Great. Good morning, everyone. My name's Jess Fye. I'm a Large-cap Biotech Analyst at JP Morgan, and we're delighted to be continuing the conference this morning with Ascendis Pharma. Presenting for the company is going to be their CEO, Jan Mikkelsen. But before I pass it over to him, we're going to let Tim Lee from IR come up and do the forward-looking statement.
Good morning. 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 cause actual results to differ materially, please see our forward-looking statements section in the press release from yesterday and our SEC filings for the associated risk factors. With that, thank you.
Thanks a lot, Tim. It's a pleasure to be here. It's nice to be with people again face to face. I will make it short today, just focus on a few items today, which I think that is the key message we would like to come up with, and also giving you a lot of opportunities and time, really, to answer questions. So there was what Tim covered in that presentation.
So we really focus on the patient life, and we're building sustainable value. This is what we always have done in our strategic framework. First, our Vision 2020, now our Vision 3x3. Coming to our global set. Yes, we are a global company. We want to think global. We want to be global. We will be where the patients are. Everything we do is built on the TransCon technology.
TransCon technology is not a stationary technology. It's quite different from when we started for about 15 years ago. We have expanded to the third, fourth, fifth generation. We have at the same time been in a position we have expanded not only to have our, what we call our soluble polymer technology, but also to the hydrogel, which we actually are applying now both in oncology and also in our neurotherapeutics area of ophthalmology.
What is the core of the TransCon technology? It's basically a combination of a classical product technology and as predictable sustained release technology. Combining these two elements, you have the TransCon technology. This is why when we start with a parent drug that basically have proven clinical data, proven safety data, proven biological action. When we take it into this system, we release the same unmodified entity.
This is what we used in TransCon hGH, daily growth hormone, the same in the dose as growth hormone. TransCon PTH, we use FORTEO PTH(1-34). TransCon CNP, we are using the same thing. This is why we expect that we basically will be in a position we have this high success rate. When you think about we started with three preclinical candidates, TransCon hGH, TransCon PTH, TransCon CNP in rare disease endocrinology. We are in a position now, TransCon hGH is approved with SKYTROFA in U.S. and Europe.
We have Priority Review with TransCon PTH, and we expect an approval of TransCon CNP in 2025. Mainly because we can get, and hope, three out of three, because we not have the high biological risk. We are not compromising.
That we are really making highly differentiated product opportunities no one else can make, really addressing major unmet medical needs. This is the algorithm we have built up for that, which actually explain exactly what I did. This is the pipeline we have built up. Going to our vision. This is the vision I presented to this in 2019.
We call it Vision 3x3, building a leading global biopharma company. You can nearly imagine one year from now on, we will have a new vision. I have not the name yet. It will not be vision 5x5. It will be too boring. We will find a new way. What we did, there was our strategic pathway, and that is what we really have executed on in a timeful manner. We had that we wanted to have growth hormone approved in 2021.
We got approved. We expect PTH to be approved in 2023. That is what we hope to do. CNP in 2025. That was our plan from 2019. Global clinical reach, we have done it. Pursue nine indications, because to develop number one brand, you need to invest, and this is what we are doing in both in label optimization, life cycle management, like TransCon PTH.
We now have both a daily and a once weekly product. We focus on new endocrinology products, which I always get asked. I always get asked, do you expand out from rare disease endocrinology? Because we are classical, coming from a classical endocrinology company, which make a lot of sense for us. That will come in our next vision.
Go to our oncology, because I want to keep the commercial thing, because I just aware that main focus on SKYTROFA. When I come to SKYTROFA, I will focus on that. Oncology, we are really making two highly differentiated product, which are now coming to the into really interesting stage where we have recommended phase II, and we are expanding in what we call expanding in single indication.
The third therapeutic area, we announced, and I will come with a few words about that. Going to SKYTROFA, why it is a best-in-class product opportunities? For more than 25 years, people have tried to develop and address the unmet medical need. Why do you have a poor outcome in pediatric growth hormone deficiency? The primary endpoint has always been height.
We are the only long-acting growth hormone that work within somatropin, the same as endogenous growth hormone, the same as daily growth hormone. This is why when we look on all the endocrine benefit you expect to have out of the treatment related to body composition, I will come back to that, mental health, cardiovascular disease, fracture. We believe we will achieve all that because we are not changing the mode of action.
This is what we see in the U.S. We see how we highly differentiated to the daily growth hormone. A classical patient from us today, because we have one commercial strategy when we wanted to go in, was to focus on one single element, how to build SKYTROFA to the leading brand in value in a growing growth hormone market and as a highly profitable product. There was the three pillar we launched SKYTROFA on.
