Great. Good morning, everyone. My name is Jessica Fye. I'm a biotech analyst at J.P. Morgan, and we're continuing the healthcare conference today with Ascendis. We're gonna go straight from the presentation into a Q&A session. If you wanna ask a question in the room, someone will bring you a mic. If you wanna ask it through the portal, I can repeat it for you up here, or you can just listen to me ask questions. But really looking forward to hearing the updates today on the back of yesterday's press release. I think Tim's gonna come up and do a forward-looking statement, and then we'll pass it over to Jan for the presentation.
Thanks, Jess. Before we begin, I'd like to remind you this presentation will contain forward-looking statements, and our actual results and events could differ materially from those in the forward-looking statements. For additional information concerning the factors that may cause actual results to differ materially, please see our forward-looking statement section in the press release yesterday and our SEC filings for the associated risk factors. With that, let me pass to Jan.
Thanks, Tim. So it's a pleasure to be here. Thanks a lot. Jess, thanks a lot. And it's not raining today, so it was a great day. So I will start from the beginning. Ascendis Pharma is a company built on a technology platform, the TransCon technology, and our specific algorithm for product innovation. And what we have managed to do with this two element, we have now got two approved product: SKYTROFA, TransCon Growth Hormone, YORVIPATH, TransCon PTH. But we are not stopping there. We started with three preclinical candidate in rare disease endocrinology, and we want to pass all three over the finish line. So in 2024, we expect to have our pivotal data for TransCon CNP, and we expect that we will do a filing. We also utilize the TransCon technology outside rare disease in endocrinology because it has a broad applicability in all different therapeutic areas.
We built up the pipeline in oncology with two unique product opportunities, and the year of 2024 will be the year of Ascendis Oncology Pipeline, where we basically will be in a position we can show you the data, where we're going into indication-specific cohort, really showing the paradigm shift we managed to do with our product in oncology. We have got in our dose escalation, amazing data, really providing huge benefit to the patient, and now we need to prove it in a more well-defined patient population. We also went out and utilizing the TransCon technology in ophthalmology, make a pipeline in ophthalmology. We also realized that Ascendis, because of the broad applicability of the technology platform, potentially some of these elements are much better managed in a situation where there is a dedicated, high-level, high-knowledgeable ophthalmology leadership.
So therefore, we basically are divesting our ophthalmology part on it out in a New Co, and we expect to finalize that here in Q1. You will see that more and more, how we focus on rare disease endocrinology, being from idea stage up to the patient on a global standing, but still utilizing the TransCon technology in a broad applicable value to really benefit patient and create value out of that platform. Going back to our products, SKYTROFA achieved U.S. market value leadership in 2023, two years after it was launched. It's the best-in-class product opportunity, the only one that can provide an unmodified somatropin product, meaning is that only product are providing the integrated endocrine benefit you actually expect to get from a somatropin treatment. And we expect full year revenue about EUR 320 million-EUR 340 million next year.
We will grow SKYTROFA to a blockbuster, and it will be done by label expansion. It will be done by geographic reach. We have the product opportunity, and we just need to capitalize, create the value out of it. YORVIPATH, our second product, will be launched in Germany here in January, and we will roll out in Europe, direct and international market in 2024. We have our PDUFA date in May 14 here in the U.S., and we hope we can launch shortly after when and if it is approved. So business model built on fast, successful drug development and commercial therapeutic synergies. There was a sentence coming from Scott, and I really didn't understand what he meant. So I really went in and analyzed the sentence and saying, he actually did come up with some really great way of thinking. Because people think about a pipeline funnel.
Why do you think about a pipeline funnel? Because typically, there is about a 5% chance if you are an average company to take a product from phase 1 until approval. Then think what we have done. We have taken two products from preclinical in rare disease endocrinology up to approval now. We're coming with the last one. So we don't have a funnel. And funnel meaning is that you go for about 20%... 20 products down to one to get through, and if you need to do it twice, you have 40 phase 1 trials to have two products. We have a pipe, so we redefine the paradigm shift. We call it not a development funnel.
