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

Good day, and thank you for standing by. Welcome to Ascendis Pharma TransCon CNP ACcomplisH Trial Top Line Results Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to turn the conference over to your speaker today, Tim Lee, Senior Director of Investor Relations. Please go ahead.

Thank you, operator, and thanks, everyone, for joining our Trial top line results conference call today. I'm Tim Lee, Senior Director, Investor Relations of Ascendis Pharma. As a part of today's webcast, we have an accompanying slide deck that you can find on the Investor Relations section of our company website. Joining me on the call today is Jan Mikkelsen, President and Chief Executive Officer; Scott Smith, Senior Vice President and Chief Financial Officer; Dr. Birgitte Volck, Senior Vice President, Head of Clinical Development and Medical, Endocrinology Rare Diseases; and Dr. Amy Su, Vice President, Clinical Development, Endocrine and Rare Diseases. Before we begin, I'd like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the under the safe harbor provided by the Private Securities Litigation Reform Act. Examples of such statements may include, but are not limited to, statements regarding our progress on our pipeline candidates and our expectations with respect to their continued progress, our strategic plans, our expectations and goals regarding our clinical trials, clinical pipeline and regulatory filings and approvals. 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 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, mergers, 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. On today's call, we will discuss the top line Phase II results from our ACcomplisH Trial. Following some prepared remarks, we will then open up the call for questions. Now I'll turn the call over to Jan Mikkelsen, our President and Chief Executive Officer.

