Ascendis Pharma A/S (ASND) Earnings Call Transcript & Summary

Good morning, everyone. My name is Jess Fye. I'm one of the biotech analysts at JPMorgan. And we're delighted to be kicking off the 2020 health care conference this year with Ascendis. I'm joined up here by the company's President and CEO, Jan Mikkelsen. And just as a heads up, after he gives his presentation, which will hopefully touch on some of the updates the company press released last night, we're going to do a breakout session for more Q&A. It's right down the hall that way in the Yorkshire room. You can follow me. So I'll see you there. And I'll turn it over to Jan.

First of all, thanks, Jess, for inviting us to come here to San Francisco. And thank you for everyone to -- joining us today to hear about Ascendis Pharma. As a reminder, I will making forward-looking statement. Please refer to our SEC filing for associated risk factor. 2019 was a transformative year for Ascendis Pharma. So I will not really start and talk about what we did in 2019 but just move directly into what we want to do in the future because what we have done with Ascendis Pharma is built a really, really strong fundament how we really can develop us as a leading biopharma company. So what -- how do we do it? We do it by creating best-in-class product, addressing unmet medical need, but by using our wholly owned TransCon technology to parent drug with clinical proof of concept. And basically, by using this concept, we have been extremely successful in our development. We have built up a pipeline of 3 independent product opportunity in endocrinology rare diseases. And we have been focused on what we call large orphan drug, not ultrarare diseases. Our most advanced product opportunity is TransCon Growth Hormone for pediatric growth hormone deficiency. We had our data coming out in 2019 basing from 2 Phase III trial. And we now are getting planned for BLA filing in Q2 and M&A filing in Q4. I will give you a further update later on. The next one is TransCon PTH for hypoparathyroidism. And we will actually have our top line data from our Phase II trial, which we actually have expanded. And I will give you some background for that and also give you a little bit of a snapshot of some of the data we see in there. And we perhaps, also extremely important, we will see long-term data in Q4. TransCon CNP for achondroplasia, our third independent product opportunity in rare disease endocrinology. We basically are dose -- doing dose escalation in our Phase II trial, but we also have decided to initiate a second Phase II trial. We want to build a leading position for each of our endocrinology product on a global basis. We will do that by different commercial routes. One of them we already have shown how we're doing it in China, our second largest pharmaceutical market today, where we basically have made a partnership where we own 50% of a company that will both commercialize but also develop this product opportunity inside China. Our second therapeutic area, oncology, we're already building up an early-stage diversified pipeline. Cash position, well financed. In the end of September, we had about EUR 660 million. Going to how we run the company. I don't believe in random process. I believe you need to have a clear direction where to go. How Ascendis have a clear direction where to go? We have it by our vision statement, our Vision 3x3. And this is how we want to build a leading biopharma company. And we do this by having sustainable growth through multiple approaches. And you can go through that. That is basic. First cornerstone is to get the 3 independent product opportunity approved in each of the independent product opportunity. The second one is make sustainable growth by our global reach. And this is what we're executing on in Japan, in China, in South Korea and then pursuing by label extension up to 9 total indication, also including life cycle management. We have clear idea how we still can go into life cycle management. But we will still focus on making new endocrinology product. We will establish our global commercial presence for our endocrinology rare diseases by building an integrated commercial organization in North America and select European countries. And then we will do partnership or other thing where we still have a major upside of the value creation of our product opportunities. In oncology, we have created our first pipeline now. And we will give a snapshot of some of the pipeline and also a little bit more in-depth of one of the product opportunity. But we are not stopping there. We're planning now and already starting to executing on our third independent therapeutic area. So this is our pipeline today. And you can see from our 2 known therapeutic area, endocrinology rare diseases and oncology. And you can see rare disease endocrinology, really late stage. All of them is past Phase II or up to -- ready to filing. And now you see the other one, oncology, coming up, maturing more and more, more. This is how we generate sustainable growth. And then you will see in the years to come, a new therapeutic area still coming up. So how do we really generate all these unique product opportunities? We do it with the TransCon technology. This is basically the TransCon technology that you have known a lot about. This is the fundament between TransCon Growth Hormone, TransCon PTH, TransCon CNP. And for example, also our IL-2 beta/gamma specific. And what we're doing here is basically