Ascendis Pharma A/S at TD Cowen Healthcare Conference Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Yaron Werber - TD Cowen - Analyst : The F filings are my favorite. Well, terrific. I want to maybe start by I'm talking about YORVI's launch. You gave us a little bit of metrics at the end of last year, and then, 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 NATPARA 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 on to YORVI now? Is it a switcher? Is it a new patient, and what kind of a physician is now coming to YORVI? Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board So first of all, we are in our initial launch of YORVIPATH in the US. We are addressing a major unmedical need, the hypoparathyroidism. The patients, we are providing treatment for our patient 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 is a lot of testimony on the burden for having this disease. We launched YORVIPATH in Germany, Australia, in January last year. In December last year, we also started the launch in the US. To 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 a patient. We -- [I and] Scott, we call something uncontrolled patients and defined them by the way, where we said that we need to see the physician at least 5, 6, 7, 8, 9, 10, 11, 12 times a year. At least, in the last 12 months having a medical hospital visit, because of hypopara, we called them uncontrolled. The other patient group, we'd call partly uncontrolled. This patient that's seeing -- and into 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 US. The second group is about 30,000 to 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 US, we wanted to be quite sure we -- utilizing the effect that many patients is seeing the endos with so high frequency, and we wanted to be quite sure that this physician 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 partly 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 patient. 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 patient coming on treatment because the pool we are talking about is 10,000 patients uncontrolled, 30,000 to 35,000 patients partly uncontrolled, and they already have predetermined meetings with the endo. So that 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. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 04, 2025 / 4:10PM, ASND.OQ - Ascendis Pharma A/S at TD Cowen Healthcare Conference So we still is in the initial stages 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 patient on treatment. But what we really see an extremely successful launch, and there is no doubt YORVIPATH will provide a significant revenue to Ascendis Pharma and also will be the product that [basically] will bring us into profitability and cash breakeven. But 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 for this treatment.

Question: Yaron Werber - TD Cowen - Analyst : In these 6,000 to 7,000, did they -- were they -- they were all, I presume based on practice size or how many patients you think they have in their practice were [hypopara]. Do they cover all the prior NATPARA prescribers? Like how much of an expansion is this? Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board Many of the physician that is doing prescription today, which have written a YORVIPATH prescription is not coming from the same physician that wrote the NATPARA. We 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 you see with YORVIPATH with NATPARA. So when we see the patients in the US, it's a complete different treatment benefit we see compared to be on NATPARA, which also indicating in clinical data labeling everything what we see.

Question: Yaron Werber - TD Cowen - Analyst : And what percentage of the market would you say is commercial?

Question: Yaron Werber - TD Cowen - Analyst : Which presumably will make it even higher now?

Question: Yaron Werber - TD Cowen - Analyst : Got it.

Question: Yaron Werber - TD Cowen - Analyst : 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.

Question: Yaron Werber - TD Cowen - Analyst : Yeah. When -- you've launched so far in Germany and Austria and that was -- I think you did 26 million, 27 million, 29 million actually. So essentially you did what NATPARA did at peak within nine months or so. You talked about launching in more territories in Europe. This year, you'll have distribution in more than 50 countries and France will have an (inaudible) now. What's the cadence of how fast Europe can grow? Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board So Europe is very different compared to US because it's a -- see, it's not a single market. So 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 is basically that you can launch in Germany and Austria. If you go to other countries outside Germany and Austria, it typically takes 12 to 24 months after the approval to be fully reimbursed. So what we expect to see in '25 is that besides Germany and Austria, where we are now fully in reverse, we will see five to seven more countries coming in the air where we call Europe Direct, meaning it's where Ascendis Pharma has its own sales force established. And it will be last country 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 could come on treatment, but we cannot do any commercial effort. There will be a country like Spain, which are the big country, Italy. And then there will be clusters where we will see Scandinavia, Benelux, and all of this cluster coming into the treatment. Outside 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 Greek, Poland coming up. And these countries, together with the international market, is going through the same system where we will expect multiple countries -- and this is about 45 to 50 countries will start to be reimbursed in '25 and fully reimbursed in '26. We still have a lot of patient in this area, but this to a system called Named Patient Program. This is where physicians make Named Patient Program for each single patient and then having a reimbursement on that typical back to German list prices on it. For example, in Greek, we have more than 100 patients on treatment now on basic Named Patient Program systems. And when we talk about revenue generation, US is unique, a large single market which can be penetrated fast. If I look outside the US, there are many more patients, perhaps four, five, six times the number of patients, but the penetration are much more slow. So what we expect to see in '25, we start to see it pick up a little bit, '26 really starting to be more and more penetrated. And then we will see the -- after '26, we will see the full commercial effort in about 55 countries where we will be. So therefore, we are in the initial launch, so US 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.