Thanks, Tim. This is always a pleasure to be up at the 5:00 O'clock here in the morning here on the West Coast. And it's a special pressure today because this is really the date where we see that we can normally get a huge benefit to the achondroplasia society, both to the patient, the caregivers and everyone. So I would like just to go to a few slides, take some key element for what without illustrating how we really wanted to develop this product opportunity. First, going back to our strategy. Our strategy was to develop a product opportunity that basically can be utilized to as many patients as possible, getting the broadest possible labeling. And it was why we enrolled patients between 2 and 11 years. So the off-front could assure that we can get the broadest possible And I think this was the right strategy because we know initiating treatment as early as possible is essential in this treatment. We didn't be in a position where we optimize it the treatment in selective group, where we can see better efficacy. The other key element for us is the fundamentals. The pillars for and treatment that we believe can give the best possible treatment for achondroplasia patient. We built it up in 3 or 4 different pillars. One of the key elements in the pediatric indication is safety. I need really to emphasize that safety is first priority in this year. And then efficacy, yes, you need to be effective to all the different ages from where we are treating. And then tolerability, we want to be sure when you start the treatment, you continue with treatment, you're not dropping out, so they really can continue for years and years. And then you need to have a convenient treatment. We only believe you can have a highly attractive with large penetration in this patient population if all these 4 pillar is fulfill. And I have to be really proud today because when I look at the data today, we're really succeeding that. Let me start in a little bit different of order because I just want to be quite sure that I go to all the 4 different points. When I start on slide -- let me start on Slide 5. Just to say a little bit about the age population we have. When we have small cohort, it is really impossible in this kind of trials really to be in a position that you can have balance between all the different groups and analyze height velocity, analyze growth velocity is the primary end point. Do we just want to treat for that? No. We believe in the holistic view of a patient. We believe that analyze growth velocity, analyze height velocity from a regulatory perspective is a primary endpoint. But we want to show benefit besides that. We want to show that we patients are -- helping this patient, giving them a better life, addressing the comorbidities, all the things that we know this patient group are suffering from. That is what I call a holistic patient view. This is why I'm proud to see when I look on our trial today. 57 patients came in for -- beginning for about 2 years ago. We still have 57 patients. No ones have dropped out. What do we give me in confident? It give me a confident that even I know the burden of a weekly injection. I'm not just talking about the daily injection, the weekly injection is high. And therefore, still, everyone feels the benefit we're getting out for that is really justifying this treatment. 40% of patient was around less than 5 years. Yes, this is really a high one, but we wanted to initiate the treatment between 2 to 11 because that was the basic patient group we enrolled here. And you can see there is a difference in the different group and analyze high velocity/analyze growth velocity is an primary endpoint that has huge variability, as I said in the last call, this is an endpoint that is very most dependent on different demographics. Some of the key elements in that is age and gender. So going to the next one, going to Slide 7. This is where [indiscernible], this drug is really function like a real drug therapy. What do I mean by that? It's titratable dose response. Look from 6-microgram 20, 50, 10, this is Slide 10. Look about how we basically are moving up from 4.09 up to 5.42. Remember, this a small group, small groups, there will be a lot of variability because this number analyze height velocity is not corrected. It's not corrected for gender, age and other things like that, which are in balance between the group. Then you also look placebo, 4.35. Then you say, why is the placebo larger than by 4.09? Obviously, because the small group, all the numbers are trend. This is the number you look at. Going to the right, look at TransCon CNP, when you go up in higher dose, what I wanted to see -- we wanted to see that we are increasing the middle of it, but still helping all the patients, everyone getting a benefit of the treatment. You're basically moving it up out from the perspective of how to explain it in a more picture way, all the children that sometimes came into the trial that was had what we call growth burst, down in our 6 to 7, got less out of the treatment, but everyone that was difficult to grow up got that boost up to where we wanted to happen. I will jump a little bit to Slide #9 because this is basically the same data. But here, we go up to height as this justified for age and gender. You see the same picture. But now you can see the 6,20, 50, 100 same dose response. But you also see now we start to correlate for gender, correlate from age, you can see the pool placebo is under. This is what you see when you go in and look on small data set where you are using analyzed height velocity without really correlate from the diversity between the different groups. That is what you do in height SDS and you see expected what you want to do. Beautiful data, exactly as you want to have highly titratable compound giving the fit exactly how you want to have it. Slide #8 is a slide, which I don't like, because it's going down to small group, and you try to split it between age 5 and over age of 5. Why do we not like it because the numbers start to be small. Every time you get small numbers, the ability, random thing moving, this is soft analysis, but what I can use it to. I see the same trends, the same effect between under 5 and over 5, exactly what we have hoped for in this way. Let me now go over to safety. This is Slide 10, this compound is extremely safe, beautiful safety profile. Basically not with any different between placebo or what we saw active treated drug on the pharmalogical doses. Going to Slide #10, 2 key elements we have defined besides what we call treated related adverse events. You can see all of them are mild, moderate, [indiscernible] little different within placebo and TransCon CNP. But 1 element I would like you to address to is achondroplasia-related AEs. As I said in the front, analyze growth velocity is basically a primary endpoint, but what we want to provide to the patients is much more. We have designed it to be because we want to be in a position that we really also want to show that from a statistic point. We wanted to show that we're providing much more than that. I'll come back later on to body proportionality. Achondroplasia-related treated adverse events is where we look on caregivers, looking on the child, seeing is, what is happening with my child? Do we have more adverse events or less? And when I look on the placebo, we had 60% score adverse event and go down, and for example, look on the 100 microgram where we have optimal treatment exposure. I think we start to see what we want to see, is starting to give the explanation why are we the only achondroplasia trial, where we have 100% retention. This is why the key bond treatment. That was safety. Going over to convenience as the last pillar. Convenience, we know for 20 years that people wanted to develop and watch weekly growth hormone product because we saw and observed how it was impossible to get the adherence persistent on such a treatment to give the expected outcome. We're starting there. We're not going back 20 years and then starting off from again. This is how we want to do it. Open-label extension trail. This is where I like the numbers because there we get 40 patients and not only everyone, 100% are continuing treatment. But when I look at the 40 patients where we have at least 6 months annualized growth velocity coming from different background, coming from placebo, coming from the 6, coming from the 20, coming from the 50 and also the 11 that was from the 100. Then we have 40. I see an annualized height velocity of 5.39. Yes, that was what we had hoped for. That was our expectation. Just go back to our last quarter call. I got asked again and again, what is we reference and the reference I went out -- we need to compare apple-to-apple annualized growth velocity to annualize growth velocity. This was what we did. And when we went out and looked at the only approved product in the U.S. and looked on the literature that basically came out on 5.39 and 5.43. Yes, this is the same as what I see here. And when I look at the demographic, I personally believe that we are inferior for what we should expect to see. So what we see in the place where you have sufficient enough data to make a really justified comparison because the other ones were about 47 on 58 in the different group. This is more apple-to-apple and not an apple to an orange comparison. So when I see this product opportunity and see how we are progressing. We will take this data here, have interaction with FDA and EMEA really have an intense discussion with this because I believe we have a responsibility to get this product as fast as possible out to the patient. We will go down to the only group that we're missing for 0 to 2 and start a trial as fast as possible. We will look for combinations between TransCon Growth Hormone and TransCon CNP and to look from a biological perspective, the most optimal synergy we have both products as a once weekly. Will we go up to a higher dose of TransCon CNP? I don't think we need it, but I'm quite sure this is a highly titratable compound with optimal effect if you dose more and we will take the global rates, both the necessary trial in China and Japan to get our global rates. So when I come today look and see of the feedback I'm not only getting for the society, but also for key opinion leaders. We have a look on our safety profile, efficacy of weekly administration for children, for achondro patients, they really believe that it's a very, very positive outcome and agree. I agree with that. There was what we hope for. We saw it. We got it. We really went up to the target profile we designed this product to have. Thank you.

