Well, welcome everybody to the 46th annual TD Cowen Healthcare Conference. I'm Yaron Werber from the biotech team, and it's a great pleasure to moderate the literally virtual fireside chat with Ascendis on the heels of the YUVIWEL approval. We moved the participation to virtual, and we appreciate that we're able to do that. Thanks so much for joining us. We really appreciate it, and congrats on the approval.
Thanks a lot for inviting me, and we are sorry we're not in Boston. We would love to be, but we also felt we needed to be here.
The conference call I think literally ended about two hours ago. The label looks very clean. As you guys showed the slide and the AEs are minimal. The nice feature of the drug is that it's weekly, it can actually be kept at room temperature for up to six months, and then can actually be put back in the fridge. That's a slight differentiator also from VOXZOGO. The label is two years old. You'll show us the long-term extension later on, and I think you mentioned you're gonna launch in early Q2, and you'll give pricing, it sounds like perhaps even next week. Maybe the first question... You also mentioned about 100 providers treat about 55% of patients, right? There's about 2,600 patients in the U.S.
About 30% of them are currently on drug. I guess the first question is, maybe what do you need to do to launch in Q2, and why can't you launch a little faster?
First of all, the launch segment is very much dependent on the information we got from FDA in the end, where we basically get the final primary, secondary packaging. We also get the element relating to the inlet. What we were waiting for to get this information. What we then need to do is to finalize the printing of the primary, secondary packing, and then get ready to go to market. You can say there is no practical elements that basic, some way we need to do, except that when we have the information back from FDA, we were in a position to get ready and roll it out. This is why we say early next quarter, we basically will be ready to deliver. The commercial effort can already start now.
What we're doing here is that from Ascendis perspective, one of the main reason for us to focus on one single therapeutic area was that we could utilizing that for all our product opportunities. We have SKYTROFA pediatric growth disorder. We have our collaboration with Europeans also in rare disease endocrine. Now we have YUVIWEL also in rare disease endocrine pediatric. What we have developed is sales effort where in basic have an indicated area or dedicated effort related to hypoparathyroid. Then we have the other one which is the SKYTROFA and YUVIWEL. Think about we already have treated more than 10,000 patient just here in the U.S. with SKYTROFA. We have a complete setup which we will utilize exactly to YUVIWEL, too. We utilizing the same structure.
We are utilizing sometimes the overlap between physician, where some physician both will prescribe both SKYTROFA and also YUVIWEL . We have expanded it and ready to go to the market, and that is exactly what is happening over time.
As you think about usage, do you have a sense what percentage of the market are not adequately served currently on VOXZOGO and would be eligible to switch? Do you think it's gonna be a wholesale switches? Is it gonna be switches in a sub-segment? How would that work?
When we look, I think with the U.S. approval, we have two segment where we can launch the product. We can launch the product as a full commercial here in the U.S. At the same time, in the international market, we can utilizing the U.S. approval to go out and use early access programs where we also can launch it. This is the two segment we are imitating the launch after the U.S. approve. Later in the year, we expect the European approval. When we come to the U.S., and why I'm saying that, because we believe each single country have their own story. When we look on the U.S., to our best estimate, there is less than one third of the patient that have hypoparathyroidism in the U.S. that really are on treatment.
You can say that the majority of patient is not on treatment today. Where will the patient come from? I believe they will come from both segment. There will be switched patients, and we were very, very, very pleased clear indication how FDA indicate how to switch when you just stop with the daily therapy, and then the day after you just start on YUVIWEL , clear indication how to switch. That is one segment. I believe I cannot find any good reason why not to switch.
When I go to the new, patient group that is not on treatment today, and I believe when you look in our publication where we really show benefit beyond linear growth, how they really can address things like leg bowing, get much better alignment of the legs, avoid potential one year's really hard life to an operation trying to do that because of pain and other complication. I feel that there will be a large portion of this patient group that didn't go into any treatment because there was no really data where you have clear data, a stable controlled data that indicate compared to a placebo group, there is clear benefit compared to being in treatment on really some important comorbidity beyond linear growth. You have added benefit like element, like muscle strength and other things like that, which also was clear statistic in this way.
This is why I believe that there will be patient coming on YUVIWEL treatment from both group. I see the benefit for both group to transfer over.