In Q2, I got asked, "Do you come forward looking related to revenue?" I said, "No, we do not do it, but I can give you a simple algorithm." I said, "You know we saw what we did in Q1. I expect we can double the rest of the year." So in my mathematic algorithm is two, four, eight, 16, and we really achieved that. Much better than we actually have hoped for, much better than we thought.
We are still doing a lot of action to really, really, really move into a situation where we getting more and more patient reimbursed. So what is the great part of this treatment in the stack? When a patient come on treatment, the typical will have a duration to four to five years. When I look on the patients, how many dropouts do we have? We have basic zero.
So when you think about and ask me, what is your algorithm now from 2023? I will make it simple again from a mathematic perspective. Yes, we have 17.1 or 17.5 related to FX. It give you, multiply that with four, then you basically have the baseline for the patient we have already established in 2022. Then we will add on, which I believe at least the same amount of patient and reimbursed patient in 2023.
I think it is a really simple algorithm, which I feel pretty confident about. I have no doubt that what we have with SKYTROFA and how we progressing, we can do it on a global basis. This is why we launching SKYTROFA now in Europe next year. We have a very interesting trial coming out next year in adult growth hormone deficiency. It is a trial where we basically have three arms.
We want to prove that we not only are better than placebo, but also will be in a position that we potentially like we did on the primary endpoint in adult, which are body composition. We also can have a potential as superior product. This is why we have 1:1 between daily growth hormone, placebo, and SKYTROFA. You do not get a leading global brand without investment. This is what we are doing. We do label expansion.
We have not only at our adult growth hormone deficiency trial, we also have Turner. We also combine it with a TransCon CNP because we are the only company that have the two pillars in growth disorder. TransCon CNP, TransCon growth hormone, both of them are the pillars in more than 20+ growth disorder. Some of them will be best treated with TransCon growth hormone.
Some of them will be best treated with TransCon CNP. Some of them will need a combination in different durations. This is why we can be the leading global company in growth disorder. We will launch in Europe, do what we did in U.S., start launching SKYTROFA next year in the middle of the year in Europe.
We have our Asia strategy where we both finalizing the trials in China and Japan to be quite sure we also go as a global leader. There is the summary on next step. I think I have really seen the current market today is a 4 billion global growing, and we believe we can increase that market. Coming to PTH, I will bring a lot of attention to PTH.
When I have heard the patient story, when I see what the benefit we give to the patients, how the physician are react, how the patient are staying on our trial, I have never seen a product like that. When you see of this series of morbidities, I understand that because we basic are addressing in all of them, because we're doing a normalization of physiological PTH.
If we thinking about having a Type 1 diabetes patient and not be in position to give them a basal insulin, this is how this patient group feel. This is 80,000 to 100,000 patient just in the U.S. Going to our trials, we actually have three trials now. We have our phase II, our phase III, and we have our phase III in Japan. All of them showed everything what we have dreamed for, and even in all the different demographic.
You can see the Japanese trial is a little bit different because we have much higher level of the genetic. For example, we have more ADH1 patient, which are hard to find because not many of them are really diagnosed as what we call chronic HP patient. When we go out and look on the results, it pretty is impressive. Number of patient eliminate concomitant therapy.
Why is that really important? Because eliminate the concomitant therapy is actually eliminating part of the cause of the disease. Because the number, a high level of active vitamin D, calcium supplement, is basic part of facilitating the disease and many of its comorbidities. This is why it's so important to eliminate current concomitant therapy.
You can see intervention of active vitamin D, basic 100 and nearly more than 90% went into basic to be in position that you only took a multivitamin tablet, which are 600 mg, like a Costco tablet. Really impressive. Every element we look at, we really see how it's benefited. Going to the Japanese trial, I just wanted to show one single slide. I like this because it's really illustrate that even if you go to Japan, which have very different way to treat hypoparathyroidism, they're taking much higher active vitamin D.
You can see they have really high serum phosphate, and as soon as we normalize them, you can see normalization all the time. This is the patient population we have just in the U.S. We have Priority Review. We are in a position, we have an Expanded Access Program now.
We established, we have a press release last week when we starting enroll patient. I believe the way that if they had giving us help, how they are helping the patient recognize that there was a product in the market that got taken away, and now the last patient that is on a compassionate use will be taken off of that product in 2024. I believe there is such a huge unmet medical need that it's really got recognized. 4,000 to 5,000 patient are PTH experienced.