Operator, we'll let the call for questions now. Thank you.

[Operator Instructions] And our first question coming from the line of Jessica Fye with JPMorgan.

This is Na Sun on for Jessica Fye. Question from us would be what do the different AHPs observed between the placebo arm here and in the vosoritide Phase III tell you about the ability to drive a benefit in those patients.

When I look at placebo data and looking from different time I can give you a lot of literature to reference to it. And I can give you a lot of personal experience. But for me, for example, look on the literature the reference where I, for example, came up with data where the people was treated with the only approved product in the U.S. and it's because there is a nice sample size there. You have a sample size of about 40 and 50. The results I'm referring to was that after treatment for 1 year with the product, that was 5.39 and 5.43. Wow, that is pretty near. But when you go back and look at the placebo, 1 placebo came from 4.26 and the other placebo came from 3.81. What do that give me of aspect, and that is what we see everywhere else that placebo arm -- I've seen placebo arm for 3.2 up to 4.5, depending on what group of achondroplasia patients you have, how lucky, how unlucky you are. So therefore, variability in a placebo arm is extremely high. Just look on that literature, 40, 50 patients going into the same treatment, ending exactly in the same level 5.39, 5.43, but the placebo arm is basically coming with huge variability from 4.23 to 3.81. That is what we see everywhere.

Our next question coming from the line of Josh Schimmer with Evercore ISI.

First, I want to provide some of the age and gender-based growth measures for the patients who are in the open-label extension like you showed us for the placebo-controlled portion of the trial? And then second question is, why are you not giving this data set looking to advance with 150-microgram dose. I think you have that option in this trial to explore? And is there any reason to not explore it, such as concerns about excessive PEG exposure?

Let me take the 2 independent question. Yes, we would like to have that data. I think it makes sense to make the data when we have 57 patients fulfill the necessary 6 months because then we have a great statistic analysis and we really look on meaningful data numbers. So I agree 110% with that. Related to the last question, we see no limitation of why we should not go up to 150 or 200, 300 what we want to go to. We have no preclinical safety issue. We have not any issue related to, for example, element you're discussing about PIC. We are not a permanent PEGylated please referring into our SKYTROFA regulatory interaction, both from Europe and U.S. and discuss why there is no mention of anything like that because we don't have this associated element because that is something that coming from a complete different technology platform. There's only 1 thing in common. We have 13 letters together, P-E-G, but it's not the same thing you have the same associated effects.

Got it. And then why not then be more aggressive exploring the 150 because there was an option in the Phase II trial and something you could continue to explore, to your point, 150, 200 or 300.

I actually believe that we have an opportunity with a compound like TransCon CNP to continue dose escalation. We have the opportunity to combine it with TransCon Growth Hormone. We have the opportunity to make more aggressive treatment regime if it's needed, what we currently wanted to be is to move the 100-microgram per kilo per week 2 regulatory approval as fast as possible because we believe the patient, the caregiver deserve that. When we are in a position, we can later on optimize treatment if it's necessary. Because what we have seen here, we are seeing a normalization of analyzed height velocity then you can say, do we want to develop cash out growth as we do in growth hormone deficiency, where we basically are developing catch-up growth for the lack of annualized growth velocity that they have got off the year of being untreated. Do we want that, Josh? Then potentially, we will develop and what we call a treatment regime that can achieve that. Is that best achieved by giving more CMP or giving growth hormone? Because we know growth hormone is the best product in the world to provide catch-up growth. And that is a different discretion. We have the aim for this target product profile, normalize annualized high velocity to the level that you see in a normal child, reassuring that. The second point, do we want to be in a position that we static treatment regime that providing cash out growth. That is what we start discussion. We need to see the necessary safety for that because that is a highly strong growth-promoting activity, we will provide to the child. Different discussion.

Can I just ask 1 quick follow-up on that point. Is growth hormone the best way to achieve proportionate growth if that's kind of the strategy.

