Joseph Schwartz: Hi there. Thanks very much. I was wondering if you could talk about the work you did to arrive at your estimate that 70,000 adults have chronic hypoparathyroidism in Germany. And who were the 20,000 patients that you’re targeting there? And how does the target population in the United States compared to the total hypopara population in the US where we have some guidelines, I’m wondering if that influences the proportion of the market that you think is most addressable here in the United States? Thanks.
Jan Mikkelsen: Thanks. I think you got all the questions into it. And when we compare the demographic between Germany and US, it consists of the basic two group, the post-[indiscernible] with one group. And then you can say the more hemological genetic, idiopathic background where you typical will see a rise much earlier in states of life. Germany potentially is a little bit unique with the last number of patients because — and I think it potentially is built on the high level of intensive head and neck operation because of really, really strong folks of diagnosis. And from that perspective is, yes, there is potentially more positive patients in Germany than you see in the US and other — for example, if you take a country like France, France will much more relate to what you will see of treatment way that you see in the US.
So, — when we see this different patient population, all of them will benefit of the TransCon PTH treatment or YORVIPATH. It’s not like one group or the other one are less beneficial in the treatment on it. So, all of them deserve to have a life with TransCon PTH. Going back to what you say when we talk about 22,000 patients. And it’s not because we see subpopulation that see more benefit or less benefit from that. When we talk about the 22,000 patients, which we try to address first is the patient that from a pharmacoeconomic perspective, have a really, really hard type on the society that can be — potentially come to the state of real impairment that can come to a state that visit hospitalization a lot. They come to a state where they cannot function because of cognitive effect, they cannot get a normal life.
So, out from that perspective is not really a treatment benefit. This is more that the burden for this society. And this is where we always need to be. We need to benefit the patient, the society and everyone as all stakeholders. And this is the burden for society as much, much higher for this 22,000 patients.
Joseph Schwartz: Very helpful. Thank you.
Operator: Thank you. And our next question will come from the line of Derek Archila from Wells Fargo.
Derek Archila: Hey good afternoon and thanks for taking the questions. Just two from us. I just wanted to clarify, is SKYTROFA a $1 billion product in the US just on pediatrics alone? Or does that assume contribution from adult EHG as well? And then just in terms of the cost structure of the Endo business, is this 600 million cost base now, how we should be thinking about it for the future? And just your thoughts about profitability of that business?
Jan Mikkelsen: Thanks, I will take the first question, and then Scott is really happy today now because he actually has an opportunity to come to some of the financial numbers is running, so dedicated over time. When we look on the potential market, yes, you can see we will have adult growth hormone deficiency. We will pursue some of the other indications, too. But we also need to say that we are liberating a normal somatropin molecule, which are well-known entity for all different indication that seen the benefit on growth hormone. And if you go to the market of the daily growth hormone and see what is the dynamic there? The dynamic is that none of the daily growth hormone basic — because they’re all so much hoping to — all of them basically are in a position, none of them have all the indication where they’re actually being reimbursed or used today because none have really take the effort to go through all the different indications.
So, it could be potential. The same thing will be applied also on the long-acting products that are providing the same somatropin molecule. Scott, will you talk a little bit about expenses and numbers in less than 10 minutes.
Scott Smith: How much time do we have? Thanks, Derek. So, it’s good to get a finance question. So, as you saw here in the Q4, we’re realizing now the benefits of the streamlined operational changes and processes that Jan has talked about with OpEx going down to about €155 mi total. And then, of course, next year, you’ll see more come off as a result of basically no P&L burden from ophthalmology. I think you should look at this as a product of the way that we’ve developed our portfolio and how efficient it can be. I think if you look at our cost for TransCon growth hormone and realize the stage of that product and how mature it is, the costs should be dropping pretty substantially in the coming years. And overall, we’re going to be pretty efficient in R&D.
So, I would expect more shift from 60/40 R&D, SG&A in 2023 to maybe 50/50 or so in 2024. Longer run, will be efficient in R&D. And as we expand globally, I would expect some increase in SG&A as we add people in 30, 40, 50 countries, but it should be pretty minimal. And as you saw going from Q3 to Q4, our SG&A was basically flat even if we launched an additional product and got ready to launch a second product in Germany.