Question: Yaron Werber - TD Cowen - Analyst : And negotiated price and then they have their margin based on that (multiple speakers) Got it. Maybe Jan to you, the (inaudible) CALYPSO trial data is coming up. My question is when we look across studies at the composite endpoint and the -- plus the albumin-adjusted serum calcium, there's been ranges. Like NATPARA used 7.5 to 10.6. I think YORVI used 8.3 to 10.6. Enebo in the previous study used 7.8 to 9, right? So each one had a slightly different. I think Enebo is now harmonized with your endpoint more or less. I think they're slightly different from the minimum sort of calcium per day requirements. Why is there a range in the endpoint? Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board Yeah, I think when we look in our Phase 2 trial and Phase 3 trial, we used exactly the serum calcium in both trials because you typically use Phase 2 to derisk a Phase 3. So you are not going into a Phase 3 with a major risk. When you talk about the calypso trial, they basically went down to 7.8 in the Phase 2 trial. And if I look on the data which are some little hard to look at in this perspective, but it looks like a big portion of the patients were not qualified to be up on 8.3 at that stage. So for me, it is some way it is not really what a de-risking of the Phase 3 because I believe all pivotal trial or Phase 3 trial need to be run between the 8.3 to the 10.6 because that is more or less being from a regulatory perspective being defined as normal level of serum calcium. You can initiate treatment in a lower amount on it, but the end point need to be fulfilled 8.3 to 10.6.

Question: Yaron Werber - TD Cowen - Analyst : Okay. Maybe a quick question, Scott, do you recall what the latest consensus is for YORVI? I'm going back to your commercial kind of outlook.

Question: Yaron Werber - TD Cowen - Analyst : Okay. So it's kind of flattish quarter on quarter.

Question: Yaron Werber - TD Cowen - Analyst : Yeah, YORVI.

Question: Yaron Werber - TD Cowen - Analyst : Yeah. And what about for the year for YORVI?

Question: Yaron Werber - TD Cowen - Analyst : Yeah, I remember on the 216 you -- again, you have not given guidance obviously, but I felt that. You remember just for everybody -- NATPARA in the US peaked again, obviously different product at around 250 or so, right? 274, 245 or so. And you essentially did what NATPARA did in year three in Europe or year five or four in Europe in one year. So if we're kind of back triangulating 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 216. How are you feeling about the 240?

Question: Yaron Werber - TD Cowen - Analyst : Is there any -- 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? Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board The NATPARA patient, which we believe that's about 300 to 400 patients on the majority of these patients are still on NATPARA. They got a letter here in Q1, where they are saying is that NATPARA is starting to stop delivery. So we expect that it will be happening in Q2, Q3 in the US, that 300 to 400. We do not know exactly the number, but the 300 to 400 patients will start switching over.

Question: Yaron Werber - TD Cowen - Analyst : I'll just repeat it for the webcast. The question essentially is whether you have confidence the orphan drug activity in Europe specifically, both in the US and Europe, will hold for YORVI? Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board I'd take it from a different perspective is that when I see all the available data. This is not a product that anyway with the data we have seen yet is providing a benefit to the level of what you see with YORVIPATHs. 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 basic will say if you have a product that is excellent in the same level on it. So I am not even taking that into consideration in this way. But you're right, we have eight years orphan drug status.

Question: Yaron Werber - TD Cowen - Analyst :

Question: Yaron Werber - TD Cowen - Analyst : Okay, maybe final question from me in the remaining time. In Q2, we are expecting the Phase 2 [code] study. This is the weekly sub combo data SKYTROFA and TransCon CNP given weekly. The primary endpoint is the annual growth velocity of 52 weeks. Are you doing a baseline AGV assessment? This is an achondroplasia, using SKYTROFA plus CMP. 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. Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board Okay, if I'm excited about anything this year from a clinical perspective, this is the (inaudible) trial. Why I'm really excited about it, because it can take a complete new standard for treatment of achondroplasia. The [standard] is here for the patients, and if we can make a new standard for treatment as we did with YORVIPATH for hypopara. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 04, 2025 / 4:10PM, ASND.OQ - Ascendis Pharma A/S at TD Cowen Healthcare Conference So I really compare a little bit the current treatment like NATPARA as what we had in hypopara so what we see in achondroplasia, and now we're coming with the YORVIPATH version in achondroplasia. So what I see with our TransCon CNP and you can look at the data again. When you address the [HyperA2 FDRT] receptor and look at linear growth, all data indicate whatever you do, the TransCon CNP or (inaudible) short-acting CNP tyrosine kinase, you hit about an analyze high velocity about 5.5 to 6 centimeter over 12 months. You can [cheat] a little bit like a little bit higher or lower by shorter time or patient or demographic. But what [TransCon C] was unique, it showed a lot of positive effect on linear growth like leg [bowing], muscle strength, and other things. Because only one thing, because we are continuous exposure of CNP 24 hours, 7 days a week. That is providing all the benefit beyond linear growth. What we're doing with a combination [tribe] is like having a car. TransCon CNP is removing the break on the tyrosine kinase. This is why everyone hit the same growth velocity, because if the car is sitting on a hill, no matter how you remove the brake, it's go up to the same speed. What we're doing by combining the SKYTROFA is that we also take a speed on. It's how you win a Formula 1. Remove the brake, put the pressure on it by the speeder. And it's not only for linear growth. It's also related to other comorbidity as muscle strengths, body composition, everything like else that you look at comorbidity in achondroplasia. And this is why we believe that the (inaudible) tribe is the starter for a new standard in treatment of achondroplasia.