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spk13: and welcome to Lumos Pharma's Interim Data Update Conference Call. Currently, all participants are in listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at the time. As a reminder, this conference call is being recorded. I will now turn the call over to Lisa Muller, Senior Director of Investor Relations. Please go ahead, ma'am.
spk00: 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 8K, 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 McHugh, our President and Chief Science Officer, and Lori Lawley, our CFO. David B. Karp, our Chief Medical Officer, will join for the question and answer session. I will now turn the call over to Rick.
spk07: Thank you, Lisa, and good morning, everyone. Thank you for joining the Illumifarma team for our announcement of encouraging interim results from our Oral Growth 210 and Oral Growth 212 trials. Earlier this morning, we issued a press release announcing interim data. On this call, we'll go through the results in additional detail and discuss how they inform the next development steps for LUM201 for the treatment of PGHD. In a moment, I'll turn the call over to John McHugh 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 LUM201, 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 LUM201 is the first once-a-day oral therapeutic targeting this indication. LUM201 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, $1.1 billion for PGSD alone, with additional upside in China of about $1.5 billion. The interim results we are reporting today are from two Phase II trials, World Growth 210, a study in moderate naivety treatment, PGSD, It's ongoing worldwide at about 45 sites, and the Oral Growth 212, a single-site PK-PD trial. Moderate or idiopathic PGHD makes up approximately two-thirds of the total treated PGHD patient population. As of the end of October 1, I'm pleased to report that we're 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 two studies in the second half of 2023 with a cash runway into Q2 2024. Now to discuss the interim data. We are very pleased to announce this morning encouraging interim results from these two trials. Growth on Loom 201 met expectations. It demonstrated a durable response and showed a favorable safety and tolerability profile. As previously guided, we expected annualized growth velocity target of 8.3 centimeters a year based on several large historical databases of moderate, not naive to treatment, PTSD subjects treated with growth hormones. In fact, the 1.6 mg per kg per day LUM201 dose at six 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 through our predictive enrichment marker, or PEM, this PEM strategy for selecting those moderate PGHD patients with the potential to respond to LUM201. Importantly, a durable response to LUM201 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 SAEs, 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 mechanism of action and oral administration, we believe these data support the potential for LUM201 to disrupt the injectable growth hormone therapeutic market worldwide. Now I'll turn the call over to our President and Chief Scientific Officer, John McHugh, to walk through the data in greater detail. John?
spk10: Thank you, Rick. We'd like to start with a quick summary of the mechanism of action. LUM201 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 two 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. The 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 molecules. 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 LIM201. 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. Our phase two trial applies that PEM strategy prospectively and evaluates three dose cohorts for lute 201, 0.8, 1.6, and 3.2 makes for cake per day. Full enrollment will consist of 20 subjects in each lute 201 cohort with a fourth cohort of 20 subjects on daily injectable growth hormone. The interim analysis reviewed today is based on approximately 10 subjects in each cohort at six months on therapy. We will also look at nine and 12-month data for a smaller number of these subjects. The fully enrolled data set of 80 patients at six 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 nine to 12 months and a smaller number beyond 12 months. As Rick mentioned, the 1.6 MIG per TIG per day LUM201 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 site 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 datasets in the first year of growth hormone treatment in moderate PGHD. The previous Merck 020 for common human growth hormone arm when filtered for PEM positive subjects provided growth rates consistent with these other datasets. 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 loom 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 site velocity, and met our expectations for growth. These interim data demonstrate a dose response between the 0.8 and the 1.6 dose cohorts, while the 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 in one 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 recovery of human growth in one arm, there were two children under the age of five 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 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 LUM201 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 and BMI and more subtle differences between cohorts in 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 two 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 three subjects under five including these subjects, were 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 Kiggs dataset. 