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

Good morning, everyone. Joe Schwartz, covering analyst for Ascendis. Very pleased to be joined by Jan Mikkelsen and Scott Smith, to give us an update at a very exciting time.

Good morning, gentlemen. Maybe we can just ask you to give us a quick lay of the land before we dive into some more specifics around each of your programs.

First of all, thanks, Joe, for inviting us. It's always a pleasure to be here. Yes. Ascendis Pharma, we have been executing the last years about our Vision 3x3, which is our strategic pathway how to be a leading biopharma company, and it's basic building a sustainable growth by multiple approaches. But one thing that it really is incumbent is everything what we're doing is built on the TransCon technology. And the TransCon technology has been our cornerstone in our rare disease endocrinology pipeline. And I will give you just a little bit a short update about our rare disease endocrinology pipeline, but also going to be the cornerstone in our oncology pipeline, where we now are progressing 2 extremely interesting product opportunities to IND-enabling later this year. One is our bias interferon IL-2 molecule and our long-acting intratumoral delivery of TLR7/8. Going back to our rare disease endocrinology pipeline, we were well known for our TransCon Growth Hormone. That was what we really got well-known last year when we came out with 2 Phase III trials that showed the superiority of our TransCon Growth Hormone. And at the same time, we could still combine and get all the benefit of what you expect to see of endocrine health of growth hormone treatment. This year is the progress of all 3 of our product opportunities in rare disease endocrinology. For Growth Hormone, we continue -- we will start on our BLA filing here in next quarter. And then later in the year, we will go to the filing for Europe. For TransCon PTH, we really are in extremely exciting stage. We are waiting for our Phase II data. That will come here at end of March, where we will be in a position where we will have 59 patients be in our Phase II trial, and we will disclose how we really can remove them out of standard of care and aiming for a true replacement therapy. For our last of our rare disease endocrinology pipeline, our TransCon CNP, we are progressing through the cohorts of how to do dose escalation. And we believe that our TransCon CNP, not only will provide growth, but really can integrate and benefit of all the other comorbidities that you will have in a disease like achondroplasia. So great progress for all our 3 product opportunities here in rare disease endocrinology.

Great. Why don't we start by diving in a little bit more on hGH. Your heiGHT data was really impressive with the stats saying superior results on the primary endpoint and maybe you have other ancillary benefits, which could be meaningful in adults as well as kids. Can you walk us through that as well as what you saw in the fliGHT study, which had some -- a few surprises? And I'd love to hear your opinion on the IGF profile there, and why it looked a little bit different to what you saw in the heiGHt study?

So I always like to go back to the fundamentals because we have really huge passion for the science and the patient. And this is how we drive decision and how we drive product opportunities. Going back to the science, you have 2 ways to treat growth hormone-deficient vector. The current treatment today is take somatropin, take it in a daily dosing. The other opportunity to take a long-acting somatropin, which are TransCon Growth Hormone. It's the same entity as daily growth hormone, the same entity as endogenous growth hormone. Then you have the third group, it's modified growth hormone. Every time any kind of clinical trials have shown data with a modified growth hormone, you basic have proven it's not function like a real somatropin. So when you ask me the question, was is there any kind of surprise in either our heiGHt Trial or our fliGHt Trial with our 2 independent Phase III trials, I will say, if you know the biology of daily growth hormone, the data came out exactly as expected to and treatment that you receive with daily growth hormone. Then you can come out and say, how could we be superior. Yes, we're superior because the PK profile we're providing compared to daily growth hormone is much more optimal compared to efficacy. So we basic can get a much more optimal exposure to target tissue, both inside the growth plate, but also to the liver, and therefore, we basic see a highly -- more highly effective compound. And I think this is the -- nothing to do with dose and different in mode of action. It's not because we make a different treatment just because we have a much more effective delivery of the same entity as daily growth hormone, the same entity as endogenous growth hormone. Specific, when we look on IGF-1, it just reflects exactly what you see with daily growth hormone. We basic have the same balance between efficacy and IGF-1, what you have common to see in daily growth hormone. And this is an association you cannot really change without changing the underlying biology. So if you have problems with IGF-1 level in daily growth hormone, you will also have problem with TransCon Growth Hormone IGF-1 level. But I think most physicians, through the last 15 to 20 years, have optimized the treatment of growth hormone. So they know exactly how really to treat and feeling confident this is the right way to do it.

Yes. Yes, I think most of the endos we talked to described themselves as IGF guys that are comfortable pushing on that accelerator were taking their foot off the gas there. I guess it's probably just PK related, where in the fliGHT Trial, you saw those things, which some people might say excursions. But what kind of monitoring requirements do you expect there to be required in the real-world? You're obviously avoiding 6 injections a week, which is a huge benefit. So I'm just wondering, like, as far as the monitoring requirements go, will they be any more or less onerous than what the daily have -- these IGF guys and how many people are not as astute do you think that you'll be going out to, to sell the product to?

What we're seeing in our long-term extension trials because the long-term extension time, our enliGHten Trial is much more reflecting, what we call, real-world because they've been treating for a long time. And we have more than 160 children now being treated here in the U.S. with our auto-injector and DCC, so our commercial presentation. That's -- only one thing you need to do different than compared to daily growth hormone is that you have a different curve during the week. So you are reflecting the average IGF-1, which are the most important part of it to basic -- to -- if you measure on day 5, yes, you miss average IGF-1. If you not measure at day 5, you correlate it with a factor that is very, very simple algorithm. If you measure day 2, you subtract. If you measure at day 7, you add something. And then you just get an algorithm for predicting the average IGF-1. So that is the only difference we have heard that we're basically taking as a difference between, what we call, daily growth hormone treatment.