This is the patient group we really want to go into our Expanded Access Program as fast as possible because they're used basic to use PTH. Then we have the 65,000 to 80,000 patient, which are the patient that mainly got recruited into our phase II and phase III trial. Newly diagnosed, more than 3,000 a year.
This is a group of patient that will expand year by year. What also was a key element last year was the change in guidelines. The basic come out with a recommendation in the last guideline that if you have any non-controlled in any of the following: symptomatic hypocalcemia, hypophosphatemia, renal insufficiency, hypercalciuria, poor quality of life, which I have to think is 95% of the patient, then you should go to PTH, which give me also confident that we will have a strong fundament to get a really optimal market assessment situation.
This is our next step. We have still 146 out of 145 with patient up to three years. Pretty impressive. Some of them that stepped out was under placebo treatment. I will move directly over to one single slide here. I will not go into so much GMP.
If someone doing the Q&A, I can take some of the slide up. Oh, now I went too fast. Wait. See. Now I need to go back. Thanks, Vanya. I want to say one thing on oncology. We are working on two unique compound in oncology, a kickstarter of the immunological system, where we use the hydrogel technology to take it into the tumor.
The other one is a general IL-2 β/γ. You will be tired on looking and hearing about an IL-2 compound because there have been 25 companies. I think why there's 25 company, because people recognize the benefit that it can provide if you succeed. We have moved both product to a state where we have recommended phase II on our TransCon TLR7/8 Agonist.
We actually have accelerated our IL-2 β/γ much more fast than we ever thought about because of the safety and tolerability, and it's not because we are compromising efficacy. This is what I believe when we come here in the beginning of next year, we will declare recommended phase II also for our TransCon IL-2 β/γ. I really want to look forward to give you the data that really show how this also is a best-in-class product. Ophthalmology. Why did we select ophthalmology?
We selected ophthalmology out from that because we have a TransCon technology platform that basically can give us product opportunities that no one else can make. Make them so highly differentiated. Because we can have a continuous local release back in the eyes, not for months, not for two months. I will give you the curve.
When I look on ranibizumab, also known as LUCENTIS, which both have been used as what we call direct injection, but also in an implant. We are in a position that we can make and really address the high unmet medical need that is still in this 10 billion + section. Because there is still patient getting blind, cannot comply with the treatment because of the huge burden.
This clinical validated programs, the compound is well-known. It fit directly our algorithm. Like we had in rare disease at endocrinology, where we expect three out of three. Going to our data. What we did, this is the best model. But first thing, you need to look on the injection volume, 50 microliter. We inject it.
We can see when we inject the 50 microliter, we are in a position that we are having coverage over the target level, because it is pretty well-known what target level you need to be on always to have sufficient anti-VEGF neutralization. And we can see we can have it more than 18 months. This technology platform open up for a lot of product opportunities that basically could be an pipeline as we have in rare disease endocrinology, but in a much larger market segment.
Going to our milestones for 2023. If I look on TransCon hGH, and I will only take selected milestone after all the milestone, because you can read the slides. What I really look forward to is our adult TransCon hGH data in the foresiGHt trial in Q4. The key program where we will see a major development next year from commercialization will be our TransCon PTH.
We have Priority Review the April 13th. We are in intense interaction with regulatory agencies both in Europe and U.S. We expect still to keep this timeline. This is a combination product, but it also building on a lot of proven technology. And we expect to launch directly afterwards. We ready the manufacturing. Everything is built up. The first wave of sales force is established, hired out there. End of the year, Q4, we will get a decision from the Europe.
Europe that is still the same high unmet medical need as the only approved product there will also disappear in 2024. TransCon CNP, we got what we hoped for in all our data. The four pillar: safety, efficacy, tolerability, and convenience. No doubt, we believe this is the best-in-class product opportunity. We are enrolling a phase II-B, which we hope is a pivotal trial.
We will be in a position that we aligning all the patient because there is a huge unmet medical need and a huge awareness about what is the profile. So we expect that we can enroll the entire trial in four or five months. Never happened before.
Going to the oncology, you can see lot of blue marks because in 2023, we really move into the indication expansion, and we will have the first analysis, which will continue into 2024, where we really hope to prove that we have a paradigm shift in all our treatment. Thanks a lot for giving me the opportunity to present today.
Great. We are going to start Q&A here. You can raise your hand and someone will bring you a mic, or you can submit a question electronically, and I can read it off the iPad up front. I will start. On your ophthalmology vertical, can you talk about how your technology is differentiated from past efforts to make long-acting drugs for the eye?