We call it a development pipeline because we basically can take with so high success rate, so fast, like if you look on TransCon PTH, it took us only 7-8 years to get it out to the market. We're now coming to the stage where we have closed what we call the biotech black hole, meaning is that we are in a position where we basically can see where we can go to cash flow break-even. Meaning is that we basically are earning to our product nearly the same amount as we expect to spend, and we hope to reach that end of 2024. So when I had J.P. Morgan here in 2019, I came up with this vision, and it was the vision, our strategic pathway for 2020-2025.
When I look at the cornerstone was to get approval of the three product, TransCon Growth Hormone, TransCon PTH, and TransCon CNP. Wow, there's also calls here. We really managed to get this done. We only missed the last one. We got the global clinical reads. We're pursuing a lot of new indication, label optimization, life cycle management, and also taking up new endocrinology product, as we did with semaglutide, expanded the TransCon technology, really utilizing and see how we can apply it in huge area where we basically potentially not will be the end company taken out to the patient. We established global commercial presence, and I will go a little bit more in depth to that because this is really how we're building up the revenue on it. And oncology, I talked about, and we also have our ophthalmology.
Going now to the first part about our rare disease pipeline and how we do direct commercialization. Two products approved, SKYTROFA got approved in 2021 in the United States, in 2022 in Europe. YORVIPATH got approved in 2023 in Europe. We hope and expect to get it approved in the U.S. in 2024. So this is our product approved. So let us go out and talk about TransCon Growth Hormone. We developed this product in an environment where there was about 30 failed programs, coming from biotech, coming from big pharma, and no one ever could prove that you could make a treatment as good as daily growth hormone. We managed to prove it, that it was not only as good, but we also provide to get a better outcome compared to daily growth hormone in our phase 3 trial. We are now developing the entire growth hormone market.
The first one we went into is basically going to the adult growth hormone deficiency. We are having a market which are smaller than the pediatric, it's only 10% of the entire growth market, but very different compared to the pediatric because it's heavily under-penetrated in the way of treatment. We come out with the data end of last year and showed that we had the same effect on all primary and secondary effect, both to the regulatory endpoint, where we got highly statistical improvement compared to daily growth hormone to placebo, but we also proved that we could get the same treatment as daily growth hormone with a once-weekly treatment. We expect to submit a BLA here in Q2 2024. Revenue. How did we grow the revenue? Just remember one thing, when we launched SKYTROFA, we came out with the strategic view, what will our success look like?
We wanted to be market leader in value, but at the same time, we also wanted to grow the entire growth hormone market. This was how we put our strategic effort behind our commercial organization. Don't go out just to be market value, but you need to grow the growth hormone market because you're providing a much improved treatment outcome. And you can see how we're succeeding in this. In the last quarter, in last year, we had around EUR 64 million sales, mainly, mainly coming from the US, as we first just have launched in Europe. And we have a guidance now for about 320-340 million EUR in net sales for 2024. But we're not stopping there. We will continue growing it to our global expansion, to our, what I also call, label expansion of this product opportunity.
So sum it up, U.S. market leadership in 2023, complete heiGHt Trial in pediatric growth hormone. Why it was really important for us? This is 6 years we followed the patients, and what we really could see, they actually got the outcome that was expected from the genetic material. Meaning is that majority of patient met or exceeded the average patient Height SDS. This is what we want to see. I've never seen that with daily growth hormone. We going label expansion with adult growth hormone in Q2. We expect top line for our Turner Syndrome in end of the year, and we building our commercial readiness, our global commercial readiness, and I will come back to explain a little bit more about. I also talk about our aspiration for the sales in next year.
But what we are committed to, to making TransCon Growth Hormone the global leading product in value in a growing growth hormone market, and that is—has been our entire strategy. When I see today, we are growing the growth hormone market in the U.S. with 50%-100%, if we had the same penetration of our product everywhere.... Going to hypoparathyroidism. This is a severe disease, a disease that is really have no really treatment option today. It has a major impact on a lot of different system. I will not go in and talk about the really, the unmet medical need here. It's really getting realized for physician, the society, the patient, everywhere. Just look on the latest guidelines.
