Good morning, and welcome to Lumos Pharma's interim data update conference call. [Operator Instructions] As a reminder, this conference call is being recorded..

I will now turn the call over to Lisa Miller, Senior Director of Investor Relations. Please go ahead, ma'am. .

Thank you, operator. Before we proceed with the call, I would like to remind everyone that certain statements made during this call are forward-looking statements under U.S. federal securities laws.

These statements are subject to risks and uncertainties that could cause actual results to differ materially from historical experience or present expectations. Additional information concerning factors that could cause actual results to differ is contained in our periodic reports filed with the SEC..

The forward-looking statements made during this call speak only as of the date hereof, and the company undertakes no obligation to update or revise the forward-looking statements.

Information presented on this call is contained in the press release we issued this morning and in our Form 8-K, which may be accessed from the Investors page of the company's website..

Speaking on today's call will be Rick Hawkins, CEO and Chairman; John McKew, our President and Chief Science Officer; and Lori Lawley, our CFO. David B. Karpf, our Chief Medical Officer, will join for the question-and-answer session..

I will now turn the call over to Rick. .

Thank you, Lisa, and good morning, everyone. Thank you for joining the Lumo Pharma team for our announcement of encouraging interim results from our OraGrowtH210 and OraGrowtH212 trials. Earlier this morning, we issued a press release announcing interim data..

On this call, we will go through the results in additional detail and discuss how they inform the next development steps for LUM-201 for the treatment of PGHD. In a moment, I'll turn the call over to John McKew to walk through the data..

For those of you who are new to our story, I'll begin with a brief overview of Lumos and the indications we focused on. We're targeting the growth hormone market with our novel oral therapeutic called LUM-201, and our initial indication is in pediatric growth hormone deficiency, or PGHD.

Injectable growth hormone has dominated this market for almost 40 years, but the LUM-201 is the first once-a-day oral therapeutic targeting this indication..

LUM-201 is differentiated in a number of ways with a mechanism of action that works within a natural endocrine pathway. The global market opportunity for growth hormone disorder is quite large at approximately $3.4 billion, [ $1.2 ] billion for PGHD alone with additional upside in China of about $1.5 billion..

OraGrowtH210, a study in moderate naive-to-treatment PGHD that's ongoing worldwide at about 45 sites; and the OraGrowtH212, a single site PK/PD trial. A moderate or idiopathic PGHD makes up approximately 2/3 of the total treated PGHD patient population..

As of the end of October 1, I'm pleased to report there were approximately 80% enrolled in both trials and continue to be encouraged by the pace of enrollment.

We have $74 million as a cash balance at the end of the third quarter of 2022, and this is enough cash to get us through a full readout of these 2 studies in the second half of 2023, with the cash runway into Q2 2024..

Now we'll discuss the interim data. We are very pleased to announce this morning encouraging interim results from these 2 trials. Growth on LUM-201 met expectations. It demonstrated a durable response and showed a favorable safety and tolerability profile.

As previously guided, we expect an annualized growth velocity target of 8.3 centimeters a year based on several large historical databases of moderate naive-to-treatment PGHD subjects treated with growth hormone..

In fact, the 1.6 mg per kg per day LUM-201 dose at 6 months on therapy achieved a mean annualized height velocity of 8.6 centimeters a year, meeting these expectations.

Now recall, this is for the enriched population we identified due to our predictive enrichment marker, or PEM, this -- PEM strategy reflecting those moderate PGHD patients with the potential to respond to LUM-201. Importantly, a durable response to LUM-201 was observed at 9 and 12 months..

We're also very pleased to say that the interim look, we have not observed any treatment-related SAE dropouts due to AEs and no meaningful safety signal across the entire dose range evaluated. In addition to that, we believe these data support the selection of 1.6 mg per kg a day for a pivotal Phase III trial.

Identifying this dose will now help with advanced planning of that pivotal trial..

And finally, I'll mention again that our molecule's unique mechanisms of action and oral administration, we believe these data support the potential for LUM-201 to disrupt the injectable growth hormone therapeutic market worldwide..

Now I'll turn the call over to our President and Chief Scientific Officer, John McKew, to walk through the data in greater detail.

John?.

