectrum.

Tazeen Ahmad, Analyst

Okay. Thanks, Jan. And then I just wanted to clarify, I think you had said that you were considering providing sales guidance for YORVIPATH for the full year, sometime in the middle of the year. Does that still the plan?

Jan Mikkelsen, CEO

I think it’s still the same. I think we would 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 launch 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 confidence. Scott always likes to give up a lot of numbers. So you can hear in his list and what he said in his prepared remark 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. Comments to you, Scott?

Scott Smith, CFO

Yeah. 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.

Operator, Operator

Our next question comes from Gavin Clark-Gartner with Evercore ISI.

Gavin Clark-Gartner, Analyst

Hey, guys. Congrats on the very strong progress so far. Just had one question on your YORVIPATH and one on CNP. For YORVIPATH, how have your discussions with payers gone so far and what are your assumptions for how some of the prior authorization criteria may read? Specifically wondering if you think it’s going to be different than the label. 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.

Jan Mikkelsen, CEO

Yeah. I think Jay will come with some flavor about the contracting situation. But also, as I said before, I’ve been lucky to see most of the UN criteria and I have been really pleased how they’re aligning to the labeling. But I believe Jay will come up with comments related to the commercial contracting landscape.

Jay Wu, President, U.S. Market

Yeah. 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 to date, really focusing on the clinical value proposition of the drug. As you can see, and based on our data from our array of clinical studies, we feel really positive about the benefit that we can convey to the patient community and we’re having a great conversation around that. Specifically, your question around prior auths and what that might look like, we’re expecting. And again, as part of those negotiations and discussions, wanting to ensure that the standard is consistent to label, both in terms of reauthorization timelines, tests that may need to be conducted to ensure that, again, it 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.

Jan Mikkelsen, CEO

So the CNP question is always looking in the crystal ball. Because you asked me, Jan, what is your expectation to a data you have not really seen? And it’s the first time, to my knowledge, everyone has done a combination trial in achondroplasia, a Phase 2 trial between TransCon CNP and growth hormone. And why I think it’s really, really interesting, because it’s two different compounds with very different physiological modes of action. And if I ever believe in science, which I always do a lot, it should be a great combination, because it’s synergistic pathway. And when I look on what you can do when you address the hyperactive tyrosine kinase system that you have in achondroplasia, you can do that with either the tyrosine kinase inhibitors, you can do it by CNP as short-acting or you can say continuous exposure. I think it’s easier to saturate the analyzed height velocity in this part of the integrated effect you expect to give as a treatment option in achondroplasia. One of them that’s easiest to hit is basically the analyzed height velocity. And when I look on all the data, it’s likely are going around 5.5 to 6.0 on analyzed height velocity, which basically are reflecting a little bit 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 get rid of the speeder. Somebody take a little bit on the speeder, get the brake off, and then you really can move. And this is why I feel this combination will give a good result. And I look forward to the results as much. I can ask you, what would a good result be, Gavin?

Gavin Clark-Gartner, Analyst

That’s helpful. Thanks, guys. We’ll leave it there for now.

Jan Mikkelsen, CEO

We don’t. We don’t.

Operator, Operator

Our next question comes from the line of Li Watsek with Cantor Fitzgerald.

Li Watsek, Analyst

Hey, guys. I wanted to add my congrats on the strong YORVIPATH launch as well. Just curious for these 900 plus prescriptions, what proportion of these patients have more severe versus more moderate diseases? And if you can share any early trends, if compliance and initial titration, whether it’s consistent with your clinical trials?

Jan Mikkelsen, CEO

Yes. It’s a question we tried to address before. But I think, Sherrie, you’re also sitting with a lot of data. Potentially, you can somehow describe the limitation that we have in our data set, really, to answer that question today.

Sherrie Glass, Chief Business Officer

Thank you for the question, Li. We don't have specific data on the enrollments based on patient severity. However, we do know a few important points. Firstly, as Jan mentioned earlier, the most severe patients are frequently visiting the endocrinologist. This suggests that those severe patients are likely to be among the first to receive prescriptions. Additionally, as Jan pointed out, there are a significant number of uncontrolled patients in the U.S., estimated at 10,000 to 15,000, along with many who are partially controlled. Therefore, as we begin to see more of these uncontrolled and severe patients receiving prescriptions, we recognize there's substantial potential for growth beyond this initial group.

Jan Mikkelsen, CEO

Thanks, Sherrie.

Operator, Operator

Our next question comes from Derek Archila with Wells Fargo.

Unidentified Analyst, Analyst

Hi. This is Yvonne for Derek. Thanks for taking our questions and congrats on the progress. A quick one from us on YORVIPATH. So can you provide some color on what type of docs are prescribing YORVIPATH? Are these, 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 drugs? Thanks.

