Great, thank you, and welcome everyone to join our next session here at Oppenheimer's 34th Annual Life Sciences Conference. We're delighted to have with us the team from Ascendis. Ascendis, as you know, is a stock that we cover, and the team in front of us is the CEO, Jan Møller Mikkelsen, as well as Scott Smith, who's a CFO, and Tim Lee from Investor Relations. We'll be joining us for a fireside chat to walk through some questions, sort of an informal discussion about the company's business and programs and prospects. Welcome all of you.
Thank you.
Thanks a lot.
Great. You know, I think let's focus first on SKYTROFA, which is, you know, the company's first product, was approved a couple of years ago here in the States, once-weekly growth hormone. We've seen a nice acceleration of the sales growth of SKYTROFA, and particularly in the second half of last year, Q4 could pick up, and, you know, you've given encouraging guidance as well. Maybe, Jan, if you could, you know, discuss what the drivers have been to the more recent acceleration, and are there particular, you know, aspects, whether it's been increasing physician comfort, whether it's been on the payer side, more switches from daily to weekly, or maybe it's all of those, but we'd love to hear kind of what's been driving the pickup.
And thanks, Leland. Look, before I turn it over to Jan, let me just make a quick statement here. You know, we may make forward-looking comments during this discussion. Actual results may differ materially from those expressed or implied, and you should not place undue reliance on these statements. For information concerning the risk factors that can cause actual results to differ materially, please see the risk factors section of our most recent annual report on Form 20-F. And with that, let me turn the question back over to you all.
Thanks, Tim. So I, I think we need to go a little bit back because we really designed SKYTROFA for TransCon growth hormone to be the only product in the long-acting era that's releasing an unmodified somatropin molecule. Why did we do that? Because we wanted to ensure that we could get all the endocrine benefit that really a patient has been used to get from daily growth hormone. And when we launched SKYTROFA, we had two objectives. One was related to being the market leader in value, and the other thing was to do it in a growing growth hormone market. And now I'll turn it to Scott because he really has the numbers, how we really proved that.
So I think, as you know, Leland, with the most recent quarter, we had about EUR 64 million of revenue, and as we said, we exited with penetration of the pediatric growth hormone deficiency segment only, which is our approved indication of about 16%. So if you take our EUR 64 million per quarter and annualize it, you get about EUR 250 million run rate, and at 16% penetration for half of the overall market, because remember, pediatric GHD is about half of the overall market,
you can see that we're growing the market potential for SKYTROFA in the U.S. up to $3 billion U.S. or more. So I think that's really meeting the objectives that Jan laid out, as he said, with the program here, that we have a product that is best in class and has the potential to grow the market at the same time we're the market leader.
What we observed was basically what we expected to see. We launched in an established market where the competition was daily growth hormone. There was six players at that time. We came in with our two objectives for how we want to commercialize it by value driver, growing the growth hormone market. And growing the growth hormone market, we basically could not provide the same expected rebate as we will see that was established by the daily growth hormone. So we needed to use the product strengths. How can we change if you have a patient, our physician recognizes you really didn't get the right treatment outcome? Yes, you can change over to a product like SKYTROFA. And it was really how we built the market.
The physician got the comfort, they saw it from the patients, saw how we got a better treatment regimen, that daily growth hormone, and had the same safety, had a really unique invention in a new autoinjector that really gave everything for the patient, the joy and action to take an injection that some of the patients had. It was fun to use it. I think this is why we'll be going to develop SKYTROFA as a blockbuster in the U.S. in the growth hormone market. We are continuing label expansion. Last year, we got the phase III data for adult growth hormone deficiency. We're going to file here in the middle of the year in a supplemental BLA. So we also will expand with different labeling.
At the same time, we have a Turner trial where we're using SKYTROFA, and we will have the phase II data at the end of this year. So we are dedicated to really develop SKYTROFA on a global basis. We are launching in Germany. We will distribute it in the international market and other places. And we are dedicated to really develop the value out of this unique product opportunity. Its patent extension is pretty long. We have a unique patent protection to basically into the middle top of the 30s. So the lifespan of this product has just started.
Thanks. That's very helpful. You know, we've, you know, we've spoken to, to physicians who really like the product. Some of them have said they've had difficulty in gaining access, and maybe that's changing. It seems like you guys are really doing a good job in the States. We've also spoken with some people who are kind of on the managed care side, and they've said that, you know, it's usually the case that, you know, dailies are kind of favored, and there's really no preference for, you know, whether something is daily or weekly. So, are there arguments you're able to present to, I guess, the payers that are really convincing for them to support SKYTROFA, even given, you know, the variety of dailies that have been on the market for many years?
