Ascendis Pharma - Earnings Call - Q4 2024

Transcript

Operator (participant)

Good day, and thank you for standing by. Welcome to the Q4 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. To ask a question during the session, you'll need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. 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. Please go ahead.

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 assets, and our expectations with respect to their continued progress and potential commercialization, our strategic plans, partnerships, and investments, our goals regarding our clinical pipeline, including the timing of clinical 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 in 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 12th, 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 will discuss our full year 2024 financial results and will 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 (President and 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 substantial, with revenue reaching around EUR 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 indication and countries, we expect sustained value creation for the TransCon growth hormone franchise in the coming year, as outlined in our Vision 2030. Importantly, Yorvipath, the only FDA-approved treatment for hypoparathyroidism in adults, is now launched in the U.S.

And has already begun to establish itself as the new standard of care. Given the long-standing 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 hypoparathyroidism 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 FDA, we are on track to submit an NDA to FDA this quarter, followed by an MAA submission to the EMEA in the Q3 this year. All three of these endocrine rare disease medicines demonstrate the value of our TransCon technology platform and its potential to address major unmet medical needs with highly differentiated products. We are also bringing the TransCon technology platform beyond endocrine rare diseases. In large patient population, through our collaboration with Novo Nordisk in metabolic diseases such as obesity, type 2 diabetes, and cardiovascular diseases, in addition 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 continued revenue growth. Let me review our key programs in rare endocrine disease in more detail. In the U.S., Skytrofa was launched just over two years ago. Today, it 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 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, SHOX deficiencies, Turner syndrome, and SGA. In the Q3 of this year, we plan to submit an IND application for this basket trial to the U.S. FDA. Planned commercial launches across multiple countries. In 2024, SKYTROFA volume increased 84% in the United States, with premium net pricing of 3x compared to once-daily growth hormone. SKYTROFA achieved revenue of around EUR 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 assess this long-awaited treatment option. Hypoparathyroidism represents a large global market opportunity for Ascendis to address a major unmet medical 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 and risks of conventional therapy and the clinical benefits seen with our PTH treatment. In the U.S., we estimate there are about 70,000-90,000 patients with chronic hypoparathyroidism, most of whom are currently using conventional therapy of oral calcium and active vitamin D. Our claims analysis demonstrates that 10,000-15,000 of these U.S. patients are uncontrolled and 30,000-35,000 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 in the U.S., Yorvipath launched. Initial demand is strong, with 908 patients with prescriptions as of February 7, 2025. This includes prescriptions from 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 approval will take about four-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 Europe's direct 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 include 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' data from our Phase 2 path forward trial, and later this year, we plan to present four years' 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 excretion. The data also showed sustained improvement in kidney function.

Listening 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 length 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 hypotensive effect, supporting TransCon CNP's potential as a best-in-class treatment for achondroplasia.

Following our productive pre-NDA meeting with FDA, we plan to submit an NDA for the treatment of achondroplasia during the Q1 of 2025 and submit an MAA for treatment of children with achondroplasia to the EMEA during the Q3 of 2025. We believe TransCon CNP will be setting a new bar for 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 outcomes in achondroplasia and other growth disorders. We look forward to sharing top-line week 26 results from phase 2 cohort trial of TransCon CNP in combination with TransCon Growth Hormone, which we expect in the Q2 of 2025.

Additionally, during the Q4 of 2025, we plan to submit an IND or similar to investigate TransCon CNP alone and in combination with TransCon Growth Hormone for the treatment of hypochondroplasia. Looking to how we are expanding our pipeline in endocrine rare disease, we are expanding into additional product candidates beyond our first three successful medicines, as we disclosed at the J.P. Morgan conference. In addition, we continue to broaden the reach of our platform outside endocrine rare disease and through collaboration in therapeutic areas affecting much greater patient numbers. For oncology, our internal development will continue to focus on TransCon IL-2 beta-gamma, aiming for accelerated approval in one or more indications. In early 2024, we announced the formation of Eyconis to explore the development of TransCon-based therapies in ophthalmology.

In November, we announced a multi-product collaboration with Novo Nordisk covering metabolic and cardiovascular diseases with a lead program to develop once-monthly TransCon semaglutide. This entitles us to escalating tiered mid-single-digit royalties on global net sales of approved products. Finally, as I mentioned earlier, we have expanded TransCon to incorporate protein degraders, a technology with very promising potential within as well as outside rare endocrine diseases. Ascendis today, with approved commercial products, 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.