Currently, what you are doing is that if you want to make it longer acting, you can nearly see going from LUCENTIS to Beovu. You can also see the Kodiak approach is to make the molecule larger and larger. But you are still doing a bolus injection. It meaning that you very much is dependent on how fast back in the eyes it is clearing the compound.
When you get older, when you have many of this disease, you have much faster clearing. What we are doing is basically applying a complete paradigm shift where we building particles that sit in hyaluronic acid inside back of the eyes and on a continuous manner, day by day, release an unmodified ranibizumab molecule. By doing that, we totally independent on the clearance in back of the eyes.
When we look on the profile we have, the profile, in my view, is providing two interesting elements. It providing an higher concentration for more than six months. Much, much higher than you really are taking as the target concentration. Just look on the half-life, 100 days. At the same time, it is extremely well-tolerated. Meaning is that it open up for many opportunities. It open up for an opportunity to have better efficacy, better safety because of the risk of injection and tolerability, but also open up for combination therapy.
Because no one can inject in back of the eyes multiple compound on a twice monthly manner or every third month. It both is an enabling technology for combination product, but also as just anti-VEGF treatment as our TransCon ranibizumab. A profile that never have been seen before, a profile that address one of the key element of inter-patient variability of clearance. It really is a paradigm shift. Kennett, you have?
Yeah, maybe just a couple of points. When we talk to a retinal specialist, what they mostly are concerned about is actually not new biology, it is extending the duration of action because people, if you have seen somebody get an intravitreal injection, you understand why you don't want to be taking this on a monthly basis. So if you can extend it to every six months, you're much more likely to keep patients on drug and keep them above that critical level you need for VEGF neutralization.
To me, also, this area reminds me a lot about our rare disease efforts, because also you can't just make the molecule larger because it needs to diffuse to the back of the eye. The retina is at the very back. You have liquid flow that goes towards the front of the eye and drains whatever you inject into the vitreous.
And there's abundance of literature showing smaller molecules diffuse better to the back of the eye. So being we able to release a Fab, we would expect to have much better efficacy at the back of the eye and not just neutralizing whatever is in the vitreous compartment.
To me, the combination of having a modular platform that allows us to take multiple different compounds together with releasing something that has the right size, we know size matters when it comes to tissue distribution, and then being able to treat patients irrespective of vitreous composition because we know it thins with age. So I think those combined makes the TransCon hydrogel technology extraordinarily well-fitted for localized treatment of vitreous diseases.
As an introduction, this is Kennett Sprogøe. He is our Head of Research and Development. He was actually one of the founding people when we founded this company in 2017. So he really knows the technology platform in and out and all the benefit we can get it in all the product opportunities, especially the person that designed all our product opportunities.
Maybe speaking of other product opportunities, there's been a lot of buzz and I think maybe some anticipation in the market about Ascendis applying your capabilities to non-rare endocrinology. I think specifically folks are sort of hoping you'll work on a GLP-1 and get into the obesity space. We obviously didn't hear something on that today. Is that on the table as something Ascendis might pursue going to more prevalent endocrine conditions?
I think it is two different discussions. What we had in our Vision 3x3 was to move out to three different therapeutic area from a strategic perspective. That is what we did by moving into ophthalmology, because we really can build up a pipeline in a huge, huge market segment of highly differentiated product that really will be best in class, really addressing some real unmet medical needs.
We are in rare disease endocrinology, and if we go outside and remove rare, for me, it is just something I will do and not really discuss it before this competitive environment that it is that before I have data, not waiting to say 18 months before we move into clinical development or anything like that. It is highly competitive area. I am here to win. I am not here to give any advancement to any competitor. If we do it, we will do it. If we feel that in some way it is fitting our pipeline, it is fitting the benefit of the patient, it is fitting the benefit of value creation, we will do it.
I had a question in my email about PTH. Maybe I will wrap it in with another question I was going to ask on the product. You are starting this Expanded Access Program to help patients initiate on TransCon PTH prior to the approval, and presumably, that is create a favorable launch dynamic where you will then be able to convert them over.
First question is: how do we think about the timing over which reimbursement for TransCon PTH could ramp up? Should that look different than TransCon hGH did? Second, and this is the investor question: what is a good assumption for TransCon PTH price? Is Natpara the right range to think about?