And coupled with that also, as we've had the recent launches of the other two products that are once weekly. And again, I guess the same question is, you know, when payers are making a decision to support, you know, a weekly product on their formulary, and presumably they'll choose one of the three to favor, you know, how, how, how are you able to, you know, convince them of the SKYTROFA benefits, you know, over Ngenla and Sogroya? Is it the kind of the, the, you know, the sophistication of the delivery and the device? Is it the data, which, you know, does, does look quite, you know, strong, given what you've shown with SKYTROFA? You know, what's, what's the, what's been kind of the sell to the payer, to support SKYTROFA?
There's only one single answer, and that is the benefit of the treatment of SKYTROFA. We launched SKYTROFA into the market where you typically use daily growth hormone of 0.32 milligrams -0.34 milligrams per kilo per week of daily growth hormone. We basically provided a better treatment outcome. That's why we did get all the medical exceptions. As you said, the majority of our patients came from daily growth hormone, got switched over to our once-weekly product. When you mentioned Sogroya, Sogroya has been through a phase III trial. The prescribing dose of SKYTROFA is basically providing an absolute lower outcome compared to 0.24 milligrams per kilo per week of daily growth hormone. That is what is in the phase III data.
So when you come to the US market, where the standard of treatment is not the 0.24 milligrams per kilo per week, but 0.32 milligrams -0.34 milligrams per kilo per week, you basically will get a lower treatment compared to what you will see and expect to get from daily growth hormone. And I think this is where SKYTROFA is coming up and always will be the value leader because of its approved treatment you are providing with SKYTROFA.
So when we saw the entrance of the two other long-acting products, we basically saw this is not changing our expected revenue growth because we actually will have an easier way to show our clinical improvement in outcome when we compare to one of the other long-acting because they basically are not providing the treatment effect that you expect to see out from an expected daily growth hormone treatment. Therefore, we are feeling that we will be the value leader that will be either daily growth hormone together with us, and if there is other long-acting potential, they will take something off the daily growth hormone market and substitute that.
You mentioned that the adult indication, you know, will be added later this year or should be, based on the timelines. And that's been an indication that's been relative to the number of people who could take growth hormone as adults, you know, less used than pediatric, maybe for obvious reasons, because growth, you know, is something which occurs during youth, and then it's sort of a different profile that you gain from these products when you're older. But how might you see SKYTROFA kind of changing the uptake, improving the uptake in adults, you know, historically maybe more limited, with growth hormone?
Yeah, the adult market is very different compared to the pediatric growth hormone market. To our best knowledge, the pediatric growth hormone market is penetrated to 70%-80%, where the adult growth hormone market, to our best knowledge, is less than 10%. So in the adult market, you can basically say it's to develop the market. And this is a huge opportunity as the adult market today is around 10% of the entire growth hormone market. So we have an opportunity if we can increase the penetration to three-four times. We basically can develop the entire growth hormone market to a start. And my hope is that the patient with growth hormone deficiency, also some adult, will really start to be treated because there is a huge benefit for them to get such a treatment.
That is not a single parameter, not just the primary endpoint, but giving them all the benefits that you expect to get related to endocrine health. That is where we see there really is an unmet medical need for this patient group. The once-weekly treatment administration is a huge improvement this way, which is much, much less burdensome compared to a daily injection.
When you say, the market's undeveloped, is it just so that we sort of know historically, did the manufacturers of the original growth hormone products not really pursue, marketing in adults? I mean, they got them approved, but were they not as, you know, active in terms of, you know, finding, you know, developing interest, I guess, among adults who could benefit from growth hormone?
It's basically hard to really get a treatment regime that will mainly address a lot of risk factors, also providing a lot of benefit, but it's not immediately like PTH. If you go to TransCon PTH, the patients know basically after one day or two days, yes, the treatment is helping me, providing me a completely new way of living. If you go to SKYTROFA and adult growth hormone, it takes weeks, months, and other things to see this benefit. And this is where the negative part of lack of adherence comes in.
Because when you start, for example, with daily growth hormone, not giving it every day, you basically will not see a real benefit of it. And I think that is the key element where it's highly differentiated with the long-acting once weekly. If you just keep up the long-acting and give it once a week, you really will observe all the benefits on a more long-term basis.