Jan Mikkelsen, CEO

Yeah. Let me take the last question before I throw it over to Jay or Sherrie. What is happening in our EAP program, the last packet 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 patients that we are converting from our EAP clinical trial over, we’d likely come into commercial drug starting in February and then the majority in March. So that was the second question. And I think Sherrie or Jay, who will take this? Would you start, Jay?

Jay Wu, President, U.S. Market

Sure. Happy to start. I think the question around prescriber breadth, I think, as we mentioned before, 539 across 44 states. We’re seeing that pretty broadly across all different types of physicians, across all deciles. Naturally, you would expect directionally, physicians that are treating perhaps a greater number of patients, right, 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 physicians. So I think naturally, you’re going 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 this.

Sherrie Glass, Chief Business Officer

And maybe I’ll just add that what is really exciting is that we see that we’re broadening a lot beyond the NATPARA prescribers. So of the 539 physicians, only about 200, a little less than 200 had prescribed NATPARA. So we see that we’re really broadening our reach.

Jan Mikkelsen, CEO

Thanks.

Operator, Operator

Our next question comes from Yaron Werber with TD Cowen.

Yaron Werber, Analyst

Thank you very much. I have a couple of questions for you, Scott. Jan, feel free to chime in if you'd like to address the next one. Scott, you mentioned that towards the end of the year, reaching cash profitability could be possible. Is that still the case, and what factors will contribute to that? Will YORVIPATH be the main driver? Additionally, regarding reimbursement for YORVIPATH, do you anticipate that prior authorizations will be necessary over time, or do you expect no prior authorizations at all? Thank you.

Jan Mikkelsen, CEO

Okay. I think Scott would like to say something.

Scott Smith, CFO

Yeah. I think you’re exactly right. YORVIPATH will be a big driver of the 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. and it’s a very profitable product. So I think we agree that that’ll be a strong driver of breakeven potential this year.

Jan Mikkelsen, CEO

Yes, I believe it’s important to consider that the figures we’re presenting today pertain to the U.S. market, but we are also implementing a global strategy. By the end of this year, we are poised to significantly ramp up our efforts in our direct markets in Europe. The international market is also beginning to show substantial engagement. I foresee that 2026 will be a pivotal year, as many countries aim for full launches. However, 2025 will mark the initiation of our efforts in at least five additional direct European countries, as well as a focus on our international market. While the U.S. market is fast and has considerable penetration potential due to its size, it's important to note that the number of patients with hypopara outside the U.S. is exponentially larger, possibly four to five times greater than in the U.S. Jay, do you want to take that?

Jay Wu, President, U.S. Market

Yeah. Sure. I mean, from a prior auth standpoint, I think the question was, what do we expect for YORVIPATH? It is a specialty product and I anticipate there to be some basic questions, even if it’s simple as who’s prescribing it, right? I think whether it’s an endocrinologist, whether it’s a nephrologist, etc. 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. I 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 auths 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.

Operator, Operator

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

Joori Park, Analyst

Hi, I’m Joori Park dialing in for Joe. Thank you for taking our questions. I believe in the last earnings conference call, you mentioned that in Germany, physicians are prescribing YORVIPATH to one to two of their patients, whereas in the U.S., you are expecting physicians to prescribe the drug to two to three of their patients. And based on the metrics that you provided today, it seems like on average, each physician is prescribing a drug to a little over one and a half of their patients. So I was just wondering if you’re still expecting each physician in the U.S. to prescribe YORVIPATH to about two to three of their patients? And where does it go from there?

Jan Mikkelsen, CEO

I believe what I previously stated still holds true. The current trend indicates that we are in the early stages of the launch. I've tracked several physicians involved in our early access program and clinical trial, and some of them have already prescribed the medication to as many as 20 patients. It's clear that usage will expand over time. However, this is still an early launch, around one to two months in, so I anticipate seeing growth in prescriptions in the near future.

Joori Park, Analyst

Okay. That’s helpful. I have a clarifying question. Are any of the 908 prescriptions included in the YORVIPATH sales from 2024, considering the drug was available in mid to late December? Thank you.

Jay Wu, President, U.S. Market

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

Jan Mikkelsen, CEO

Yeah. So in practical, no.

Operator, Operator

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

Kelly Shi, Analyst

Congrats on the great quarter. And on the manufacturing front, how should we think about the capacity to meet the increasing demand of YORVIPATH throughout the year? Thank you.

Jan Mikkelsen, CEO

Yeah. I think one of the things we have been very, very proud of at Ascendis is really our robust supply chains. And 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 requirements for all issues for having, for example, the scratch over brand. And when I look at the YORVIPATH, we’re using the same solid supply chains, the same infrastructure. We follow the same way. I personally get a weekly report on every compound in every region, in every place where we are selling product, how many months that is on storage. And we some way 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.