saying, when you start with the parent drug, we basically released an unmodified parent drug. So when you talk about true replacement therapy like PTH and growth hormone, we basically are liberating the same unmodified entity as nature created as an endogenous entity for growth hormone. And by doing that, we basically have a low risk. And this is why we have been extremely successful. We have expanded our technology platform also now to sustained, localized delivery. And this is not just injecting into a place. No, it's sustained, localized delivery that can have an exposure profile from weeks, months, quarterly up to half yearly, a complete new technology which actually FDA recognized by giving our -- the same as an emerging technology. So I will give you a short update about our growth hormone product opportunity. TransCon Growth Hormone, our most advanced one. Just recall, growth hormone is not only for height. Growth hormone has an integrated effect on what we call endocrine health. And this is everything from body composition, mental health, cardiovascular diseases, fracture, but also something like exercise capacity further on, further on and further. Sure, we measure height in children. In adults, we measure change in body composition. So therefore, when you look on the integrated effect on growth mode, you need to look at all the expected effect you have seen with daily growth hormone for the last 20, 30 years. And that is what the physician expect to see. This is what the patient need to have, all the integrated effect. So our Phase III program is basically 3 program: the heiGHt, which are basically the pivotal trial; then you have the fliGHt trial, which are switch trial; and then you have enliGHten, which are our long-term extension trial. Going to our heiGHt trial. This is where this year or last year, we showed our data from that where we clearly could see a superior growth effect of the same equivalent dose of TransCon Growth Hormone on 0.24 milligram per kilo per week compared to daily on 0.24 milligram per kilo per week. Why was that really, really unique? Because the goal for all this have been just trying to get the same effect as daily growth hormone. What we managed to achieve was that we can actually get a superior growth velocity without compromising anything related to either safety or tolerability. Just recall, when you look at this growth data here, if you look in other areas like, for example, growth hormone deficiency, but also achondroplasia, all of them have the same base growth before treatment. So when you see what we're doing with a child with growth hormone deficiency growing on a base level from 3 to 4, the first year, we basically move them up to 11.2 centimeter. Just seeing the treatment difference is about 7, 8 centimeter. Just seeing what is the effect that we do in growth hormone efficiency. Achondroplasia have the same basic growth deficient -- and basic -- have the same basic of about 3 to 4 centimeter. So when we do subanalysis, you can say, is that only on a small portion of the subjects that you really see this kind of superior fit? No. Everywhere when we started to analyze it, 8, 6 baseline growth hormone stimulation, which are basically the effect where we see what is the level of growth disorder. We also look on different isolated idiopathic, isolated organic, or you have multiple hormone deficiency, all of them show the same improvement. When we go to the marker of what we call IGF-1, which basically are, you can say, both the efficacy, safety marker, but illustrating the effect of in the body on basic stimulating IGF-1 generation up from the liver. We basically see the same effect when we are reflecting on that there is a different in analyzed height velocity. From daily growth hormone, we know if you have about 1 centimeter different in analyzed height velocity, you expect to see a delta IGF-1, 0.7, and it's exactly what we see. And we see the same kind of variability, indicating everything what we have learned about TransCon Growth Hormone, it basically mimic the same effect as daily growth hormone on all different kind of element you expect to see out from a daily growth hormone treatment. So now we have basically locked all the databases in all our Phase III clinical trial for basic filing and what was first learning was -- we -- learning was, we have the same safety and immunogenic profile as daily growth hormone. We have a superior effect, but we believe the superior effect is not changed -- caused by change in mode of action. It's change that we have a much better distribution of the growth hormone inside the target tissue in the growth plate. And this is why we see this superior effect. We also saw a really nice linear response, which makes it extremely predictable, meaning is the physician have the opportunity to titrate up or down exactly to the treatment our customer want to have. And when we look on all the indirect and direct effect, we see exactly the same balance between that. We have now made further data analysis, mainly on the enliGHten trial, where we will give you a few update. If you now go to the safety, we show heiGHt trial. We show in the heiGHt trend where there's a direct comparison to GENOTROPIN exactly the same safety. When we went into the fliGHt trial, we saw the same thing. When we go into enliGHten trial, we saw the continuation of both trial. We see exactly the same safe compound. The other thing that's interesting, if we take a