Good morning, everybody, and thanks once again for joining us for the 45th Annual TD Cowen Healthcare Conference. I'm Yaron Werber from the Biotech Team, and it's a great pleasure to moderate the next fireside chat with Ascendis Pharma. To my left, really needs no introduction, Jan Mikkelsen, President and CEO, and to his left needs no introduction, Scott Smith, EVP and Chief Financial Officer. Gentlemen, thanks for joining. We appreciate your. Thanks for having us. Thanks for inviting us. Do you want to make some opening remarks? Go for it. Yeah, this is my favorite part. Yeah, we are. In addition, thank you for the invitation and the great crowd. I would just like to tell everyone, before we begin, I would like to remind you that this presentation contains forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act. Examples of such statements may include, but are not limited to, statements regarding our commercialization and continued development of SkyTrofa and Yorvipath, as well as certain revenue and growth expectations, our pipeline candidates and expectations with respect to their costs, continued progress, potential commercialization success, our strategic plans, partnerships and investments, our goals about our clinical pipeline, including timing and results, and ongoing and planned regulatory filings. These statements are based on the information available to us today. Actual results 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 affect results, please see our forward-looking statement section in our current and future reports filed with SEC, including the Form 20-F filed on February 12, 2025. Anything specific we should read in that? It depends on how late at night it is or if you're on a long flight and you want to get. Yeah, the F filings are my favorite. Well, terrific. I want to maybe start by talking about Yorvi's launch. You know, you've given us a little bit of metrics at the end of last year, and then, you know, obviously early this year, you had 908 new prescriptions. 80% of them were new to Yorvi, up to 500, almost 40 unique providers, only 200 prescribed it prior in the past. So you're really seeing a broadening of the prescriber base. Presumably, the lack of a black box obviously is a big draw to bringing new prescribers in. And I guess my real question is kind of twofold. What kind of patient is coming onto Yorvi now? Is it a switcher? Is it a new patient? And what kind of a physician is now coming to Yorvi? So first of all, we are in our initial launch of Yorvipath here in the U.S. We are addressing a major medical need, the hypoparathyroidism. The patients we are providing treatment for are patients that already are diagnosed with hypopara, so they know this disease. And if any one of you have not really listened to the patient voice, you should try to go and listen to the FDA-arranged PTH hearing of the patient group, where there's a lot of testimony on the burden for having this disease. We launched Yorvipath in Germany, Austria, in January last year. In December last year, we also started the launch in the U.S. In some way, to do our targeting of the physicians that we want to address with our commercial effort, we defined the patients out from the ICD-10 codes because they're already recognized as patients. We, to the honor of Scott, we call something uncontrolled patients and defined them by their way, where we said that they need to see the physician at least five, six, seven, eight, nine, ten, eleven, twelve times a year. At least in the last twelve months, having a medical hospital visit because of hypopara, we call them uncontrolled. The other patient group we call partially uncontrolled is patients that are seeing an endo two, three, four times a year, and in the medical history also have hospitalization because of hypopara. The first group is about 10,000 patients here in the U.S. The second group is about 30,000-35,000 patients. Why did we do that? We did it out from this perspective is that we know because of the limitation of seeing an endo in the U.S., we wanted to be quite sure we utilizing the fact that many patients are seeing the endos with so high frequency, and we wanted to be quite sure that these physicians really could see and learn about the benefit of Yorvipath treatment. So we don't believe that any patient group with hypopara, even if you are controlled, uncontrolled, or partially controlled, is not benefit of having Yorvipath treatment. But we also believe that the initial patient we often get into our system here is coming from the more uncontrolled patients, but not because they have a higher medical need and not getting the right benefit as the rest of the patient population also will get, but because they see the endos so much more often. So from that perspective, we expect a steady state of patients coming on treatment because the pool we are talking about is 10,000 patients uncontrolled, 30,000 to 35,000 patients partially uncontrolled, and they already have predetermined meetings with the endo. So there was our initial effort. We have not reached all the endos yet with our sales effort. We believe in Q2, we will basically have reached the majority of our target endo at that time. So