Jan Mikkelsen: One comment. What you see the result of something was basic element that happened in 2023. You don’t suddenly change the company. You don’t suddenly streamline the company. It takes a lot of effort. It took us — started in the beginning of 2023, really find out how can we build a leaner Ascendis more productive, really focused on really optimizing processes, administration and everything like that. And we were very, very, very successful to that. It was a hard task, not already always pleasant, probably there now. We are where we want to be now. We’re still optimizing our processes because we’re scaling for potentially having 5,000 to have 50,000 processes. And you cannot use the same PV system that you use to 5,000 to 50,000.
So this is why we really are still optimizing process, changing the company because we cannot be a leading biopharma company at the same way we operate it as a large biotech company, where we basically were focused on clinical development and few commercialization. So, we are still transforming. We’re still changing our processes, and that is what we need to continue to be truly competitive in this landscape.
Operator: Thank you. Our next question will come from the line of Kelly Shi from Jefferies. your line is open.
Kelly Shi: Thank you for taking my questions. Maybe switch topic or two TransCon CNP, you have talked about the improvement on muscle function and other companies, we feel like talk about mal proportionality like upper to lower body ratio. I’m just curious, have you also looked at a proportionality as well? And also, when it comes to the combination with SKYTROFA what would be the most differentiated clinical benefit compared to TransCon CNP alone? Thank you.
Jan Mikkelsen: Thanks. I will start from the back because if you have a child born with achondroplasia being started treatment as a newborn, our belief is that basic will nearly have normal growth in this period of time where you have growth related to linear growth. You will not really address and stop or can stop to address the comorbidities because they will exist rest of the life. And this is when we see on the integrated aspect of achondroplasia, we see the linear growth as one part of the disease, and we see the other impact of the hyperactive pathway have another aspect, like, for example, muscle weakness and other aspects, which are really from a mode of action is different compared to what you see on the achondroplasia that really are limited in the way, they get linear growth.
So, when we think about how we are positioning our combination trial is that what everyone have seen of data for the impressive amount of clinical data that’s come out from BioMarin related to vosoritide, all of that showing that you normalize growth for the vast, vast majority of the patients. But if you have a child that got born and first started treatment of eight years, they still have a lack of growth. So, when we saw all the data that has been generated by daily growth hormone, more than 30-40 publication, really intensive trial with 40, 50 children. And we see that that basically can induce catch-up growth as you can do in growth hormone deficiency because that is what we do in growth hormone deficiency. The more of growth hormone is that you can reset the growth to be normal as a final height if you are on a good adherent treatment.
But you can only do that in other growth hormone deficiency, if you have a catch-up growth, meaning that you grow more in the first two, three years then you basic will see of a normal growth. That is why when you think about a child with growth hormone deficiency, not have been treated for eight, nine years, starting potential treatment and then suddenly hit the parents’ height as expected. This is because of catch-up growth. And you see the same thing in achondroplasia. If you start to give them growth hormone. I see growth effect up to seven, eight centimeters, not as fast as you see in growth hormone deficiency and is likely because they still have a block down on the achondroplasia, because they also need CNP. So, when we think about the perspective of combination trials, this is the children that not get treated, and this is basically the majority of children today.
That is not got treated from they got newborn and really need some catch-up growth really to get a burst in the growth. And this is why we are running this trial. My expectation and now I can be trying to do something that is very, very dangerous. But I believe you can potentially grow them up to eight, nine centimeters just by combination treatment because you get the catch-up growth for the first one, two years. And this is the rationale really for us to go out and make that treatment regime because we do the same as vosoritide, we normalize growth. So, proportionality, yes, we see the same positive trend in proportionality that we have seen and expected to see. And we will see more and more when we see more data from longer part of treatment because it takes longer time to really to see the right benefit on this or change of this proportionality, but we definitely are seeing the same positive development.
Kelly Shi: Thank you.
