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

Good afternoon, everyone. Thanks for joining us back here at the Bank of America Healthcare Conference. It's my pleasure to have our next presenting company. Several members from the management team of the Ascendis are going to be chatting with me for the next 30 minutes. Unfortunately, they can see me, but I can't see them. So Jan and team, I'm going to turn it over to you guys to introduce yourselves. And then hopefully, we can just get into some Q&A, if that makes sense.

Thanks a lot, Tazeen. And I can start, Jan Mikkelsen, and then we have.

Scott Smith, CFO.

Dana Pizzuti, Head of Development, Operations and CMO.

Tim Lee, Investor Relations.

Excellent. So you guys have a lot going on at the company, obviously, and this is an important year. Not only could you potentially as to a commercial-stage company, but you do have several programs that are in the clinic, which differentiates Ascendis from other companies, including other rare disease companies. So I wanted to maybe ask some general questions about some key data readouts that are expected. But maybe we can start off with your most recent update which would be 58-week data that you have now released as it relates to your program for hypoparathyroid. So Jan, I'm wondering if you can give us a quick summary of that.

Thanks, Tazeen. Yes, we were really thrilled to come out with this data set. At the 6-month point, we really showed that we had a hormone replacement therapy that basically did normalization of serum calcium, normalization of phosphate, normalization of phosphate calcium complex, normalization of urinary calcium. And we also saw the major impact it had on quality of life. Where we saw SF-36, which are really a validated measure in how to compare to a normal population, that we really improved on all sub-domains and summary domains, really provided the patient a normalization of the life. Now we are over in the open-label extend trial. The open-label extension trial is, first, to game the knowledge about how this treatment will actually help this patient group on a long-term basis. And if I should sum it up, what we saw, we saw the durable response that we had hoped for. All the elements that we saw at 6 months continued to the 12 months. Other element that was important for us to observe was that we saw long-term risk factor like 24-hour urinary calcium still kept low. We also observed the expected biological effect on bones. An HP patient, when you look on the start, he had very low bone turnover because the patient lack PTH. PTH is an essential hormone for bone turnover together with other hormones. And when we initiated the treatment, we saw for the first 6 months that being increased. The bone markers, both the anabolic and the catabolic bone markers, up from the low level to the high level of the normal level. We saw now here with the 12-month data that it basically peaked at 6 months, and we see now it's trending to the mid normal level for bone markers. We know from data that is from case studies that if you generate physiological level of PTH in long-term studies, and they are I mean 3, 4, 5, 6, 7, 8 years, we're actually getting a normal bone structure. And that is also what we expect to see on a physical measuring like bone density. Bone density is not reflecting anything else than a physical measuring under bone density. And what we saw in our patient group and demographic at time 0, that they have, as expected, a higher bone density than a normal population. Is this bone density healthy? No. No one is claiming that because it's an unnatural bone density that's being generated to an abnormal low level of bone remodeling. And when we now started the normal remodeling, we expect that we will see, when we have in next quarter also the bone density, that it will trend to the same level that we expect, trending to 0. So when I look on the data, I feel so optimistic, so hopeful that we really can address the more than 200,000 patients that is in the U.S., that is in the Europe and Japan only, with and for the first time providing a hormone replacement therapy that basically are providing a treatment that are normalizing their life for them, not only on short-term symptoms but also on long-term complications. And when I look at this trial, Tazeen, I've never been part of a trial, where we basically started with 58 patients and have 58 patients more than 1 year into an open-label extension, where opportunities to drop out, anything else happening, all of them are there. And I just looked at the adherence level, it was 99.8%. Meaning is that how it really provides the short-term in terms of really the quality of life is driving that. Because we also know, sadly enough, if its only long-term complication, it's really hard to build up the right adherence. So I've never being more hopeful for treatment for this patient group. And we trust to be in a position that end of this year, we will have the 84 weeks open-label data. And hopefully, we also will have our Phase III data end of the year. Will give us extremely strong package for a filing and getting this important product as fast as possible out to the patients.