Thank you, Rick. We'd like to start with a quick summary of the mechanism of action. LUM-201 is a small molecule that's specifically designed to interact with the growth hormone secretagogue receptor 1a. When that receptor is expressed in the hypothalamus and the pituitary, our molecule binds and agonizes that receptor.

The net result of that action across the 2 organs is to increase the natural pulsatile release of growth hormone, increasing the amplitude of the natural peak sequence..

By increasing the amplitude of those peaks, we increase the amount of circulating IGF-1. This circulating growth hormone and the IGF-1 then act on the open growth plates of these children with growth hormone deficiency and help them grow.

We don't expect to achieve super physiological levels of growth hormone and IGF-1 because of the naturally evolved feedback mechanisms..

Another important factor to remember is that not every child with growth hormone deficiency has the ability or the physiology to respond to our molecule. The subset of patients who are severely growth hormone deficient and can't make, store or release growth hormone upon stimulation with our molecule won't respond to treatment with LUM-201.

We developed a strategy to enrich our trials and subjects with the potential to be responsive. We call that strategy, the predictive enrichment marker strategy, or PEM, which selects for the more moderate end of the growth hormone deficiency spectrum..

0.8, 1.6 and 3.2 mg per kg per day. Full enrollment will consist of 20 subjects in each LUM-201 cohort with a fourth cohort of 20 subjects on daily injectable growth hormone. The interim analysis for read today is based on approximately 10 subjects in each cohort at 6 months on therapy.

We will also look at 9- and 12-month data for a smaller number of these subjects..

The fully enrolled dataset of 80 patients at 6 months on therapy is expected to be available in the second half of next year. At that point, we will have data from a significant number of subjects on therapy for 9 to 12 months and a smaller number beyond 12 months..

As Rick mentioned, the 1.6 mg per kg per day's LUM-201 cohort met our expectations for growth. I thought it would be helpful to review where that expected value for growth came from. We utilized Eli Lilly's large historical database called GeNeSIS, representing 20 years of treatment with their daily injectable growth hormone, Humatrope..

We applied our PEM cutoffs to this data set of naive-to-treat subjects to understand their first-year growth response to growth hormone. This analysis showed a mean annualized height velocity of 8.3 centimeters per year in the first year of treatment in this moderate PGHD population.

This growth rate is consistent with values from other published data sets in the first year of growth hormone treatment in moderate PGHD..

The previous Merck 020 recombinant human growth hormone arm when filtered for PEM positive subjects provided growth rates consistent with these other data sets.

Expectations from these data are that PEM-positive subjects in our trial should grow about 8.3 centimeters per year regardless of whether they're treated with LUM-201 or with the daily injectable growth hormone..

As Rick mentioned, the 1.6 mg per kg per day cohort grew at 8.6 centimeters per year mean annualized height velocity and met our expectations for growth. These interim data demonstrated a dose response between the 0.8 and the 1.6 dose cohorts, while a growth rate at 1 point -- growth rates at 1.6 and 3.2 mg per kg per day are similar..

Based on the pharmacodynamic response that Merck generated early in their clinical development of this molecule, we expect a smaller dose response between 1.6 and 3.2 mg per kg per day doses since this 3.2 dose lies above the pharmacodynamic plateau.

The annualized height velocity observed in the growth hormone arm of 11.1 centimeters was above what historical data would have predicted in that group..

In order to understand the surprising level of growth in this arm, we examined baseline characteristics and looked for growth outliers in the cohorts.

In the recombinant human growth hormone arm, there were 2 children under the age of 5, with 15.6 and 12.7 centimeters per year growth, among other imbalances and baseline characteristics predictive of greater growth on treatment..

A key predictor of growth is age at the start of treatment. Younger PGHD subjects are known to grow faster on treatment. Other factors, including baseline height; standard deviation score, or SDS; baseline IGF-1 SDS; the delta or distance from mid-parental height and weight; or BMI are all measures of how growth hormone deficient a child is..

As these values lie further from the mean, faster first-year growth would be predicted. The power of these baseline characteristics to predict first-year growth is well-known to pediatric endocrinologists. The baseline characteristics for the LUM-201 treatment cohort at 50% enrollment are well-balanced for the key variables just mentioned.

However, the growth hormone arm shows a different story..

There are significant differences in age of BMI and more subtle differences between cohorts and the delta from mid-parental height and IGF-1 SDS. The baseline characteristics in the rhGH arm predict that these subjects will have a greater response to treatment.