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 Q4 and full-year financial results, but for further details, please refer to our 20-F file today.

Skytrofa volume increased 37% in the Q4 of 2024 compared to the Q4 last year, while reported revenue was €58.5 million compared to €64.2 million reported in the Q4 of 2023. In the Q4 this year, Skytrofa revenue benefited from volume growth and a favorable sales adjustment of EUR 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 EUR 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, Q4 Yorvipath revenue increased to EUR 13.6 million, bringing total 2024 revenue to EUR 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 top line, total revenue for the Q4 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, the 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 spinoff. 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 Q1 of 2025 to preserve approximately 200,000 ADS held as treasury shares. With that, operator, we are now ready to take questions.

Operator (participant)

As a reminder to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. In the interest of time, we ask that you limit yourself to one question and one follow-up. Please stand by while we compile the Q&A roster. Our first question comes from Jessica Fye with J.P. Morgan.

Jessica Fye (Managing Director and Equity Research Analyst)

Hey, guys. Good afternoon. Thanks for taking my question and congrats on the strong Yorvipath script number and breadth of prescribers. 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 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 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.

Jan Mikkelsen (President and CEO)

Thanks, Jessica, a lot for the questions. I think we can confirm nearly all the answers. So Jay and Sherrie, will you confirm all the numbers so we're sure?

Scott Smith (CFO)

Happy to. Jessica, thank you for the question. The first part of your question, from an enrollment standpoint, we can confirm that it 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 to eight weeks. That is our estimate of what we think it should take. But keep in mind, too, that based on the time frame 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. So we'll need more time to get a better sense of that, but that is our initial estimate today.

Jessica Fye (Managing Director and Equity Research Analyst)

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

Jan Mikkelsen (President and CEO)

We have not broadened that number down. It is 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 in France, a non-promotional program that also is enrolling reimbursed patients. And then we have our international market in this way. The patient numbers are increasing exactly as we have expected, but we have not broken down the numbers.

Operator (participant)

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

Tazeen Ahmad (Security 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 (President and 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 patient group, which we call the 10,000-15,000 patients, which we will call not controlled 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 out from 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 setup 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 on label, 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 (Security 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. Is that still the plan?

Jan Mikkelsen (President and 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 launches 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 confident. Scott always liked 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 foundation to build up a solid model in your own way. Comments from you, Scott?

Scott Smith (CFO)

Yeah. 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 (participant)

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

Gavin Clark-Gartner (Managing Director and Biotechnology Equity Research)

Hey, guys. Congrats on the very strong progress so far. Just had one question on 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, 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 Q2, can you just remind us your expectations specifically on AHV? Thank you.

Jan Mikkelsen (President and CEO)

Yeah. 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 most of the criteria, and I have been really pleased how they are aligning to the labeling, but I believe Jay will come up with further comments related to the commercial contracting landscape.

Scott Smith (CFO)

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. 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 PA is consistent with 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 (President and CEO)

So the CNP question is always looking in the crystal ball because you asked me, as what is your expectation for the data you have not really seen. And the first time, to my knowledge, anyone has done a combination trial in achondroplasia, a Phase 2 trial between TransCon CNP and growth hormone. Why I think it's really, really interesting because it's two different compounds with very different physiological mode of action. If I ever believe in science, which I always do a lot, it should be a great combination because it's a synergistic pathway.

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 high 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 high velocity.

And when I look on all the data, it likely is going around 5.5 to 6.0 on annualized height velocity, which basically is reflecting a little bit what the science also will say. You are removing 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. Suddenly, 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?

Scott Smith (CFO)

That's helpful. Thanks, guys. We'll leave it there for now. We don't know.

Operator (participant)

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

Li Watsek (Director)

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 of compliance and initial titration, whether it's consistent with your clinical trials.

Jan Mikkelsen (President and CEO)

Yes. It's a question we tried to address with before, but I think, Sherrie, you're also sitting with a lot of data potential. You can someway describe the limitation that we have in our dataset really to answer that question today.