Kelly Shi, Analyst

Thank you.

Operator, Operator

Our next question comes from the line of Ellie Merle with UBS.

Ellie Merle, Analyst

Hey, guys. Thanks so much for taking the question and congrats on the launch progress. Just in terms of how we should think about the U.S. YORVIPATH script cadence, I guess, sort of what’s the latest that you’re seeing in terms of the cadence of new starts? Are you sort of seeing a steady number of adds 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.

Jan Mikkelsen, CEO

I think the question related to what we call control to party control and patient we have somebody answer this to our best of knowledge. We have no clear data of the patients that have already received a prescription. We have a gut feeling and the gut feeling is that we believe many of them belong to the uncontrolled part because they see the endo in a much higher frequency than anyone else. Related to the pattern of 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 a pattern being developed. We don’t believe that there’s really a huge bolus coming in because there is not a huge availability by the endo really to come in and say, oh, I just want to have an appointment run into an endo and now I have a prescription. It’s not like that. It is, like, Aimee sitting here. If you want to see Aimee, our CMO at Stanford, it takes how many weeks now, Aimee? 12. 12 weeks to see her. So it takes a little bit of time to get an appointment. So we don’t believe that it’s a lot of build-up demand. It basically is patients that come in and have the need to be on a treatment. And I think it’s pretty obvious for me when I see the benefit of all the patients get, yes, everyone should have a treatment option and come on PTH like everyone on type 1 diabetes should have insulin. This is hormone replacement therapy in this perspective. Related to the reimbursement system, I do not know, Jay, if you have further comments, compared to that.

Jay Wu, President, U.S. Market

Yeah. As we mentioned before, because this is such early days, I don’t think we would be able to draw a meaningful pattern or a trend based on just the 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 on an exception by exception basis and we believe that after at least a few more months, we’ll have a better sense of how these policies shake out and what that more stable trend should be.

Operator, Operator

Our next question comes from the line of David Lebowitz with Citi.

David Lebowitz, Analyst

Thank you for taking my question. First on SKYTROFA, 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?

Jan Mikkelsen, CEO

Yeah. I think Aimee can explain on the unmet medical need that really exists in adult growth hormone deficiency. From my perspective, there are two key things I really, in some way, are reflecting over a lot. First of all, it’s an error with extremely low penetration to our best knowledge, it’s under 5%, 6%, 7%. So you can say there is a huge opportunity for growth. And the other thing is that has been a huge burden basically to be in treatment with daily growth hormone. But Aimee, you can explain and tell about what is really the unmet medical need, the burden of having adult growth hormone deficiency.

Aimee Shu, Chief Medical Officer

Many individuals develop growth hormone deficiency in adulthood due to issues related to the brain, such as tumors or cancer and its subsequent treatments like surgery or radiation, which accounts for at least half or more of these cases. Often, these patients are missing pituitary gland function and need multiple hormone replacements, with growth hormone being one of them. They have expressed a desire for simpler solutions that the community can provide, recognizing the benefits this would have on their metabolic and overall endocrine health. However, their primary concern remains the critical hormones from the adrenal and thyroid glands, which must not be overlooked and are typically taken as pills. After addressing those, patients are open to considering less frequent injectable therapies, understanding the health benefits. While growth hormone deficiency isn't life-threatening in the same way that missing thyroid or adrenal replacements is, we believe there’s an opportunity here. Growth hormone replacement should be considered if it aligns with patient expectations, as we think they would welcome it.

David Lebowitz, Analyst

Thank you for that. And just jumping over to YORVIPATH. 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?

Jan Mikkelsen, CEO

Yeah. If you reflect on pivotal data, I don’t think there is anyone else than one compound, the amyloid compound. And to our best knowledge, when we talk with centers, the last patient in was in the beginning of November. So I’m still waiting to see the results of the pivotal trial. It’s a small trial with a little bit more than 100 patients. So it shouldn’t take too long time to clean the data and come up with the topline data. But I have not seen anything else. When I go back to the science and one of our key values, this is not a hormone replacement therapy. This is a substitution of the long-acting effect, where you basically are placing part of the receptor system into a fixed position and therefore have a long-acting effect. It’s not even reflecting the normal biology where you are basically activating both the PTH1 receptor and the PTH2 receptor. And by doing the different mode of action, you already can see from the data that it can never substitute as a hormone replacement therapy element where you see it’s not restoring normal function, for example, in the kidney, for example, related to phosphate excretion. 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 hemogenic potential that is in the compound. So we are looking forward to seeing the data. We would like to see the data and we hope one day it will come out. There should be out there now because it’s so long time since the last patient came into the visit.

