Good day, and thank you for standing by. Welcome to the BridgeBio Webcast to D iscuss Month 12 and 18 phase II Results of Infigratinib for Achondroplasia. At this time, all participants are on listen-only mode. At the end of the prepared remarks, we will take questions from our analysts on the call today. I would now like to introduce you to your speakers today. Dr. Ravi Savarirayan, Clinical Geneticist and Group Leader of Molecular Therapies Research at the Murdoch Children's Research Institute in Australia. Dr. Daniela Rogoff, Chief Medical Officer of Skeletal Dysplasia, BridgeBio Pharma. Justin To, Chief Executive Officer of Skeletal Dysplasia, BridgeBio Pharma. I would now like to hand it over to Dr. Neil Kumar, Chief Executive Officer, BridgeBio Pharma.
Thanks, operator, and thanks, everyone, for joining this call, the second webcast we've had the privilege of hosting in this past week. Today, we focus on our program for achondroplasia, hypochondroplasia, and related FGFR skeletal dysplasias. I'm grateful to be joined today by the BridgeBio team and immensely grateful to have the opportunity to hear from and to learn from Dr. Ravi Savarirayan, a pioneer not only in achondroplasia and related conditions, but indeed in rare disease writ large. Today, you'll hear about a molecule designed from the outset to target this condition at its source, mutated gain-of-function FGFR3, with the premise that in doing so, we could more efficaciously, more safely, and more conveniently serve children with achondroplasia and related conditions. Before we get there, I'll remind everyone that we're making forward-looking statements today.
The slide deck associated with this call is publicly available, and we'll refer to specific slide numbers as we progress the discussion. I'll start with what is always the most important slide in our documents, slide three. A thank you to the amazing and inspiring children and families, advocates, physicians, clinical research staff, and collaborating research partners that make our work possible. Yours are the efforts that make whatever impact infigratinib is to have possible, and in turn, we recognize our responsibility to you to move quickly, to provide this medicine to patients as broadly as possible, and to continue to explore its full parameter space of usefulness. Indeed, it was the community and leader like Ravi's push to explore efficacy beyond the primary endpoint, which matters a great deal to the children and families we have spoken to, that led us to explore efficacy against proportionality.
We are listening to you, and when we fail, please push us. Today's findings related to proportionality represent the beginning of that exploration, which I hope will continue to expand in both magnitude and scope over time. With that, I'll turn it over to my colleague, Justin To, who leads our infigratinib efforts to provide further context.
Thanks, Neil. Before we get into the data, I'd like to spend a few minutes on the opportunity at hand and the design rationale for this program. As a reminder, on slide four, the opportunity for infigratinib is vast and largely untapped, with a total addressable population of up to 25,000 people in the U.S. and EU alone. The market for therapies in achondroplasia is now well-validated, with the continued growth and uptake of Voxzogo, although much of it remains untapped due to many families' concerns around daily injections for their children. Like achondroplasia, hypochondroplasia is also caused by an activating FGFR3 variant and has a similar prevalence and incidence to that of achondroplasia. Today, we have announced the launch of our ACCEL program in hypochondroplasia.
Finally, we will be planning to expand in the future to other FGFR3-driven conditions, such as Crouzon syndrome, where there's tremendous unmet need. Moving on to slide five. When we first initiated this program in achondroplasia, we had three key design criteria that we believe we have now met. The first was targeting the condition directly at its source to unlock not only a new level of efficacy, but also new types of efficacy, as Neil mentioned. Second, we wanted to demonstrate a favorable safety profile, avoiding frequent injection site reactions and hypotension. We also wanted to avoid inhibition of VEGFR3, which is a liability of other FGFR3 inhibitors. Third, based on consistent feedback from the community and from advocates, we wanted to avoid the significant burden of daily injections.