This could certainly be helped by the GLP-1 use, right? So we know that weight loss, you know, is accompanied by lean, lean body mass loss, and the use of GLP-1s has made that a larger societal problem. I think on the last, one of the more recent calls you've had, there was a question about this, and I think, Jan, you said you were interested in looking at it. Do you have plans to look at SKYTROFA in combination with GLP-1? I mean, these are drugs that are also given once weekly by injection, so perhaps those could be used in some sort of pairwise format. How should we think about the company's, you know, plans to maybe evaluate that?
It's a very interesting way to see, because we see the entire market segment in obesity treatment coming in, and that is a huge benefit to the society. That's a huge benefit to the patients. For some patients, sadly enough, also have a negative effect because you are basically losing muscle mass. And if you then have not a consistent treatment, but potentially iron deficiency, you stop, you build up fat mass faster than you start again on a new treatment, then you can go into a situation where you have a lot of muscle wasting.
And this is potentially mainly this kind of patient population where a growth hormone treatment could potentially help them if the clinical data supports that kind of system. Having it in a standard way in combination therapy, I think it potentially will be not fitting how the obesity landscape treatment is really being developed today.
All right, good. Let's move on to TransCon PTH. This is YORVIPATH in Europe. It's launching in Germany. I know it's very early. I know it's only been a few weeks. Wondering if there's anything you can say. I know at the last call you had, it was too early to say anything. Maybe now it's been another week or two. Is there anything you could say, or should we stay tuned for some observations there? I guess maybe too even if you can answer that question, how do we, you know, how should we understand the way hypoparathyroidism is treated in Germany? Is this treated, you know, similar to in the States, or are there special centers where patients go, who, you know, are deficient?
It's the same patient population. It's basically the same patient defining into big groups. One group coming as post-surgical, meaning is that you have been through a head and neck operation, and someway by an unlucky manner, the parathyroid gland got damaged, so you don't have not enough sufficient induction of PTHs. The other group is one that you can basically come to development where you have either genetic causes, you have immunological causes, and you have other things, which are in a different percentage compared to different countries. But typically, the majority of the patients are coming from the post-surgical group. In Germany alone, there are about 80,000 patients. It sounds pretty high because when you go to France, which is the neighboring country of Germany, nearly the same size of population, there are about 25,000.
Some countries where you have a very intensive diagnosis of head and neck cancer, you will actually always get a higher level of patients with post-surgical hypoparathyroidism. We are addressing in our first part of the launch, the first 20,000 patients. These 20,000 patients are patients where you can say that they're coming to the states where they really are more intensive in the treatment. We know all 80,000 patients will all benefit from having YORVIPATH or TransCon PTH. But from a pharmaceutical economic perspective, the 20,000 we are now addressing already have a huge burden from that perspective. Meaning is that they often will go very, very often to the hospital, which is very expensive. Perhaps they're going to start to have rehabilitation.
The cognitive function potential coming to the States where they need a lot of help really to help themselves get things to function, etc., etc., all the different things you have. And this is where we believe just the treatment itself. We have a list price, our initial list price of EUR 105,000 per yearly treatment. We believe that it really benefits not only for the patient but also for the society because we really can help them with all the comorbidities, just short-term symptoms, but also long-term risk in this way.
And this is what we are addressing. We have different what we call areas, how we are enrolling and really getting to where all the patients are in the world. We have something called EU Direct, where we basically are building our Ascendis Pharma own salesforce, own commercial infrastructure, and it's basically built on the different clusters in Europe.
You have single countries like France, Italy, and then you have a cluster like Benelux. You have Iberia, Spain, and Portugal. You have Ireland and the UK, and all of them are being built up now with different speed because it will take us from these different clusters. The fastest one will be 10, 11 before we are fully reimbursed, fully commercial. If you take the more slow one, it takes 18 months. So the first one is always Germany, where you basically have immediate reimbursement. And then in the end of 2024, 2025, you basically will see lots rest of EU Direct.
Then at the same time, we are building up sales and distribution agreements where we take all the countries that are coming from the US, not EU Direct, and not from the two places where we have two strategic alliances, one with Teijin in Japan and VISEN in Greater China. We will go to sales and distribution agreements, and we have already signed the first series of agreements. So when we come into 2025, we basically will have a reach of about 45-50 countries. So by doing that, we basically are building up our global reach. We expect to be in the US market shortly after our PDUFA date here in the middle of May. So we are ready to launch. We have already our infrastructure that is selling SKYTROFA, and we will be utilizing the same infrastructure to really get YORVIPATH or TransCon PTH out to the patient there.
