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

Good evening, everyone. My name is Jeff, and I'll be your conference operator today. At this time, I would like to welcome everyone to the Ascendis Pharma Top-Line Phase II PaTH Forward Data Conference Call. [Operator Instructions] Thank you. I would now like to turn the call over to our speaker today, Mr. Scott Smith, Senior Vice President and Chief Financial Officer of Ascendis Pharma. You may begin your conference.

Thank you, operator. Thank you, everyone, for joining our Top-Line Phase II PaTH Forward data results conference call today. I'm Scott Smith, Chief Financial Officer of Ascendis. Joining me on today's call is Jan Mikkelsen, President and Chief Executive Officer; and Dr. Dana Pizzuti, Head of Development Operations. Before we begin, I would like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act. Examples of such statements may include, but are not limited to, our progress on our pipeline candidates and our expectations with respect to their continued progress, statements regarding our strategic plans, our goals regarding our clinical pipeline, statements regarding the market potential of our pipeline candidates and statements regarding planned regulatory filings. These statements are based on information that is available to us today. Actual results or events could differ materially from those in the forward-looking statements, and we may not achieve our goals, carry out our plans or intentions or meet the expectations or projections disclosed in our forward-looking statements, and you should not place undue reliance on these statements. Our forward-looking statements do not reflect the potential impact of any licensing agreements, acquisitions, merger, dispositions, joint ventures or investments that we may enter into or terminate. We assume no obligation to update these statements as circumstances change, except as required by law. For additional information concerning the factors that could cause actual results to differ materially, please see the forward-looking statements section in today's press release and the risk factors section of our most recent annual report on Form 20-F filed on April 3, 2020. Please note that our TransCon product candidates are investigational product candidates and not approved for commercial use. As investigational products, the safety and efficacy of the TransCon product candidates have not been reviewed or approved by any regulatory agency. None of the statements made on the conference call regarding our TransCon product candidates shall be viewed as promotional. On today's call, we'll walk through a presentation on our Top-Line Phase II PaTH Forward data. Following some prepared remarks, we will then open up the call to questions. I will now turn the call over to Jan Mikkelsen, our President and Chief Executive Officer.