Okay. Maybe a quick. Also, when we look at the two labels, VOXZOGO, as we all know, does have a tangible blood pressure risk, and it calls the need for hydration, pre-hydration, almost like 300 cc's or so. In your label, there's also a caution about the potential for blood pressure changes. I think it refers in the safety section to a once-a-day CNP drug, and it mentions the need for the patient to be hydrated, right? There's no need for like pre, you know, IV hydration. Can you discuss that and why is that even mentioned? It sounds like it's obviously mentioned via class effect.
Yeah. I think it comes into where there is a warning and precaution, risk of low product. They are basically explaining their reason to take it out. The reason why they are taking this, because the kidney state transition decreased in blood pressure have been reported with a once daily CNP analog. They're not saying it has been observed with YUVIWEL , but it has been observed with a once daily CNP analog. This is exactly how they have it more, as you 100% right, indicated some kind of class warning about. I think the key element, don't forget, why are there such a big difference between the once daily product and YUVIWEL ? YUVIWEL is built on the TransCon technology platform. When we went into the design of this molecule, there was two thing we clearly wanted to achieve with the TransCon technology.
To have a sustained release over one week. You can see, yes, we get the benefit on the one-weekly dosing profile, but we also avoid the high Cmax that provide the risk of hypotension. It was how it got designed. We were far, far away to have any kind of vasodilation effect on near the Cmax. The other thing we did with the TransCon technology was to build it into a prodrug. Prodrug itself is an inactive product of an active path. When you inject YUVIWEL , the active ingredients is basically inactivated in the prodrug. First when it's in the blood compartment, it get released the active ingredients. This is why we have 4.4 injection site per year.
Meaning is that you only see one injection site every second year compared to the once daily that have major injection site reaction.
Mm.
This because it's not really in a tube when you inject it, the once daily. Therefore, you see the high effect of vasodilation. All that is science. It was how we designed it. What were perhaps the most surprising was that we saw all the benefit beyond linear growth. That was added benefit, and this is why I'm so proud of this compound. I'm so proud of the compound that we really can go out and address the comorbidity. When we talk with the patient organization, that is what we really want to see. We address the comorbidity. We accept linear growth is the desire for some parents, for some children, but everyone see a huge benefit to really address and solve comorbidities. That is what we've done. When we combined it with Calcitriol, we saw an acceleration of this benefit.
Okay, maybe a question next from me. If anybody has questions in the audience, maybe raise your hand and I can relay it this way. On the price. The price, it sounds like you'll announce it over the next two weeks or so. VOXZOGO is currently priced on a gross basis is around, at around $330 or so. I think on a net basis it's around $240. In, you know, in the past when, and even with YUVIWEL and certainly SKYTROFA early on, you weren't really contracting. I think in this situation, would you contract with payers more because it is more of a competitive dynamic? It sounds like you'll price it at a premium, because it's a premium product.
is this something that we should expect as sort of a modest premium or a more tangible premium?
I think when you look on both SKYTROFA and YORVIPATH, yes, both of them has been priced on a fair price with a premium. Clearly, it's reflecting the superior benefit it's providing to the patient, to the society, for everyone. We believe that we split it in a way where everyone is winner, the patient, the society, reimbursement system, and everything like that. They always have been our team. When we see on YORVIPATH, I think, yes, we will realize on the benefit that we see with YORVIPATH compared to established treatment from that perspective. When we look on the element on contracting, we are not really so much dependent on that because we have a great system how to live and a life with medical exception. We did that with SKYTROFA in the beginning.
We did that with our YORVIPATH . Still doing that with YORVIPATH . This is where we are as a company extremely well-built, well-acquired, have all the knowledge, experience, how really to be sure that the patient journey will be so optimal as possible for the patient. When the prescription is written, they can go out and pick up the drop by the pharmacist. That is exactly the same system we are using from both the SKYTROFA, more than 10,000 patients on this system, and YORVIPATH and other things like that.
The, I think in Q3 you said you'll have the data from the under two-year-olds, if I remember correctly.
Yeah.
What portion of the market is under two? Obviously, it's all a lot of the newly diagnosed market, but in the prevalence pool perhaps.
Yeah, I think the key element, I think we will separate it a little bit out because I think there likely will be a difference in the labeling between EMEA and U.S. In the EMEA case, we can still adding in all the new data we are getting from this trial. We have only efficacy data for a small portion of the patient. There were those when it was not randomized, and we have seen all the benefit we have expected. When we take the entire randomized that is blinded, we can see the safety is exactly as we have expected. The benefit we get in there is exactly how we expected it to be, really addressing some of the comorbidities that need to be addressed there early.