patient from the heiGHt trial, what is happening with them when they go into the enliGHten trial? It's meaning is that both the TransCon Growth Hormone and the GENOTROPIN are -- got actually transferred over to TransCon Growth Hormone. We see actually the same growth, meaning is that we keep up the superiority. But it's not enough to have that. You also need to have optimal product feature. And this is what we have with our product: room temperature, small needle, small volume. Everything you can read through. And this commercial presentation has now been transferred over for more than 160 patients, really in an extremely successful manner. On track to our filing? Yes. We have completed the fliGHt, the heiGHt trial. We have included the rollover in the enliGHten. We have the necessary 2 years data. Everything has been locked. We have completed manufacturing of PPQ batches. We have completed the development of the auto-injector. We have introduced the auto-injector and DCC in the enliGHten trial. We have obtained the necessary data that was necessary for us in initial filing. We have 2 BLA meetings. We are also in the designation in Europe. We both got orphan drug status, and we also got the CE mark for auto-injector, really on track to our BLA filing. What have TransCon Growth Hormone -- yes, it has raised the bar from daily growth hormone. The current benchmark is not daily growth hormone. TransCon Growth Hormone is an improved product compared to daily growth hormone. And we are ready to be filing, both in Europe and U.S. We create further growth as according to our vision. China, we have initiated a Phase III trial in growth hormone deficiency. Globally, we're going for the adult growth hormone deficiency Phase III trial expected to be initiated here in this quarter. Japan, we will have a pediatric Phase III trial initiated in 2020. We have the auto-injector as part of our initial filing. Commercial manufacturing is ongoing. We are producing as much material as possible to be ready for the launch. We're getting the commercial team ready, so we [indiscernible] to launch the product. And we have a very, very strong IP designation. Going to TransCon PTH. Yes, large orphan drug disease, more than 200,000 patients. You can see how it's split in different geographic regions. The textbook for this product opportunities was really, really obvious. It came out when you basically look on NATPARA briefing -- FDA briefing document. They came out and saying, what is the optimal product. This is when you look at the shattered line where you're saying there is that product that always in the normal physiological level 24 hours, 7 days a week. What did we show in our Phase I data in our healthy volunteers? Exactly that profile. This is the profile you see, which really are mimic what we call the normal PTH level, exactly as we had predicted. And that was not only the PK profile we saw, but we saw also -- I should say, the PD and other effect, exactly as expected. This is -- was our Phase II trial design. What was the purpose of our Phase II was really to find out what is the optimal starting dose to have complete removal because to -- of all standard of care. To have complete removal of all standard of care is essential to have a true replacement therapy. That is necessary. There was settling of a recall of NATPARA in the U.S., meaning is that around 2,000 patient that was on NATPARA treatment suddenly didn't have any kind of treatment option. When we heard about that, we basically tried to expand our trial. We did that by making addendum here in the U.S., so we actually can also take patient in from there that just have stopped using NATPARA. And what we have done now, we basically gave us an opportunity. We both have 2 part of, you can say, population in our Phase II pathway, what we call really naive patient, but also someone that has been transferred there shortly over for NATPARA treatment. We will have in our open-label extension trial, basically an end point that will be evaluated after 6 months: normal serum calcium, off activated vitamin D, taking less than 500 milligram per day of calcium, normalized urinary calcium. Why is that important? Because that basically are reflecting exactly the same end point we had discussion with regulatory agents. So what we have done, this is just to give you a small update, a small snapshot on our pathway forward on. We have sites in really broad perspective, both Canada, U.S. and Europe. We have stopped screening. We're just getting the last [ px ] enrolled now. We expect to get at least 55 subjects. We had initial 40 subjects planned for. No patient today have dropped out of the double-blinded part of the PaTH Forward. Preliminary data. This is just a snapshot on the [indiscernible], where we can see how patients are doing in an open-label extension. And this is 4 weeks in the open-label extension. A [ cut point ] for [ me ]. Why is that essential? Because at that time, we know that the patient that were on placebo actually also has been transferred over to TransCon PTH drug. Then we say, what are the use of standard of care? All subjects are completely out of standard of care. 8 out of 8 subjects require no activated vitamin D. 7 of 8 subjects no longer require calcium supplement, meaning they are taken late. So top line data, end of March, 6-month data in Q3. We have already introduced our auto -- our pen device in our Phase II trial. This is our commercial presentation, really