Good morning, welcome to the Lumos Pharma KOL event. At this time, all attendees are in a listen-only mode. A question and answer session will follow the formal presentations. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player or by emailing your questions to questions@lifesciadvisors.com. As a reminder, this call is being recorded and a replay will be made available on the Lumos website following the conclusion of the event. I'd now like to turn the call over to your host, Rick Hawkins, Chairman and Chief Executive Officer of Lumos Pharma. Please go ahead, Rick. Hi, good morning, and thank you for joining our KOL call for a review of the LUM-201 data presented at the Endocrine Society annual meeting this past weekend, and discuss the opportunity for an oral therapy for pediatric growth hormone deficiency. As a reminder, this conference call is being recorded. In addition, certain statements made during this call are forward-looking statements under U.S. federal securities laws. Please see Lumos Pharma's website for more information regarding our programs and related forward-looking statements. This morning, we issued a press release highlighting the updated interim data from our OraGrowtH210 and OraGrowtH212 trials presented at ENDO this past weekend. Before we get into the discussion of these data, I will first introduce the speakers on this call. It's our President and Chief Scientific Officer, John McKew, is on. We will then make a few comments regarding Lumos Pharma's upcoming clinical milestones. Today, we're pleased to have two key opinion leaders in the field of pediatric endocrinology on the call, who will review data presented at last weekend's ENDO meeting. Our first speaker is Dr. Fernando Cassorla, principal investigator of our mechanistic PK/PD OraGrowtH212 trial, who will be followed by Dr. Michael Tansey, an investigator for our OraGrowtH210 trial. Dr. Cassorla will review some additional data from our OraGrowtH212 trial, and Dr. Tansey will review additional combined data from both OraGrowtH210 and 212 trials. After the discussion, there will be a question and answer session with instructions to follow at that time. Dr. Cassorla is currently Chief of Pediatric Endocrinology at the University of Chile, previously served as the Clinical Director at the National Institute of Child Health, a division of the NIH. He has authored over 200 articles, numerous abstracts in his field, has been a recipient of numerous international awards for his work. Dr. Cassorla received his MD from the University of Chile, completed his residency in pediatrics at the Albany Medical Center in New York, and a scholarship in pediatric endocrinology at the Children's Hospital of Philadelphia. Dr. Tansey is currently Clinical Professor, Department of Pediatrics, serves as Clinical Director for the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Iowa. Michael Tansey has been a co-investigator for one of five clinical centers for the NIH-funded Diabetes Research in Children Network, called DirecNet group, since 2001, and has authored numerous scientific publications on brain function and growth in children with Type I diabetes, and has received several awards for his work. Dr. Tansey received his MD from Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois, and completed his residency in pediatrics at the University of Iowa Stead Family Children's Hospital and his fellowship in pediatric endocrinology at the University of Iowa Hospitals and Clinics. For those who might be new to our story, Lumos Pharma is a clinical-stage biopharmaceutical company focused on rare endocrine diseases. Our lead therapeutic candidate is LUM-201, an oral growth hormone-stimulating small molecule that works naturally within the endocrine feedback loop and is currently being evaluated in several phase 2 clinical trials for moderate idiopathic pediatric growth hormone deficiency, or PGHD. Prior data suggests that LUM-201 has the potential to address up to 10 other growth hormone disorders, representing a total market of approximately $3.5 billion. This does not include China. Currently, the only treatment for PGHD and 10 other growth hormone disorders consists of either daily or weekly injections of exogenous growth hormone. If approved by the FDA, we believe LUM-201 has the potential to disrupt the sizable injectable recombinant growth hormone market. Our interim data from our Phase 2 OraGrowtH210 and OraGrowtH212 trials showed that the LUM-201 produced growth in line with historical data from moderate PGHD and demonstrated a durability of effect out to 12 months. We look forward to our primary data readout in Q4, where we will have 6-month data on a total of 104 patients