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

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. So thanks so much for joining us. We really appreciate it, and congrats on the approval.

Thanks a lot for inviting me. We are sorry we're not in Boston. We would love to be, but we also felt we needed to be here.

So the conference call, I think, literally ended about 2 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 6 months and then can actually be put back in the fridge. That's a slight differentiator also from VOXZOGO. The label is 2 years old. You'll show us the long-term extension later on. And I think you mentioned you're going to launch in early Q2, and you'll give pricing, it sounds like perhaps even next week. So maybe the first question, you also mentioned about 100 providers treat about 55% of patients, right? And there's about 2,600 patients in the U.S., about 30% of them are currently on drug. So 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 now most 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 related to the inlet. So what we were waiting for to get this information. And what we then need to do is to finalize the printing of the primary secondary package and then get ready to the market. So you can say there is no practical elements that basically are some way we need to do except that when we had the information back from FDA, we were in a position to get ready and roll it up. And this is why we say early next quarter, we basically will be ready to deliver. But the commercial effort can already start now. And what we're doing here is that from SMEs perspective, one of the main reasons for us to focus on one single therapeutic area was that we couldn't be utilizing that for all our product opportunities. We have SKYTROFA, pediatric growth disorder. We have our [indiscernible] in rare disease, endocrine. And now we have YUVIWEL also in rare disease endocrine, pediatric. So what we have developed is sales effort where we basically have a dedicated effort related to hypopara and then we have the other one which is the SKYTROFA and YUVIWEL. And think about we already have treated more than 10,000 patients just here in the U.S. with SKYTROFA. So we have a complete step-up, which we will utilize exactly to YUVIWEL too. So we're utilizing the same structure. We are utilizing sometimes the overlap between physician where some physicians 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 the time.

And so 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? And do you think you're going to be -- it's going to be a wholesale switches? Is it going to be switches in a subsegment? How would that work?

So when we look -- and I think with the U.S. approval, we have 2 segments 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 be utilizing the U.S. approval to go out and use early access programs where we also can launch it. So this is the 2 segments we are initiating the launch after the U.S. approval. And then 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. And when we look on the U.S. to our best estimate, there is less than 1/3 of the patients that have achondroplasia in the U.S. that really are under treatment. So you can say that the majority of patients is not on treatment today. But where will the patient come from? I believe they will come from both segments. There will be switch patients. And we were very pleased with clear indication how -- if they 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. So that is one segment. And when 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 at our publication where we really show benefit beyond growth, how they really can address things like going, get much better alignment of the legs, avoid potential 1 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, placebo-controlled data that indicate compared to a placebo group, there is clear benefit compared to be in treatment on really some important comorbidity beyond growth. Then you have added benefit like element, like muscle strength and other things like that, which also was clear statistic in this way. And this is why I believe that there will be patients 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 2 labels, VOXZOGO, as we all know, does have a tangible blood pressure risk, and it calls the need for hydration, prehydration, almost like 300 cc or so. In your label, there's also, I think, a caution about the potential for blood pressure changes. But I think it refers in the clinic -- in the safety section to a once-a-day CNP drug and it mentions the need for the patient to be hydrated, right? So there is no need for pre IV hydration. Can you discuss that? And why is that even mentioned? It sounds like it's obviously mentioned via class effect.

Yes. I think it comes into where there is a warning and precaution risk of the product. And then they are basically explaining the reason to take it up. And the reason why they have taken this because that clearly state transition decrease 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. And this is exactly how the [indiscernible] as you 100% right indicated some kind of class warning about. But 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. And when we went into the design of this molecule, there was 2 things we clearly wanted to achieve with the TransCon technology. First, to have a sustained release over 1 week. You can see, yes, we get the benefit on the 1 weekly dosing profile, but we also avoid the high Cmax that provide the risk of hypertension. It was how it got designed. So 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 [indiscernible]. So when you inject YUVIWEL, the active ingredients is basically inactivated in the [indiscernible] and first when it's in the blood compartment, it get released the active ingredients. This is why we have 4.4 injection site. Meaning is that you only see injection site every second year compared to the once daily that have major injection site [indiscernible]. And this is because it's not really [indiscernible] when you inject it the once daily because -- and therefore, you see the high effect of vasodilation. All that is science. So that was how we designed it. What perhaps the more surprising was that we saw all the benefit on linear growth. That was added benefit, and this is why I'm so proud of this compound. We are so proud of the compound that we really can go out and address the comorbidity because 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 but some children, but everyone to see a huge benefit to really address and solve comorbidities, and that is what we've done. And when we combined it with SKYTROFA, we saw an acceleration of this benefit.