That is a good question. And this is why potential it will be optimal to try both options. We know that at least from growth hormone deficiency, we are not inducing a wrong disproportionality when we give catch-up growth in growth hormone deficient children. Achondroplasia is different because we're basically up born with this proportionality. The positive we saw here in our trial relatable body proportionality, we saw the 100% expected development in body proportionality. We look forward when we have more data in the open-label extension trial really to go out and really show how powerful we also are on body proportionality compared to all elements will be addressing other things like not just height because we're doing this treatment for having a holistic view of the patient, not only addressing annualized height velocity.

And next question next question coming from the line of David Lebowitz with Citibank.

When looking at the data and actually all investors are going to try to make whatever comparisons they can to other improved therapies. Given that there's no baseline data, what is the best way for us to look at what has been done? Obviously, caveats of small patient population aside at what was demonstrated today versus what we know about VOXZOGO.

First of all, I come from a math, physic background and I like mathematic algorithm. And when you do into mathematic algorithm, you can really get what number you want. What I want to go back to fundamentals compare, annualized growth velocity with annualized growth velocity really taking an apple-to-apple under the understanding that demographic can have an impact on annualized height velocity. And as you said, there is a 1 approved product. There is a 1 peer-reviewed publication, where they're coming with 2 groups which have the sufficient number where it's meaningful, a group of 58 patients that came from being untreated went up to 15 micrograms per kilo per day and hit an annualized high velocity of 5.39. Then there was another group that came from placebo treatment for 1 year and then come up to the 50-microgram per kilo per day and hit 5.43. Pretty amazing that they're hitting exactly the same annualized growth velocity. When you think about, they are coming from a background where they have completely different kind of untreated annualized height velocity. One had 4.26, one had 3.81, 0.4 centimeter different in the untreated period, but when they go to treatment exactly the same element. I think that is exactly illustrating everything. So when I see our 40 patients. 40 patients, okay, now we're in the same number try to compare that, we have 5.39. I think that is the only way you can compare it. Anything else trying to take small placebo away looking another thing. Placebo is going everywhere, as I said before, I think placebo for 3.2 up to 4.8, it's the most variable one. But what I see when they go on CMP treatment that are basically hitting the same element, which surprised me a little bit because I had thought we will be lower because we have much more younger children under 5, which we know is more difficult to treat. So when I see this year, I actually believe this is really a powerful compound TransCon and giving us exactly the target product profile efficacy we wanted.

With that in mind, could you actually drill a little deeper into the under-5 population, I know there has been some limited data from VOXZOGO to date in that population, not necessarily completely comparable. But was there anything that surprised you in that population? And how meaningful is that going forward as far as how the drug fits into the paradigm?

It's extremely meaningful because you want to take the optimal product as early as possible and then stay rest of your life on that treatment. So what surprised me was our amazing effect on the youngest children down to 2 -- age of 2. I'm still trying to get my own brain into a biological explanation. I'm starting to get 1 of them. And 1 of the thing is that when you go to a child, and having a product opportunity that is short acting, they typically have a much, much faster clearance. When you go to a compound like us that basically are providing a continuous exposure, you have complete different clearing mechanism. So now we're looking on going down to the PK of the younger children and what I believe and hope, and I think I'm right, we received a much higher exposure there compared to what you will see from a short acting. So it's basically not a different mode of action, but just because TransCon CNP is being developed to give continuous exposure. So the fast clearance in the small children are less affected than you will see on the short acting. I hope it gives some kind of rational 5:00 here in the morning, Western Time, but at least from a basic PK/PD effect, it makes a lot of sense.

And our next question coming from line of Li Watsek with Cantor.

So thank you for taking my questions. I guess just first one, I'm curious if you can share any insight maybe from the secondary endpoints, for instance, like patient-reported outcomes, measures, the cost of life that can explain why these patients stay on this therapy. And then second, just sort of follow-up on the treatment benefit perhaps different age groups. I understand that we're looking at into here, but just walk me offer any thoughts on if TransCon may offer differential treatment benefit in different age groups. And it sounds like you think the benefit may be greater in younger patients?