It's specifically the development and avoiding to get stenosis and other things like that in the forearm, manual fusion of that. I think that is what we hope we can see with also the X-ray when we unblind. The benefit we have here is that I believe that patient, when do they really start? Yes, everyone get born, and perhaps it will be necessary for them to start an early treatment to address some comorbidities. This is why we want always to do it. When you also see that the majority of patient are still age two and older, because they basically will be in a treatment much, much longer.
Sure, one thing we also disclose when we start the trial for adult achondroplasia, because we still believe there is a benefit for getting treatment after you have fused your growth plate. I believe this is where we look on the holistic way, how we ensure we can get the best for every subject that is born with achondroplasia to the benefit of them.
You know, one of the things that I think we noticed is the quote from the Little People of America, the society group, the patient representation group in your press release was slightly different than it was when VOXZOGO got approved. I think that's a little bit of an aperture into the relationship with the group. Can you maybe talk about, you know, how you engage with them perhaps a little differently than BioMarin and what maybe some of the missteps BioMarin did initially and how that's provided an opportunity for you?
In general, I can say our approach to every patient group, it's not only LPA, which I believe we have an extremely good working relation with also. We are there to listen. We're there to understand what we really need to get out for and treat. If we don't do that, how can we be patient-focused? When you look on our values, number one is the patient. I believe always to continue to listen to patient group, to patients, because in the end, it's really how you make a successful product that really provide them benefits. That has been our focus for each single product, and it will continue to be. I will be very, very disappointed if I didn't have a positive interaction with all the patient group.
I like to come to this meeting because I always get extremely inspired by the benefit and really understand how much it mean for people. I was sitting with them and talk about the leg bone. I heard them talk about one year in high school need to be out. They're saying, if we have known that basic treatment like your world could change, and they have really the data. When you could look on the placebo arm, yes, there is changes because it changed to ages. When they compare to what we saw on the treatment arm and compare the placebo treatment to that, it was clear you can solve this problem. That was really something we are saying, "This is extremely meaningful for us.
This is somewhere we want to focus, this is why we continue to work with them to ensure we make a patient-focused treatment for everything what we're doing.
One of the questions we get a lot is, and you mentioned only 30% of the 2,600 are you think are currently being treated. The 2,600, is that the total number of diagnosed patients with achondroplasia, or is that the 2,600 is patients still with open bones that you can actually target? Secondly, we do hear from clinicians that penetration is still low. Morphologically these patients are fairly recognizable. Now, of course, not every parent is gonna wanna get their child treated necessarily. Maybe give us a little bit of a sense, what can you do to really boost the treatment rates?
When you look at this 70% in the U.S., and then I can take another country, Italy, 70% aren't treated. I believe that illustrate extremely well the issue in U.S. In Italy, there have been much, much more focus on linear growth, and that is why 70% of the patient are treated. If I look in U.S., I believe 70%-80% will be on treatment because the basic can see, yes, I am really not... My main focus for me is not linear growth, but my main focus for me is addressing comorbidities. I think you will see and it's telling you penetration happening in U.S. when you really going out and telling the story, and there is clear data that's showing that you address comorbidities.
I believe that illustrate exactly when everyone see the benefit of the treatment, and everyone have a diversified view about what the benefit of treatment should be. That is illustrated between Thailand and Italy and U.S. You can really be in position, yes, everyone should basically go on treatment, and where everyone will be on treatment. I don't think any parents will ever believe to take a child out of high school for one year, go through suffering of all this pain just to try to align legs if you can go into a treatment regime for that. I think that is the compelling fact. This is why I believe Italy in penetration will be the same in U.S. after some years.
Okay. Let's maybe move to YORVIPATH a little bit. In Q4, gross to net increased a little bit as it's typically the case, right? In Q1, typically, there's obviously a lot of patient support that still goes into it. You know, you're constantly thinking about what's the right level of contracting to maximize access as well. I believe you also did a price increase as well. Can you talk about sort of the net-net effect on gross to net? Is the price increase going to in many ways neutralize any gross to net impact? Secondly, we did see a little seasonality in Q4. This is sort of the first year on the market now in the U.S.