we still are in the initial stage of the launch, and more and more activity is getting started. For example, activity related for physician to physician meeting, telling about the experience they have by having patients on treatment. But what we really see is an extremely successful launch. There's no doubt Yorvipath will provide significant revenue to Ascendis Pharma and also will be the product that basically will bring us into profitability and cash breakeven. Don't forget, it's a life-changing event for these patients, and we really get the testimony for all the patients how they benefit from this treatment. And Jan, how many physicians are in your target majority, target, you know, initial tranche? The initial target is about 6,000-7,000 physicians. And it's managed with our sales force that basically, or I would say it's integrated commercial effort because it's not only sales force. There are also our field reimbursement team. This is our ESSA program. Just remember, we are a company that has been working in rare disease endocrinology for years now with SkyTrofa. We're not working in small rare diseases. We are working in large rare diseases. We are taking more than 10,000 patients to the system, and we are utilizing exactly the same established system. We're not going out to build it up from scratch. We had it already. This is also why we see this successful launch, because we are launching this product, Yorvipath, from an entity that already has the setup, experience, the knowledge, knows what to get done to work with a large amount of patients in rare diseases to medical exceptions. These 67, did they, were they all, I presume, based on practice size or how many patients you think they have in their practice who are, you know, hypopara? Do they cover all the prior and the paraprescribers? Like how much of an expansion is this? Many of the physicians that are doing prescription today, which have written a Yorvipath prescription, are not coming from the same physician that wrote the Natpara one. We are totally expanding out for what we saw with Natpara. So I think one of the things I can give you as a kind of reminder, don't use Natpara as a way to think about Yorvipath. It was a quite different product. It was a product with a labeling as an adjunct basic to conventional treatment, not a treatment labeling as we have with Yorvipath. You didn't see the majority of the benefit we see with Yorvipath with Natpara. So when we see the patients in the U.S., it's a completely different treatment benefit we see compared to being on Natpara, which is also indicating in clinical data labeling everything what we see. Scott, I think you've talked about 10%-15%. I'm going to ask a question about gross-to-net. I think you mentioned 10%-15% of patients are uninsured and maybe qualify for the patient assistance program, but the rest of the patients typically, there is no free drug program, right, for Yorvi. You know, how do you think about maybe gross-to-net patient support, you know, and kind of stability of price? On the government portion, there's mandatory rebates that we can't get around, and those are likely low 20%, right, with Medicaid and now with the new redesign on Part D for Medicare. On the commercial side, I would not expect, at least at this time, to have, let's say, contracting as such, right? And then in the channel, you typically have like low single-digit fees related to the channel. If you go in and do some kind of mix, you can have, I would say, a reasonable estimate of yield per patient. The question on would it be stable, I don't see any reason why, I don't see any reason for disruption in this market. What percentage of the market would you say is commercial? Historically, it's been a higher percent. It's been, I would say, like 70%-80%. We have to see with the new redesign if the cap on out-of-pocket draws more patients in. Which presumably will make it even higher, no? With the redesign, if the cap on out-of-pocket, I would assume more government coming in potentially, but historically it was, you know, close to 80%, at least with Natpara. Got it. Commercial, that is. Yeah. So the Part D redesign will draw patients into Part D, right? But I guess the question, I guess it then becomes, is it a government Part D or is it a government outsourced Part D? Exactly. So it's to be seen. Yeah. When you've launched so far in Germany and Austria, and that was, I think you did EUR 26 million, EUR 27 million, EUR 29 million actually. So essentially you did what Natpara did at peak within, you know, nine months or so. You talked about launching in more territories in Europe, you know, this year. You have distribution in more than 50 countries, and France will have an ATU. I think it has an ATU now. What's the cadence of how fast Europe can grow? Europe is very different compared to the U.S. because it's, say, it's not a single market. When you're getting approval in Europe, for example, many countries are into the EMEA system, then you get approval of all these countries. But that is not the same thing that you are fully reimbursed. Being fully reimbursed is only happening at the immediate time of approval. It is basically that you can launch