What I believe is that when I see that, I think we see the same huge treatment benefit in all patient group. And as I said, my underlying explanation is how TransCon CNP is designed by giving a continuous exposure. So when you go to the smaller, smaller infant where we will go now, we basically are in a position that you never get the same exposure with a short acting because there's a faster, faster clearance mechanism in the smaller children. So when I see this here, I actually believe that we see the same benefit across all age, and that is where you want to be. And this is what I call a much more robust treatment regime. Going back to 1 of your earlier questions. The earlier question is, yes, that is what we are analyzing. We are looking on everything when you go into the slide, which I refer you to in the presentation, this is Slide #11. Yes, we are looking on why is this impact that we see. And why do we get a much, much lower scores of the patient when they're treated with 100 micrograms per kilo per week. I did an initial look, and it looked like expected. It looked expected element that we can address and other things. This is the effect we see missing. So this is what I think is extremely positive for me. And I agree with you. I agree so much with you. They are not staying on this treatment because of 1.4 centimeters. They are staying on a treatment because it gives them a holistic view of an improved quality of life. And -- what is important, we can provide this treatment in a safe environment and together with a high tolerability. When you look on our injection side, it's not water. It's really providing an enormous benefit to the patient that is not in a high treatment burden. We have integrated that by once-weekly treatment regime. Basic low level of injection site reaction really providing high tolerability of this treatment. This is how you can provide continued benefit to the patient and have the patient stay on treatment. Get the benefit.

Next question coming from the line of Paul Choi with Goldman Sachs.

I believe at a meeting -- a medical meeting earlier this year, you disclosed that the baseline HV for the 100-microgram dose was 5.1 centimeters and a range as high as 5.7 for the other dose cohorts. So therefore, the baseline population baselines here are approximating normal healthy kids and on average are about 1 centimeter higher than the baseline seen with vosoritide and [indiscernible]. Can you maybe comment on the incremental benefit of these baselines that you're seeing with 100-microgram and other doses? And then as a follow-up for the Phase IIb study, should we think about the patients being recruited into the Phase IIb as having similar baselines as what you showed here today and just how you think about the potential incremental benefit being shown there.

Going to your last question. The IIb will include patients from 2 to 11, the same patient group that we have in this trial here. We added the 2 to 10 to screening, but when we enroll patients, they are basic for 2 to 11. So we will go for the broad labeling in 1 step. Not try to split it up and then stock them to get everyone in, because we want to treat as low as possible. When you look at the demographically enrolled, we basically have the patient rating of the patients are waiting the site where we have been the TransCon CNP, the C, the treatment option we're providing with TransCon CNP is such that the basic stacking patient to do it. So why we expect to roll all the patients in a few months because they're just ready to be taken in. Will we have fewer children in the 2 to 5? Yes, we believe when we look at the demographic, we expect to have about 15% to 20% of the patients being between 2 to 5, which are different for the around 40%. So it will be a little bit different, still in the age group 2 to 10. And potentially ever provide higher annualized height velocity because I think this group is much more prime for providing that. But that is not really the important -- that is not important why we run this trial. The important part is basically to recognize what is the other benefit we are giving besides annualized height velocity. This is why we're powering to the 80 patients. because we know now what we need to look for. We will take these common patients up on end points, secondary end point. So we're quite sure their optimal proof being recognized both from regulatory agencies, from regulator, caregivers and other things. We are analyzing our big pro. We saw how we TransCon PTH Pro really gave the story of the patient, proved how the patient could restore a normal life. We want to do the same thing in achondroplasia, make a new standard for treatment, not only on height, but basically providing the benefit to the patient, how they really can be normalized to the best we can give them in this way. And this is why we're running the study.

Our next question coming from the line of Leland Gershell with Oppenheimer.

Just 2 for me. If you could again remind us the relationship between the 100-microgram per kilogram per week and that you're developing with TransCon CNP and the weight-based dosing of VOXZOGO currently? How close are those in terms of actual amount of CNP activity would you expect? And secondly, for the upcoming Phase IIb trial, will you be -- given that's 2:1 randomization, will you be looking to match with respect to age and/or gender?

