Welcome. I'm Jessica Fye, a Biotech Analyst at JP Morgan, and we are continuing the 43rd annual healthcare conference this morning with Ascendis. I'm going to turn the mic over in a minute to the company CEO, Jan Mikkelsen, but just a quick reminder, silence your cell phone, send me questions on the iPad, and yeah, we're going to do a 20-minute presentation about 20 minutes of Q&A. If you have a question, raise your hand or, you know, iPad, and let me pass it over to Jan.
No, we're good. Scott.
Oh, Scott.
Fantastic. Okay. Before we begin, I'd 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, 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, and success, our strategic plans, partnerships, and investments, our goals regarding our clinical pipeline, including timing and results of clinical trials, and our ongoing and planned regulatory filings and expectations regarding the timing and results of regulatory decisions. These statements are based on information as available to us today.
Actual results may differ, 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 statements section in today's press release and the risk factor section of our prospectus supplement filed on September 20, 2024, and our most recent annual report on Form 20-F filed with the SEC February 7, 2024.
Thanks, Scott. I will slow down a little bit compared to Scott. So I think it's, for me, it's some way an emotional time to stand up here. I've been attending the JP Morgan for 25 years. We started Ascendis Pharma in December 2007, and I have now been the CEO of Ascendis Pharma for 17 years. In 2008, we designed TransCon Growth Hormone. In 2015, we designed TransCon PTH and TransCon CNP. So 17 years after this major effort, we're now sitting here for the first time with such a strong fundament that we really can strive to drive really our revenue growth. And I call it the black hole to be in biotech. There's a big black hole you need to fill up before you can hit to profitability. And it's not even the chance and the success rate to hit that is really, really, really hard.
We came there because we have two strong fundamentals, our TransCon technology and our algorithm for product innovation that really enables us to develop two product opportunities that now are approved in the U.S. and Europe, and the last rare disease endocrinology product. We really have strong proofs of data, and we are in a position that we are coming to the next stage, going for an FDA submission here in Q1, and we're going for an EMA submission in Q2. In short, Skytrofa, the best-in-class growth hormone in an established market. We have shown how we really are driving revenue with this product, and I will go into more detail on this product opportunity. Last year, we generated a little bit more than EUR 202 million, mainly driven out of the U.S.
But we're not stopping there, as we already have the PDUFA date for our first market expansion activity, the supplement BLA for adult growth hormone deficiency. Yorvipath, the only treatment that is indicated for the treatment of adults with hypopara. And we launched last year in the beginning of the year in Germany and Austria, and through the rest of Europe and also outside Europe, we have named patient programs that really are providing patients access to Yorvipath. And we generated last year around EUR 29 million. We launched here in the middle of December. People say we should never launch in the middle of December. We did it because we knew that the patient came to us, and we wanted to be out and giving the product to the patient. CNP, I will come up with some more data from that.
I really believe this is a product that gives me a huge, huge pleasure to see when I talk with the parents, when I talk with the patient, when I talk with the physician, how for the first time they believe they can get a treatment for hypopara. But as I said, we're building up the TransCon technology. The TransCon technology platform is expanding and expanding, and you can see that we are also utilizing the power of the TransCon technology outside our focus area, rare endocrinology, forming Eyconis in ophthalmology, and now have partnered with Novo Nordisk in metabolic and cardiovascular diseases. We have our internal development in oncology with a strong focus on our TransCon IL-2 beta/gamma, and we just expanded the TransCon technology. Last time, we talked about our new platform.
We called the Ability Platform, and we saw the results of that immediately with the collaboration with Novo Nordisk. It's easy to follow Ascendis Pharma because we followed our vision. This is our strategic roadmap in 2025- 2030. And you can see it's already built on three different bullets with all three different segments. The first bullet is really, really clear. We want to be the leading endocrine rare disease company, and we want to have active blockbuster status of all our three independent products. And I will come back to that later in the presentation. We want to be leader in growth disorder and hypopara, pursuing all different LCM and other activity to do it. And we're also starting to expand our pipeline now with new chemical entities.