ready-to-use liquid formulation, room temperature, stability for 2 weeks, low injection volume, exactly our optimal product opportunity. So Phase I, data support infusion-like profile of TransCon PTH. And the regulatory agencies recognize that. Because we are saying, yes, there's no need to make a carcinogenicity or CAD study. And I think this is the first PTH product that basically are not going to do that. We have really expanded but also getting the NATPARA patient into it. We are really doing everything for PPQ batches. So we also have material ready at the time we're ready to go to the market. And we have done [ maximal ] enrollment. CNP, just one single slide. I'm extremely excited about the CNP. So this is after we saw the latest Phase III data that really validated that pathway. It's really validated that pathway. But it also validated that if you only have exposure for 10% of time, you only have small effect too. And this is where we come in because if you have an activated pathway [ fine ] 24 hours, 7 days a week, yes, if you want to normalize it, you need to have continuous exposure on the CNP. And that is what we have proven in our Phase I data, where we basically see that we have a half-life of 120 hours, really a record. Taking a peptide for 2 to 3 minutes up to 120 hours without any kind of adverse event seen. We basically have a natural history study which are going on. We have started our ACcomplisH Trial, which are our Phase II trial. And remember, we're going down to 2 -- age 2 from the beginning. There are differentiation to what other company has done. And it just illustrate really the safety of this product opportunity. And what we want to do in China is to actually open up a second Phase II trial when we basically have done a dose escalation in our first ACcomplisH trial. We basically can take a large portion over to a second Phase II trial. So we basically have 2 independent Phase II trial would -- can keep more than 100 subjects. And what we want to do, not only look on height. We believe height is one part of it, but we really want to address the comorbidity of this disease. Oncology. This is where we're building up our early stage. And what we want to do, we want to use the same proven algorithm that has been extremely successful in rare disease endocrinology. We want to use exactly the same thing in oncology. There's just many, many, many more options in oncology compared to what were in rare disease endocrinology. We have built up a pipeline on 3 independent product opportunities now. This is what we're discussing now. One is TransCon IL-2 beta/gamma specific. Then we have 2 intratumoral delivery compound, TLR 7/8 and TransCon VEGF-TKI. Today, I will only focus on our IL beta/gamma because it's also very much reflecting a little bit what you saw in growth hormone, PTH and CNP, the same technology platform. But what we wanted to do is really building up the best-in-class rare disease, the best-in-class bispecific IL-2 compound. And what we wanted to do, separate the 2 different processes, how to have optimum selectivity, potency, how to have optimal exposure. And we separated this 2 process, and we can do that. So what we did, we took the IL-2 to get -- introduced a cysteine directly into the alpha-binding site. Then we took a small, small PEG. Why take a small, small PEG? Because you disrupt with a small, small PEG, total the alpha-binding but you don't want to disrupt too much because then you also interfering the beta/gamma potency. And that was exactly what. So we only took a small 5 PEG [indiscernible]. And when you see this data here, yes, this is how good it can be really shown how on Treg cells, you're really [ changing ] [indiscernible] in potency and basically keeping all to the CD8 cells, exactly what you had hope for. The next thing is to go over to the TransCon technology. We basically take our established system that you have for TransCon Growth Hormone. Take it together this molecule, we already have GMP manufacturing on that. So we basically just coupled into what we have for growth hormone. And what do we then see? You see exactly what you want to see in primate. You see small amount of molecule, 0.1 milligram per kilo, really showing extremely potent enhancement of lymphocyte counts, only one single dose of 0.1 milligram. And what you see at the same time, exactly the right selectivity, which basically mean that you can avoid vascular leak syndrome. And that's exactly what we have seen in this. And we've also seen antitumor effect, single dose, multidose in this one. Going back to our oncology summary, this is our emerging market. But for perhaps our 2020, this is our expected milestones. You saw what we achieved in 2019. We built, and this is what we have done in the last 10 years, built the fundament, how to be a leading rare -- leading biopharma company. And what we're doing now, executing on this one. We have all the product opportunities. We know the product opportunity have a high success rate because it's proven on already established mode of action. So what we're building is now and what we're executing on have the best possible team really to get this product opportunities as fast as possible out in the market. Q1, initiate global Phase III in adult growth hormone deficiency, top line data, submit U.S. BLA for growth hormone, 6-month PTH for PTH, and you can also take the rest in Q4. There are so many in Q4. I think it's hard to read all of them. So thanks a lot.