On average, with a daily injectable, more than 4,000 injections would be given to a child from birth until the closure of their growth plates. Moving on to slide 6 now. As a reminder, infigratinib is the only treatment and an option, treatment option in development for achondroplasia and hypochondroplasia that directly addresses both downstream effector pathways: the MAPK pathway, which impacts chondrocyte hypertrophy, and the JAK/STAT pathway, which affects chondrocyte proliferation. We believe impacting both signaling pathways are key to unlocking not only maximal improvements in linear height, but also improvements in key measures like proportionality that matter to the community. With this, I'll pass it over to my colleague and our Chief Medical Officer, Dr. Daniela Rogoff, to present our exciting data update today.
Thank you, Justin. Good morning, and thank you for calling in. I will be sharing the updated data on cohort 5 for up to 18 months of treatment and assessment. On slide 8, we have the summary of the safety in cohort 5. Infigratinib continues to be well-tolerated, with no safety concerns identified throughout the participation of the children in the study, which was up to 18 months. There were no serious adverse events or adverse events that led to treatment discontinuation. Most of the adverse events were mild in severity and assessed as not related to study drug. No adverse event on excess of growth or adverse events associated with excessive growth were reported.
No hyperphosphatemia was observed, and most importantly, and as expected at these doses, no adverse events at the eye level were reported. On slide 9, we have here the adverse events reported for more than 10% of the children enrolled in the study. As you can see, these are all common conditions seen in pediatric population and in children with achondroplasia. Moving on to efficacy now, on slide 10, we have represented the change from baseline in the annualized height velocity at month 6, month 12, and at month 18. We can see that treatment with infigratinib results in a robust increase in the annualized height velocity, which is sustained throughout the study, meaning that the effect of infigratinib persisted for up to 18 months.
The change from baseline at month 12 and month 18 was 2.5 cm per year, which is highly statistically significant, with a P value of 0.0015 at month 18, and greater than any other treatment approved or in development at all time points. It is important to remark that the month 12 or month 18 data is based on 11 children, as one child dropped out before the month 12 visit for reasons unrelated to safety or efficacy, but due to the closure of the site as the PI was leaving the institution. This child was considered as responder at month 6. Slide 11 shows the scatter plot of the annualized height velocity up to 18 months of the treatment for all children in cohort 5.
We can see that the response to infigratinib was broad, with 10 out of 11 children having an increase in the annualized height velocity at month 18, and 73% having an increase in the annualized height velocity of at least 25% compared to baseline. Going to slide 12. Here, we have the effect of infigratinib on body proportion, represented by the upper to lower body segment ratio. At month 6, we had already seen a trend towards improvement in body proportion, which continued to show persistent decrease with longer duration of treatment, reaching statistically significant at month 18, with a P value of 0.001. This improvement in the upper to lower body segment ratio after only 18 months demonstrates strong potential for a meaningful effect on body proportionality.
And to, yes, explain more about what this data means from the clinical perspective, I will hand it over to Ravi to provide a context of the results shared today. Robbie?
Thank you very much, Daniela. And it's a pleasure to be on the call. I've been working in the field of rare bone diseases for 30 years, with an aim of bringing new treatments that will promote health for children, through rigorous science and clinical trials. Why is proportionality so important? Proportionality is crucial because achondroplasia is not an isolated short stature syndrome. It is a skeletal dysplasia with disproportionate growth of the skeleton. And in fact, the upper segment to lower segment ratio is double the average value at two versus one. That is important from the day-to-day living of these children, because disproportionality with a relatively large head is associated with delayed motor milestones in infancy and impaired functionality with regards to toileting, with regards to running, with regards to increased fatigue and exercises.
So it's really important that as we gain height, any treatment that gains height with achondroplasia also can improve proportionality. And the cumulative improvements that we're seeing in proportionality are extremely encouraging in these children because they are the unfiltered needs of parents and children who want to have longer arms and legs, so they can perform their activities of daily life with much more efficiency and much more easily. So that's why proportionality is such a critical endpoint in achondroplasia, and I've encouraged the team to really pursue this and to see that we are trending and getting significant changes at the 18-month level is extremely, extremely promising, with results to enhancing these factors in the children's life. And I'll now hand over to Justin.