At only 50% enrollment, it is not uncommon for cohorts to show imbalances, which should normalize as the trial approaches full enrollment..

As I mentioned earlier, we identified 2 outliers in the growth hormone arm who grew significantly more than expected in this moderate PGHD population at 15.6 and 12.7 centimeters per year, respectively. Two of the 3 subjects under 5, including these subjects are randomized to the growth hormone arm.

Remember that age is one of the most important variables to predict faster growth on the start of treatment..

These outliers are represented by red stars on the graph of expected first-year growth and less severe growth hormone deficiency as predicted by Ranke's analysis of Pfizer's KIGS data set.

Our trial is stratified by age, so as enrollment progresses, we would expect these baseline ages to be more evenly distributed across all cohorts, diminishing the impact of these early outliers..

As Rick mentioned, we are now at approximately 80% enrollment, and we can examine baseline characteristics for all subjects currently randomized. As we have predicted, age differences and BMI differences have become much less pronounced between the growth hormone and LUM-201 treatment cohorts.

While we don't have annualized height velocity on these new subjects, we know that older subjects have been enrolled in the growth hormone arm, which will likely offset the effect of the youngest subjects enrolled early in that cohort..

Let's examine durability of response to LUM-201 next. Particularly, for the 1.6 mg per kg per day arm, growth rates are similar at 6, 9 and 12 months. On the other hand, the well-known propensity for injectable were common human growth hormone catch-up growth to decline over the 6- to 12-month time frame is observed in our comparator arm..

The LUM-201 1.6 mg per kg per day cohort achieved a mean annualized height velocity of 8.1 centimeters per year at 12 months. The recombinant human growth hormone arm showed a mean annualized height velocity of 9.9 centimeters per year. A pivotal non-inferiority trial is 12 months in duration..

So we were pleased by the durability of LUM-201 growth with the difference in growth between these 2 arms of 12 months aligned within the non-inferiority margin used in recent PGHD registrational studies.

Also as cohorts continue to enroll and more subjects achieve 12 months on treatment, we would expect a better balanced characteristics to be reflected in the convergence of these 12-month growth rates..

We will now discuss our OraGrowtH212 trial. This trial is a single-site open-label trial evaluating the pharmacokinetic and pharmacodynamic effects of oral LUM-201 in up to 24 treatment-naive PGHD subjects at 2 dose levels, 1.6 and 3.2 mg per kg per day.

These data will supplement the PK/PD data at 0.8 mg per kg per day from an earlier study in PGHD demonstrating the unique mechanism of action of LUM-201 to stimulate pulsatile release of growth hormone. Annualized height velocity is also being evaluated at these 2 higher LUM-201 doses.

This trial will continue until the subjects reach near adult height..

Today, we are announcing interim data on 10 subjects in this trial and expect to provide top line data on up to 24 subjects in these 2 dose cohorts in the second half of next year. We will review the annualized height velocity for 5 subjects on 1.6 and 5 subjects on 3.2 mg per kg per day at 6 months on therapy.

We expect to release the PK/PD data once it has been fully analyzed. All subjects in the OraGrowtH212 study are PEM positive..

The interim OraGrowtH212 data showed a mean 6-month annualized height velocity of 7.1 centimeters per year on 1.6 mg per kg per day and 8.6 centimeters per year on 3.2 mg per kg per day, demonstrating a similar growth rate seen on these 2 higher LUM-201 doses in the OraGrowtH210 trial.

Again, the number of subjects in each cohort is small, but we believe these OraGrowtH212 data represent a secondary validation of the results that we observed in the Phase II OraGrowtH210 trial..

When we evaluate growth at 6, 9 and 12 months on LUM-201, durability of effect is evident. The 1.6 mg per kg per day arm produce mean AHVs of 7.1 centimeters per year at 6 months and 7.2 centimeters per year at 12 months on therapy. The 3.2 mg per kg arm produced 8.6 and 7.8 centimeters per year, respectively, at 6 and 12 months on therapy.

The error bars are tight for both cohorts at all time points, suggesting a rather homogeneous population..

Again, both of these cohorts showed durability of growth out to 12 months at interim data, confirming a similar trend observed in the OraGrowtH210 trial. From the comparability data from these 2 independent trials, we feel confident that we should see similar growth patterns for our selected LUM-201 dose in a pivotal Phase III trial..