Welcome, everyone, here in the Ascendis breakout. We have a number of members of the management team up front. They're going to repeat the question because it's being webcast. But maybe just with -- I'll take the first one, still my favorite question. Can you give us an update on your progress towards fulfilling any CMC requirements for the TransCon Growth Hormone BLA filing? And what's your confidence in manufacturing adequate commercial supply after the launch?

Thanks, Jess. Before we start and answer the questions, I would like to introduce the team I have with me here today because I think it's important that you see the broad net that we have in our management team. So I think most of you know this person that's sitting to my right here, so would you allow to introduce yourself. Okay. So perhaps, Dana, can you introduce yourself?

I'm Dana Pizzuti. I'm Head of Development Operations, which includes clinical operations, regulatory affairs, pharmacovigilance and biometrics.

Tom Larson, Chief Commercial Officer.

Good morning, everyone. This is Juha Punnonen, Head of Oncology.

So not because I want to forget your question, Jess, because it's a question I potentially have got one other times before from you. But going back to the question, the question is related to what do we need or further requirement for our BLA and MAA filing related to our TransCon Growth Hormone product. So what we have done, we have finalized everything that was needed related to our validation batches. And that is including everything from starting for -- starting materials into filling in DCCs. We are still compiling the rest of the data. We're finalizing the reports. So we are in a position that all the physical manufacturing, all the thing that happened for last 2 to 3 months. Related to the requirement for a launch, do we have sufficient production capacity and was the second question from Jess. Currently, we are in a position that we having a one large manufacturing site. This site is already producing on the highest speeds and it will be giving off sufficient material for a very, very, very successful launch of this product opportunity. As you will see, we are focused on a global reach for TransCon Growth Hormone. We are taking this product opportunity and saying is that we want to have a leading position on a global basis. Sure that would require that we will have more manufacturing capacity and that's already have been built in into our further plans. To be quite sure, we also have the capacity that are needed when we want to have this product opportunity being launched on a global basis.

Are you able to demonstrate the economic value of the improved height velocity for your product over the standard of care?

So the question was, can you demonstrate the economic benefit of your products over time? Probably for the reimbursement purposes, I'd assume..

Yes. And specifically the...

Growth hormone.

Yes.

I can make the initial answer and perhaps Tom will add on. So what we have in our organization, we have a strong focus on the healthy economic outcome, basically because we are a European company that think in a global perspective. In -- from the European setting, you don't go out and come with a price. You -- from a European setting, you go out and making a justification of a price related to the outcome you will provide to the patient. So out from that perspective, we can easily, easily do the justification of the price structure we expect to enter in the market because that is integrated part of thinking as a global company.

Yes. First of all, certainly the payer communities, they certainly value Ascendis. You look at our -- at TransCon, they understand the platform and the power of that and that's critical. They certainly see and value the rare disease endocrinology portfolio and they definitely want to do business with us. They see the value of that. But then looking at TransCon, the value proposition is very unique. Achieving a superior height velocity, we're the only long-acting that developed -- that did that with a statistical significance. You look at the switch trial, we're the only long-acting that has done the switch trial, the only unmodified and the only one to have room temperature. So they definitely see the value. So that's going to be the foundation of the value proposition.