Thanks so much, Ravi, for taking the time to kind of talk about why we're so excited about the change in proportionality. Yeah, moving on to slide 16. Here we're talking, reminding folks that currently, PROPEL 3, our registrational phase III program for achondroplasia, is now underway with full enrollment anticipated by the end of this year. The primary endpoint for PROPEL 3 is mean change from baseline in annualized height velocity at 52 weeks, which has been aligned with both the FDA and EMA. In parallel with this momentum, on our achondroplasia program, we have also announced this morning the initiation of our ACCEL program for hypochondroplasia, with the first child consented into our observational run-in last month. I'll hand it back to Robbie to talk a little bit about hypochondroplasia and then to Daniela to talk about our clinical development program.
Thanks very much, Justin. Yes, hypochondroplasia is another FGFR3-driven skeletal dysplasia that is also a dominant condition. It has a similar incidence to achondroplasia, meaning there could be up to 250,000 people in the world living with this condition. It has a greater genetic heterogeneity. Clinically, it is a milder version, although some people with hypochondroplasia have similar and overlapping features to achondroplasia. The most important thing, again, to point out here, is this is another disproportionate short stature in which there can be functional problems as well, in which head circumference is larger than average, and there can be medical complications as well. Also in this condition, it is also associated with features such as epilepsy and other cognitive features, such as mild cognitive impairment.
Most importantly, the condition is FGFR3-driven, and this molecule will also potentially combat this medication at its very origin as it directly targets FGFR3 signaling. Thank you very much, and I'll hand over to Daniela Rogoff.
Thank you, Ravi. Now moving on to slide 20. We are very excited to initiate our ACCEL program, which is our program in hypochondroplasia. It consists of an observational run-in study, a single pivotal interventional study, and a long-term follow-up study. We are very pleased to have the FDA and EMA alignment on our plans. The ACCEL study, which is an observational run-in, will enroll the children with hypochondroplasia that will participate in the interventional study, ACCEL 2/3. The ACCEL study will collect the baseline data, not only in linear growth, but also in body proportions and medical complications, quality of life, among others. The ACCEL 2/3 is a single pivotal study that consists in an initial open-label phase II portion, followed by the pivotal phase III portion that is a double-blind, placebo-controlled trial in children with hypochondroplasia.
All of the children participating in either the phase II or the phase III portion need to have completed at least 6 months of observation in ACCEL. The primary endpoint is the change from baseline in annualized height velocity versus placebo, and a secondary endpoint. We will evaluate other indicators of growth, body proportions, quality of life, complications described in hypochondroplasia, including the evaluation of cognitive functions, that as Ravi mentioned, difficulties in certain aspects like attention, comprehension, have been described as potentially more prevalent in individuals with hypochondroplasia compared to the general population. And as infigratinib crosses the blood-brain barrier, it has the potential to have a positive effect on these cognitive functions. The study will enroll children between 3 and less than 18 years of age with potential to grow, and they will be treated for 52 weeks.
After completion of either the phase II or the phase III portion of the study, children will be offered the opportunity to receive treatment with oral infigratinib in the ACCEL OLE study, where the long-term efficacy and safety of infigratinib in children with hypochondroplasia will be evaluated. The observational study, ACCEL, is already underway, and this is the first step in our program to evaluate the potential of infigratinib as a treatment option for children with hypochondroplasia. Now I will hand it over to Justin for closing remarks.