across both trials, plus 12, 18, and even 24-month data on a subset of enrollees. Finally, we have sufficient cash on hand to get us into Q3 2024, which is well beyond our key data readouts later this year. I'm now going to turn this call over to John McKew, our Chief Scientific Officer, who will review our upcoming clinical milestones. John? Thank you, Rick. I just want to make a few brief comments regarding our upcoming phase II milestones and our anticipated phase III registration trial. Our OraGrowtH210 and OraGrowtH212 trials, evaluating orally administered LUM-201 in moderate PGHD subjects, have completed enrollment, and we expect to read out primary outcome data in Q4. Both of these trials have enrolled subjects based on our predictive enrichment marker, or PEM, strategy. Only PGHD patients with baseline IGF-1 greater than 30 nanograms per ml, and stimulation test growth hormone levels of greater than or equal to 5 nanograms per ml after a single oral 0.8 mg per kg dose of LUM-201 are enrolled in the study, thereby de-risking our trials. Our OraGrowtH210 trial is an 82 patient study evaluating LUM-201 at 3 doses for the comparator arm, where patients are administered a standard dose of recombinant human growth hormone. The purpose of this trial is to evaluate annualized height velocity, or AHV, at several LUM-201 doses and determine the optimal dose for a Phase 3 trial. Subjects will be on therapy for up to 24 months. The OraGrowtH212 trial is a mechanistic PK/PD trial evaluating LUM-201 in moderate PGHD at the 2 higher doses administered in the OraGrowtH210 trial. AHV will be assessed. The main purpose of this trial is to further illustrate the unique natural pulsatile mechanism of action of LUM-201. In this study, subjects will remain on therapy until near adult height. It is important to remember that these Phase 2 trials are not powered to show efficacy, but instead to provide evidence of a drug effect, confirm the unique pulsatile MOA of LUM-201, and serve as a basis to design and determine stratification factors for a Phase 3 trial. That said, in order to set expectations for growth in this moderate PGHD population, we have mined several historical databases where this specific patient population was treated with recombinant human growth hormone. Across the larger data set seen here, the Lilly Genesis PEM positive data set, the moderate slice of the Pfizer KIGS data set, and the idiopathic PGHD data set from a Spanish study. These moderate PGHD subjects all grew between 8.3 and 8.6 centimeters per year at 12 months of treatment on growth hormone. The smaller Merck 020 study assessed annualized growth of PEM-positive subjects at six months. We believe this 8.3-8.6 centimeters per year range is a good proxy for the growth expected on either growth hormone or LUM-201 in the patient population included in our trials. Last November, we read out our interim data on 50% enrollment of our OraGrowtH210 trial. We were pleased to see that our 1.6 mg per kg per day LUM-201 arm grew in line with expectations based on the historical ranges I just mentioned. The growth hormone cohort demonstrated outsized growth, presumably due to two outliers randomized to that arm, impacting the mean in this small sample-sized cohort. These two outliers were two of the three youngest patients in the trial, with younger age being one of the strongest predictors of faster growth on therapy. Other baseline characteristic imbalances between the growth hormone and the 1.6 mg/kg/day arm at the interim data cut are also suggested the growth hormone arm would grow faster than the LUM-201 treatment arm. As you can see here, at 100% enrollment, the imbalances in some of these key baseline characteristics have moderated. We would expect this to lead to more balanced AHV values in our full readout later this year. Because of these outliers and the small ends inherent in any phase 2 trial, we believe historical data serve as a better measure by which to evaluate our phase 2 data. The learnings from our phase 2 trial have proven invaluable. As these phase 2 data mature, our confidence in the potential LUM-201 can demonstrate in a well-designed phase 3 registration trial grows. Based on recent phase 3 trials in PGHD, we anticipate that our registration trial will enroll approximately 180-200 subjects, who have met our Predictive Enrichment Marker baseline IGF-1 cutoff and our peak stimulation GH cutoff based on a single dose of LUM-201. These subjects will be stratified by age and two other factors determined by our phase 2 data and randomized 2 to 1, LUM-201 to a standard daily dose of growth hormone. Subjects will be on treatment for 12 months, at which point annualized annual height