in Germany and Austria. If you go to other countries outside Germany and Austria, it typically takes 12-24 months after the approval to be fully reimbursed. What we expect to see in 2025 is that besides Germany and Austria, where we are now fully reimbursed, we will see five-seven more countries coming in in the area where we call Europe Direct. Meaning is where Ascendis Pharma has its own sales force established, and it will be large countries like France. France, currently we have a system called AP2. It's a non-commercial system, but fully reimbursed system where the physician can request a patient to come on treatment, but we cannot do any commercial effort. There will be countries like Spain, which are the big country, Italy, and then there will be clusters where we will see Scandinavia, Benelux, and other of these clusters coming into the treatment. Outside the US, outside our effort in Europe Direct, we have a segment called International Market and Europe Indirect. Europe Indirect is mainly the countries to the east of the middle of Europe, so it's basically all the countries starting with Greece, Poland coming out. These countries, together with the international market, are going to the same system where we will expect multiple countries, and this is about 45 to 50 countries, will start to be reimbursed in 2025 and fully reimbursed in 2026. We still have a lot of patients in this area, but it's to a system called Named Patient Program. This is where physicians make Named Patient Programs for each single patient and then have a reimbursement on that, typical back to German list prices on it. For example, in Greece, we have more than 100 patients on treatment now on basic Named Patient Program systems. When we talk about revenue generation, the U.S. is unique, a large single market, which can be penetrated fast. If I look outside the U.S., there are many, many more patients, perhaps four, five, six times the number of patients, but the penetration is much more slow. So what we expect to see in 2025, we start to see it pick up a little bit. 2026, really starting to be more and more penetrated, and then we will see the after 2026, we will see the full commercial effort in about 55 countries where we will be. So therefore, we are in the initial launch. So the U.S. will be the driver, main driver in the initial years, and then you will see the rest of the world pick up, mainly because of the time it takes to be fully reimbursed in all these different countries. Yeah. And maybe, Scott, for you, when you're using, you know, sort of commercial partners in some of these sort of, you know, secondary tertiary markets, it's not going to be direct. Is that a percentage of sales that goes to them? Or how are these contracts typically written? So we would. We sell product to them. They put in purchase orders and we sell product to them periodic, right? So it'd be like once a quarter or twice a quarter. At a negotiated price, and then they have their margin based on that. Correct. Got it. Maybe, Jan, to you, the eneboparatide CALYPSO data is coming up. My question is, when we look at across studies at the composite endpoint and the albumin-adjusted serum calcium, there have been ranges like Natpara used 7.5-10.6. I think Yorvi used 8.3-10.6. Eneboparatide in a previous study used 7.8-9, right? So each one had slightly different. I think eneboparatide is now, you know, harmonized with your endpoint more or less. I think there's slightly difference on the minimum sort of calcium per day requirements. Why is there a range in the endpoint? Yeah, I think when we look in our phase II trial and phase III trial, we used exactly the same serum calcium in both trials because you typically use phase II to deal with risk of phase III. So you're not going into a phase III with a major risk. When you talk about the CALYPSO trial, the baseline went down to 7.8 in the phase II trial. And if I look on the data, which are somewhere a little hard to look at in this perspective, but it looked like a big portion of the patients were not qualified to be up on 8.3 at that stage. For me, it's somewhere. It's not really a de-risking of the phase III because I believe all pivotal trials or phase III trials need to be run between 8.3-10.6 because that is more or less, from a regulatory perspective, being defined as a normal level of serum calcium. You can initiate treatment in a lower amount on it, but the endpoint needs to be fulfilled 8.3-10.6. Yeah. And across studies, you each had a different criteria as to how you're reducing the background meds or the standard of care. They're also dosing higher in the phase III than they did in the phase II. In the phase II, they did have a slightly higher serum calcium reduction than you did. They obviously also had immunogenicity, which I'll come back to. But why do you think they've had a higher serum reduction, serum urinary calcium reduction? First of all. Not serum, urinary calcium. Yeah. One of the things is when we talk about treatment of hypopara, it constitutes three pillars. You give back the missing part. You give back the hormone that they're missing. And if you have hypopara, you're missing native PTHs. So what we're giving