Okay. And thanks for that summary, Jan. So given how impressive the data has been for HPT, I think some have wondered, why would you need to do a Phase III program when you had a pretty robust Phase II study with a good number of patients in it given this is an area of undermet need? Maybe you can kind of walk us through what you expect to show in the Phase III program that maybe FDA wanted either clarity or more durability on? Any kind of color you could provide would be super helpful.

There's a lot of good reason to make the Phase III program. First of all, we're talking about a global product. We want to address all the patient, and that's more and more patients in Europe that have this disease than in the U.S., potential nearly double up. That is one thing why we make a combined European-U.S. trial. The other thing is that we wanted the strongest possible labeling to do it. And one of the things we wanted to ensure and give to the regulatory agencies is that we can show, and we could only do that by having 18 months data, that we have always the bone markers in the normal level all the time. We are not generating superficial logical anabolic bone marker that potentially could give a restriction to a potential REMS program that you have on all our short-acting PTH program. So out from that, there was a lot of good reason we wanted to do it. Also, we wanted to have the quality of life being confirmed into our validated patient-reported outcome, which we just got validated to FDA. All that will provide us with the strongest possible labeling. And that is what we want to do in the end, getting it out to as many patients as possible as fast as possible. And that was why we were dedicated to take this pathway where we would get the open-label extension trial with 84 weeks of data, proving the long-term effect of this treatment, combined with the 6 months data that just show what I call the short-term effect on normalization of PTH to a normal level. And this is where we see it as, if we want to get it out in this broad perspective to the majority of this patient group in the U.S., we also need to have a strong labeling. And having the strong labeling we can generate just by basically postponing it for 9 months, and we believe that was to the benefit of the patient.

Okay. Now as we look forward to the 84-week data, what is it that we could see there that we haven't already seen at week 58? Are we just simply looking for durability and extended safety?

I think that is exactly right, Tazeen. We are looking on to durability of the treatment, and we are looking for the normalization of the bone markers to trending more to the mid of the normal level, we will see that bone density also will start to be normalization. So everything what we want to is happening there. One of the other thing we also saw, which was very impressive, that when we actually started, we actually had some patients that are already starting to have kidney impairment. And we actually can see how we actually also can help this patient group. And that is also what we want to see in the long-term data because we're also following filtration rate and other things like that. And this is really the strong package that will give us the strong pharmacoeconomic that all this patient group in the U.S. because it's really helping the patient, also helping the society.

Okay. Now I guess as it relates to the PaTH Forward study, how are you thinking about rate of enrollment and when you think the study should be able to read out?

I think, Scott, in his press release confirmed the timing of the data.

Q4 this year.

Okay. And are you noticing any, I guess, acceleration of the study just based on the light level of reopening that we're starting to see, which we would expect to accelerate over the summer? Or has COVID not been as much of a driver?

You know, we tried that when we had the first wave, we had a patient in Italy. What we managed to do there, together with the hospital and the physician of the patient, we managed to keep all the patients in the trial, even if we have many patients in Milan. One of the worst places. So what we see here is that there is such an unmet medical need that everyone is working together to get that. And we don't see any restriction, except that is like everyone else, there is some supply issues for some kit somewhere or something where we reshuffle kit from one place to another place, but that is just logistic, and we're pretty good to deal with logistics. I can guarantee that.

Okay. Okay. That's good to know. I'm sure we can spend more time on PTH, but I did want to talk about the other programs as well. So maybe let's back up to your lead program, which is, of course, the once-weekly GHD treatments. Can you talk to us with any level of qualitative commentary about how interactions with the agency are going, with FDA, as it relates to your application for pediatric approval?

I think Dana will give you an update related to our regulatory interaction, both in U.S., but don't forget Europe, too, because we are also marching forward there, too.