Okay. Maybe a question next for me. And if anybody has questions in the audience, maybe raise your hand, and I can relay this way. On the price, so the price, it sounds like you'll announce it over the next 2 weeks or so. VOXZOGO's currently priced on a gross basis is at around $330 or so. I think on a net basis, it's around $240. In the past and even with YORVI 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, and 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 best price on with a premium. And clearly, it's reflecting the superior benefit it's providing to the patient, to the society for everyone. And we believe that we split it in a way where everyone is winner, the patient, the society, reimbursement system and everything like that. And they always have been our. And when we see on YUVIWEL, I think, yes, we will realize on the benefit that we see with YUVIWEL 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 not to live and [indiscernible] with medical exception. We did that with SKYTROFA in the beginning. We did that with our YORVIPATH and still doing that with YORVIPATH. And 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 that they can go out and pick up the drug by the pharmacist. And that is exactly the same system we are using from both the SKYTROFA, more than 10,000 patients to this system and YORVIPATH [indiscernible].

I think in Q3, you said you'll have the data from the under 2-year olds, if I remember correctly. And what portion of the market is under 2? Obviously, it's all a lot of the newly diagnosed market, but in the prevalence pool perhaps.

Yes. I think the key element, and I think we will separate it a little bit because I think there likely will be a difference in the leading between EMEA and U.S. because in the EMEA case, we can still be adding in all the new data we are getting from this trial. We have only efficacy data for a small portion of the patient that was dosed when it was not randomized, and we have seen all the benefit we expected. When we take the entire randomized that is blinded, we can see the safety is exactly as we have expected. And the benefit we're getting there is exactly how we expected it to be really addressing some of the comorbidities that need to be addressed there early, and it's basically the development I'm avoiding to get stenosis and other things like that in the [indiscernible] fusion of that. And I think that is what we hope we can see with also the x-ray when we are on it. The benefit we have here is that I believe that patient when do they really start? Yes, everyone get borne and perhaps it will be necessary for them to start an early treatment to address some comorbidities. So this is why we want always to do it. But when you also see that the majority of patients are still aged 2 and older, because they basically will be in a treatment much, much longer. And sure, one thing we also disclosed when we start the trial for adult achondroplasia because we still believe there is a benefit for getting treatment after you have fused. And I believe this is where we look on the holistic way how we ensure we can get the best for every subject that is with achondroplasia to the benefit.

One of the things that I think we noticed is the quote from the Little People of America, the Society Group, the patient support group and the patient representation group in your press release was slightly different than it was when VOXZOGO got approved. And I think that's a little bit of an aperture into the relationship with the group. Can you maybe talk about how you engage with them perhaps a little differently than BioMarin and maybe some of the missteps BioMarin did initially and how that's provided an opportunity for you?

In general, and 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 a treatment. And if we don't do that, how can we be patient focused. And when you look at our values, number one is the patient. And 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 provides the benefit. And that has been our focus for each single product and will continue to be. So I will be very disappointed if I didn't have a positive interaction with all the patient group. And I like to come to this meeting because I always get extremely inspired by the benefit and really understand how much it mean for [indiscernible]. I was sitting with them and talk about the bone. I heard them talk about [indiscernible] I heard them talk about 1 year in high school need to be out. And they're saying, if we have known that basic treatment like YUVIWEL could change and they have really the data. When we look on the placebo arm, yes, there is changes because it change to [indiscernible]. But 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. And that was really something we are saying this is extremely meaningful for us. This is somewhere we want to focus, and this is why we continue to work with them to ensure we make a patient-focused treatment for everything what we're doing.