back is basically the active part of PTH molecule, which gives exactly the same biology as endogenous PTHs. Then you need to give back in the same physiological level, 24 hours, seven days a week. And then you also need to be sure that it's distributed in the same amount in the body as the endogenous PTHs do because typical endocrine diseases are multi, multi-organ. So you need to basically be in many different organs in the body. So when I look on the Amolyt compound, it has nothing to do with PTHs, normal biology. It's basically the PK as a short-acting PTH molecule like Tymlos, like Forteo, which have half-lives for two or three hours in the body. So then you can say, why can it have a more long-acting effect? It's because when you look on the biology of a normal PTH molecule, it both activates the receptor and then it also activates inside the cell. So what you did when they generate Tymlos, and it's basically leading up to the next discussion you had about ADA, it's a fusion peptide between PTHs and PTH-related hormone. Then you fuse these two peptides, and then you make multiple mutations into the molecule. One of these mutations it does is basically fix the receptor configuration in the signal pathway inside the cell. From that perspective, it is that when we look on the body, it's never providing the same benefit as endogenous PTHs. For example, when you look on different biological systems, for example, phosphate clearance, one of the elements of comorbidity in hypopara is basically the element of cardiovascular issues because of high calcium phosphate complex. And when you measure their data, you can see they only measure phosphate after two hours because that is the same as PK, because this is where you have the active on the membrane system, because that is the one that promotes phosphate clearance. So when you look on the CALYPSO data on calcium phosphate complex, they basically are not eliminating the risk factor, which is really one of the high-risk, long-term risks of having hypopara, is calcification. The other part is they're not really doing the remodeling on the bone because of the same reason. What you have in hypopara, you have an unnatural bone density that has a higher bone density because in a typical normal person like Scott, his entire skeleton will be taken over by remodeling in five or six years. It's not happening in hypopara. So therefore, you get a bone structure that is not healthy. And it has a high bone density. And that really changes when you normalize PTH level. So you get a normal bone structure again. But why is that important? And this is why we have a problem with calcium. Because if you look at calcium homeostasis, how the body really has a normal way to deal with calcium is that you have three major components. First, uptake from the intestinal system when you eat food, and that is happening with active vitamin D from the kidney. Then you have the kidney reabsorption, and then you have the skeleton. The skeleton is the key element of having calcium reservoir in the body. But when you cannot do anything with the bone, you basically, when you have no calcium to take from the food or anything like that, where do you get the calcium from? And this is why we have a problem with calcium homeostasis in it. So everything is pretty clear from the mode of action, biology, and everything like that. And this is what I like with science. You cannot cheat science, but sometimes you cannot really understand science in the beginning until you see more data coming out, and then you go to the next realization. Okay. Maybe a quick question, Scott. Do you recall what the latest consensus is for Yorvi? I'm going back to Yorvi commercial kind of outlook. Yeah, for Q1, it's EUR 29. Okay, so it's kind of flattish quarter over quarter. For Yorvi? Yeah, Yorvi. That's for the quarter. Last year was 29. Oh, I'm sorry for the year. EUR 13.6 to EUR 29 for Q1. Yeah. And what about for the year for Yorvipath? I think, yeah, I better not say it because I don't remember the latest for the year. I think it was 2.16 at around the beginning of the year. Correct. Correct. Yeah, it's gone up a little bit, but I don't want to say for sure because I don't remember. It's probably 2.40-ish is what I'm thinking. Yeah. I remember on the 2.16, again, you have not given guidance, obviously, but I felt that you remember just for everybody, Natpara and the U.S. peaked again, obviously different product at around 2.50 or so, right? 