Consider PTH replacement taken in patient that is not really controlled on conventional therapy, and it's basic, when I looked at, where not sufficient control is the symptoms there, and all of them in 95% of the patients. So the basics, the guidelines saying to us that already European states that 95% of the patients should be on PTH therapy. So we presented last time at a medical conference, all our product, TransCon PTH, our phase 3 data, our phase 2 data. I can say we still have an unbelievable retention in our trial. We still enrolling patients, both in our EU in Europe and also in the U.S. We also started to analyze, do we see really other benefit that we not really have disclosed before?
When I look on this data here, which basically are eGFR data, I have never seen data that really are giving such a treatment effect. Look on the patient, why we define with over and under 60, because it's some kind of clinical diagnosis of having renal impairment or not having renal impairment. If you are under, you basically have renal impairment. And what you can see, if you take the blue, the patient that have already the diagnosis of renal impairment, we really can improve this with +10. And we continued at week 52. But more interesting, try to look on the placebo patient, meaning is that for the first 26-week, the baseline were in position that they didn't have treatment. And you can see the decrease, exactly as you see when they're on conventional therapy.
And then when we started the treatment, yes, it returned back. Really unique data that just describe one thing more. TransCon PTH is a product opportunity that are providing and restoring of normal and dosage PTH 24 hours, 7 days a week. And this is what we see through all the benefits. So commercial organization, how we going to launch TransCon PTH? E.U. direct, we will first take Germany, because there you get full reimbursement immediately from the beginning. There's about 70,000 adults with chronic hypoparathyroidism patients in Germany. It sounds very, very high, high. I think the incidence is 3-4 higher than what you see in U.S., but they have much more surgery in head and neck. So this is why they have it, because majority of the patient come from head and neck surgeries.
We will launch here in January with a list price about a little bit more than EUR 100,000 per patient per year. EU Direct is also where we're building up a direct Ascendis commercial organization. You can go down and look on all the different European countries there. There's about 8, 9, 10 European countries built up of clusters, where there's more than 100,000 additional patients. We will penetrate them with full reimbursement, beginning in end of 2024 and 2025. We will be in a position during this period of time; we will still help the patient if they really come to us and need it, we will help the patient with a named patient program, which also is a reimbursed system in Europe. In the US, there is about 80,000 patients.
We have the PDUFA date, and we have already the team ready. We don't need to build it. We'll be ready to launch basic immediately after any potential approval. PTH program summary outlook: completed two successful phase 3 trial, PaTHway and PaTHway Japan. Post hoc analysis showed really a significant improved renal function with the treatment with TransCon PTH. We approved in Europe and other territories as YORVIPATH. We have a German launch, and we are rolling out all different places in Europe. In the U.S., PDUFA date, May 14, and what we really want to do, we will launching TransCon PTH through our established proven endocrinology rare disease infrastructure. And this is what we have built up into our pipeline, having three independent product opportunity in one single therapeutic area. Meaning is there is so much commercial synergy, so much synergy, economy of scale between the products.
Going to achondroplasia. Achondroplasia is our last product in the rare disease endocrinology, and people have always talked about it's a growth disorder. Our view is that it's not only a growth disorder, but also a muscle disorder. And why did we got that feeling? Why did we got and started to explore that? Because when we looked in our patients, now, 3, 4 years after, all the patients we have, we only lost one patient, and there was a good explanation for that. Why do they stay on this trial? I don't believe they're just staying because of they're getting 1.4, 1.5 cm in height.... They get it because they basically get something else. And this is what we got inspired with, trying to look at, do we already have in our data, really this effect?
We have a long biological explanation, and Kenny can talk about one hour, half hour about it, why we are the only product that can really provide this benefit. So what we look on, this is our height velocity, and it's really on par what we expect to see, what CNP is providing, about +5.2, 5.4, 5.5 cm during, depending a little bit about what is the patient demographic, what is the age group, is from 2 to 10, is from 5 to 13. You can always get all different things. It's more important to look on height SDS, because height SDS, compared to achondroplasia, you're basically incorporating difference between groups, different compared to age, gender, and other things like that. So much more solid and look on height SDS.
You can see consistent growth, and you can see how we consolidate it when we have all the different patient there. We went back and look, can we already start to look on some of this element and try to explain why the patients stay on the trial? We started to look on health-related quality of life measurements, because we wanted to look on the patient that came from placebo or came directly on 100 microgram per kilo. We use SF-10, which are validated instrument, mainly for children over five, and this is why we also separated five. Then we have developed our own Achondroplasia Child Experience Measure. This is the data.