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 LUM201 treatment cohorts. While we don't have annualized site 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 LIMTU-01 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 recombinant human growth arm catch-up growth to decline over the 6- to 12-month timeframe is observed in our comparator arm. The LUBE201 1.6 mg per kg per day cohort achieved a mean annualized height velocity of 8.1 cm per year in 12 months. The recombinant human growth arm run arm showed a mean annualized height velocity of 9.9 cm. A pivotal non-inferiority trial is 12 months in duration, so we were pleased by the durability of Loom 201 growth with the difference in growth between these two arms of 12 months lying 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 the better balance characteristics to be reflected in a convergence of these 12-month growth rates. We'll now discuss our Oral Growth 212 trial. This trial is a single-site, open-label trial evaluating the pharmacokinetic and pharmacodynamic effects of oral lume 201 in up to 24 treatment-naive PGHD subjects at two dose levels, 1.6 and 3.2 mg per kg per day. These data will supplement the PKPD data at 0.8 mg per kg per day from an earlier study in PGHD demonstrating the unique mechanism of action of LUM201 to stimulate pulsatile release of growth hormone. Annualized height velocity is also being evaluated at these two higher LUM201 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 two-dose cohorts in the second half of next year. We will review the annualized height velocity for five subjects on 1.6 and five subjects on 3.2 makes per day at six months on therapy. We expect to release the PKPD data once it has been fully analyzed. All subjects in the Oral Growth 212 study are PEM-positive. The interim oral growth 212 data showed a mean six-month annualized height velocity of 7.1 centimeters per year on 1.6 mgs per kg per day and 8.6 centimeters per year on 3.2 mgs per kg per day, demonstrating a similar growth rate seen on these two higher LUM201 doses in the oral growth 210 trial. Again, the number of subjects in each cohort is small, but we believe these oral growth 212 data represent a secondary validation of the results that we observed in the phase 2 oral growth 210 trial. When we evaluate growth at 6, 9, and 12 months on LUM201, durability of effect is evident. The 1.6 mg per kg per day arm produced 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 R-Growth 210 trial. From the comparability data from these two independent trials, we feel confident that we should see similar growth patterns for our selected LUM201 dose in a pivotal Phase III trial. In a further effort to determine an optimal dose for our phase three trial, we combined the growth velocity data for both cohorts from each oral growth 210 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 two LUM201 doses at six, nine, 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 at PGHD. In addition to efficacy data, we also reviewed the safety data for our molecule for all subjects enrolled in the oral growth trials to date. We believe LUM201 will demonstrate a favorable safety profile as our interim data from both oral growth trials shows comparable safety and tolerability to the common 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 Orgoff 212 trial is consistent with the data in the Orgoff 210 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 Laurie to run through financial highlights for the third quarter 2022.
spk03: Thank you, John. Lumos Pharma ended the third quarter on September 30, 2022, with cash and cash equivalents totaling $73.7 million compared to $94.8 million on December 31, 2021. The company expects a cash use of approximately $8.5 to $9.5 million in Q4 2022. Cash on hand as of September 30, 2022, is expected to support operations into the second quarter of 2024, inclusive of the primary outcome data readout from ORA Growth 210 and ORA Growth 212 trials, anticipated in the second half of 2023. Research and development expenses were 4.1 million for the quarter ended September 30th, 2022, flat compared to the same period in 2021. General and administrative expenses were 3.9 million for the quarter ended September 30th, 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 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 10Q filed this morning. And with that, I will turn the call back to Rick to conclude for us.
spk07: Thank you, Lori. We're very pleased to report that we've meaningfully de-risked our entire program in not just one study, but across two separate studies. In the oral growth 210 for off-the-date, subjects on 1.6 mg per kg per day of LUM201 grew at a mean annualized height velocity of 8.6 centimeters per year at six 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 LUM201 across all doses. These interim data support the identification of 1.6 mg per kg per day dose of LUM201 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 LUM201 has the potential to disrupt the growth hormone market that's been dominated for almost 40 years by injectable products. LUM201 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.
spk13: Thank you, sir. Ladies and gentlemen, we will now be conducting a question and answer session. If you would like to ask a question, please press star and then 1. A confirmation tone will indicate your line is in the question queue. You may press star and then 2 if you would like to remove your question from the queue. Again, if you would like to ask a question, please press star and then 1 now. The first question we have is from Charles Duncan from Council Fitzgerald.
spk08: Yeah, super. Good morning, Rick, and thank you. Morning, Rick and team. Thank you for taking our questions and 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 that?
spk07: Yeah. So, John, or actually, David, why don't you answer that first question about screen failure rate? And then, John, why don't you answer the second question?
spk11: Our screen failure rate remains really quite low, which is why our enrollment is going so well for both trials.
spk02: So I don't see that improving.
spk11: I mean, the sites remain very engaged, and the kids are happy with the growth in the trials. That's helping a lot. Second question was?
spk02: Just response, and I think John's going to answer that question.
spk10: Yeah, so Chas, if you remember, you know, we've showed you the pharmacodynamic dose response curve that Merck generated in their early trial. And, you know, we've kind of, our lowest dose was 0.8 mg per kg. And on that PD dose response curve, that was about a third 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 1.6 and 3.2, we expected a little bit of a dose response, but they're essentially the same by the time we, you know, we look at them across both studies and combine the cohorts.
spk08: 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 know, you being able to really operationalize a pivotal program with Loom 201? John, go ahead.