Thanks so much, Daniela. We're now on slide 22. To conclude, we are extremely pleased that the continued best-in-class efficacy and well-tolerated safety profile of oral infigratinib are sustained out until the end of study at 18 months. Even more exciting for us and for the community is the statistically significant improvement in proportionality with a p-value of 0.01, which represents a functional improvement beyond just linear height. To our knowledge, this is the first clinical trial in achondroplasia showing a statistically significant change from baseline proportionality. We continue to make excellent progress at enrolling PROPEL 3 and are thrilled to build on our momentum by expanding to hypochondroplasia with initiation of our ACCEL clinical program, which has been aligned with both the FDA and the EMA.
I'd also like to acknowledge our commitment to capturing the full potential of infigratinib as a potent and selective FGFR3 inhibitor. We will be continuing to evaluate ongoing expansion indications into not only FGFR-driven conditions with high unmet needs, like Crouzon syndrome, but also potentially larger FGFR wild-type growth conditions as well. With that, I'd like to thank Dr. Ravi for joining the call, and I'll stop here and open it up to questions.
Thank you. If you'd like to ask a question, please press star one one. If your question has been answered and you'd like to remove yourself from the queue, press star one one again. Our first question comes from Tyler Van Buren with TD Cowen. Your line is open.
Hey, guys, congratulations on the data, and thanks for the presentation. I have a couple for you. The first one is, the statistical significance on proportionality is pretty exciting. So can you put this magnitude of improvement into context, with the existing body of clinical data and discuss how that might improve over time? And the second one is, just discussing your confidence in this 12- and 18-month AHV data holding up in a larger phase III trial that is ongoing.
Yeah, thanks so much, Tyler. This is Justin. I'm happy to address both parts of the question. With regards to proportionality, as Ravi mentioned, you know, disproportionality is a key clinical measure of achondroplasia, and we've been hearing from the community and from clinicians that it's important for a treatment option to show efficacy beyond just improvements in AHV. So we're excited to see a statistically significant change in such a short period of time. In 18 months, I think we kind of saw a change from 2.02 to 1.88, and I think we believe other trials around 18 months have only seen like a 0.04, 0.05 change. So we're effectively kind of seeing more than 2 times the effect on proportionality as other treatment options in development for achondroplasia at this time.
Then the effect on proportionality should also be cumulative and only continue to grow from here, so we're really excited for what this means. And as a reminder, change in proportionality is a key secondary in our phase III trial, and so today's result gives us more confidence that we can potentially hit that and be the first product in achondroplasia with a label for not only improving linear height, but also potentially improving proportionality as well. With regard to your second question around kind of the confidence that today's results give us for the phase III, I think we're really pleased to see the continued durability of our AHV response from month 12 to month 18, where we've seen some other kind of phase II trials diminish a little bit during that time interval.
It's also kind of nice to see the dispersion, the standard deviation kind of coming around a bit as well. For other phase II trials, we've seen that there month 18 results map quite nicely to our phase III results. So I think seeing today's durability of 2.5 really gives us confidence that would be found potentially be around that for our phase III.
Thank you. Our next question comes from Salim Syed with Mizuho. Your line is open.
Great. Good morning, guys. Congrats on the data. Just a couple from us on the proportionality and also just the commercial landscape here. So maybe for Dr. Ravi, just curious, how
Hey, hey, Salim. Sorry about that. It's just gonna be just us off on the Q&A. Dr. Ravi had to jump off.
Oh, okay, I apologize. Okay. Yeah, I'd still love your opinion. So I guess on the proportionality, Justin, just, I know it was stat sig, but just how are you thinking about clinically meaningful changes? Is there a particular number that the physician community or the patient community looks at as a clinically meaningful change in proportionality? And just how that number changes over time. Do you expect this to be an increase as time goes on, or more sort of like a linear change? And just on the commercial side here, just curious, you know, I guess this is for Dr. Ravi, but I know I just want to get your view.
Just curious, what the- what is the theoretical argument now in your guys, as you speak to physicians, why anybody would take Voxzogo, or are you positioning infigratinib also to switch patients from Voxzogo or just new patients? Thank you.