Great. And maybe a question for Scott. From what we see, you know, at least the most recent check last few days is this consensus for TransCon PTH kind of, you know, total sales for this year. I think I saw EUR 77 million per Visible Alpha. I know you guys are pretty good at collecting models from analysts, wondering if that joins with what you have and if you could, you know, share with us your comfort maybe on that figure.
I think, Leland, that's consistent. Maybe around EUR 75 million-EUR 80 million is the estimate. I think as we laid out at the JPMorgan conference, along with guidance for SKYTROFA revenue expenses and operating cash flow break-even later this year, just as we did with SKYTROFA. You could say that's very early to do that, but I think our intention is later this year, provide an update on TransCon PTH revenue for the rest of the year.
Okay, great. That's helpful. We have a few minutes left, so touch on CNP. You know, this is obviously a kind of a dynamic space with, you know, another product is in the market, and then there's the oral. That's a late-stage development. You guys have TransCon CNP. You've also introduced recently kind of a changed perspective on the pathophysiology and kind of what contributes to the overall disorder, you know, in terms of the, you know, muscle as well as bone. And I know you're looking at combination therapy with SKYTROFA.
So I guess, Jan, I want to ask your opinion. Do you see, you know, that being kind of the primary opportunity for TransCon CNP? Should we think of it as, you know, if we see strong results with SKYTROFA in the achondroplasia population, that that would be an area that you could kind of call your own? At the same time, we're waiting for phase III data as monotherapy, so maybe we'll, you know, we'll see where the chips fall. But I want to kind of get your further thoughts on how TransCon CNP might be differentiated eventually in the marketplace alongside the other therapies.
Let's go back and look on what do we really want to achieve. We want to achieve a treatment of achondroplasia, not just provide linear growth. If you just want linear growth, take growth hormone, 40 clinical trials showing that the best annualized height velocity ever seen in treatment achondroplasia has really been done by monotherapy treatment of achondroplasia with daily growth hormone. Daily growth hormone will not provide any benefit to comorbidities. It's never been proven, but a lot of annualized height velocity or linear growth. What we want to do is the treatment of achondroplasia, and we will also provide linear growth. Everything got started when we looked at our long-term extension data in our phase II study. There was a phase II study, the only phase II study, 12 months placebo controlled. No one else had done that. We enrolled 57 patients.
Now, nearly four years after, we have only lost two patients. It took the question to us, why do we see this unique height retention on it? Is that just because we are providing the same annualized height velocity that you typically see with all the CNP treatment, about 1.4%-1.5%, or just moving up to what we call more normal growth velocity of a child? All the feedback we got back, no, it's not there. The child is behaving differently. The child suddenly can coordinate, can start biking, can start running, and have much more self-esteem, feeling much more like a normal child. We started to analyze and then go looking at the biology and found out, yes, we can provide a treatment regimen that basically... We showed it with the data that came out here in the beginning of the year.
When we looked at the patient-reported outcome on physical activity, even in small groups, we can see a statistically significant improvement on it, never seen before. That got us to believe that now we really can address achondroplasia with a treatment. We built it into the secondary endpoint in our pivotal trial now, where we look on different parts of muscle strengths. We look on different elements where we basically use radiological endpoint really to show how the texture of the child is changed. We look on physical function, strength measuring, and other things, ensure body composition, but also the quality of life, where we have different instruments to measure that. All of that is part of us to ensure that we have a treatment regimen that is addressing really the comorbidity of achondroplasia. Then you can ask me, why do we make a combination trial?
We mainly do it because if you were a newborn today with achondroplasia, got treated with, for example, TransCon CNP from day one, you would basically have normal growth. But if you have a lot of children with achondroplasia that first started treatment late, seven, eight, nine years, you basically have not achieved the annualized height velocity because what we have observed in all places is you're just normalizing annualized height velocity when you start treatment.
If you go to growth hormone deficiency that nearly has the same low growth from achondroplasia and you start a child seven, eight, nine years, you have catch-up growth. Meaning is that you grow more than the normal growth of a normal child. And this is why we make this combination. If you really would like to have more linear growth, if the child wanted it, the parents wanted it, we will make a treatment option available for that. This is why we are also making the combination trial.
Great. Well, I think we're up at our time here. So thank you again and team. We look forward to the, obviously, the phase III in achondroplasia data coming out toward the end of the year, PDUFA date for TransCon PTH in the States in May. And of the oncology, we didn't get a chance to touch on those. Those two assets will have some more data late this year. So thank you very much again, and thanks everybody who joined us for this discussion.
Thanks for inviting us. Thanks for us.
See you.
See you.
Absolutely.