spk10: So I think the first part is we, you know, we got the key, one of the key answers that we wanted out of this, which is the dose for phase three, right? So now that we have the dose, we can actually start to plan a lot of the, you know, make sure the CMC activities are going to align with having, you know, that dose ready and all the other pieces of, you know, protocol writing we can start with. I think we would like to, we would like to wait a little bit longer and see the full data set and the variability in an N of 20. You know, 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 two standard deviations as we start to plan for what our variability will be in the larger study. So I think our estimates for phase three remain about the same that we've been projecting. And I think once we have a broader data set, we'll be able to, you know, essentially calculate better and then go negotiate with the FDA and agree on what our margin will be.
spk08: Okay, last question for Rick. You mentioned China. I was intrigued with that specific call-out in terms of incidence or prevalence of pediatric growth hormone deficiency. I guess I'm wondering, is there a specific strategy that you're contemplating with regard to XUS, and can you provide any color on that and one you would like to maybe pursue partnerships?
spk07: Yeah, sure, Chas. Look, you know, there's no question about it. The China market is probably going to be or 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'll probably step up activity in terms of the outreach. But it is no question a very important market. And when we do a global clinical trial, we'll include Asian patients, of course.
spk08: Very good. Thank you for taking our questions.
spk02: Congrats on these data. All right. Thanks, Chad.
spk13: Thank you. The next question we have is from Yasmine Rahimi from Piper Sandler. Please go ahead.
spk04: Good morning, team, and 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, you know, 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, you know, that 25% that's coming in also doesn't account for any variability? And then maybe like one more follow-up question for you, Tina. Yeah.
spk07: All right, go ahead, David, once you answer the question.
spk11: Yeah, so we only have two factors for stratification, high SDS and age. And it becomes problematic to stratify for more than two factors in a trial. But we are getting a more homogeneous population 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, really provided the imbalance in this current interim analysis. The BMI in particular was a significant factor after age, I think, in driving that group's response.
spk02: And John, why don't you? Yeah. Yeah.
spk10: Yeah. Yeah. Yes. If I may add, I mean, I think one of the biggest issues for the interim was age, right? There was about a nine and a half month difference between 1.6 and the growth hormone arm. And we are stratifying by age. And so, you know, when we added five 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 four 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, you know, 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 five kids will continue that trend.
spk04: Great. And then, team, I know that there was going to be additional analyses in 2-12 in terms of the pulsatility, the PKPD. Like, when should we be expecting that data to be shared with us?
spk02: Go ahead, John. So I think that data will be shared before the end of the year.
spk04: Okay, great. All right, I'll jump back into the queue. Thank you so much, and congrats again.
spk02: Thank you. Yeah, I appreciate it.
spk13: Thank you. The next question we have is from Ed White from HC Wainwright. Please go ahead.
spk09: Good morning. Thanks for taking my questions. The first question is just on those two patients that were seen as outliers in the growth hormone cohort. How many months have they been on treatment?
spk02: Good morning, Ed. And John, you want to answer that question?
spk10: Yeah, so the fastest growing child, the 15.6, we have data through nine months, so six and nine months.
spk02: And 12.8, I think we have six, nine, and 12 months on it. Okay, thank you.
spk09: 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 zero in more on that? And, you know, you did mention the phase three 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?
spk02: John, go ahead.
spk10: So I think we feel pretty confident with the selection of 1.6, right? So we have two separate trials. You know, they are slightly different populations, but they both point to very similar growth rates between the two doses. We know from earlier work that the plateau for growth hormone release is somewhere in between those two doses. And I don't I don't think we're going to gain much by trying to split the difference between those two doses and come up with like a 2.4 mc per kick per day arm. I think the 1.6 should be sufficient. And, you know, the FDA is always going to want us to use the minimum drug to, you know, get a good effect, right? And I think looking at this data, that looks to be the 1.6 arm.
spk02: Okay, thanks, John.
spk09: 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 three protocol? And would you accept those patients under five years? Do you think that perhaps you look at older patients? I just wanted to ask that question.
spk07: Thank you. David, do you want to answer that?
spk11: Yeah, I'll say two things. One is that the much larger patient population in a phase three trial usually results in very good balance for all of these factors. And secondly, we could focus on that and do a three-part stratification per age just to make sure that we get the same number of youngest, mid, and oldest 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.
spk02: Okay, thank you. That's all the questions that I had. Thanks, Ed.
spk13: Thank you, Seth. Ladies and gentlemen, just a reminder, if you would like to ask a question, please press star and then 1. The next question we have is from Catherine Novak from Jones Research.