Sherrie Glass (Chief Business Officer)

Sure, and thanks for the question, Li. So 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, as Jan said earlier, the most severe patients are going most frequently to the endocrinologist. 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 as Jan also mentioned, there are a number of those uncontrolled patients in the U.S. There's 10,000 to 15,000 of them, and then a number more of 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.

Jan Mikkelsen (President and CEO)

Thanks, Sherrie.

Operator (participant)

Our next question comes from Derek Archila with Wells Fargo.

Yvonne Cruz (AVP and Business Execution Consultant)

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

Jan Mikkelsen (President and CEO)

Yeah. Let me take the last question before I throw it over to Jay or Sherry. What is happening in our EAP program? The last batch I got was a three-pack of basic three months, and some of them got them in December into January. So the 100-plus patients that we are converting from our EAP clinical trial over will 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 the, will you start, Jay?

Jay Donovan Wu (President of Ascendis U.S. and EVP)

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 decile.

Sherrie Glass (Chief Business Officer)

And maybe I'll just add to that that what is really exciting is that we see that we're broadening a lot beyond the Natpara prescriber. 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 (President and CEO)

Next.

Operator (participant)

Our next question comes from Yaron Werber with TD Cowen.

Yaron Werber (Managing Director and Senior Biotechnology Analyst)

Right. So thanks so much. 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 reach profitability on a cash basis. Does that still sort of hold? And what would drive that? Is it going to be Yorvipath is the biggest driver? And then secondly, as you think about reimbursement for Yorvipath, are you expecting with time prior authorizations, or are you expecting not to have any prior auths? Thank you.

Jan Mikkelsen (President and CEO)

Okay. I think Scott will 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 break even. 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 break-even potential this year.

Jan Mikkelsen (President and CEO)

Yeah. But I also believe you need to look at the U.S. in the numbers we're giving you today. But we basically have a global effort. And we're also seeing that by the end of this year, we're starting to take it to a much, much higher gear in our European direct countries. We will also see the international market is starting to really, really get engaged. I expect 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 2025 will be where we start in both Europe directly in at least five countries more, but basically also our international market. So the U.S., sure, is a fast market. It's a fast penetration we can get because it's so large single market. So sure, it will dominate in the beginning of the year. But just remember the number of patients outside the U.S. with hypoparathyroidism is so much, much, much larger, perhaps four, fivefold than what you have in the U.S. The second one, will you take that?

Scott Smith (CFO)

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 (participant)

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

Joori Park (Equity Research VP)

Hi. I'm Joori Park 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 the 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 (President and CEO)

Yeah. 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 were part of our EAP and clinical trial. And some of these physicians have been already making prescriptions up to 20 patients. So I'm no doubt the boldness of that will come, but in some way, this is an early launch, one to two months in the launch. So I would expect that to see and come in the future.

Joori Park (Equity Research VP)

Okay. Great. That's helpful. And then a clarifying question. Are any of the 908 prescriptions included in the Yorvipath sales from 2024, considering the drug was available mid to late December? Thank you so much.

Jan Mikkelsen (President and CEO)

Scott.

Scott Smith (CFO)

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

Jan Mikkelsen (President and CEO)

Yeah. So in practice, no.

Operator (participant)

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

Kelly Shi (SVP and Senior Research Analyst in Biotechnology)

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

Jan Mikkelsen (President and CEO)

Yeah. I think one of the things we have been very, very proud of is 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 requirements for all visions for having, for example, the Skytrofa brand. And when I look on the Yorvipath, we're using the same solid supply chains, the same infrastructure. We follow it 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. We somehow are taking that as a really serious thing because we will never be in a position that we will go short. That is our vision, and I hope we never come to this position.

Kelly Shi (SVP and Senior Research Analyst in Biotechnology)

Thank you.

Operator (participant)

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

Ellie Merle (Executive Director and Biotech Equity Research)

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 (President and CEO)

I think the question related to what we call non-controlled to partly controlled and patient we have somewhat answered is to our best of knowledge. We have no clear data of the patients that already have 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 on prescription, we are not breaking it down in weeks or anything.

This is something we are following very, very, very tight. And we would like to see a pattern being developed. We don't believe that's really a huge bolus coming in because there is not a huge availability of 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 life is that like Aimee's sitting here. If you want to see Aimee, our CMO at Stanford, it takes how many weeks now, Aimee?

Aimee Shu (EVP and CMO)

12.