We still will be in areas outside rare disease endocrinology because of the broad feasibility of utilization of TransCon technology in other areas. We want to go for accelerated approval in oncology. It will be the focus on IL-2 beta/gamma, but you also see how we assume big indications like metabolic disease, obesity, with the collaboration with Novo Nordisk. When I think about what we want to do, we really want to outperform, make a new paradigm shift how to make drug development. We did that in our rare disease endocrinology. Seven years for start from the idea to approval for TransCon PTH. We have made three products preclinical, got three products approved. I do not know any company that had managed to do that, but it's only possible for us through the TransCon technology, our algorithm for product innovation.
So this is how we have expanded, and you can see we have TransCon ability. Now we have a protein degrader. The protein degrader is really going back to the fundamentals. Today, we have addressed a lot of diseases where there are deficiencies or what we need to do, what we call pathway modulation. But many, many path diseases in rare diseases actually have too many things of a product. It could be a hormone, it could be a cytokine, it can be in others like it. So what if you give a protein degrader into that? And this is a classical protein degrader with one that binds to the liver, get it away, and one that binds to the ligand. It disappears in a few minutes because of the extremely fast clearance.
If you have a continuously produced hormone, you can never, never get it removed sufficiently because the degrader is back after a few. At least everything's done in less than one hour after you did the injection. What we're doing is we use the TransCon technology to establish the normal algorithm for Ascendis Pharma, and then we totally shield it, and then you liberate on a continued basis, like a continuous infusion, the protein degrader. On a continued basis, you can very basically turn up and down exactly where you want to have the hormone in the level you want to have it when you have a super physiological concentration and want to lower it. This is how we're building a new series of product opportunities. Going to our pipeline, you can see our pipeline.
We have a strong focus on label expansion, and you can see we are going into label expansion now mainly on Growth Hormone and CNP, strong focus on CNP, but it will expand further. You can also see in our partner program, we have also the geographic reach everywhere, Japan, China, Europe, and U.S. Going to our worldwide commercialization. Why do we do worldwide commercialization? Because we want to be where all patients are. And when we look on PTH, that's everywhere. When we look about CNP, we are building up the global commercialization for all our products now. And we do it by three different means. We have our direct commercialization where we do U.S., we do it in Europe direct, and we still have Greenland up here. We still consider that the east. So we still took the right color on it this time here.
Next year, potentially it will be different. But from our perspective, this is the Europe direct and the U.S. And then we have partnerships with sales and distribution. You can see how we're covering the entire world. And then we have other partnerships like VISEN and Teijin, where we both have a classical partnership and other more SRJV-like type. But we will be everywhere. Growth hormone. We launched it in the U.S. in the end of 2021. We're in Germany in Q3 2023. We have now done all the necessary clinical trials to be worldwide with pediatric growth hormone deficiency. We are expanding now across multiple countries. And you can see that we generate sales of EUR 200 million, mainly from the U.S. We have a strong activity on label expansion because with the pediatric growth hormone deficiency indication, we are only addressing around 50% of the market.
We have positive results from our phase II in Turner, and we are initiating a basket trial that likely will be an SGA, ISS, and SHOX where we, for example, have Turner included that. Meaning is that in the next years, we basically will have a label expansion to the entire growth hormone market. And you can ask me, hey, how can you make that to a blockbuster status when you have this modest increase in revenue for 2024? And I can say, yes, because the fundamentals are right. We still, compared to a daily growth hormone, have a value creating 3x compared to a daily growth hormone. Meaning is that we can expand the growth hormone market. We grow the volume about 84% from 2024 to 2025. And we still only have 6.5% of the market share in the U.S. So do a simple calculation.
We believe our best-in-class product opportunity will go up to 40%-50% of the market when we have the necessary label expansion through the entire market. Meaning is that we will be in a position that we easily can make it to a blockbuster status. We are committed to TransCon Growth Hormone. We are committed to Skytrofa, and we will continue to really get this out in all the different countries where it should be. Going now to Yorvipath. Yorvipath is one of the largest indications in endocrinology rare diseases where there's no treatment today.