2.74, 2.45 or so. And you essentially did what Natpara did a year or three in Europe, a year or five or four in Europe in one year. So if we kind of back triangulate and of course the price is higher as well and obviously a much bigger prescriber, I guess putting it all together, I kind of felt you felt okay about the 2.16. How are you feeling about the 2.40? Maybe I should say it like Jan said at our dinner. In one year, we accomplished what took Natpara in four years in Europe. That's a good challenge for us to do the same thing in the U.S. What are the key barriers? Is it just switching patients? I mean, obviously expanding the market. How fast are you able to switch patients off Natpara also at the same time right now? The Natpara patients, which we believe that is about 300-400 patients on, the majority of these patients are still on Natpara. They got a letter here in Q1 where they're saying is that Natpara is starting to stop delivery. So we expect that it will be happening in Q2, Q3 in the U.S., that the 300-400, we do not know exactly the number, but the 300-400 patients will start switching over. Yeah. Okay. By the way, I've not asked the audience. Any questions from the audience? Go for it. For Yorvi in the U.S. and the EU, the barricade right now on it is obviously the Amolyt drug, but vaguely speaking, you have confidence that orphan drug exclusivity still matters. I'll just repeat it for the webcast. The question essentially is whether you have confidence that the orphan drug exclusivity in Europe specifically, both in the US and Europe, will hold for Yorvi? I take it from a different perspective is that when I see all the available data, it's not a product that any way with the data we have seen yet is providing a benefit to the level of what you see with your patch. So I don't think even we need to discuss orphan drug status, which we have for eight years in both places, as a restriction to do it because that is something you basically will say if you have a product that is equivalent in the same level on it. So I'm not even taking that into the considerations in this way. But you're right. We have eight years of orphan drug status. What would be the mechanism to break an orphan drug designation once it's actually received? You need to have a better product. In a head-to-head study. That is always the definition on. If it's so clear that you don't need a head-to-head study, you can potentially break it, but it always will be better to have it head-to-head. Okay. Maybe final question for me just in the remaining time. In Q2, we're expecting the phase II combo study. This is the weekly subQ combo data, SkyTrofa and TransCon CNP, given weekly. The primary endpoint is the annual growth velocity at 52 weeks. Are you doing a baseline AGV assessment? This is in achondroplasia actually using SkyTrofa plus CNP. Are you doing a baseline assessment to get a baseline AGV or are you doing a change from baseline? I mean, there's no control. That's why I'm asking. Okay. You know, if I'm excited about anything this year from a clinical perspective, this is the Coast trial. Why I'm really excited about it? Because it can take a complete new standard for treatment of our achondroplasia. The science is here for the patients, and if we can make a new standard for treatment as we did with Yorvipath for hypopara, so I really compare a little bit the current treatment like Natpara as what we had in hypopara to what we see in our achondroplasia, and now we're coming with the Yorvipath version in our achondroplasia. What I see with our TransCon CNP, and you can look at the data again, when you address the hypoactive FGFR3 receptor and look at linear growth, all data indicate whatever you do with TransCon CNP, vosoritide, short-acting CNP, tyrosine kinase, you hit about an annualized height velocity of about 5.5-6 centimeters over 12 months. You can cheat a little bit by getting a little bit higher or lower by shorter time or patient organ demographic. But what TransCon CNP was unique, it showed a lot of positive effect beyond linear growth, like leg bowing, muscle strength, and other things. Because only one thing, because we have continuous exposure of CNP, 24 hours, seven days a week, that is providing all the benefit beyond linear growth. What we're doing with a combination trial is like having a car. TransCon CNP is removing the brake on the tyrosine kinase. This is why everyone hits the same growth velocity, because if the car is sitting on a hill, no matter how you remove the brake, it goes up to the same speed. What we're doing by combining with SkyTrofa is that we also take a supercharger. It's how you win a Formula One. Remove the brake, put the pressure on it by the supercharger. And it's not only for linear growth, it's also related to other comorbidity as muscle strength, body composition, everything like else that you look at comorbidity in achondroplasia. And this is why we believe that the Coast trial is the starter for a new standard in treatment of achondroplasia. So, is the goal to then we should compare it to the 5.5-6 of CNP of TransCon alone? The design is simple. We have two arms. We had a problem. We got over-enrolled a lot because we couldn't stop patients coming in. We have two arms, one that has CNP therapy for at least one year. We know the baseline of annualized growth velocity for that is about 5.5-6. Then we have new patients too that come in without any treatment, start directly on SkyTrofa and TransCon CNP. There is a two-arm study. Both of them, we have the pre-annualized height velocity of both of them. And it's one-to-one randomized? No, it's nearly the double amount of the naive, I think. It's not right, Scott. I think I cannot exactly remember the number between the two groups. We'll have essentially control, a CNP control. Yeah. Yeah. Terrific, Jan and Scott. Thanks so much for joining. We appreciate it. Thanks so much for having us. Thank you.