Yeah. No, thanks, Salim, for that, for these two questions. With regards to proportionality, in terms of just kind of setting the context, you know, as what Ravi mentioned, you know, children with achondroplasia typically have an upper to lower body ratio of about 2, and children of average stature are kind of closer to 1.2 range. So kind of seeing a meaningful change, there would be kind of a decrease of 0.1 or so, which I think we've already kind of cleared. But what would you like to see over time is a deepening of that response, and that these effects should be cumulative as well, as we've noticed in other kind of trials with achondroplasia.
So what we expect from here is that, you know, the longer the follow-up, the more deepening of the response and proportionality that we should see. So we should expect that it would be cumulative. With regards to the potential commercial commercial story here, I think really we're starting to see a very compelling target product profile for both clinicians and the community, having a safe, potentially safe, daily oral, with best-in-class efficacy and AHV, but most importantly, changes beyond just linear height, such as proportionality. And so I think that would be very compelling for not only new families diagnosed with achondroplasia, but also existing families using just Voxzogo.
Got it. Just a quick follow-up, if I can. Somebody asked me to ask you. Are you guys planning to release the patient-level data or just these absolute AHVs? I know there's a dot plot, but anything on the teams?
Yeah. No, so, so we did share the dot plots, which kind of shows some of the individual-level data. You know, based on feedback we've heard from the community and from clinicians, we're not kind of releasing kind of e-exact kind of individual-level data at this time, although we might explore doing so, at a later time, but that's kind of some feedback we've heard from the community, which is why we kind of chose to show the dot plots this time around.
Okay, got it. Thanks so much, and congrats again.
Yeah, thanks, Salim.
Thank you. Our next question comes from Anupam Rama with J.P. Morgan. Your line is open.
Hey, guys, thanks so much for taking the question, and congrats on the data. Maybe following up on the comments that were just made right now. I'm wondering if there's still a plan to have a detailed publication in a journal later this year. To the extent that you plan on sharing some of these data to the phase III investigators near term, I know enrollment's going well, but I'm wondering if these data could further kind of accelerate your enrollment timelines. Thanks so much.
Yeah, thanks for the question, Anupam. Yeah, I think as we mentioned at a previous conference, our plan is still to kind of put this together for a major publication. Again, exact timing to be determined, depending on kind of the review timelines, but it's our every intention to have submitted to a kind of a top top journal, given the excitement around this data, especially around proportionality. With regards to the kind of excitement that we've heard from our investigators, we have shared this data with our investigators, and they are extremely excited about the results that we're seeing. And, you know, enrollment is already going very well. And so, you know, I would expect that this would only kind of continue to fuel that as well. Did that answer your question?
Yeah, man, thanks. I'm good.
Yeah. Thanks, Anupam.
Thank you. Our next question comes from Mani Foroohar with Leerink. Your line is open.
Hi, good morning. This is CJ on for Manny. Congrats on the data. A couple questions from us. Do you have any details on the one child that did not have an increase in AHV from baseline to month 18? Like, did that child have an FGFR variant that is unique from all the other children? And then second question is whether the upper to lower body segment ratio changes at month 6 or month 12 were also stat sig. Thanks.
Yeah. No, thanks, thanks for the question. With regards to the 1 participant who did not have an improvement in AHV from baseline, you know, there's no kind of particular baseline characteristics or anything that would suggest why they would not have a response. I think the only thing to kind of point out is that I think I believe they had a pretty high baseline of about 6 from the start, which is kind of on, on the very high end for children with achondroplasia. So, you know, the, the fact that they've, we, we didn't see an improvement from there is not discouraging, given the fact that, you know, even potentially maintaining that would be quite encouraging, given the, the baseline characteristics.
With regards to your second question, just wanna make sure I hear it correctly again, around. It was around proportionality, you said, or?
Yeah, exactly. The upper to lower body segment ratios-
Ah, that's it.
6 months, 12, if those are also stat sig.