When you look at SF-10 physical summary, which really indicates something, muscles, endurance, and other things like that, just with the patient population, we already got a statistical effect on an improvement. When we go over to look at the Achondroplasia Child Experience Survey, also mainly looking at daily living function, emotional well-being, physical function, we also saw the same trend. There's no doubt we are not only providing linear growth, we are providing a treatment of achondroplasia, where we basically are integrating all the different elements that provide the benefit for the patient. We are now initiating and have initiated different trials. If you want to focus on linear growth, and I was surprised that I really didn't catch it before. If I look at linear growth, we went around and saw all places where you have provided growth hormone to achondroplasia.
About 12, 14, 15 clinical trials, lot of different places for, lot of different doses. But what we saw, we saw the most impressive linear growth ever seen in an achondroplasia patients. And this is why we want to make a combination trial. We take TransCon Growth Hormone and SKYTROFA, and we take TransCon CNP, and we combine them, because if you want really to have more linear growth, you can get it. We start with two arms. One arm, they basically are treatment naive, where they start to get both growth hormone and CNP. The other one, they're already initiated on CNP, and we expect to give you data later this year. Going to the pediatric patients, we have our ApproaCH Trial coming up here in end of the year. The combo trial, which are the combination trial, we will have also end of the year.
We also plan to submit an FDA for treatment of achondroplasia in the same quarter. It will be tight, but I believe we can do it. The infant trial has already been started, and this is where we look on the benefit on children down to basic newborn, but not older than two. We also will go into our adult patients. Why should we not help adult patients? Help them with the element that provide the poor quality, the shorter lifespan, and we believe that you can really change that. So TransCon CNP treatment goal is to improve linear growth, quality of life, but we also look on radiological endpoints to ensure that this kind of muscle improvement also going out and look on the skeletal function and physical function and body composition.
This is a slide that's dedicated to the rest of the world, because now I've talked about U.S., and talked about EU direct. In China, we have our VISEN, our joint venture, where we basically are providing a platform for providing patients with TransCon Growth Hormone, TransCon PTH, and CNP. They have finalized the phase 3 trial for growth hormone and the phase 2 trial for CNP. Japan, we just signed a license with Teijin for all three product opportunity, and we have our phase 3 pathway Japan trial completed. Our pediatric trial is also being finalized 100% enrolled, where we will have the data later this year. Then we're going to international market for the endocrinology rare diseases, and this is where we go to exclusive distribution agreement with geographic leaders. And to date, we have signed three. This is just the beginning.
We will continue, continue to sign this kind of agreement so we can reach where there will be patients, Ascendis will be there. Financial update. SKYTROFA Q4 revenue of EUR 64 million. Full year SKYTROFA revenue of about EUR 180 million. Full year total revenue of EUR 267 million, including the element that we basically got from Teijin.... we have ending the year with about EUR 400 million in cash. How it's going in 2024? Revenue just for SKYTROFA, we expect EUR 320 million-EUR 340 million. During the year, we will give you an update about our revenue projection for Yorvipath, when we somewhere going through the launches in the different geographic region.
Our operating expenses is going down to EUR 600 million, mainly because we have finalized a lot of huge upscaling of SKYTROFA to have the global commercial manufacturing capability, which was a major investment and other elements like that. So we also expect operating cash flow, expected to be breakeven end of 2024. This is the pipeline for some of our selected milestone in 2024. We can start in the first quarter with PTH launch, which will happen here in January. Q2, we will have our FDA decision. We will expect to launch in Q3. TransCon Growth Hormone, Adult Growth Hormone, submit BLA. This is our label expansion that will continue, and we also will have the Turner Syndrome end. Oncology, coming out with really the data that is really our key, where we come up with clinical update from indication-specific dose expansion cohort.