So 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? And then secondly, we do hear from clinicians that penetration is still low. Morphologically, these patients are fairly recognizable. Now of course, not every parent is going to want to get their child treated necessarily. But 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% are on treatment, and I believe that illustrate extremely well the issue in U.S. In Italy, there has been much, much more focus on linear growth, and that is why 70% of the patient [indiscernible]. If I look in the U.S., I believe 70% to 80% will be on treatment because the basic can see, yes, I'm really not -- the main focus for me is not linear growth, but the main focus for me is addressing comorbidity. So I think you will see a tiny penetration happening in U.S. when you're really going out and telling the story there is clear data that's showing that you address comorbidities. And I believe that illustrates exactly when everyone see the benefit of the treatment and everyone have a diversified view about what the benefit of treatment should be. And that is illustrated between Italy and U.S. and you can really be in a position, yes, everyone should basically go on treatment and everyone will be on treatment. I don't think any parents will ever believe to take a child out of high school for 1 year, go to suffering of all this pain just to try to align things if you can go into a treatment regime for that. And I think that is a comparable fashion. This is why I believe Italy in penetration will be the same in U.S. after some [indiscernible].

Okay. Let's maybe move to YORVI a little bit. And in Q4, gross to net increased a little bit as it's typically the case, right? And in Q1, typically, there's obviously a lot of patient support that still goes into it. And you're constantly thinking about what's the right level of contracting to maximize access as well. And I believe you also did a price increase as well. So can you talk about sort of the net-net effect on gross to net? Is the price increase going to allow, in many ways, neutralize any gross to net impact? And then 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? And again, you need to offset that a little bit with typical seasonality. So it's a lot of questions about how to think about Q1.

Yes. And 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. Everyone knows that it's a seasonal factor for going from Q4 to Q1. There is a new way of patient group that need to go to a new reimbursement system, how fast is this system going? What we know, and 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're first starting to have under 5% of the patient -- established patients under treatment. The benefit of that is the same thing, will you believe 5% of type 1 diabetes patients should only have insulin. No, you will say the majority of them should have. And this is where we see this linearity in quarter-by-quarter new patients coming in. And don't forget that the day when we really also can tap into the 3,000 to 4,000 new patients that come in every year, we are much, much better off. And new patient today should that not be blamed to be on treatment? I believe, yes. So this is where we see the seasonal factor. I believe the key element for me, are we still on the launch projected thing where we see the continued demand for this product? Yes, we are. And I believe that is the key element. I got asked a lot why do you want to stop giving a new enrollment in Q1? And then I heard people coming back to me and say, Jan, there's a lot of shorts or anything like that you hear from the Wall Street of where they are on the short really meeting them. There are somebody coming in and saying is, Jan, I didn't want to come out with a new enrollment in Q1 because it's horrible. And I said, okay, I have no problem by giving Q1 new enrollment if that somebody can give you the comfort. And sure we will give it to you in Q1, too because they don't want to listen to all the short discussion about that enrollment is not going fine. And I said it's fine to give them a number, then at least I can be wrong one time more.

It keeps us in business on the sell side. We appreciate it. Sarah has a really nice figure. When you're thinking about 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 different from country to country. What in general, what we have seen in every country is that when you started on your path, you stay on it. And it's obvious in this way. But sure the patient because it's a chronic treatment, you will be treated until you come to the final part of your life. And sure, there will be patient that's stopping because it's part of the life -- cycle of life. But it's a chronic treatment for rest of your life. So there will be patients stopping at some time. Most of them will stop [indiscernible]. So on from that idea, you can see there will be some turnover. But from that perspective is we see a product that really are living up to all the aspect 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, [indiscernible], where we have more named patient program because then we can follow every single patient. And then you can say it's a named patient program and more artificial one. I don't think really in adherence and retention, no, and we see nearly all the patients, only few percentage are dropping up. And if we have drop up, it's mainly in the beginning of the titration phase, and this is where we're trying now to get the patient much more in the titration phase where they go out of conventional therapy and basically are in a position to start the [indiscernible].

Okay. Maybe in the last 45 seconds or so, on the weekly version of YORVI, is that something you can take right into a pivotal? Do you have to run -- or is the pivotal going to be a Phase I PK program, bioequivalence program?

So what we try to do with once weekly and why we designed it? We designed 2 or 3 time points. Because we wanted to take over the entire week. You have seen the complete flat profile on your [indiscernible]. So we said we want to have a bioequivalent solution. So every day on every time point, 24 hours, 7 days a week, you need to be bioequivalent. And we're 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 clinical 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. But this is not a -- once-weekly product can never be life cycle management. It's only dedicated to patients 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 a weekly product, how it only can function today.

Well, terrific. Jan, Scott, Chad, and I -- sadly I can't see the rest of the team right there. So 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, Yaron.

Thank you.

Bye-bye.