Is there sort of a little bit of pent-up demand that we should think about hitting Q1? You need to offset that a little bit with typical seasonality. It's a lot of questions about how to think about Q1.
I think we will be much, much, much smarter when we are coming to end of March because then we have the realized numbers and seeing how our first real first quarter is. Everyone knows that seasonal effects are forgotten for Q4 to Q1. There is a new way of patient group that we need to go to, a new reimbursement system. How fast is this system going? I mean, know, I can continue to confirm that the demand is still there, and it's still the same kind of demand that we have seen every quarter. This product we first starting to have under 5% of the patient, established patient under treatment. The benefit of that is the same thing. Will you believe 5% of Type 1 diabetes patient should only have insulin?
No, you will say the majority of them should have. This is where we see this linearity in quarter by quarter new patient. Don't forget that the day when we really also can tap in, into the 3,000 - 4,000 new patients that coming in every year, we are much, much better off. A new patient today, should that not demand to be on treatment? I believe yes. This is where we see the seasonal factor. I believe the key element for me, are we still on the launch projecting thing, where we see the continued demand for this product? Yes, we are. I believe that is the key element. I got asked a lot, why did you want to stop giving a new enrollment in Q1?
Then I heard the people coming back to me and say, "Jan, there's a lot of shorts," or anything like that you hear from Wall Street or where there are the shorts. Never really reading them. There are some that are coming in and saying, "Jan didn't want to come out with a new enrollment for Q1 because it's horrible." I said, "Okay, I have no problem by giving Q1 new enrollment if that somebody can give you the comfort. Sure, we will give it to you in Q1 too, because I don't want to listen to all the short discussion about that enrollment is not going fine." I thought this fine just to give them a number, then at least they can be wrong one time more.
It keeps us in business on the sell side.
Yeah.
We appreciate it. Sarah has a really nice figure. When you're thinking about, you know, now that it's been on the market for a year, what can you tell so far about potentially durability or maybe a little bit of dropouts? What kind of patients decide ultimately not to continue on therapy?
First of all, we have a global launch, and it's very different from country to country. What, in general, what we have seen in every country is that when you start it on YORVIPATH, you stay on YORVIPATH. This argues in this way, but sure there is patient, because it's a chronic treatment, you will be treated until you're coming to the final part of your life. Sure, there will be patient that is stopping because it's part of the life cycle of life. It's a chronic treatment for rest of your life. There will be patients stopping at some time. Most of them will stop wanting it. Out from that idea, you can see there will be some turnover.
From that perspective is we see a product that really are living up to all the expect of the patient want to see, physician want to see, and you see that in the adherence. If we go to Germany, we can have different parameter how to look at that. The best one is, for example, look on where we have more named patient program, because there we can follow every single patient. Then you can say it's a named patient program and more artificial one. I don't think really in adherence and retention, no. We see nearly all the patient, only few percentages are dropping off.
If we have dropout, it's mainly in the beginning of the titration phase, and this is where we try now to help the patient much more in the titration phase, where they go off of conventional therapy and basic eye in a position to start the treatment.
Okay, maybe in the last, 45 seconds or so, on the weekly version of YORVIPATH, is that something you can take right into a pivotal? Do you have to run, or is the pivotal gonna be a phase I PK program, bioequivalence program?
Yeah. What we tried to do with our once-weekly, and why we redesigned it, 2 or 3 x more, because we wanted to take over the entire week. You have seen the complete flat profile on your packs. We say, we want to have a bioequivalent solution. Every day, on every time point, 24 hours, seven days a week, you need to be bioequivalent. We liberating the same compound, using the same system, we just changed the entire linker setup. Would that qualify to a bioequivalent strategy so we can get approval on PK profile or we need to show a limit in E-cadherin data? That is what we're discussing with regulatory agencies, and it could be different between U.S. and Europe, but I believe this product will come out. Don't... This is not an...
Once-weekly product can never be life cycle management. It's only dedicated to patient that have been titrated on the daily product to a stable dose for some period of time, and then you can transfer them over to the weekly product, if how it only can function today.
Okay. Well, terrific. Jan, Scott, Chad, and I, sorry that I can't see the rest of the team right there. Thanks, everybody. Good to see you. We appreciate it, and congrats on the launch, and we'll be in touch.
Thank you so much.
Thanks, Jan. Thank you.
Bye-bye.
Bye-bye.