Okay. That's helpful. Let's switch gears and talk about your next major catalyst, the PaTH Forward data expected at the end of March. Can you give us an overview of that program, and how it's evolved? And what the trial design looks like and what you expect to report in the first quarter?

So today, there's 1 major disease left in endocrinology rare diseases where there's no treatment. And it's basic hypoparathyroidism. And this is not because it's not needed. If you just look on the statistic, more than around 35% of patients stop working. More than 40% go on part-time. If you look on the long-term complication about hazard rate for renal damage, basal ganglia calcification, cardiovascular risk and everything like that, yes, it's a severe disease. And the problem today is that you basic trying to compensate short-term symptoms by giving long-term complications. You can compensate for the short-term symptoms, take activated vitamin D, calcium supplement every second hour, take 3, 4 gram, that's a lot of tablet to eat. You need to wake up during the night, take it too, so you're sure don't go cramp. But it promote the negative part, the long-term complication, both related to calcification, high phosphate level and other element. So we have a disease with a substantial patient population, more than 100,000 in the U.S., around 150,000 in Europe, 35,000 in Japan, really substantial patient population. So today in the market, if you go about 9 months back, there was 1 approved therapeutic drug in the U.S., which was not a treatment. It was adjunct to, what we call, standard of care. Adjunct is something where you can withdraw typically some of the standard for care and then add on. A treatment is basic when you take all the standard of care off and then you treat the disease. So what we want to do with TransCon PTH, to come with a treatment, a true replacement therapy. And then you can say, is that really possible? Yes. There's a lot of scientific data. A lot of peer-reviewed literature related to how to optimal treat a patient with HP. You buy FORTEO, or you buy PTH 1-84 [indiscernible] when you can buy it. Buy an insulin pump, take it into an insulin pump, provide 24 hours, 7 days a week. All this PTH in the physiological level. By doing this, you address all aspects of the disease. Meaning, you can normalize serum calcium. You can normalize serum phosphate. You can normalize urinary calcium. You can normalize bone turnover. You can get the right CNS effect. So what we proved in our Phase I trial in healthy volunteers that we can exactly mimic this consistent exposure of PTH, 24 hours, 7 days a week, always in the physiological level. We showed that in Phase I. We also saw all the expected associated PD effect, everything from serum calcium, serum phosphate, bone markers, urinary calcium, all of that was associated with this, you can say, continuous exposure. So by just providing a simple, daily subcutaneous injection, like an insulin treatment, you're basic is providing this continuous exposure, 24-hour, 7 days a week. So now we are reading out the Phase II trial. In the Phase II trial, we have now enrolled 59 patients. We expect it only to enroll 40, but because of the NATPARA recall, we took extra patient in and ended up, like, 59. We have now 59 patients with our randomized to 3 different doses of TransCon PTH, 15, 18 and 21 microgram per day and then placebo. This is a double-blinded trial. And what we want to do in the first 4 weeks is basic to find out how can we remove on the optimal algorithmic old standard of care. And this is basic what we're doing. We have disclosed some data here at the beginning of the year, where we didn't look of -- after the 4 weeks that a study is double-blinded, but 4 weeks in the open-label extension because you need to imagine that placebo arm when they're finished with Phase II study, they're basic going into a titration exactly as they have -- should have been on active drug inside the Phase II study. And when we looked on 4 weeks in the Phase II study for the first 8 patients, basic all patient was out of standard of care. It gave us a strong belief that we are in a position that we can provide a true replacement therapy. We are looking forward to have this data coming out here end of Phase II. And we hope, in some way, we can work with regulatory agencies. So we, as fast as possible, can go out and provide this product opportunity to the patients that is really need of -- where they basic have no treatment options today in the U.S. because NATPARA has been recalled from the market. And that is what we want to aim for. This is what we're trying to address as fast as possible.

So will you provide us with more open-label patient data in March when you give us full fixed dose portion of the study data?

What we have said to public is that when we come into Q3, we will provide open data, 6-month data for all patients. And I think that is really important because there will be about 50 to 60 patients that will basic be on 6-months treatment that have been evaluated at that point, the 6 months endpoint exactly to, what we call, the expected Phase III clinical endpoint, meaning normalization of serum calcium, withdrawal of activated vitamin D, withdrawal of the calcium supplement and normalization of urinary 24-hour calcium or improvement of that. And that is exactly the endpoint that is basic a speculation that we more or less have discussed with all regulatory agencies.

Yes. Okay. That's helpful. And then when you reported the data in January on the 8 patients, you highlighted the ability to remove the current supplement, standard of care. You did not talk about serum calcium or fractional excretion of calcium. Why was that and -- yes?

This is very simple, Joe, because we have an electronic diary. So we basic can very fast approve the data. So I won't meet a data lock going in -- undergoing the data of the electronic diary because of only single patient, what we're taking on supplements. So from that perspective, it was very, very easy to clean that data and to conduct for the 8 first.

Okay.

This is mainly because Scott got very excited we need to disclose it.

Yes. All right. He looks pretty excited over there.

You need to have a financial question.