In a further effort to determine an optimal dose for our Phase III trial, we combined the growth velocity data for both cohorts from each OraGrowtH210 and 212 trial in a post-hoc analysis to find the mean growth rates for each dose. In that analysis, we observed comparable mean growth rates for the top 2 LUM-201 doses at 6, 9 and 12 months.

Our analysis of the separate and combined data support the selection of 1.6 mg per kg per day as the optimal dose for a pivotal Phase III trial in PGHD..

In addition to efficacy data, we also reviewed the safety data for our molecule for all subjects enrolled in the OraGrowtH trials to date. We believe LUM-201 will demonstrate a favorable safety profile as our interim data from both OraGrowtH trial shows comparable safety and tolerability to the recombinant human growth hormone subjects in the trial..

There were no treatment-related serious adverse events, no dropouts due to SAEs and no meaningful safety signals observed in either laboratory values, adverse event data or in ECG values. The safety data for the OraGrowtH212 is consistent with the data in the OraGrowtH210 trial.

A summary of some of these adverse event tables may be found in the supplementary slides available on our website..

I will now turn the call over to Lori to run through financial highlights for the third quarter 2022. .

Thank you, John. Lumos Pharma ended the third quarter on September 30, 2022, with cash and cash equivalent totaling $73.7 million compared to $94.8 million on December 31, 2021. The company expects a cash use of approximately $8.5 million to $9.5 million in Q4 2022.

Cash on the end as of September 30, 2022, is expected to support operations into the second quarter of 2024, inclusive of the primary outcome data readout from OraGrowtH210 and OraGrowtH212 trials anticipated in the second half of 2023..

Research and development expenses were $4.1 million for the quarter ended September 30, 2022, flat compared to the same period in 2021.

General and administrative expenses were $3.9 million for the quarter ended September 30, 2022, as compared to $3.4 million for the same period in 2021, primarily due to royalties paid to the Public Health Agency of Canada for revenues received from Merck for the sale of the Ebola vaccine..

The net loss for the third quarter was $7.3 million compared to a net loss of $7.5 million for the same period in 2021. Lumos Pharma ended the third quarter of 2022 with 8,375,271 shares outstanding. Additional information may be found in our quarterly press release and 10-Q filed this morning..

And with that, I will turn the call back to Rick to conclude for us. .

Thank you, Lori. We're very pleased to report that we've meaningfully derisked our entire program in not just 1 study, but across 2 separate studies. In the OraGrowtH210 trial to date, subjects on 1.6 mg per kg per day of LUM-201 grew at a mean annualized height velocity of 8.6 centimeters per year at 6 months as expected.

Our patient population that are PEM positive, in other words, those with moderate idiopathic growth hormone deficiency, were predicted to grow about 8.3 centimeters in the first year on treatment..

We also are very pleased to report a durability out to 12 months with the margin between treatment and control arms within the non-inferiority range used in recent growth hormone registrational trials. Also, as John just reported, interim data has not identified any safety and tolerability concerns to date for LUM-201 across all doses..

These interim data support the identification of 1.6 mg per kg per day dose of LUM-201 for our Phase III trial, enabling us to initiate advanced planning for this important pivotal study.

Also, these interim data reported today corroborate prior data suggesting LUM-201 has the potential to disrupt the growth hormone market that's been dominated for almost 40 years by injectable products..

LUM-201 is once again a small molecule given orally once a day, and we believe as our preliminary market research demonstrates that the majority of pediatric growth hormone-deficient children with moderate PGHD would prefer an oral alternative..

We should thank all of our investigators and the PGHD patients and their families involved in our trials. And to say the least, we're excited to continue to advance our programs and look forward to disclosing top line data in the second half of 2023. Thank you very much. .

[Operator Instructions] The first question we have is from Charles Duncan from Cantor Fitzgerald. .

Congratulations on these interim results. I had a question regarding the interest of the investigators and patients and the screen failure rate.

How is that going? It seems like this can even further help enrollment?.

And then second question is related to the dose response, at least numerically forgetting about the error bars, it looks like there's a little bit of a U-shaped dose response.

Do you have a mechanistic rationale for them?.