Okay. Going back to the actable dose comparison. One compound is giving 15-microgram per kilo per day. If I multiply that with 7, I assume Scott is running the algorithm now on his spreadsheet, but I think he gets about 100 microgram, 105, and we give 100 microgram. But that is not really important. That is just the dose you're doing. Then you can say, do we look on plasma exposure, PK exposure? Is that equivalent? You can do that regulation. We have done that. There's also some kind of equivalent. But that really don't care either. What is really important, what is the concentration into a growth plate because this is where we least get the effect when we talk about analyzed height velocity. When we talk about other comorbidities, potentially, this is the plasma exposure that you get all the time, and this is why we also designed it. So not only have exposure for 2 to 3 hours a day, but have a continuous exposure as you see in a normal human being. And this is how we designed it this way to ensuring that other comorbidity is potential addressed with a much more constant expose much more constant balance between a hyperactive FDR2 pathway and basic [ residuation ] where you normalize it by increased CNP level. It was the element we basically signed in our target product profile. Going back to the question related to our IIb. Yes, as I said before, we are in a position. We are enrolling patients from 2 to 11. We expect for what we already know, the patient is ready now, that will be about 15% to 20% in the group from 2 to 5 lower than what we saw in our ACcomplisH trial. We expect that is the element that will be primary endpoint would be annualized growth velocity again. But the key element for that trial is really get into the element, what is the overall holistic benefit we're giving this patient and get that qualified by different means, and that is what we are running this trial for. We don't need to confirm our p-value. Our p-value is pretty good even with 15, 15. We could run the trial by 25 patients and still be statistic significant with 15, 20 patients. This is so easy. But the question is that we want to quantify by other things. This is why we go up to the larger patient population.

And our next question coming from the line of Andreas Argyrides with Wedbush.

Could you better explain maybe the impact -- and there's a lot of comparisons to VOXZOGO and their data and looking at placebo rates here. Could you talk about the impact that the lead-in portion of the VOXZOGO trial had on placebo or may have had? And then also, what are your thoughts on exploring CNP in hypoparathyroidism and foramen magnum compression.

Yes. Some great question. Let me start on the last one. When you look at achondroplasia and some way looking at the developing of a child with achondroplasia. And you look on the form -- some of the irreversibility of this disease is actually happening early on. So when we go to the infant trial, and this is 1 of the elements that we really will focus on in the infant trials is really to avoid the closest offers and closes. But we know that if you are untreated to the ACI, you likely will have them already closed and is an irreversible process. So when we go to this element, we will expect to see a positive benefit on that. But we need to start basic on newborn children to avoid that effect. This is not something you can observe in children in the age group we have now, it needs to start on the infant stage. And that's why we're running the infant state. Now we know that our drop is really highly potent and function, also in the younger, younger, younger children. So that is 1 element. The second element was a question that we have addressed multiple times today. Placebo is for achondroplasia when we think about annualized height velocity and annualized growth velocity, highly, highly, highly variable. And I illustrated by having the reference to where I see a large statistic number, the 40 to 50 patients where basically some may come with before treatment had an annualized hypervelocity on 4.26, that other group had an annualized height velocity of 3.81, and both of them ended on 4.39 and 5.43 illustrate what you're coming on with basic you untreated annualized height velocity is unpredictable for any kind of effect you get look independent on you are down on 3.5 or you're up on 4.5, you're ending up in the same level of 5.4, 5.5. That is my learning. So when you start to do that, you only lock it, unlock it, with your annualized height velocity, I were not call it luck, it's just reflecting gender, age, growth, 5 other cofactor in it. But what we see when you treat with CNP, because I believe all CNP products are providing the same thing you end of about 5.4. Is that a clear message?

Yes. No, I didn't try to ask the same question again, maybe in a different light and just maybe focus on a bit of a difference in the way that the comparator trial was run with that leading portion, if that had any particular impact that you talked about just general variability. So I appreciate that. And congrats on the data.

And our next question coming from the line of Yaron Werber with Cowen.

This is on [indiscernible] for Yaron. I was wondering maybe if you could touch on what you saw in 5- to 8-year olds versus 8- to 10-year olds because we know that VOXZOGO benefit in Phase III was primarily driven by the 8- to 11-year-old age group. And I think you previously mentioned on the Q3 call that you guys have a lower proportion of 8 to 10 year-olds versus 5 to 8-year old. So I was wondering if you could tell us if you saw the same thing, just any more detail on that first.

Yes. Great. When we looked on the double-blinded placebo-controlled period of 12 months, the number got so small because there will only be 1 or 2 of 8 to 11 in it. So any kind of analysis was totally meaningless. What we would like to do, we would like to wait until we have all the 57 in having 100-microgram on the expected dose, 100-microgram, they are there, we're collecting the data. When we have 57 patients, we will start to make the grid analysis and then look about it, do we see the same thing like what's happening with vosoritide that 8-11 was growing better. But we have not really sufficient statistic numbers to come with meaningful conclusion, you can come with a perception conclusion. I believe we receive the same thing, but I cannot justify it out from the numbers. I cannot be data-driven, which I always like to be. This is not data driven when you have so few number of patients. Wait until we have all 57.

Ladies and gentlemen, that does conclude our conference for today. We thank you.