Thanks, Scott, and good afternoon. Thanks to you for joining us today. We are having today's call to announce the top line results from the 4-week fixed-dose portion of our Phase II PaTH Forward trial for TransCon PTH. We believe that these data are great news for HP patients. These patients are in urgent need for therapy that can sustain physiological levels of PTH 24 hours a day, 7 days a week. They need a true replacement therapy that can normalize all aspect of the disease. The 4-week data from the PaTH Forward trial are the first step to demonstrate that TransCon PTH is not an adjunct to but a first-line therapy for HP patients, one that replace the current standard of care. We all know the burden of this disease is enormous. Standard of care with active vitamin D and calcium supplement means patient and physician must balance their trade-off between short-term symptoms and risk of long-term complications. With this treatment, they have to manage and stabilize serum calcium on levels in the low end of the normal typical around 8.5 million per deciliter. Another problem is that treatment of short-term serum, the calcium on active vitamin D also increased the long-term complication due to increased urinary calcium. Urinary calcium is a known renal risk factor, and increased calcium phosphate product is a known risk factor related to atopic calcifications. These results shows that TransCon PTH can address this burden and create a new standard for first-line treatment for HP. You will recall that the primary goal of PaTH Forward is to identify a safe and effective starting dose, one that allows for complete removal of standard of care, [ EKE ] activated vitamin D and calcium supplements, proving that it can be a true replacement therapy. And as a Phase II trial, the fix doses, compared to expected optimized titration for each patient, it was not really our primary uptake to achieve statistic significance. Also we were still able to do that. I would like now to move over to the deck that has been presented and posted on our website. And I would like to go to the slide in a way where I hope we will see that we are providing a lot of data. This is the typical way how we want to release data, to give you full transparency about the entire deep concept of our dataset. And in this case, you will also see the same thing. So going to Slide #3, and the overall conclusion is that PaTH forward top line data support TransCon PTH as a potential replacement therapy for adult HP. TransCon PTH basically eliminates standard of care, defined as off-activated vitamin D and less than 500 milligram per day of calcium supplements in 100% of the subjects being treated with the 21-microgram per day in just 4 weeks. And if you go across all 3 cohort, 15, 18 and 21, we basically had 82%. That was one of the primary goals we wanted to show. One of this really key element to show that we really can remove standard of care so we have a true replacement therapy. If we go to the more strict secondary end point in the 21-microgram per day, we really could also see that we had the -- hit the end point there. We also have expected take on mean serum calcium. We also reduced urinary calcium excretion. And also have the expected positive effect on serum phosphate and calcium phosphate product. Perhaps really important, too, all doses of TransCon PTH was well-tolerated. No serious or serious adverse events at any point. No treatment-emergent adverse events lead to any discontinuation of the drug. And all, when we compare, it was comparable between TransCon PTH and placebo. Also illustrated with there was no dropouts in the blinded period. Just on Slide 4 is basically giving you the recall of how it was designed. I will not go into the topic of that slide. And go -- move forward to Slide 5, which gives you the PaTH Forward trial profile. 59 subject got randomized. All of them continue through the treatment period. We had 2 patients being excluded because they received less than 0.25 microgram BID of calcitriol that activated vitamin D. Going to the demographic and baseline characteristic. And the main element, and I will go to the slide, but I can give you the overall conclusion from the beginning that is pretty well-balanced clinical trial. We can go to -- go to yourself, the age group, the body mass, typical female. You can see that, as expected, around 80%, exactly as what we have expected. Slide #7 show you the breakdown of the demographic. And you will see there was a trial that was balanced between North America and Europe. Going to Slide #8, we'll go in and show you all the data related to HP disease characteristic and history. You can say there is potential an imbalance on renal insufficient history where all 5 patients with renal insufficient history was actually in the treated arm with TransCon PTH, and none of those patients were in the placebo arm. Going to Slide 9. And we have defined it in the way of calcium and defined calcium in 2 groups. This is calcium supplement, and you can see we defined it from up to and/or even to 2,000 milligrams or larger than 2,000 on a total daily dose. And when you compare the different group, the basic are well-balanced. If you go back to calcitriol, you can see all the calcitriol that is in the trial started on 0.5 milligram -- microgram of calcitriol because that was the minimum amount, which we think representing the treatment, the patient group that we want to treat and with other vast majority of all patients. When you look at the minimum and max, you can also see that there is in the TransCon PTH arm from 0.50 up to 3 in the PTH treated arm and for the placebo, is from 0.0 to 1. The same as alfacalcidol, you can see the breakdown there. So if there is any kind of, you can see, imbalance between the different arm, it's definitely are favoring that the less severe patient is in the placebo arm, if you look on total calcium dose and also for example, on calcitriol. On Slide 10, you have the Spot FECa. Recall this is a Spot FECa that is done in the morning, meaning is this is where you have the less food intake, meaning is there where you have less flow on calcium from the -- in tested system, so expected it to be lower. And when you see that is potential the partly explanation where you see around [indiscernible] of the patient already at that time had basic FECa number that is less than 2%. When we compare the demographic in other HP trial, we actually see pretty much aligned to what is being seen in other trial, except that it has been hard for us to compare really with FECa number because it not has typically been used a lot into clinical trial, where the most clinical relevant factor has been 34 hours urinary calcium. Important part is now the safety part. And when we look on AEs, you can see its basic are very, very balanced. And I can start from the bottom on the list where you go about leading to death, leading to discontinuation of -- in the trial, leading to discontinuation of study drug. None of them happened. Perhaps also more important is the TEAE related to hyper and hypocalcemia leading to ER or urgent care visit and hospitalization. In the next slide, you can see how we break down the treatment-emergent adverse events, and it's including events that is happening in more than 2 subjects. And then we have included hyper and hypocalcemic episode. And what you can see here, there was 2 episodes in the 21-microgram arm of hypocalcemic and 1 hypocalcemic episode in the placebo arm. But just record, none of them led to ER or urgent care. The conclusion on Slide 13. All doses of TransCon PTHs were well-tolerated. No drop-out during the 4-week blinded period. No serious or severe TEAEs were reported. No TEAEs leading to discontinuation of study drug. Overall, incident of TEAEs comparable between TransCon PTH and placebo. And the TEAEs we see in the TransCon arm reflect the known PTH pharmacology. Injection was well-tolerated, and we also had already introduced the pen injector that is planned for as a commercial presentation. So overall conclusion, TransCon PTH showed in this trial really and the expected safety profile that really also aligned what we have seen initially in our Phase I trial. And more important, the titration algorithm we're using to remove, eliminate standard of care did not demonstrate any hypocalcemic AEs, meaning