Operator, Operator

Our next question comes from Paul Choi with Goldman Sachs.

Paul Choi, Analyst

Hi. Thanks. Good afternoon and congrats on the early launch success with YORVIPATH in the U.S. My first question is on YORVIPATH. And as we look at consensus numbers, the street is modeling less than 900 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 not and the reimbursement is a work in progress, just your level of comfort with the street revenue number for the full year possibly or any color around that would be great. My second question is regarding CNP and the hypochondroplasia 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? Any color there would be helpful. Thank you very much.

Jan Mikkelsen, CEO

Yeah. Let me take the first part together with Aimee, because we are really dedicated to be the leader in growth result. And when we see the two cornerstones we have, TransCon Growth Hormone and TransCon CNP, we really will do the best for the patient in each case. How can we design an optimal treatment in this way? And what we’re doing now in hypochondroplasia is defining what is really the pathway forward for us. Is then just a TransCon CNP treatment or will it be a combination treatment between TransCon CNP and TransCon Growth Hormone? And we are now in a position that we are starting the discussions with regulatory agencies. But I think Aimee can give you a little bit of background. Why we think that when we’re moving into hypochondroplasia, it’s one of many growth disorders we actually would like to focus on, and the actual design can also be a different stage process.

Aimee Shu, Chief Medical Officer

So exactly, we are taking the time to give hypochondroplasia the opportunity it deserves. While some of hypochondroplasia overlaps highly with achondroplasia and the genetic variant arises on the same FGFR3 receptor. The gene changes are very different along that whole receptor and we are understanding that hypochondroplasia 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 much time do we put 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 condition and other conditions of short stature, especially on the skeletal dysplasia genetic side, right, deserve a very good, thorough understanding to find the best way to accomplish it.

Jan Mikkelsen, CEO

We are in this position that potentially we will start both trials at the same time, and CNP and a combination trial, and then we will basically evaluate the data and find out that potentially we will go for an approval for both, and then they can choose the optimal treatment from the position, how the best can serve the patient needs in this way. If they really want to have a much more extensive linear growth, likely the combination therapy will be the preferred option. Related to your last first question, I think we said in Scott’s 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 and likes to talk with people, so I think if there is any element of model discussion, I think he likely will engage in it.

Operator, Operator

Our next question comes from the line of Alex Thompson with Stifel.

Alex Thompson, Analyst

Hey, great. Thanks for taking my questions. I guess on YORVIPATH, I wonder if you could talk a little bit about how titration is working in the real world with patients, whether that requires additional visits with their HCP, etc., if this is done at home? And then maybe could you talk a little bit about your expectations around growth and that stability in 2025 for SKYTROFA? Thanks.

Aimee Shu, Chief Medical Officer

Sure. The first question was about titrations with YORVIPATH. From what we’ve seen so far, this is a key area for endocrinologists. They are skilled in titrating medications. However, I don't have direct oversight of each prescriber’s practices on a weekly basis. So far, they seem to find the process straightforward and have received the guidance they need. The occasions when we might interact with them would occur as they transition between different dose pens, but we don't have that detailed insight yet. Anecdotally, it appears that endocrinologists are well-equipped to manage this process.

Jan Mikkelsen, CEO

At least what we have seen now, but being in the market in Germany for one year now, we are not seeing any issues to the titration and patient-physician field that is not complicated and an easy element to do it, and they’re getting up on conventional therapy exactly at the same speed that we saw in our clinical trials, which surprised me a little bit that they’re doing in the same speed as we do when we have much more regional framework for a patient to come into and talk with the physician. It’s the same thing happening in real life. They’re out of conventional therapy extremely fast.

Operator, Operator

Our next question comes from the line of Yun Zhong with Wedbush Securities.

Yun Zhong, Analyst

Excuse me. Good afternoon. Thank you very much for taking the questions. The first one on YORVIPATH. 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 from the U.S., please?

Jan Mikkelsen, CEO

That’s a good question. We will decide when we come to that state exactly how we report the data.

Yun Zhong, Analyst

Okay. Then follow-up question on the SKYTROFA. I believe what I heard was that the adjustment has largely been over for 2024, but you haven’t really given any guidance, unlike in January last year, you put out the guidance for 2024. And are there any uncertainties surrounding the schedule? Is that related to the adult launch or more related to the pediatric market, please?

Scott Smith, CFO

Thank you for the question. We anticipate that revenue growth will continue to align more closely with script growth moving forward, provided there are no significant changes in payer mix. This expectation is mainly due to the absence of major contracting changes when compared to last year.

Operator, Operator

That’s all the time we have for questions today. This concludes today’s conference call. Thank you for participating. You may now disconnect.

Jan Mikkelsen, CEO

Thank you. Bye-bye.