Yes. So John -- or actually, David, why don't you answer that first question about screen failure rate. And then, John, why don't you ask the -- answer the second question. .

Sure. Our screen failure rate remains really quite low, which is why our enrollment is going so well for both trials. So I don't see that improving. I mean the sites remain very engaged and our -- the kids are happy with the growth in the trial. So it's helping a lot. Second question was... .

Dose response, and I think John is going to answer that question. .

Yes. So Chaz, if you remember, we've shown you the pharmacodynamic dose response curve that Merck generated in their early trial. And we've kind of -- our lowest dose was 0.8 mg per kg, and on that PD dose response curve, that was about 1/3 of the way up the dose response curve.

When we go to 1.6, our mid-dose, it's about 75% of the way up the curve, and then when we go from 1.6 to 3.2, you're kind of above the plateau..

So we knew the dose response curve would be -- or the dose response change between 0.8 and 1.6 would be larger than 1.6 and 3.2 based on that data.

So it's not too surprising for us that the 1.6 and 3.2 -- we expected a little bit of a dose response, but they're essentially the same by the time we look at them across both studies and combine the cohorts. .

And then if I could ask a follow-up, Rick, John or David. It looks like the error bars are actually quite reasonable despite the sample size. And I guess I'm wondering how might this impact the sample size calculus that you're doing and/or design of a pivotal study.

And then could this fast forward, you being able to really operationalize a pivotal program with LUM-201?.

John, go ahead. .

So I think the first part is we got the key -- one of the key answers that we wanted out of this, which is the dose for Phase III, right? So now that we have the dose, we can actually start to plan a lot of the -- make sure the CMC activities are going to align with having that dose ready and all the other pieces.

So protocol writing, we can start with. I think we would like to wait a little bit longer and see the full data set and the variability in an n of 20..

The error bars are very tight actually for the 212 study, they're a little bit larger for 210, and I think we'd like to know where we're going to be in between those 2 standard deviations as we start to plan for what our variability will be in the larger study. So I think our estimates for Phase III remained about the same that we've been projecting.

And I think once we have a broader data set, we'll be able to essentially calculate better and then go negotiate with the FDA and agree on what our margin will be. .

Okay. Last question for Rick. You mentioned China. I was intrigued with that specific call out in terms of incidence or prevalence pediatric growth hormone deficiency. I guess I'm wondering, is there a specific strategy that you're contemplating with regard to ex U.S.

And can you provide any color on that? And when you would like to maybe pursue a partnership?.

Sure, Chaz. Look, there's no question about it. The China market is probably going to be approaching the second largest market in the world. It's already about $1.5 billion in sales per year, and it's growing 20%, 25% a year. So we certainly have to pay attention to it..

I think there are a number of Asian partners who certainly would be interested in talking to us. It's a little too early right now, but I think that in the coming months and year, I think that we'd probably step up activity in terms of the outreach. But it is no question, it's a very important market.

And when we do a global clinical trial, we'll include Asian patients, of course. .

The next question we have is from Yasmeen Rahimi from Piper Sandler. .

Congrats on the data. It would be really great if you could maybe comment a little bit more on the baseline characteristics of 210. I appreciate you sharing the baselines on the 75% of the population that's complete. But when we look -- in terms of the mid-parental height and the variability in the BMI, it still seems to be slightly as an outlier..

So just kind of help us comment a little bit more why those would be balanced.

And then b, is there a reason to -- as you're screening the additional patients for full enrollment, is there a way to maybe homogenize that population so that, that 25% that's coming in is also doesn't account for any variability? And then maybe like one more follow-up question for you, team. .

All right. Go ahead, David. Why don't you answer the question. .

Yes. So we only have 2 factors for stratification, high SDS and age. And it becomes problematic to stratify it for more than 2 factors in a trial.

But we are getting a more homogeneous population in the latter half of the trial than the first half of the trial simply because we're closely scrutinizing all the factors at a prescreening form before we allow them to screen. So we're making sure that they're all reasonably similarly GHD. So that should help..

And I do expect the full population to be much more homogeneous than the interim analysis. You did highlight some of the key features that I think in addition to the outliers, provenly provided the imbalance in this current interim analysis because the BMI, in particular, was a significant factor after age, I think, in driving that group's response. .

And John, why don't you add anything there?.