is this was a safe algorithm, really already a great win. But then we come to the more important, how did it go really with our titration? And when we look on not taking activated vitamin D, and you can see, we both have defined it in 3 different groups, and we also defined it for total PTH objective. And when you look on the groups, you can see that for both 15- and the 21-microgram, 100% had complete withdrawal of activated vitamin D. There was 1 left in the 18 that first came out, I think, 1 week after in the open-label extension study. So basic, 98% of all subjects managed to get out of activated vitamin D, taking less than 1,000 milligram of calcium supplement. And you can see the different doses where you see the 100% of the 21. And taking less than 500 milligrams of calcium supplement, 100% also in the 21 group and about 90% or 86%, so it's basically in the 15 microgram. This is really impressive, also when you go down and look on the taking serum calcium supplement, 50% of the patient basic after 4 weeks, only 4 weeks on a fixed dose, where we know some patients will not have sufficient PTH, and sure someone will be treated in the upper level, but at that time, it's still possible to take 50% total out of calcium supplement. And when we see not taking activated vitamin D or taking less than standard or less than 500 milligrams of calcium supplement, which are typical how you define standard care, we have more than 82% succeeding that, which are really, really impressive. And just as expected, where we believe, and it's just confirming that we could do it, the element that was interesting is, could we do it as fast in this 4-weeks period of time because we not only needed to be in a position that we got the right algorithmic independent, but also the patient had this physiological thinking about I have for many, many years, been used to take this as a rescue therapy for me, not to end up in a hospital setting. And we need also to convince, yes, it's safe. So potentially, the psychology have been the most important part that actually ask why we see a continued down titration of calcium supplement. Go to Slide 15, you can see the time how we down titrate activated vitamin D. And recall from the protocol, we down titrate activated vitamin D first. So it's the easiest one to get off. It's always the second medication that is the most difficult. And you can see that in Slide 16, where you can see there is a continued fall in the amount of calcium supplement. For the 18, you can see there's a huge standard deviation on week 4, and that is mainly driven by an outlier in one single patient that took up to 8-gram of calcium supplement exactly at that time point. Now I'm going to the impact on FECa. Remember, as I said before, it was done in the morning, where you actually have the lowest uptake through the system, how body take up calcium for the food that you basically will see a lowest FECa. And what you see here is that from the 3 treatment group on Slide 7 to the left mean serum calcium is going up, up to the level, which we think is the nice place, the 9s. You also see that placebo arm is stable or going a little bit down, which exactly is reflected in the FECa for the placebo, where it's going a little down. But what is impressive? We can basically increase serum from calcium. And what we're seeing, we basically see an decrease in spot FECa still. Meaning is that the reabsorption capacity that PTH is facilitating on the kidney system is really also being exactly illustrated here as we also show in our Phase I trial. Going to a different way to represent this data here is going to look on each single patient, how did they respond to be under the 2%. And clearly, from baseline to week 4, you see an effect on subject with normal AM FECa. You also see that clearly on 18. And despite we really are increasing serum calcium on the 21, you also see that. And when you look placebo, complete unchanged. Everything is supporting what we have seen in our previous studies that we have exactly the expected positive effect on the kidney in reabsorption as calcium as expected. Other data which are essential in the treatment. Can we lower phosphate? A really one of indicator of cardiovascular risk. Yes. That is one of the main element you see with PTH 2, and we see a clear response just in 4 weeks. And you see how placebo is unchanged. The other way to look on the risk of atopic calcification is calcium phosphate product. The same thing is observed exactly the same benefit there too. In Slide 21, we summarize the primary end point. And it was not really a trial that was basic -- was powered or intended to show statistic significant. But when we look on the 21-microgram per day dose and the total PTH subject, we basically see a p-value that is lower than 0.45. I think that is pretty impressive in a 4-week period. In a 4-week period, where we know that we basically have fixed those, which are, I will not say the word, but it's artificial compared to how you will treat and evaluize each single patient. So we know, and you can see that, when you look at the serum calcium, you can see in the low dose, there's 2 patients that basically have less than 8.3 milligram per deciliter of serum calcium. Meaning is, there's nothing wrong with the product, but they're not getting the right dose. They should just have a higher dose. When you go to the 18, one in each group, one getting too much and one getting too less. And when you go up to the 21, you can see that is one that actually are getting too much compared to the optimal each person dose. Going to the key secondary composite end point. And this is where we lower the calcium supplement and see there the same thing. When you look on the p-value, you basically can see that the 21-microgram per day arm shows significant response compared to placebo. Going to 23. And yes, we also met the primary end point. Yes. There was pretty surprising for me in some way because there was a short study duration of 4 weeks. We know that typically it takes much, much longer time to specific move. The last part of the calcium supplement fixed dose, meaning is that we know that some patient potential with [indiscernible] in the 15 dose will have too low dose really to be treated in the way that ever hit the primary end point. And we know in the high dose, obviously it will be, and perhaps the 18 will be a mixture because we don't do individualization of each patient to the optimal dose. And we saw that continuation where we see calcium supplement is being continued titrated down. And other times, there was not a large study population. So what are we doing now? All the patients, the 58 patients, they're enrolled now over in the open-label extension, where they basically get how we want to treat in real life. Each patient will be optimized to the optimal PTH dose, where we're elevating long-term safety and efficacy. 58 of a 90% went over in the open-label extension. One subject that was randomized to placebo withdraw for reasons unrelated to safety and efficacy. And in the long-term study, we will basically [indiscernible] rate them in the 6-month point here in Q3, but we will not use FECa, but perhaps they are more relevant clinical end point, urinary calcium as an end point to evaluate the composite end point of all 4 elements. Planned next steps. Yes. We got the data that we have hoped for. Now we need to talk with the regulatory agencies and decide on the next step for TransCon PTH. We will have the open-label extension 6-month data in Q3. We will also suppose and propose an PRO instrument for FDA review in Q3. And depending on all our discussion related to regulatory pathway, we have as a base case, an opportunity to initiate a Phase III trial, which will be a global trial. We have already successfully achieved our ethnobridging, so we basically can perform a global Phase III trial. Slide 26 is just summing up what I basically have told. And I will not go to it again. But for my and I think for Ascendis, but I think much more important for patients with HP, they the results that we hope for. And as we are dedicated to our values about patient signs, we definitely are looking forward to develop this year as a treatment for patients with HP, which is one of the last, last endocrinology diseases where there is no replacement therapy.