On the PTH front, many patients are -- that seems like they're doing reasonably well on vitamin D and calcium. So what's so much the significance of taking them off vitamin D? And what type of outcome benefit do you show in the trial?

So the question was, what is the benefit of removing standard of care from the patients who are taking -- hypoparathyroid patients who are taking standard of care. And how can maybe TransCon PTH improve their treatment.

So going back to the signs, the fundamental of this disease, you have short-term symptoms, you have long-term complication. What do you want to have? You can compromise the short-term symptom by just eating 3 to 5 gram of calcium every day, meaning is that you wake up during night 3 to 4 times [ just to take calcium ]. Yes, it control that you have basic calcium in your blood. But it's not solving the underlying fundamental that you still will have a high phosphate, will give you calcium complex throughout the body. This is why you get the long-term complications. So basically when you talk about symptoms, you find it out from this way, yes, when you talked with patient they say, "We're dealing very, very well with the symptoms." But the problem is then -- introduce the long-term complication. And this is where you see the issue in this kind of disease here. But when you're just going back to the short-term complication, when we see what happened when -- about more than 2,000 patients suddenly couldn't even get NATPARA, which are not a true replacement therapy, and we saw how dramatical episodes came out and moving them into emergency room and other things are stabilizing. It just illustrate the severity of this kind of disease. And this is why you have a system perhaps more introduced in Europe where you take patient on infusion pumps because that is a way you basically can be in a position that you can provide the optimal treatment option, basically providing PTH 24 hours, 7 days a week in the physiological level. By doing that, you basically address all aspect on the disease. But everyone know the huge patient burden, the huge complication basically to go and being -- if we drip with an infusion pump all the time. So I have no doubt when we see all the basic element on this kind of disease, we really, really addressing a major unmet medical need. And what we can do with our TransCon Growth Hormone for first time, basically providing a true replacement therapy. And when you see the patient population, it's more than 200,000 just in the regionally, say, if you include China, that's more than 150,000 to 200,000 patient, additional patient. So it's a major, major area for unmet medical need and there has never been any kind of treatment opportunity except if you go on an infusion pump. And that is what we can mimic with an insulin-like treatment. Just a single subcutaneous injection daily and you have 24 hours physiological PTH.

And if I may just add, how long term is that then? And what are those major complications of the disease? Obviously, you don't see outcome in the trial, but...

So the question was what are the long-term complications of treating hypopara patients with standard of care.

And after how many years do patient's symptoms [indiscernible].

The short-term symptom you will just see immediately. You will see it already after 4 to 6 week, perhaps 3 months. You will already see that the patient are functioning like normal patients because there are also CNS effect that -- other things like that. Yes, you see that immediately. And this is like being in a position that the patient have no idea what they really are missing before they get a treatment option. And this is what you will see when you have for first time a true replacement therapy.

You have set the stage for the data readout towards the end of March 4-week study to establish starting dose for future trials for PTH, the different dose levels and kind of what we can learn from them [indiscernible].

So the question was set the stage for the data readout, probably talking about trial design, the purpose of the trial, what to expect from the results on the top line, dose response and so on.

Yes. So one of the aspect of our Phase II trial, and now I'm talking for myself, is that I'm convinced TransCon PTH is going to function because when you look at the data in the Phase I, everything what we saw in our healthy volunteers kidney function. What we get out of our Phase II trial is basically find out what is the optimal algorithm for initiating a treatment for basically taking all supplements away from the patient and stabilize them on a PTH level. Are they best to stay in a recommendation starting on 15, 18 or 21. So the overall process in my view is basically to come out and say, "Yes, we know 15 microgram is potentially the best or 18 is the best starting dose." And in less than perhaps 6th, 8th day, you can withdraw all the supplements and then you are in position that you can stabilize the serum calcium in such a manner that is optimal for the patient afterwards. That is what I think. The data you will see here is basically what I hope to see. What I expect to see is we can take, for example, for 15, 18 or 20, we can basically take the vast majority of all the patient away of standard of care in this 4-week period. We also would like to see that we're basically are in a position that we can still keep a fractional excretion of calcium in the normal level and that is also what we expect to see. But at the same time, if we have 55 to 60 patient, what do we give us as a unique opportunity? It give us a unique opportunity to have an open-label extension trial with about 55 patients. Then we can go and follow for 6 months. And this is when you look in the slide deck in the JPMorgan presentation that after 6 months, we analyzing basically what we call our expected Phase III end point. And I think it give us very, very, very strong data to -- and positive discussion with regulatory agencies what is this product really providing a really good efficacy. Remember, NATPARA got approved for 6 months data for 84 patient.