Think about having type 1 diabetes without insulin. Think about having TransCon Growth Hormone deficiency without TransCon Growth Hormone. Think about having hypopara without PTH replacement therapy. And that is what we're providing to this patient group. When you look on the serious comorbidities this patient group has, you understand the need, the huge unmet medical need.
So when you look on the guidelines, when we go through the guidelines, we believe 95% of all patients should be in treatment. And that's exactly what we also saw in our clinical trial. In sub-analysis, we saw the benefit in all patient groups. We launched in Germany in the beginning of last year. And you can see we grow quarter by quarter. We have a list price of about EUR 100,000 per patient per year. We launched in Germany and Austria. And outside Europe direct, we have named patient programs where you can take a single patient into a product that will be reimbursed. We're ready now to launch in 2025 through the majority of Europe direct. So you will see a major acceleration in this region. We have eight exclusive distribution agreements in 15 countries now.
We have revenue recognition from three different regions, Central and Eastern Europe, and Israel and Canada. Next year, it will expand dramatically both in Europe direct and our international market. We have around 700 patients on treatment. So when you look on this revenue increase, think about, and people asked me four years ago, will you beat Natpara? Will you be better than Natpara? First of all, Natpara was an adjunct without treatment. But when I looked at Natpara, after four years, Natpara made in that treatment EUR 400 million. When I look after 10 months and analyze that, we did it in 10 months. So what Natpara did in four years, we did in less than one year. Just illustrate what is the treatment benefit we have with Natpara compared to Natpara. So Natpara is now available in the U.S. as the only treatment. This is the patient population.
We defined it in segmentation, PTH experience, the total group, newly diagnosed. There will be around 3,000 patients coming every year, mainly from the post-surgical part. This was our initial launch. Remember, we started before Christmas. In the beginning of December, we started with taking prescription for patients that were in our EAP program, in our clinical trial. In the middle of December, we basically started with the other group. The other group meaning is that it suddenly got available to patients that now were on conventional therapy. What we saw here, we cut it January 9 at 1:00 P.M. Why did we cut it at 1:00 P.M.? Because we thought there would be many more. Therefore, we cut it at 1:00 P.M. We saw at that time 374 prescriptions, where the majority was coming from conventional therapy.
Meaning is that it really is expanding out in the big group as we have expected when we think about the unmet medical need and they have no treatment. The other thing which is unique, we have 150 unique prescribers. In our EAP program, in our clinical trial, we only have about 30- 40 prescribers. Meaning is expanding extremely well out. When I look on the perspective on Yorvipath, we have the perspective that we can make it in a blockbuster outside U.S. and inside U.S. When I look at the initial data, I'm feeling so much more confident about that statement. It's the first and only approved product for hypoparathyroidism adults. We are going on clinical regulatory approval in several countries. Currently, we have four countries on regulatory approval outside the places where we already have approval.
We have 700 patients in Europe direct and international market end of 2024, and we will launch in more than five countries in Europe direct in 2025. Strong enrollment and 150 unique prescribers from 38 states. Meaning it's not centralized to a few academic places. Just the U shape is everywhere. There are still 51 states in the U.S. CNP, we came out with the phase III data, the pivotal data. There were actually an echo of our phase II data, but with much more patients. We want to develop a treatment, and that is what we want to achieve. I will not start to repeat what we saw on the primary endpoint growth because we are providing linear growth, amazing linear growth, exactly what we can do when we address the hyperactive tyrosine kinase.
What we wanted to focus on today is what can we provide of benefit, help the patient related to the comorbidity they have beside linear growth, and this is where we want to focus. This is why we see this unique retention in our clinical trials, why we couldn't recruit our pediatric trial in three months at a site that had access to available products today and other clinical products today. Three months, we recruited our pediatric trial. What they have seen there, they have seen it in the patient-reported outcome. We saw it against all the different domains. The other thing we have seen, muscle functionality. And you can say, why do we see this different compared to other things? Because how did TransCon CNP get designed? What was the fundamental behind it?