Operator, we're now ready to take questions.

[Operator Instructions] Our first question is from the line of Jessica Fye.

On the topic of your plan to engage with regulators on the next development steps, should we expect that to happen before or after completion of the open-label extension portion of the study?

I think Dana can explain more clear. It's something we're just starting preparing for tomorrow.

Yes. So our plan is to engage the agency before the end of this week to begin to discuss these data in the context of potential breakthrough designation. And then we'll see how that goes. But that's the initial plan. I think, also we need to have an official end of Phase II meeting. And so we'll be preparing the documentation for that in parallel. But the first step is to restart the breakthrough designation discussions that we have had with them earlier in the fall.

Okay. Got it. And then a couple of specific questions just that we're getting from investors this afternoon. On the 21-microgram dose, where the data looked the strongest, if we look at Slide 9 on the baseline characteristics, that arm happens to have a lower percentage of patients on 2,000 milligrams of calcium. What do you make of that as we interpret these results?

I think if I look on Slide 9 and look on the 21 microgram -- larger than 20 -- 2,000 microgram, I actually think that it's the arm that actually have the more severe disease. If you do [indiscernible] of large amount of calcium supplement, they have 60% have more than 2 [ time ] where the other group was about 20% and the 30%. So basically, it was the most severe arm.

Okay. Got it. And then sticking with the same slide, I think the entry criteria on clinical trials say that patients were supposed to be on a minimum of 400 milligrams of calcium BID or a total of 800 milligrams calcium supplementation. And when I read across the daily dose, it looks like the minimum for some of the arms was 500 not 800, curious how those patients kind of fit into the protocol definition.

I think you're right. This is a good question. There should be 800. I need to go back and double check. It's a good point, I give that.

Next question from the line of Michelle Gilson.