Can you elaborate on why that 6-month end point is slightly different from the 4-week end point?

The question is why is the 6-month open label extension end point different from the end points in the 28-day blinded portion of the Phase II?

Okay. The main difference is fractional excretion of calcium compared to 24-hour urinary calcium. Why do you use fractional excretion of calcium? Because in our imagining, it could be that in the -- for example, the 21 microgram PTH, that a group you basically will make some patient hypocalcemic. When you make a patient group hypocalcemic, you use fractional excretion of calcium as a way to show that you have a normal kidney function. Because there is a calcium independent transfer mechanism in the tubular system of the kidney, so independent of PTH, it will make a balance between what is in the blood and what is in the urinary. So when we come to the 6-month data, we expect all of them will be really nicely balanced as well normal serum calcium level and none of them will be hypocalcemic. Then you will be in a position that you can use 24-hours urinary calcium measurement. And that is the main difference. Because we -- if you look at our Phase I data, there could be a chance that some of them will move up to 10 to 11 in serum calcium, and then it's much more relevant to use fractional excretion of calcium measurement at that time. Yes? Yes?

What's the next step after the PTH data? What is the pathway for that?

So the question is, what is the pathway after the Phase II 28-day double-blinded portion of the PaTH Forward trial?

We have a baseline. The baseline is that we have our Phase II data. We go over and talk with the regulatory agencies about this and they will look at the data. We have different possibility for breakthrough and other things like that which give us a different kind of interaction. Would we make a Phase III trial? Yes, we will potentially make a Phase III trial. But Dana, if you have any comments to it, you can talk from a regulatory perspective.

Yes, sure. The key issue will be sort of when the data are available, we take it to the agency. We've already had discussions with them about the requirements for breakthrough therapy and we're pretty clear about that. And the data that we've -- are generating should, assuming the results are what we expect, should be able to provide that evidence for them. If we get breakthrough therapy, then we begin discussions about what a Phase III program would look like and what the possible approval path would be. But that would be like our first ever, right, would be to approach the agency about that. And then depending on how we agree on the -- how compelling the data are, then we can move forward with that. But then a Phase III, as Jan said, is generally what you would do. Whether or not there is a pathway that might be an alternative to that, we'll see after the breakthrough.

Still we have a huge issue here in the U.S. We had a large patient population basically not having opportunity to -- even to have a treatment opportunity that was basically not a true replacement therapy, but it was a treatment opportunity. And that don't exist today. So I think we are in a position where our feeling with our patient focus, we have a huge opportunity to be in a position that we can go out and help this patient population as fast as possible. We have the capacity in manufacturing. We have everything ready. So I think that is basic to have a positive dialogue with the regulatory agencies. And I think both Ascendis and regulatory agencies have only one wish, it's how to do the best for the patients. And that is what we will try to address as fast as possible. You had a question? Go ahead. Yes?

Can you give us an idea when we should expect to see data from the TransCon CNP trial?

So the question was timing for the TransCon CNP Phase II program.