spk12: Hi. Morning. Congrats on the data. Thanks for taking my question. Just going back to some of the baseline characteristics, I'm curious about, you know, trying to understand how to think about remaining imbalances in characteristics that we might be seeing at 75% enrollment. You know, which of these characteristics, few characteristics would have had the greatest impact in difference on AHV?
spk02: Can I have a follow-up? David, go ahead.
spk11: Yeah, in most of the models, including RENKI, the number one and two are basically the growth hormone dose and age. In the trials, growth and growth 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 particularly 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-prandial height or delta from mid-prandial 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, better growth and lower IGF-1. So they're all factors, but the two, 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?
spk12: Yes, that's very helpful. And then the second one, just thinking about, you know, expansion of
spk07: indications now that you've selected an effective you know what you expect to be an effective dose are you planning to disclose additional loom 201 indications we haven't given any guidance uh yet but but we've had some ongoing plans for quite some time and i think sometime in the near future we'll we'll make an appropriate announcement got it thanks very much for taking my questions
spk13: Thank you. The next question we have is from Yuen Yang from Jefferies. Please go ahead.
spk14: Thank you. So, yeah, hi. 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?
spk11: David? I think that there will be some tweaks to the enrollment criteria for phase three, but just getting more to what kind of standard entry criteria.
spk10: But there will still be the PEM positive entry criteria, right? That has been well validated. Sure.
spk14: Yeah, for sure. Yeah, and that, the screening rate, Would you still stand by PEM-positive kids would be about 50, 60% of all growth hormone deficient kids?
spk11: Yeah, I think it's two questions. One is what percentage of kids are PEM-positive, adiabatic, CHD, and based upon all the available data, that's about two-thirds 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.
spk14: Right. And then if you mention this, I apologize. So in the daily growth hormone injection arm, the two youngest kids showing the highest growth velocity. If you actually exclude those two kids, what would have been the growth velocity in that population, in that cohort?
spk07: John, do you want to answer that? I didn't get the question.
spk10: So one way to, you know, one way to do that is to, instead of using the mean annualized height velocity, is to look at the median. manualized type velocity, right? So that gets you, because that minimizes the impact of outliers. So you get down to about, I think, 10.8 centimeters, eight-month growth, or I'm sorry, six-month growth in that growth hormone cohort. So it does go down pretty significantly.
spk14: Okay. And the last question is on the pattern. So the competition role matter pattern has expired, but you have orphan exclusivity. And you have a use of patent, but what do you, how do you think about the strength of your other patents for 201? Thank you.
spk07: Good question, Eun. And, you know, we do have a use patent. And it's the diagnosis and treatment of not just PGHD, but across the board with all of these growth hormone disorders. 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 executing it 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.
spk02: Thank you.
spk13: Thank you. Our final question comes from Elema Pires from Ross. Please go ahead.
spk01: Yes. What I'd like to ask is were there any other groups in which there were children that were under the age of five that have been enrolled in the study?
spk02: Yeah. John? I'm sorry?
spk10: Yes, there was one other subject. So there were three subjects under the age of five. Two were in the growth hormone arm, and one was in the 0.8 mg per kg per day arm.
spk01: Okay, and maybe a follow-up to that. And after taking out those two outliers, and I know that the sample size is still very small, but 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 Ascendus 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?
spk07: David, one more.
spk10: So, let me. Sure. Yeah.
spk07: Let me. John, you go first and then David, you.
spk10: No, let me just. So, I. Correct, yeah. I gave the wrong, I gave the wrong number, Elmer, the first time. It's, the median for the growth and run arm is 10.5. So, I just wanted to clarify that. I remembered the wrong number. It's 10.5. Okay. And then, David, you could talk about the baseline for ascendance.
spk11: Right, yeah. There's no question that the ascendance phase two trial that we're comparing again, six-month trial, enrolled a much more severely GHG population than we did. It wasn't as deficient as the APCO Phase II trial, but significantly more. So, the somatopacitin trials and the Ascendus trials were pretty comparable in enrolling about 50-50 organic and idiopathic GHG. So, their baseline height SDS was at least an SD lower than in our trial. High GF1 SDS was lower. Delta middle-level height was lower. So, all in all, 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 Somopatzen 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 driven by baseline differences and a couple of outliers in that trial.
spk01: Thank you. Thank you very much.
spk10: The baseline height standard deviation. Yeah. The baseline height standard deviation score, Elmer, for the ascender star was about minus 3.3. Ours is about minus 2. So it's a full standard deviation, kind of closer to the mean, so a much less growth of a deficient population.
spk02: I understand. Thank you very much for clarifying. Thank you, Soph. Ladies and gentlemen, at this stage, there are no further questions in the queue.
spk13: Thank you for joining us and enjoy your day.
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