Yeah. So I believe neither month 6 or 12 were stat sig, but month 18 was a stat sig.
Okay, got it. And then the patient that didn't respond, you said they had 6 cm per year baseline. That's also the highest, absolute level of the cohort, right?
Uh, correct.
Okay, great. Thank you.
Thank you. Our next question comes from Josh Schimmer with Cantor Fitzgerald. Your line is open.
Great. Thanks so much for taking the questions. Just have three of them. First, can you remind us what the AHV is that the PROPEL study is powered to detect and the extent to which, that is consistent with these data?
Yeah. So the PROPEL 3 study is powered to detect a change from baseline of approximately 1.3. So we kind of powered the study to be quite conservative, actually, given what we're seeing in treatment effects.
All right. Got it. And what is your latest thinking on potentially exploring the safety of a higher dose for kids who might need some catch-up growth?
Yeah, no, thanks for that question, Josh. It's a good one. It's one we've thought about. You know, I think just given the very strong efficacy and safety profile we've seen today, both kind of best-in-class change in HB, stat sig and proportionality, but also a pretty clean safety profile, as well as the kind of feedback we've gotten from the community that they really want an oral option as soon as possible. We've really prioritized on pushing for the 4-5 dose level in development right now, and same for that in hypochondroplasia as well. We think it's, it's one we really want to prioritize.
I get you're prioritizing that, and that's what you're studying in PROPEL, but would you consider a separate analysis to push the dose higher and see if it's well tolerated to get some potentially stronger growth for kids who might need it?
Yeah. No, I, again, I think it's a really good question and one we'll continue to explore. But I think at this time, we'll be focusing our efforts at the 0.25 mg per kg dose for the time being.
And then in the
It is an interesting question, sorry, Josh. So like we, we had thought about, as you and I had discussed, dosing all the way up to hyperphosphatemia each child individually so that you could max out the dose and then figure it out and then come down slightly. But that's not really. Well, not what the community physicians nor regulators wanted to see.
Sure.
So, you know, you could imagine individualizing doses, but that's obviously not as doable when it comes to interrogating something in a clinical trial or commercially.
In the AE table, there was pain in extremity noted and up to around almost 30% of patients. Maybe you can better characterize that. Is there any reason to think that that's an on-mechanism side effect? How severe was it? And were there any lesser common side effects that might be mechanism related?
Thank you for the question. The pain in extremity was reported as you mentioned in approximately 28% of the children. Pain is one of the most common also symptoms in children with achondroplasia. The ones that were reported during the participation in the trial were all mild or moderate in severity, and none of them were assessed as related to the study drug. I hope this answers your question.
Yeah. And Josh, just to pick up on your other point here around kind of potential on-mechanism off-target effects, right? Again, just to reiterate, we didn't see any cases of hyperphosphatemia or kind of off-target effects as well. So that's nothing. A pretty clean and encouraging safety profile overall.
Okay, great. Thanks so much.
Thank you, Josh.
Thank you. Our next question comes from Paul Choi with Goldman Sachs. Your line is open.
Hi, thanks. Good morning, and thank you for taking our questions. Congrats on the data. I was wondering if you could maybe comment a little bit on some of the responses by age group or age bucket. I know the majority of the patients are under eight, but just curious if you're seeing any differential based on age at baseline, and just sort of what that looks like. And then my second question is, for the hypochondroplasia study, I know you're gonna do a bit of a run-in here, but just sorta thoughts on what dosing levels might be appropriate for this particular population.
Would the amount of drug be similar to what you've seen here and required for achondroplasia, and just sort of what sort of treatment frequency might look like there? Thank you for taking our questions.