That is a discussion we have a lot of internally. What is really the expected cohort that will give the optimal effect in this way? And this is why -- first of all, what is the main difference that we're doing compared to other companies? First of all, we already, from the beginning, are enrolling patients down to 2 years. Patient -- other company is just starting to go down to 2 years now. So this is where we're starting. The other part is that we basically are qualifying to a natural history study, a big patient population in China that basically when we are in a position that we see a really active growth, we can initiate a second Phase II trial, taking a last patient just on this trial. And all of them are done in a double-blinded manner. So it's really giving the optimal opportunity both to see poor efficacy, safety, not only height because we basically believe is the -- for example, the mortality is not driven by lack of height. The mortality is driven by the severe comorbidities these children have. And this is why we were really, really extremely -- when we saw the regulatory agencies, we understood -- they also understand. This is why they cleared us to go down to children at age 2 as fast as possible because they didn't want us to start with the older children, just go down to age 2. And when you're first down there, you easily go down to newborn childrens. And this is where we believe you need to initiate the treatment, really, if you really need to some way balance the entire development of a child where you're basically normalized to a normal bone growth.

What kind of dose cohort are you on in that study? Are you past the first cohort yet?

No. We are still in the first cohort. Jess was asking where are we in it. We're still in the first cohort.

[ Have you dosed the first ] [indiscernible]

We are in a position where we have all the element aligned to basically be in a position that we will hopefully conduct multiple cohort acceleration during 2020. Because there is only 6 months treatment period of each cohort. And then we haven't readout.

Just following on clinical trials. You can always update this at times but [indiscernible] it's not [indiscernible] the first quarter as a target?

So the question is, do we continuously obtain clinical trials to reflect the current situation? And is that the case for TransCon CNP?

I think you can answer that.

I think the answer is no. We don't. We update it as required, not to give competitive information out.

Can I ask you a question of the primary data for the IL-2 beta/gamma, when you talk about the 0.1 mg per kg dose, is that just the second primate or does that include the TransCon?

This is just for IL-2. We always just discuss the dose and milligram only of the active ingredients. I'm pretty -- the team Juha has built up in oncology is really, really, really unique. And really moving into the IL-2 was a dream for me because I [ failed ] for 20 years ago. And I actually believe that when I see all the data that's out there, we really have a chance to really develop the best-in-class IL-2. And why we -- how we can do it was to separate the 2 important elements, how to make it optimal selectivity, potency and how to give it optimal half-life. And what you're seeing in the data we just showed in primate -- because [ accessing ] primate are pretty, pretty good model for this compound that what we saw is exactly what we expected to see. First, selectivity is the best selectivity, which you have seen in our product one more. And I think it's really optimal selectivity. What we see in primate is optimal potency, optimal duration of response. Meaning is that we can keep it very, very, very long time in the right therapeutic area. And why I believe a lot in IL-2 is because I think it's the same kind of immunostimulator. And PD-1 is a brake, removing a brake. IL-2 will be the stimulator. And sometimes it's easier to take the speed on instead of just removing the brake sometime. And this is why I'm really, really in it. And what we saw with -- how to avoid the capillary vascular leak is that [ it's over ] eosinophils, but we also see the same qualities with IL-5, so everything fit very well there. Juha, do you have any comments to it?

I think that sums it up well. And maybe just to point to the concept of fixing the PK in that, I do believe we have potential for the best-in-class duration of the effect. And that is important because we expect to be able to achieve every 3-week dosing, which would be important to align the treatment with the current checkpoint inhibitors, which often are given every 3-week dosing. So anything other than that schedule will complicate the treatment of the patients quite significantly.

Which oncology product is going to IND this year?

This isn't a competition we have.

So the question is which oncology product is in the lead to be filed this year.

We have 2 team that's competing. So I hope both of them will win, but I hope at least one of them will win.

Can you talk about pricing for TransCon Growth Hormone? Should we expect you to price it at a premium with your experiment data, at parity, at a discount for [indiscernible]?

So the question was pricing strategy: premium, parity or discount for TransCon Growth Hormone?

Will you take that, Tom?

Yes. So I think you look at the real important objective is what are we trying to do here, and the objective is really get to the market as fast as we can and be able to make it available to patients as quickly as possible. So I think that's the most important. We believe that we've got the best of the long actings, and we want to help patients, so making it available to people quickly is critical. So our pricing needs to be aligned with accomplishing that and supported by the value proposition, of course.