Jan Mikkelsen (President and CEO)

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 built-up demand. It's basically patients that come in and have the need to be on a treatment. 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 everyone on type 1 diabetes should have insulin. This is a hormone replacement therapy in this perspective. Related to the reimbursement system, I do not know, Jay, if you have further comments compared to that.

Scott Smith (CFO)

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 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 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. 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.

Ellie Merle (Executive Director and Biotech Equity Research)

Great. Thanks.

Operator (participant)

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

David Lebowitz (Senior Research Analyst of Biotechnology)

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 (President and CEO)

Yeah. I think Aimee can explain on the unmet medical need that really exists in adult growth hormone deficiency. From my perspective, there's two key things I really somewhat are reflecting over a lot. First of all, it's an area with extremely low penetration to our best knowledge is 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 on the 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 (EVP and CMO)

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 at least 50% 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. They have oftentimes said, "If it's something we can make simpler, right, that the community could provide more simply to them, it is something they would consider knowing that it adds to their metabolic health and overall endocrine health," right?

But of course, their first priority always are the two life-saving hormones from the brain, that is, from the adrenal gland and the thyroid gland. Those you can't forget, and those are pills. 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 the way that if you don't take thyroid or adrenal replacement is. We think we're in a nice sweet spot here. It's a hormone that should be replaced, and if it meets patients' expectations, we think there would be a take.

David Lebowitz (Senior Research Analyst of Biotechnology)

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 (President and CEO)

Yeah. If you reflect on pivotal data, I don't think there is anyone else than one compound, the Amolyt 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 a top-line data. But I have not seen anything else. When I go back to the science at 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 a 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 PTH-1 receptor and the PTH-2 receptor. By doing the different mode of action, you already are from the data can see that it can now substitute as a hormone replacement therapy. One element where you see it is not restored normal function, for example, in the kidney related to phosphate excretion.

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. Then I'm not talking about the immunogenic potential that is in the compound. 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 (participant)

Our next question comes from Paul Choi with Goldman Sachs.

Paul Choi (Biotechnology 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 the reimbursement is a work in progress, just your level of comfort with the street, a 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 and enrollment? Any color there would be helpful. Thank you very much.

Jan Mikkelsen (President and CEO)

Yeah. Let me take the first part together with Amy because we are really dedicated to be the leader in growth disorder. 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 the States. 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 that just a TransCon CNP treatment, or will it be a combination treatment between TransCon CNP and TransCon Growth Hormone? We are now in a position that we are starting the discussion with regulatory agencies. But I think Aimee can give you a little bit of the background why we someway 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 (EVP and CMO)

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.

Jan Mikkelsen (President and CEO)

And we are in this position that potentially we will start both trials at the same time and CNP in a combination trial. And then we will basically evaluate the data and find out that potentially we will go for an approval for both. Then they can choose the optimal treatment from the physician, 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. 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 (participant)

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

Alex Thompson (Managing Director of Biotechnology)

Hey, great. Thanks for taking my questions. I guess on Yorvipath, I wonder if you could talk a little 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 about your expectations around growth and that stability in 2025 for Skytrofa? Thanks.

Jan Mikkelsen (President and CEO)

Aimee, would you take the first?

Aimee Shu (EVP and CMO)

Sure. The first question was about titrations with Yorvipath. From what we've heard so far, right, this is in the domain, this is the sweet spot for endocrinologists. They know how to titrate medicines. So, we are, but that being said, I'm not sitting on the shoulder of each prescriber, and I can't see what they're doing week to week. I think so far they have found it 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.

Jan Mikkelsen (President and CEO)

At least what we have seen now, but being in market in Germany for one year now, we are not seeing any issues to the titration. And patient physician feel that it's not complicated and easy element to do it. They're 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 it at the same speed as we do when we have much more rigid 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 (participant)

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

Yun Zhong (Biotech Equity Research Analyst)

Excuse me. Good afternoon. Thank you very much for taking the questions. The first one on Yorvipath. So when you report Q1 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 (President and CEO)

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

Yun Zhong (Biotech Equity Research Analyst)

Then, follow-up question on 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 Skytrofa? Is that related to the gout launch or more related to the pediatric market, please?

Scott Smith (CFO)

Yeah. Thanks for the question. 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 compared to last year, Q4 last year.

Operator (participant)

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