Congratulations on these data. I was just hoping to talk a little bit more about the fractional excretion of calcium. Just could we get a little bit more clarity on why we aren't necessarily seeing this moving as quickly? Is it time dependent? Or is it that the end point, the morning spot versus 24 hour? Or is it because of the lack of dose titration? Or is there something related to baseline characteristics? I guess could you just talk a little bit about what we're seeing there? And then also in the open-label extension, what we should expect as far as we readthrough on 24-hour urinary calcium?

So in the 6 months data point that we will have in Q3, we were using urinary -- 24 hours urinary calcium, and we already have that asset baseline. So that will be much more what we could call the more common way to use what I call evaluation about the reabsorption capacity of the kidneys. What we saw here, and I think it's potentially reflecting a little bit that is a morning spot test, meaning is, if you look on the normal PTH level, you basically also have the lowest level of PTH in the time of where we take it, meaning is that you have the lowest amount of uptake from the food. So what we are seeing here is potential that if the spot test potentially was being performed in the late afternoon, potentially, you will see a higher value. And this is where potentially the explanation why, when you look on spot testing, you basically see that many of the, for example, the patient already at baseline have 50% or I think it was about 50% are in a position that they have less than 2% in FECa. What is the impressive thing for me is to see that you basically can increase serum calcium. And then your basic, at the same time, improve both the absolute mean number but also number of patients that will have lower or even to 2% of fractional excreted calcium. Just illustrate that it's really our TransCon PTH is providing the expected effect on the kidneys.

Okay. And then could you also just help us work through what's most important from a patient and a regulatory perspective. You gave us a lot of data. Is it the statistical significance? Is it the full reduction of calcium supplement in patients? Or the lower instance of hypo and hypercalcemic events? What -- is it the urinary calcium? What's most important kind of around these events when we start to think from a patient and regulatory perspective?

I think it's really important from a regulatory perspective, and this is why we ran the Phase II trial, that we basically could show that we could eliminate standard of care without hypocalcemic episodes. And this is what the data showed in just in a short period of time: 4 weeks. Even on a fixed dose, it is possible to eliminate standard of care for this patient group. That is the most important result because no other drug have even been near to show that effect. Then you can say everything else we have on we can add on, the [ phosphor effect ], the calcium phosphate complex. But doing that in a safe manner, where we eliminate, wait out any AEs related to hypocalcemic or anything in general, we can eliminate standard of care and basically take the intake down to a level, which are starting to be much more like a normal person. That was the positive effect. For me as a person, and I think from the regulatory perspective, this is not hitting a p-value, this is a Phase II trial. We need to show that the drug is functional. We have showed that the drug was functional in healthy volunteers, exactly as expected. Now we're also showing that the drug is functioning exactly as expected in patients. That, I think, is a main element for us.

Yes. I think from what we learned when we discussed this with the FDA in the October timeframe is the most important thing is being able to establish the normal calcium, withdraw the standard of care. I think the 82% of subjects being on higher than 500 of calcium and no vitamin D is, in my mind, the single most important point. But obviously, the safety is important and some of the other implications for long-term efficacy are important, too. But we won't have those data until we get the open-label extension.

Next question from the line of Joseph Schwartz.

Congrats on the results. Now that you've done this study and seen the data, do you think patients would necessarily get fixed doses for 4 weeks in Phase III in the real world or is the opportunity to titrate them sooner? And how would you do that based on what you've seen so far?

Yes. This is where we will go into a dialogue with regulatory agencies because sure we can have recommendation, but in the end it will be a dialogue with regulatory agencies to really balance the safety compared to how fast we will take them out of standard of care. But what we are proving now with this data is that, yes, it's possible to do it, and we can definitely define an algorithm to do it. And it looks like we can do it in extremely fast period because we are providing the national physiological PTH. How they exactly will be for the algorithm that will be used in clinical practice, I think we are still evaluating that. We're still discussing that and also will have an interaction with regulatory agencies before we basically say, this is how we see it. But definitely it's extremely encouraging to see that 21, we can eliminate -- have retained it so fast for all patients. We also saw that 18 looks really, really impressive, too. And this is where we need to compensate and discuss speed compared to how fast we will do it. But from a safety perspective, we definitely don't see any issue with all 3 doses.