It was to give it continuous exposure of CNP, seven days a week, the entire year. Actually now, I'm really, really happy to see other companies accepting that. They're coming back and saying, now we want to develop the same profile that the Ascendis profile, continuous exposure. Really also understanding and believing in the biology about what is the benefit of having continuous exposure. It's extremely well tolerated. And because we inject a prodrug, injection site reaction is basically the same as placebo. Meaning is that we have 0.5 injection site reaction mild in a yearly treatment and no risk of hypotension. Because we don't have high Cmax, we have a flat continuous exposure. I wanted to focus on some of the data we've seen. This is part of our analysis.
We are looking and seeing what do we provide behind linear growth that is extremely meaningful for the patients, so one of the things we take up today, and you will see other things being presented by medical conferences and other things, leg bowing, and when you look on the leg bowing, there's two different means you can look at it and two different ways you can measure it, and we presented both to you here. The one is the femoral angle, and you can basically see if you decrease the TFA, the angle you're measuring there, you actually are improving the condition with less leg bowing, so when you go over and look on the placebo, you can see in 52 weeks during the trial that it actually got worsened with + 0.39 degrees. What did you see with the treatment now? It improved with 1.4 degrees.
Highly statistical improvement in it. Then you go out and say, are there other ways we can measure this? Possibly radiological. Yes, we look on MAD. This is where you basically are seeing in between the distance of the knee compared to the line between the skeletal system. Is that getting less? Meaning is you're improving it. If it gets larger, it's getting worse. When you look on the placebo in 52 weeks, they've got increased with 1.78 mm. When you see the treatment benefit for just one year, improved in one millimeter. All that is extremely meaningful for the patient, and this is why we continue on the trial. This is why we believe in continuous exposure of CNP is providing all the benefit behind linear growth, so we are filing now. We have a very successful pre-NDA meeting with FDA, and we're filing here in Q1.
We are developing a lot of other clinical trials. Our infant trial between 0 cm- 2 cm are really getting rolling with huge speed now, really as we expected to see. We have our cross trial. Why do we make our cross trial? Because there will be patients that want more linear growth. And I'm not talking about the 5.5 cm-6 cm. This is what you go when you start to interrupt the super active tyrosine kinase in the FGFR3. You could get 5.5 cm-6 cm. We want to combine it higher up. And this is why we're running the cross trial where we combine it with two different meanings. This is why Ascendis is positioned to be the leader in growth disorder because you have the big huge two fundamental TransCon growth hormone and TransCon CNP. So what do we do besides that? You saw the degrader platform.
One of the first ones we were looking at and continue working on now, where we really believe there is a huge unmet medical need. Kennett will join me later on today. He will explain some of the unmet medical need and why we're taking this up, but his basic is that we want to remove the supraphysiological FGF23 levels down to the normal level. Same algorithm as we did in all our other Ascendis programs, where there is already proven clinical program, clinical endpoint, and we just need to execute. We have made three out of three. We want to make four out of four. Our collaboration with Novo Nordisk. Yes, we wanted to be in obesity metabolic disease.
The TransCon technology is the best platform ever to make one monthly product where we can take a semaglutide that has proven efficacy, proven efficacy, really go out and use the algorithm. De-risk it because semaglutide will function because we liberate semaglutide. And we know we can do it over and once monthly profile. We believe the economy first is great, totally funded by Novo Nordisk, and we're sitting with a royalties that really can be us also a player in obesity metabolic diseases without any kind of investment. I don't believe any biotech company ever can take the burden of being a player into this era because of the huge investment. Other investment, Eyconis in ophthalmology, Teijin is our Japanese licensee, VISEN our Greater China licensee. So let's go to a little bit more the fundamental thing. This is Scott's error, but he wanted me to do it today.