Okay. Great. Well, as far as the BLA goes in the U.S., there are several different channels of interactions with the agency. The first area is around the facility inspections. And as we had mentioned previously, FDA had an interest in inspecting the Fuji Film facility in the U.K. However, we were able to get the FDA to communicate with the MHRA, which had a preplanned inspection of that facility in March. They coordinated ahead of time. And after the inspection, MHRA shared their findings with FDA. And since that time, there have been a couple of interactions going back and forth where FDA is requesting additional documentation from Fuji, along the lines of the 704 pathway that they detailed in a recent guidance. And so we're cautiously optimistic that, that could satisfy that need for that specific inspection. Separately, we had a BIMO inspection here in the Bioresearch Monitoring program inspection, which is related to our GCP practices and the generation of our date for the growth hormone trials. The FDA came in and was here for 6 days with us. Left last week, and we did not receive a 483 at that time. So we're very pleased about that, and that was an expected event that would enable an approval so we were good on that score. And then with respect to other interactions related to the review. We had our late-cycle meeting in April. After that meeting, we got 2 final information requests. One was sent to us. One was sent to the manufacturer of the device. And we responded to ours. They've responded to theirs. And we're waiting for FDA's assessment of those things. So everything is on track. And then the last piece is that we expect the next round of labeling negotiations to begin this week with FDA. And I mean we were pretty happy with the label that was provided back in March. And so now, we're really just interested in tweaking it a little bit to optimize certain sections. But otherwise, it was very close to what we were looking for. As far as the European -- go ahead.

Maybe -- yes, if I can interrupt you for a second. So you did give us a lot of information, and I just wanted to clarify a couple of points. So just based on your experience so far, are the types of questions that have been received, thus far, from the inspections and questions about manufacturing, et cetera, in line with what would you expect at this stage? Or is there anything that was a little bit out of the ordinary?

No. I think they were fairly routine types of questions. And so we just need to address it. And we have a combination product, so it is a little more complicated than just a simple sort of biologic or small molecule, so we're expecting those questions.

To sum it up, Tazeen, related to the U.S. market, we are exactly where we expected and hoped to be at this time. Yes. That is exactly where we are. And we are less than 50 days from the PDUFA date. We are exactly in the place where we wanted to be and hoped to be related to all interaction related to FDA. I think in the big picture, what I'm more surprised about and I'm more pleased about most pleased about, I'm most pleased about the understanding from FDA related to our product proposition, related to understanding the TransCon technology, understanding and seeing how if they recognize, understand from our product release an unmodified somatropin that have the same distribution, same mode of action as normal somatropin that you'll find as an in doctor's PTH, in doctor's growth hormone and in doctor's daily growth hormone. Understanding that we are not a permanent PEGylated product, yes, we use PEG, but we use it as a carrier in a product, which is different than a permanent PEGylated, not having the class labeling of permanent PEGylated product. Understand that we have a superior product. Understanding the safety part of our aspect in the entire 8 group we have tested and used and be part of our clinical trials down to 8 of 1, I believe that was unique for me to get that knowledge because I actually believe if they understand our products, they understand the strength of our product, they'll also understand our long-acting products in the same potential manner. And that gives me very, very, very strong belief that TransCon growth hormone can be the leading product in the U.S. market.

Okay. Maybe one more question for Dana before we talk about Europe. I guess as it relates to the -- you mentioned the original label that you were given back in March. How does that work? Are you presented with a proposed label and then than you as the company provide feedback to the agency and then the agency has the authority to consider it or not? I guess I'm a little bit unfamiliar with how the specifics of that work. I don't know if you can provide some color on that.

Well, sure. When you put up your filing in, you have a proposed label that you sent to them. Right? But of course, that's just a starting point. And then during the course of the review, you get an understanding of what the concerns are of the agency. And then usually, after the mid-cycle meeting, the agency starts working on their version of the label based upon the information you provided and what and what they see. And so then it comes back to us. And as I mentioned, their first sort of version that they sent to us was very encouraging to us. And then we sent back a response to that. And then that's kind of where it stands at the moment. They're reviewing our response to theirs, and then we'll see what they think. And then there'll be maybe 1 or 2 more rounds. But I think we're very close to where we'd like it to wind up already, and we're pleased with all the big things, right? So that's very important.

Okay. That's good to know. And thanks for that additional color. So Dana, I interrupted you just as you were going to start to talk about the European application. So can you just let us how you're thinking about that process.