We'll provide you how these two products are paired downshift. TransCon CNP, really Q4 is going to be the busy quarter. We will come up with our top line data from our pivotal trial. Achondroplasia, H2 we'll submit NDA to FDA, TransCon CNP. Growth Hormone, SKYTROFA combination trial, we will come up with the 26-week data, and we will also have filing of adult TransCon CNP. So next, this is the last slide. This is the slide that I'm really looking forward to, because in 2019, I came up with the Vision 3x3. Now we have our Vision 2030. And it's really building on our last two visions, and it's mainly building on achieving blockbuster status for multiple products and expanding our engine for future engineering. It's how we really believe we can develop Ascendis Pharma up to a leading biopharma company.
Achieve blockbuster status for TransCon PTH, and TransCon Growth Hormone, and TransCon CNP to worldwide commercialization. So out from the rare disease endocrinology in this time frame, from 25 to 30, we will have three independent blockbuster. Be the leader in growth disorder and hypoparathyroidism, pursue clinical condition, innovative lifecycle management, complementary patient offering. We will expand the pipeline in rare disease endocrinology. We are expanding our TransCon technology all the time. But we will also get value out from additional therapeutic area to innovative business model. For example, what we do in our ophthalmology spin-out. We will both be equity owner, we will also have milestones and royalties. Really, it's a way where we always can be part in all kind of upside. We will... Oncology, we will not be an oncology company. We will be a situation where the oncology will be divested in some way.
We will still be part of the oncology effort. We will still be part of the value creation that will happen. We just need to find out when the value creation is optimal for us. We will pursue TransCon product opportunities on an opportunistic manner in other therapeutic area, where there is a large market potential in it, and we will do it by market leaders. We will go out and find market leader, as we will do with Semaglutide, find a market leader that basically will take our TransCon technology platform, the product we have done, out in the best possible manner. We will still be different with the Ascendis fundamentals.
As we said before, we have outdone industry drug development benchmarks, both with our success and our time, and we have not compromised how we are clinically differentiated, best in class, and basically, no one else can make the product we have done. We also see ourselves coming to the next stage, being more and more independent. As we're getting profitable, we will be independent of the financial markets, because we can finance ourselves. But we will never forget our values: patient, science, passion, that really are driving how we operate. So that was my speech. Thank you a lot.
So, I guess first question I have is, TransCon PTH is approved in Europe already. I still hear some skepticism from time to time from investors about U.S. approval, on the heels of the deficiency letter and then CRL and our resubmission. So I guess, what can you say about your level of confidence about a U.S. approval for TransCon PTH?
PTH will be approved.
I think you also flashed up on the slide a price of EUR 105,000 for PTH in Europe. Is that net of any mandatory government rebates? Is that kind of the- the true net price in Europe we should think about?
Yes, Scott is really here looking forward to answer that question. He spent so much time on it. Scott?
That's the list price, so pre-mandatory discounts or anything.
Okay. So what-
It's a percent?
7% now, but a little bit less when you take into account the VAT impact.
Factor is between 5% and 6%. So net price will be 5-6% less than 105.
Okay. Okay. Question in the audience?
Hi, thanks for the presentation. Two questions from me, both on the growth hormone franchise. The first is on what you're seeing from other long-acting competitors and their approach to value versus market share. Are you seeing aggressive rebating from Pfizer and Novo? And then second is on, as SKYTROFA expands outside the U.S., where average prices have historically been lower for growth hormone, what type of gross margins do you expect on the franchise on a global basis? Thank you.
Yeah. First of all, when we launched Skytrofa, there was no other long-acting growth hormone in the U.S. We launched it directly in the competition with daily growth hormone. And daily growth hormone, to my knowledge, is one of the most rebated product that is in the U.S. market. We managed to show, because of our product strength, that we basically could get to medical exemption, the patient need, the patient benefit we could provide. We really overcome all the challenge in not being reimbursed. When we see the other long-acting product coming into a market, they are basically providing a treatment outcome less than daily growth hormone. So I don't really believe that is changing our strategy at all. We see still, Skytrofa is the best-in-class product opportunity.
We're never willing to go into the same rebate that was in the daily growth mode because we don't need it. Going to the other market, yes, there is a huge difference in price structure in a lot of different elements. But we are not coming in and trying to say we just are something equivalent to daily growth hormone. We're coming in and position us, look at the patient, see how many patients that not really get the treatment outcome they should have. Take them to SKYTROFA, see the benefit it provide to them, then they're also willing to accept a different price structure.