You can see we ended with the revenue about EUR 226 million. And what is more important is that when we take all the revenue, we got all the different collaborations, we're ending up on EUR 364 million. We are really well funded in our financials. In cash, sitting with about EUR 650 million, including the EUR 100 million that we will receive from Novo Nordisk. Meaning is that with our projected expenses, we will have really, really a well-capitalized company where we see the cash generation we are doing in the future. Milestone for 2025, yes, you can see it's going to be from the research and development. This is research and development. The revenue will come in, and that will be a major driver for us in 2025. But when we go to research and development, it's clear it's going to be a CNP year.
Finally, FDA top-line data, European Summit, and then we have Hypopara Summit in the end. Growth hormone, you can see first label expansion, and then we're going into further label expansion. So when I look on the future of Ascendis Pharma, we are here to build a leading biopharma, and we will continue to do it in the next year. And we are coming to the transition state where we really can grow the revenue now. So thank you so much.
Great. So I guess first question for me is you gave us that initial stat on Yorvipath having 324 patients enrolled in the U.S. in the specialty, sorry, in the EAP program or with specialty pharmacies. What does that mean? Do those patients have reimbursement? Is the reimbursement still in process?
When we take patients in, we take them into our ASAP program with our internal hub that basically does everything for the patient or they go with the prescription to the SP. That meaning is that they are starting the reimbursement process. Our way we look on reimbursement is that we expect the vast majority of the patients will receive the level of reimbursement between four and eight weeks. That is the time it takes. Some of them already came after one week, some came after two weeks. But when we look back and see what we have received on other products, the vast majority is between four and eight weeks from the prescription it's being written.
Okay. And then of those, the 324, there was a subset, actually the majority, I think, who had not been on your Yorvipath in the past. How many of those have been on Natpara in the past?
That's a good question which we cannot answer because we don't have the insight in each single patient if they are from five years ago or six years ago really have access to Natpara. We don't know that. But we know that they're coming from conventional therapy, but we do not know if they're for five and six years actually tried Natpara for just four weeks or five weeks or half year or something like that. We cannot see that.
Okay. And then I think the numbers you gave on those initial kind of patient enrollments also suggest that there may be like 50 or 60 Yorvipath patients from clinical trials or the EAP who have yet to transition. Should we expect those? And if so, when?
It will come in the first next months, we believe. There are about 60-80 patients that still need to be transferred. There also need to be transferred that currently are on Yorvipath. It's something that just has been running for three or four weeks, so it's really pretty impressive because they need to come into the physician. And typically what we learn, the big group of patients, the 40,000 patients which are what you when you look on their status being controlled or in a severe or moderate manner, they are seeing the physician about up to four, sometimes more, some of them seeing at least two to three times a year, and we ask the physician, are you starting to stockpiling the patient?
They say, no, we're not doing that w e wait until they come in, because the waiting line just to get an appointment is basically about 8-12 weeks. So they're just waiting to have already their regular appointment with the endocrinologist and then they meet and get the prescription.
Okay. So that kind of gets to my next question. How sustainable is this extremely rapid rate of enrollment that you've seen just over these first few weeks?
I think it would be stable. I cannot see anything that is going down. We only see it's accelerating.
What about ex-US? So you had a really robust rate of patient pickup in Europe already. I'm curious how you think about kind of volume for 2025 from this level and also price. What's the right way to think about kind of the evolution of the price in Europe?
Yeah. So what we have now and just give you the background for people that not have so much common knowledge about the European price structure. The key country in what we call outside the U.S. as a reference price is Germany, so Germany is the key country that will be taken as a reference pricing. And today we have EUR 105,000 on a list pricing.
You have a few percentage, what we call mandatory rebate in the German market. What we expect to do is in the middle of the year to finalize the final price in Germany. And it will be some way you can say the reference price from Natpara was around EUR 80,000, a little bit larger today if you incorporate inflation and other things like that, so it will be between what we call the list price of Natpara and up to the EUR 105,000 price.