Great. And then as a follow-up, now that you've seen this fixed-dose data, how or what is the bogey that you're aiming to hit at 6 months on the composite end point and some of the more important components?

I think the most important thing for us is that we know this drug is function in the intended patient population. That is the most important element for us. And I believe when we start to do the optimization in the open-label extension study, just to recall, we actually have the first patient for 6 months dataset now. So this is not like -- and all of them are staying in the treatment. Everyone is staying in the treatment. Just -- must illustrate that we see a huge benefit of this product opportunity. And this is where our actual arm are really, really happy, really feeling pleased that is providing the benefit and the benefit and the patient really also recognized this benefit because of staying on treatment.

Next question from the line of Tazeen Ahmad.

Congrats on the data. Just wanted to see, Jan, if possibly you could talk a little bit about the patients, the 17 patients that were previously on NATPARA. Can you talk about whether or not there were any differences that you observed in the way they responded versus the rest of the patients that were in the study?

Exactly. What we did is that we try to do -- in the database, it was easy to lock the -- I cannot remember exactly, it was 9, 10 or 11 patients that just came out of NATPARA treatment. And then we did a statistic analysis of this group compared to the rest. And to my best knowledge, when we look at the data, I could not see any difference on the primary end point related to that you just came out of NATPARA or you have been, what I call, a net new patient. So from that perspective is, we have not seen any data that indicate related to the primary or secondary end point. There is a difference related to the 2 patient groups.

Okay. And then as far as your Phase III plans go, what is it that you -- what information is it that you think you would be able to get from running a Phase III that you wouldn't be able to get from the dataset that you just collected or the open label extension? And then to follow on with that, if you were to run a Phase III, how should we think about the titration schedule there?

Yes. You're right. Now we have basically achieving long-term data of TransCon PTH. As I just said, we basically have the first series of patient is now hitting the 6 months' mark. And still, everyone is in well-treated situation. So we are in a position that I believe that we are accumulating sufficient amount of data that also show 6 months, what I call, long-term effect of PTH's treatment, which I actually think is pretty impressive. But what we also want to do, which people are working intensive, is our patient-reported outcome. And when we come to the 6 months' data, we basically will have a great evaluation of that. So when combined what I see here in the 4 weeks' fixed dose double-blinded period compared to acceleration combined with the data we will generate for the 6-months patients, and therefore you also know that basically on the 6 months' timeframe, some of the patients will already start to generate 12 months' data. So we really are accumulating a lot of patient base for all 58 patients now. And that is what basically are coming into the Q3. Related to the titration we're seeing, I think the uniqueness was that we -- it looks really good. All the doses are basically providing what we wanted to achieve, and then we start to discuss is one dose better than the other compared to how fast we can titrate from a risk-benefit analysis. Yes. That is something we will have our own internal discussion about, but also we'll be in a position that we need to discuss it with the regulatory agencies.

Next question from the line of Josh Schimmer.

Just following up on the titration question that Joe had raised because it seems fairly intuitive that with the right dose, you could get most, if not all, patients to kind of that perfect level of calcium homeostasis. But as you think about specific patients, what are the drivers of intra-patient variability in their own calcium homeostasis that as you follow patients over a longer period of time might require ongoing titrations either up or down over the course of a year to kind of maintain that pristine balance?

That is an interesting question that we really will get the data from our open-label extension, where we basically will see data for up to the 6 months' mark what -- how the different -- changed the doses and as stated the information that we are collecting now. Going through the infusion pump studies and the literature, it gave us some kind of guidance how often they are changing. And often that we don't see the big change in that perspective, but it can happen if you change the dose. But if you need to change basically how you are -- what kind of intake of food and other things like that. So these two things need to be regulated in this way. But I think the final answer for your question is one of the data we will have in Q3 later this year. First of all, we can also see on legacy effect, do we have a different, you can say, average maintain doses from the 21 group compared to the 15 group, which also are an interesting question to ask. And this is some of the data that we will get out in Q3.

Is it fairly straightforward to determine if patients are adherent to diet because I guess at the end of -- I mean this would hold true for any hormone supplement, you don't want to be titrating up and down just because patients are not adherent to diet, in which case, you're kind of chasing your own tail. So is that fairly straightforward to differentiate excursions that are diet related from none?