Let me take that first one, because I think what we did in terms of SKYTROFA, we had in the boardroom, we went through a lot of different strategies. How do we want to launch SKYTROFA in the U.S.? We are going to go the rebate way, giving a lot of revenue in the beginning for less profit. We decided to build on the strengths of the product because we have the best-in-class product that is highly differentiated to heavy daily growth hormone, but also other long act.
So we took the long-term, we launched into an established market. We did not go to the classical way to basic provide a lot of rebate. We went to the medical exemption pathway because we did not accept that the rebate that was given to us. How can we do it and why we can do it extremely successful?
It is because we have the best-in-class product opportunity that really make a meaningful differentiation for the patient. So both the physician and everyone is willing to take the work to get the medical exemption, because it is really benefiting. TransCon PTH is complete different. We launching into a segment where the only opportunity that was there is taken away from the market. We launching into an era where there is basic no competition.
There is a huge recognition of the unmet medical need. There is a huge recognition of the benefit we can provide to the patient, which I think is supported by two things, and I call it validation. The guidelines. I have never been in a position, never been in a position that basic before you launch the program, there is a guideline that is saying that you should utilize this product for most patients. First time.
Guidelines is something that come one or two years after launch. The other thing is also being recognized, at least from my perspective, is as recognized to the regulatory agencies by providing us a Priority Review, providing us the way of making an Expanded Access Program for the patient before we basic can launch the product, really to help the patient. Yes, now I forgot the second question.
Price.
Price is something we decide when we just before we launch. We are doing a lot of analysis related to price today. We actually are not compares to Natpara. We are thinking about this product opportunities out from a complete different label that was given to Natpara. We are position this product out from the benefit we providing to the patient, and this is how we think price structure.
Questions, anyone? I think consensus is, I want to say in like the 40 million, maybe 50 million range for TransCon PTH for 2023. Is that a number that you are comfortable with, thinking about the initial launch ramp?
I think as always, I like to see and be quite sure when I come up with an algorithm. I like always to come up with algorithm because I am a mathematic. From my perspective is when we come into the launch, when we coming in and seeing where we are, I think it is a good timing to give you some kind of guidance on it. Just think about it.
There are 5,000 patients that was used to use PTH. 5,000 patients in the U.S. People that have experience with using PTH, where the drug got taken from them. Then you have where we basic recruited in our phase II and phase III, the 8,000 patient, where we now have all of them basic staying, staying on treatment. What did that tell me? It tell me all patients will benefit for this treatment. That I think is the key element.
I think for TransCon CNP, you have talked about filing in the back half of 2024 on the back of your phase II-B trial. Have you talked to the FDA and confirmed that they are good with your endpoint and trial design, stuff like that?
I think the endpoint is really well-recognized, annualized growth velocity, and we active doing the simple form of annualized growth velocity, which also recognized by FDA and other regulatory agencies that we are not making a difference between pre-treatment, but just looking on the absolute annualized growth velocity. So the endpoint is pretty simple.
Our aspiration is not have a labeling on linear growth. Our aspiration is to have a treatment of achondroplasia and also address the comorbidities. This is why one of the thing that is struggling me, we have now accomplished trial with patient more than two years. What is our retention in our study? 100%. 100% of 57 patient. What are we providing to this patient group that is not recognized in annualized growth velocity? Because I do not believe that everyone just believe that getting height is the important thing of achondroplasia.
At least this is my understanding when I talk with parents and listen to some of the patient group. What are we giving to them? That is what we want to qualify in our pivotal phase II-B study, so we can ensure that we also can have that part of our labeling discussion. I think that is the key element of what we are doing. It is pretty clear no one have any questions.
You talked about SKYTROFA and the nice kind of trajectory that is starting to emerge there. I think you could have another long-acting competitor coming to market as well. How do you think about that competitive dynamic once you are not the only kind of long-acting growth hormone?
That is the thing, and when we look on the data that is on the other long-acting product, and then compare to daily growth hormone. On absolute level, when you look on outcome related to a low European dose, that could much lower, just hitting statistic non-inferior on a absolute low. When we go to body composition, the phase III, the basic proof that only have the half of the activity compared to daily growth hormone.
When I see our SKYTROFA, we highly differentiated, best in class. We had an annualized growth velocity that was statistically higher than the one we got from daily growth hormone. We hope we can show the same thing in body composition. This is why I am not really believing it is changing anything, because we basically will be in the best in class product opportunity. Potentially, we change a little bit how much that is left of daily growth hormone. It is not changing any our basic forecast.
Great. Well, we're about out of time, so we'll leave it there. Thank you.
Thank you so much.