Yes. Yes. If I may add, I mean, I think one of the biggest issues for the interim was age, right? There was about a 9.5 month difference between 1.6 and the growth hormone arm, and we are stratifying by age.

And so when we added 5 more kids to the growth hormone cohort, we've cut that differential in half, right?.

So I think that is probably -- we're down to about 4 months difference between growth hormone and the 1.6 arm. So I think that's going to have a big effect and things will gradually -- to be honest, the youngest kid in the growth hormone arm was also the kid with the largest BMI, right? So I think we will add kids.

As older kids come in, these will balance out even more, right? The next 5 kids will continue that trend. .

Great.

And then, team, I know that there was going to be additional analyses on 212 in terms of the pulsatility, the PK/PD, like, when should we be expecting that data to be shared with us?.

Go ahead, John. .

So I think that data will be shared before the end of the year, yes. .

The next question we have is from Ed White from H.C. Wainwright. .

The first question is just on those 2 patients that were seen as outliers in the growth hormone cohort.

How many months have they been on treatment?.

John, do you want to answer that question?.

Yes. So the fastest-growing child is 15.6, we have data through 9 months, so 6 and 9 months; and the 12.8, I think we have 6, 9 and 12 months on. .

Okay. And then just looking at the dosing and you had mentioned about why we shouldn't have seen a dose response, are you giving any consideration to doing a dose perhaps between 1.6 and 3.2, perhaps 2.4 to sort of 0 and more on that. And you did mention the Phase III dose is probably going to be the 1.6.

But is it really too early to tell that right now? And shouldn't you wait for more data?.

John, go ahead. .

So I think we feel pretty confident with the selection of 1.6, right? So we have 2 separate trials. They are slightly different populations, but they both point to very similar growth rates between the 2 doses. We know from earlier work that the plateau for growth hormone release is somewhere in between those 2 doses..

And I don't think we're going to gain much by trying to split the difference between those 2 doses and come up with like a 2.4 mg per kg per day arm. I think the 1.6 should be sufficient. And the FDA is always going to want us to use the minimum drug to get a good effect, right? And I think looking at this data, that looks to be the 1.6 arm. .

Okay. And perhaps my last question is just when you see the data from the outliers being the youngest patients, how are you thinking about your Phase III protocol? And would you accept those patients under 5 years? Do you think that perhaps you look at older patients? I just wanted to ask that question. .

David, do you want to answer that?.

Yes. I'll say 2 things. One is that the much larger patient population in a Phase III trial usually results in very good balance for all of these factors. And secondly, we could focus on that and do a 3-part stratification per age just to make sure that we get the same number of the youngest, mid and older subjects in each group.

There's different ways to handle that. But I think the sample size itself takes care of most of those issues. .

[Operator Instructions] The next question we have is from Catherine Novack from Jones Research. .

Congrats on the data. Just going back to some of the baseline characteristics. I'm curious about trying to understand how to think about remaining imbalances in characteristics that we might be seeing at 75% enrollment. Which of these characteristics -- few characteristics would have had the greatest impact in difference on AHV.

And then I have a follow-up. .

David, go ahead. .

Yes. In most of the models, including Ranke, the #1 and 2 are basically the growth hormone dose and age. In the trial, the growth hormone dose is fixed. So that's taken out of the equation.

So age is probably the single most important factor and that's followed then by basically BMI, higher BMI being faster growth than lower BMI or higher weight versus lower weight. And then the other factors are also meaningful..

So if you have big differences in IGF-1 SDS or in higher mid-parental height or delta for mid-parental height, all of the -- so the shorter you are compared to what you should be will give you better growth. And the greater -- farther away you are from that the better growth and lower IGF-1.

So they are all factors, but the 2 -- the ones that we -- that are effective in our trial, probably age is the single most important because the growth hormone dose is fixed.

Does that answer your question?.

Yes. That's very helpful.

And then the second one, just thinking about expansion of indications now that you've selected an effective -- what you expect to be an effective dose, are you planning to disclose additional LUM-201 indications?.

We haven't given any guidance yet, but we've had some ongoing plans for quite some time. And I think some time in the near future, we'll make it an appropriate announcement. .

The next question we have is from Eun Yang from Jefferies. .

So it sounds like for upcoming Phase III trial based on the data today, you don't feel that you have to modify the enrollment criteria.