I like to think for all of the experience, for example, we have any diabetes, I like to think it's very well, the same way you will think about it in the same way, there you also think about what you're eating. You're thinking about what is the content and what you're eating. Because you know basically, it can have an effect on your glucose level. And I think this is the same algorithm, I think, in the era of patients with hypoparathyroidism. They have the same thing that the dairy company will have an effect on the intake of calcium as the same as in diabetic. I like to potentially the diabetic is much more, you can see, affected by the dietary impact because there's sort of what I call fast glycolysis, if you take most calcium basic bound, for example, into milk and other elements like that.

Next question from the line of Alethia Young.

Congrats on data today. Maybe a couple for me. One, can you talk a little bit about of the 60,000 to 70,000 people, perhaps, in the United States, like how many are kind of severe and truly might need something where you're [indiscernible]. Do think this medicine could be available for everyone, but just if you can give a little bit more granularity on that and then -- so we can think about what the subgroup of the opportunity is. And then the second question is, can you just talk a little bit about -- obviously, you have a platform technology, and these data do help confirm that, so just talk about what these data mean to the programs that you have going forward as well?

Yes. When we look on the patient population just in the U.S., we always describe it to be around 70,000 to 110,000, and it's actually increasing. And for Europe, we have larger population. And then we have Japan and we have South Korea. So when we look on the target population, it's more than 200,000 patients. From that perspective is that you should see and this is what I really see that benefiting when I look about the heterogeneity of the patient population we took in, this is not and then look on the long-term extension data, all of them are staying in it. Meaning is, yes, they see a benefit of this year. You don't take the burden of daily injection if you not have a clear benefit. And that is what we're seeing in our long-term extension study that they're staying in it, even they are coming in a heterogenic [ thing ]. So when I look on the potential of our product opportunity, and actual [indiscernible] are getting more and more convinced that the vast majority of the patient with HP should have this treatment, and it should be available for them. Going back to the general thing, I think we have proven the TransCon technology with TransCon [indiscernible]. We're continuing to prove the TransCon technology with HP. We will continue to prove it with CMP. And now we're coming out with our oncology product, you will see the same thing. We are a company built on a platform technology, and we're dedicated to bring as many product opportunities out to the patients as possible, really addressing major unmet medical for them, and we will do it in many different therapeutic areas. So I think this is just a further validation of our platform technology.

Next question is from the line of Adam Walsh.

Adam Walsh from Stifel. So a couple of quick ones here. Going into the data, KOLs had kind of suggested to us that you wanted to see -- they wanted to see a response rate of about greater than 50%. And in the 21 microgram dose, you achieved 60%, so that checks a very nice box there. But they also had questions about whether or not symptoms were improved. And I know these are really tiny numbers, and I don't need to get nitpicky here because the data looked pretty good, but if you look at fatigue, for instance, on Slide 12, in the 18 and 21 micrograms, you had some -- at least one patient in each of those versus no on placebo. What can you tell us at this point in time about symptom improvement after 4 weeks? I know we're going to see it in the OLE data, but what can you say about that now?

I actually think the best way, Adam, I can answer your question is, today, how many patients are dropping out? How many patients are staying on treatment? And when I see patient going in an open-label extension studies and everyone stay on it is because I believe that the benefit on being a daily treatment is really, really overcome with the -- for the burden of a data injection, Adam. This is how we see it, and this is what I look for. The more claims space part of that will come from our [indiscernible] as Dana, she explained before that its first something we basically will have ready in the Q3. But I get the confidence when I see because I typically never see that this kind of consideration where everyone stays on it, everyone continue on the treatment. And this must because they're really, from their own personal aspect, see a huge benefit to be on the treatment.

That's helpful. And then just one follow up, if I go ahead. The other point that was raised in some of our discussions is the potential for tachyphylaxis with increasing doses being necessary over time. I guess we'll know a little bit more about that when we see the OLE data, but my question is...

Adam, can I comment on that? Because I think that is typical a theoretical consideration. And if people look on patient on infusion pump and it has never been observed there. I cannot see either why it should ever should be possible for TransCon PTH that generate the same infusion-like profile to observe that effect. So I think the underlying biology, also when you look on the normal PTH level in normal human physiology is not supporting any kind of that point.

Next question from the line of Jim Birchenough.