Yes. Sure. As we had mentioned, we got the day 120 questions at the end of January. And then we put together responses, I believe there was like 180 questions in total. And so we sent those responses in on time in the second or third week of April. And so the clock has restarted. During the course of our evaluation and responses to those questions, we were able to address one of the major sort of manufacturing issues that they had around starting materials and reached a combination on that. So that sort of eliminate one potential significant objection that they had. And then most of the other ones actually were things that were not particularly difficult for us to address at all. So the response went back in and then by the end of June, we should be getting a list of outstanding issues, which is -- of those 180 questions, which ones still may not be sufficiently addressed by them. And then we have another opportunity to work on those things as we go towards an opinion in the September time frame.

Okay. And up till now, are the comments that you've received from Europe any different from what you've interacted with the FDA on?

Not particularly. I think that they are just different types of reviews. Because the European agencies don't have their own statisticians and we don't send them the raw data like we do FDA, so they don't have an opportunity to go through and manipulate things on their own. So a lot of the questions are around them asking us to do things for them to just give them a better flavor for the data. But there actually weren't anything -- wasn't anything there that we hadn't been expecting. But -- so we don't see any real showstoppers at all, particularly -- and any particular differences between how they view the data and how the FDA views it.

Okay. That's encouraging. And maybe in the last 3 minutes or so that we have left, I wanted to get your thoughts as a team from the commercial angle, if we could, about how we should think about the ramp of this particular launch. So on the positive side, GHD is an established market. There are several players that have been marketing daily growth hormone, obviously for some time and so maybe patient finding efforts may not be as difficult to some other rare diseases. But can you talk to us about how long you think it will take just to institute this paradigm shift, even though on paper, it looks obvious, at least to me, that once per week injection that on a clinical basis is actually superior to a daily, would seem like something that parents of children would want. But how, in the real-world setting, should we be thinking about it?

Yes. I think there's some different facts, potentially, we should take up first. One of the fact that if you look on the really turnover of all the population that is being treated in, for example, pediatric growth hormone region, they are basically in the U.S., in average, is only treating about 3 to 4 years. So basically, from that perspective is that you actually have a very, very, very fast turnover of the entire patient population. This is not like a chronic treatment. This is a patient that basically are getting out in treatment than out of. So you will see that is basically why we talk about penetration model, you only see the importance of this therapy in the first 1 or 2 years because there basically are not so many patients to switch out of 1 or 2 years because if they have an opportunity to take a once-weekly that is superior to a daily growth hormone I think that decision is very, very simple from that perspective is. So where we see the -- the other part that is important is to see that we have seen a consolidation of the daily growth hormone for the last years now, and we're seeing accelerating more and more where many of the daily growth hormone providers are starting to find out how they can have the terminal value out of that product. And typically, you do that definite by some way having what I call a strategy how to get that done. And this, in my knowledge, have not really involved the price drop. So -- but we also see a strong, strong consolidation of the daily growth hormone market because they know that the conversion will come. So what we're working in from the commercial strategy, we're working on a pipeline of product opportunities. We're working with our TransCon growth hormone. We're working on -- we're getting ready for our PTH and potentially, the CMP next in -- with utilizing the same established commercial infrastructure. And what we have done with growth hormone is working about what we think one of the key element is to get sufficient market access. And I'm feeling that we are really, really in a great position. So in all, when I look at TransCon growth hormone, we have all the ingredients, everything that is needed. But infrastructure, I think we have a great commercial infrastructure, really, to build up TransCon growth hormone as the leading brand in the next year.

Okay. Any kind of directional thought about pricing? I know we shouldn't expect to hear about this until it gets approved. But is it still on the table? Are all options still on the table, pricing at a premium, pricing on par?

I think there is some logic in if you have a superior product, you also get a premium pricing. I think that is, in my view, is a pretty logical connection.

Okay. Good enough. With that, we are out of time this afternoon, but I wanted to say thank you guys for participating in our conference this year. It's a great time to be covering Ascendis because you are at the presses, as I said, it's becoming commercial, but you are still an R&D engine. So we're looking forward to the many updates that are upcoming later this year and into next. So thank you, Ascendis team, for joining us.

Thanks a lot , Tazeen.

Thanks a lot.

See you. Bye-bye.

Bye.