The gross margin impact as you go to growth?
The gross margin impact will be in some region, lower than you see in U.S., but it will always be in what I call the range of a highly profitable product.
Coming back to PTH, can you talk a little bit about how you're thinking about the initial launch curves and the overall opportunity for that product in the U.S. relative to Europe, and I guess which patients in each of those regions could represent sort of the low-hanging fruit?
Yeah. Now we're launching in Germany here in January. We already have done what we call having an EAP program activated in Germany, where a patient that both was naive and patient that was coming out from the PTH, which are getting taken out of the market in this year in Germany, too. What we have seen is what. And the aim of that was help the patient, but also provide the physician the knowledge of it, because we didn't have a lot of clinical sites in Germany. So what we really went out to some of the key opinion leaders in Germany that really could get the patient experience, treatment experience with PTH and take the first series of patient and do it. So we feel pretty, pretty confident with the benefit we can provide to the patient in Germany.
What we will do, we will be fully reimbursed in all major European countries in the end of 2025. We will start in the beginning of 2024. So there will be a ramp up, part on it. The U.S. is different because you have basic and different reimbursement system. And what we will expect to see, what we will hope to see, is that the majority of this patient are realizing the need of having and coming for TransCon PTH. But this is what we would like to give you update during 2024. Every time we come, every quarter, it will be more and more interesting when we grow also the TransCon PTH revenue, besides the SKYTROFA.
Thanks. Given the perceived unmet need, why do you think the FDA gave you a Class 2 Review for PTH?
But the unmet medical need is not really defined in what class you're getting. It's defined on what we're providing on materials in the refiling, and nothing to do with the unmet medical need.
Can you remind us again what you gave the FDA after the CRL?
In the end, it's basically an element of the FDA to decide if it's a Class 1 or Class 2. What we did was a refiling of our BLA, all the data we had provided to them before, except that, as we have described, we have updated some of our control strategies that we, as we had discussed, that was the item of the CRL.
Morning, again. Can you just elaborate a little bit on the cost structure going forward? So the EUR 600 million for '2024 that you're committing to, is that sort of a fixed cost structure on a relative basis? And are you committed to earnings leverage in '2025 and beyond as the top line accelerates?
Yeah, I can give a high level, and Scott can give two hours detailed discussion about all his forecasting being happening. But the high level is that we had some major expenses with the upscaling of SKYTROFA to have our global commercial reach. We spent EUR 120 million-EUR 160 million in the last 24 months just to reach that. That is one of the things we see we get down now. We also see the maturation of PTH now. We see stopping of clinical trial, like the enliGHten Trial, with all our pediatric is now being stopped. So we see a lot of clinical activities. We see a lot of expensive CMC activity, basic being rolled over because now they are commercial product.
So when we look on the forecasting, the team, 2024, 2025 and 2026, we don't see a lot of what we call a sales-driven operating expenses coming up, except what we typically will see, inflation, we will see a little bit more expansion in some of our commercial organization, but it will not mean a lot. For example, if we launch TransCon PTH in the U.S., it's not going to be a major financial burden for us. We have the infrastructure, we have everything there. So it basically is not heavily financial. So when we look in 2025, 2026 and 2027, yes, we likely will have an increase as all companies, but it's not like we will have an acceleration.
You've, you've talked about capturing, sort of non-height benefits in the TransCon CNP phase 3 study. Where do you stand in terms of, you know, prioritizing those endpoints as we get closer to that phase 3 readout?
Yeah, it's actually really well described here. The linear growth is the primary endpoint. We then use radiological endpoint to see benefit on, for example, structure of the skeleton. We couldn't do that because we didn't have that implemented sufficient enough in our phase II trial. So we couldn't go back and see that. We first got that implemented now. The physical function, yes, we have taken some physical measuring on endurance into a trial, which will be placebo-controlled and body composition. And what we have seen now is the quality of life element we have seen, which I believe is first time I ever seen that really coming out in any kind of CNP treatment.
So basically, it will be a combination of all this quality of life, radiological endpoint, physical function, body composition, that basically define all the different element, where we really believe we can prove that we have a treatment and not only providing linear growth.
Great. Great, we're out of time. Thank you.
Thanks so much.