Congratulations on the data. Can you remind us what your expectations are for longer-term bone effects of PTH delivered more 24/7? And if you saw any changes either way in bone marker? And is that something you'll follow in the open label extension?

Yes. What we have seen in continuous infusion pumps is that you do a normalization and basic are not providing an anabolic effect. We only have data now for the first 4 weeks. And what has been observed is supporting the same thing that you see in continuous infusion pump. Meaning, your basically are not seeing an anabolic effect. We will follow that in the open-label extension study and be quite sure that this is an important element. But I think from the scientific fundamentals, and this is why we discuss that with regulatory agencies in both EMEA and with FDA that basically give us a waiver for not making a carcinogenic study. Also this idea, yes, from a scientific justification that should not be possible to see an increase anabolic effect when you just do normalization of PTH to the normal physiological level. You see the anabolic effect when you make super physiological effect as you do in compound in the osteoporosis era.

And then Jan, just on the PRO, I'm just wondering if you could maybe share with us thoughts of what components of the disease burden you'd want to capture in the PRO? And do you think 6 months will be enough time to assess that? Is that something we should be looking for? And maybe just guide as to what you think the major symptoms might be to track over time.

Hi. Yes. This is Dana. I don't have right now all the different end points and domains that we're looking at. We have a fairly extensive list. I mean it encompasses cognitive and physiologic and general well-being. But what we're in the process of trying to do right now is to look at the different domains and specific responses to make sure that we have significant sort of ability to distinguish, right, a treatment effect. And then what we're trying to do is see whether the 4-week data might be enough to support those or we may need to extend it a little bit longer and look at the first couple of weeks of the open-label to just have a robust enough idea about the robustness of these end points to take it to the FDA and try to get an approval to validate it in a parallel data set so that we could use it in Phase III.

Next question is from the line of Liana Moussatos.

Congratulations on this great data. If you get breakthrough designation, which seems likely, how should we think about timing of Phase III? Is there a potential for accelerated approval on interim data since this is a high unmet need? What should we think about timing?

I think from a corporate perspective, we cannot really come with any forward-looking statement relating to what is happening with regulatory interaction. But I can say, we are committed to bring this product opportunity as fast as possible to the patient, and I believe we have a strong package. We are in a position that we have the commercial presentation in our Phase II. We have acceleration where we basically are in acceleration where everything what we have shown from clinical data, it was actually living up to our expectations.

You next question from the line of Leland Gershell.

My congratulations on the terrific data. I just wanted to ask on the OLE, if you could remind us, how frequently patients are assessed for their term calcium? And if you could offer at this point any qualitative commentary on patients who may have achieved dosing stabilization?

Well, right now, the plan is to see the patients monthly. But we're actually trying to get creative because of the COVID situation. And so we're trying to be able to establish some workarounds to make sure that we continue to collect the information we need because some of the sites were impacted. And we have some limitations on patients being able to access their providers. But we've actually been pretty successful in maintaining the continuity of the trial. So I think that, again, what we're trying to do is just make sure that we have them on a stable dose, and that we have the documentation for that.

I actually think a great thanks to not only Ascendis employees but a lot of other people that have supported us on hospitals and other things. We really had great support in this trial, also in the open-label extension really to ensuring all patients get the drug, which was needed for them. And basically is because everyone can see the life-threatening condition there will be, if not suddenly happen, the patient getting the right drug. And there was why there had been so huge support for all different places to ensure that none of any of our patients ever were coming to in a situation where they didn't have the necessary drug.

Okay. And then just on Phase III, I know it's early and you get to meet with the regulators, but wanted to ask if you can provide any indications as to what your current thinking is in terms of the length of that trial and the likely primary end point as well as size?

I think we had initial discussion for regulatory agencies. And what we basically has summary and design of our Phase III trial will basically reflect the compositive end point that you actually saw will be independent in our Q3 measuring. This basically is reflecting how the compositive end point in our regulatory interaction. And the length of the trial was also 6 months, and this why we collect this data under 6 months' time. So this is why I think I personally am extremely cannot wait until I can be in a position to really to have one major disclosure again, the Q3 data related to the 6 months' data.

There are no further questions at this time. Please continue for closing remarks.

Thanks, everyone, for joining us today. We look forward to following up. Have a good evening.

And that concludes today's conference call. Thank you, everyone, for participating. You may now all disconnect.