Am I understanding it correctly?.

David?.

I think that there will be some tweaks to the enrollment criteria for Phase III, but -- just getting more to what kind of a standard entry criteria. .

But there will still be the PEM positive entry criteria, right? That is -- and we'll validate it, right... .

Yes, for sure. Yes.

And the screening rate, would you still stand by PEM-positive kids would be about 50%, 60% of or growth hormone deficient kids?.

Yes. I think that it's 2 questions. One is what percentage of kids are PEM positive, idiopathic GHD. And based upon all the available data, that's about 2/3 of the population.

In terms of screening for the study, what we found in this trial as long as we educate the investigators to identify kids with idiopathic GHD, then the vast majority of them are PEM-positive. So the PEM itself does not factor really meaningfully into the screening or enrollment process.

As long as you identify the right subjects to screen, it works very, very well. .

Right. And then if you mentioned this, I apologize. So in the daily growth hormone injection on the 2 youngest kids showing the highest growth of velocity.

If you actually exclude those 2 kids, what would have been the growth of velocity in that population in that cohort?.

John, do you want to answer that?.

I didn't get the question. .

So one way to do that is to instead of using the mean annualized height velocity, if you look at the median annualized height velocity, right, so that gets you -- because that minimizes the impact of outliers -- so you get down to about, I think, 10.8 centimeters 8-month growth -- or I'm sorry, 6-month growth in that growth hormone cohort.

So it does go down pretty significantly. .

Okay. And the last question is on the patent. So the competition [indiscernible] patent has expired, but you have orphan exclusivity and you have U.S. patent.

But what are you -- how do you think about the strength of your other patents for 201?.

Good question, Eun. And we do have a U.S. patent, and it's the diagnosis and treatment of not just PGHD but across the board with all of these growth hormone disorders. And it's the application of our predictive enrichment marker strategy is where that lies. That patent has been issued in the U.S.

It goes out to 2036, and we're executed in other parts of the world right now. But of course, we have orphan status in the U.S., Europe, and we'll get it in Japan and other parts of the world when it's appropriate. .

Our final question comes from Elemer Piros from ROTH. .

Yes.

What I'd like to ask is, were there any other groups in which there were children that were under the age of 5 that have been enrolled in this study?.

Yes.

John?.

I'm sorry?.

Yes, there was one other subject who is -- so there were 3 subjects under the age of 5, 2 are in the growth hormone arm and 1 within the 0.8 mg per kg per day arm. .

Okay. And maybe a follow-up to that. And after taking out those 2 outliers, and I know that the sample size is still very small. But you -- I think you mentioned that there is a 10.8 centimeter annualized height velocity that would seem to be congruent with if you were to look at the Ascendis pivotal trial, both the daily injection and the once weekly.

Have you been able to look at the baseline characteristics of your study versus that pivotal trial?.

Yes. David, why don't you go ahead. .

Sure. .

No. John, you go first and then David... .

So let me correct something -- just so I gave the wrong number, Elemer, the first time. The median for the growth hormone arm is 10.5. So I just wanted to clarify that. I remember the wrong number. It's 10.5. And then, David, you could talk about the baseline for Ascendis. .

Right. Yes. There is no question that the Ascendis Phase II trial that we're comparing against a 6-month trial enrolled a much more severely GHD population than we did. It wasn't as deficient as the OPKO Phase II trial..

But significantly -- so the somapacitan trials and the Ascendis trials were pretty comparable than enrolling by 50-50 organic and idiopathic GHD. So their baseline height SDS was at least an SD lower than in our trial. IGF1-SDS was lower, Delta mid-parental height was lower. So all in all, in a much more severe population..

So we wouldn't expect to see the same growth hormone response in our trial as in either the TransCon trial or the somapacitan trial. Yet, in fact, it behaved like it was in those populations. That's what's so unusual. And that's why we really feel it's built driven by baseline differences and in a couple of outliers in the trial. .

But baseline height standard deviation -- the baseline height standard deviation score, Elemer, for the Ascendis trial was about minus 3.3. Ours is about minus 2. So it's a full standard deviation kind of closer to the mean. So much less growth on a deficient population. .

Thank you. So ladies and gentlemen, at this stage, there are no further questions in the queue. Thank you for joining us and enjoy your day..