And that will be the final price. We don't need to go to further price negotiation because we are not launching Yorvipath as an orphan drug product. We take it in as a normal product. So there's only one price negotiation. About the volume, it's really simple. Germany and Austria basically beat Natpara for four years what they did in the same region. And so we don't have no benchmark more because Natpara was only the market for four years in Europe, but we beat that in 11 months. But it's just illustrate the power of the product.
Just to spend one more moment on price, you talked about kind of the where you might land for price in Germany, but you're also broadening out to more countries this year, right? So.
Yeah, but many of them are reflecting our German market. And then there can be countries where the demand are higher discount. There could be other countries that do that. But everything is reflecting in what we call the German reference prices. It's really one of the fundamental price setting and a lot of other segments.
Got it. You've got a competitor data readout coming from eneboparatide at some point, maybe over the next few months, who knows? What are you going to be watching for when we see that clinical data?
I think first of all, you know that, yes. I like to go back to the science. How did this product get designed? It got designed out from a fusion peptide between PTH and PTH related hormone. It's a compound that's very much alike Tymlos, but have further mutation in it. Meaning is that it's from a mode of action. It has not what we call itself a long half-life to give a continuous exposure. It locks one of the mode of action, only one of the mode of action, and that is the element of intracellular activation in the lysosomal system. It locks there and therefore it has a continuous exposure. First of all, let us look on the molecule itself. It got designed as a PTH1R receptor analog.
We know the benefit we see in all of the patients, mainly for cognitive effect and other things, are to the PTH2 receptor that's sitting in the brain. And we therefore believe it can never be a replacement therapy because it basically is a hormone that only activates one of the receptors. The other element is that when we look on the data itself, it has not the positive effect on phosphate because it can't do that because it has a different mode of action. It will have a different effect on bone. And I think it was best illustrated by a physician that asked the company. W hen you look on the mode of action of this compound, you know that hypoparathyroidism is a disease that affects multiple, multiple organs with a lot of different receptors.
How can you really show us that you have the right activation on all the different organs in the right manner? and the physician for the trial said, we cannot ever show that. So it's now going to be a replacement therapy. The other main thing is that when you look on the molecule, when I look at it from the protein side, if you look on the Tymlos, 35%-40% had neutralizing antibodies up to 8 after 18 months. But it's not a big issue for Tymlos because it's restricted to two years treatment. So there's a lot of other things in it. So when I really look on this compound, I really don't believe that it's hard for me to see it would be better than Yorvipath. It would be a provable product. We need to look at the data.
Okay. Maybe switching to CNP, you've had your pre-BLA meeting now, and you're still talking about pursuing a label for the treatment of children with achondroplasia. Can you expand on why you want to go for that indication?
Because we don't just want to provide linear growth. This is what we've shown with all our data, the muscle data, body proportionality data. Now we see the body also leg bowing. So we have so much evidence we're providing much more than linear growth. If you really want to get a lot of linear growth, wait for the cross trial.
Maybe switching to Skytrofa, when I look at the IQVIA data, and I know it's probably not perfect, it seems like the conversion from dailies to the long-acting category has sort of slowed recently. What could make that pick up again?
That is why we have such a strong commercial organization. We have Jay now heading up our commercial organization as a president of that. And we have such a strong team of established people in the commercial organization. I'm quite sure they can get this going again as we did other times. What we did for between 2024 and 2025, we really didn't change our what we call the element of our contracting. So when we really are building up more demand, we will see much more revenue. And that is our strong focus now.
Great. Maybe just a last one on the financial side. I wasn't sure if this is how I should interpret it on one of the slides at the end, but are you still expecting to reach cash flow break-even by the end of this year?
Scott, now you have a question.
We believe we can, and we're at least well capitalized to achieve break-even eventually. I think that before we come out with specific guidance, we want to see the trajectory of Yorvipath, but we feel pretty confident that we can achieve break-even with the cash we have and potentially this year as well.