Yeah. Thanks, Paul. Yeah, to your first question around kind of differences in age baselines, no, we don't see kind of any difference in treatment effects, across different ages in our study. I think, you know, the only ages where there could be, potentially be a treatment difference is looking at very young kids, you know, kind of younger than 3 and, and kind of much older kids who are kind of near in puberty, you know, over twelve or so, where we kind of don't really have them in the PROPEL-2 study. I think those really are the only two age buckets where there could be different treatment, treatment effect, size difference, but we're not seeing that those differences in our, 4 or 5 study.
With regards to your question around hypochondroplasia, we are planning to interrogate the same dose of 0.25 mg per kg daily in our achondroplasia study as well. Just kind of based on what we've been seeing preclinically, but also thinking about the same level of inhibition will be quite important here. We have regulatory buy-in of kind of using that same dose as well for the phase II and phase III program in hypochondroplasia. Did that answer your questions?
Yes, it did. Great. Thank you very much.
Yeah. Thanks for the question, Paul.
Thank you. Our next question comes from Corey Kasimov with Evercore ISI. Your line is open.
Hey, good morning. Thank you for taking my questions. I have two as well. First one is, do you have any plans to evaluate infigratinib in the 0- to 3-year-old patient population or I guess, 0 to 2.5 year-old? Is there anything about the formulation that would prevent it from being used in these younger kids? And then the second one is similar to Josh's question on safety. Can you contextualize the roughly 30% vomiting as well? I assume it's not overly significant, given there are no discontinuations and obviously no grade 3 plus events, but any color could be helpful. Thank you.
Yeah, happy to take it. So I'll take the first one about infant tolerance first, and I'll hand it over to Daniela for the question around the vomiting, which is really not concerning. With regards to the infant tolerance study, yes, we do have plans to kind of go down to the youngest age range, the 0-3, which, you know, we've heard consistently from clinicians and from the community, remains the age bracket with the highest unmet needs. So we do have plans that we'll announce in the future about our plans to go to the younger ages. That remains a core component of our development program and one we're committed to.
The administration shouldn't be an issue for kids who are about 1-3, and we might explore some sort of oral solution, essentially, for the youngest kids. But it shouldn't be anything too difficult. I'll hand over to Daniela for the question around the 30% vomiting.
Yes. Thank you for the question. So the vomiting as well, they were considered as mild in severity. They were not associated with infigratinib in the sense of they were not highly connected, or there was no association in the intake of infigratinib and the vomiting. And as well, there were other, in many cases, there were other signs of GI dysfunction or intercurrent at the time of the vomiting.
Yeah. Did that, did that answer your question, Corey?
Yeah, definitely. Thank you very much. Appreciate it.
Thank you. Our next question comes from David Lebowitz with Citi. Your line is open.
Thank you very much for taking my question. When you look at the design of the pivotal trial, the age range is from 3 to under 18, and the mean age for the phase II is about 7.5. How do you see the mean age of the study and the overall distribution of patients changing with respect to what we saw in the phase II, and how might this affect the results in the phase III?
Yeah. Is your question around the achondroplasia program or the hypochondroplasia program?
Uh, the
Achondroplasia.
the achondroplasia.
Great. No, thanks, thanks for that question. You know, the one of the main reasons why we expanded the age range in our phase III compared to the age range in our phase II, is ultimately we want to have a little bit of a broader label than just five and up. And as I mentioned before, and I think on the previous question, from what we've seen, there's really no impact of age differences within this particular age range on efficacy on HP. It's only when you look at the youngest kids and look at kids who are in puberty, that you might have an impact on the treatment effect. So I think having a broader age range in our phase III shouldn't meaningfully kind of change the expected impact on HP.
Thank you.
Yeah, thanks for the question.
Yes, it does.
Thank you. That's all the time we have for questions. I'd like to turn the call back over to Justin To for closing remarks.
Great. Well, again, thanks so much for the time in joining today. And I want to make sure we again thank the clinical trial sites, the clinicians, and the families who participated in the study for kind of what we're making possible in the community. So again, thank you all.
Thank you for your participation. This does conclude the program. You may now disconnect. Everyone, have a great day.