velocity will be measured. The FDA have historically determined success in phase 3 trials in this indication by comparing the treatment and control arms' average height velocities at 12 months and requiring a non-inferiority margin of approximately 2 centimeters to deem them comparable. We would expect a similar measurement of success, of success expected for our phase 3 trial. With that brief introduction, I would like to now turn the call over to Dr. Fernando Cassorla. Thank you, John. This paper was presented at the recent Endocrine Society meeting that was held in Chicago over the weekend, and it's called Dose Responsiveness of LUM-201, as Measured by Acute Growth Hormone Response and IGF-1 and Annualized Height Velocity measured at 6 months in the Interim Analysis of the OraGrowtH212 Study in Idiopathic Pediatric Growth Hormone Deficiency. I present this on behalf of our group, our research group at the University of Chile and of Lumos Pharma. These are my disclosures. I will move on to the mechanism of action of this particular drug. LUM-201 is an oral growth hormone secretagogue. It acts as a durable agonist of the growth hormone secretagogue receptor, both of the pituitary and the hypothalamus to stimulate growth hormone release. LUM-201 has been observed to increase the amplitude of endogenous pulsatile growth hormone secretion over 24 hours. A very important differentiating feature versus growth hormone is the natural negative feedback mechanism, which limits the potential for hyperstimulation and excessive increases in IGF-1, because it's preserving the negative feedback mechanisms that operate normally. LUM-201 promotes pulse-per-day growth hormone secretion in a selected pediatric growth hormone deficient population, I emphasize the word selected. These are patients with moderate idiopathic pediatric growth hormone deficiency, whose axis is responsive to this particular secretagogue. These are the vast majority of patients that we see in our clinics. Patients who are short, who are not growing well, and who have a response to provocative test, stimulation tests that are intermediate, not really exceedingly low, as would be the case in severe growth hormone deficiency, but moderate, with responses that are showing that the pituitary is actually working in these patients to some degree, but not to the degree to sustain adequate growth. Our Phase 2 pulsatility PK/PD study design is as follows: We recruited 22 naive idiopathic pediatric growth hormone deficient patients, prepubertal patients, with a standard growth hormone stimulation tests, that had a response between 3 and 10 nanograms per ml, following the concept that these would be patients with moderate growth hormone deficiency. In addition, they had a peak growth hormone to a single LUM-201 stimulation above 5. Actually, in fact, most of these patients, of the 22, had levels that were way above 5, but 20, 25, a very robust response to the acute stimulation with this drug, even though they had a relatively poor response to the growth hormone, classical growth hormone stimulation tests. Indicating that they have a responsive pituitary. At baseline, we measured their height, their serum IGF-I levels, and they underwent a period of 12 hours of measurements of blood samples every 10 minutes, in order to measure growth hormone pulsatility. They were randomly allocated to either a dose of 1.6 milligrams per kilo per day of the drug, or 3.2 milligrams per kilo per day. Equal numbers, 11 and 11, for a total of 22. At six months, we measured again height, serum IGF, and we performed another pulsatility study with blood samples obtained every 10 minutes for 12 hours in these patients in order to look at pulsatility of growth hormone secretion. The idea is to continue treating these patients until near adulthood. It's an open-label study with an N of 22. These patients are growth hormone treatment naive. They had to have the classical kind of characteristics that would make them candidates for treatment, a height below two standard deviations, delayed bone age, a peak response, as we said before, to a clonidine stimulation test between three and 10 nanograms per ml. This was all conducted at a single specialized clinical site at the University of Chile, where I work. The primary endpoints were to assess LUM-201 effect on endogenous growth hormone pulsatility and annualized height velocity, and to evaluate PK/PD in these children. The goals are to confirm prior PK/PD data in adults and subset of the previous study, and to support future regulatory filings and commercialization. Now, if we look at the questions that we posed for this particular study, these are the following: Does LUM-201 dose-dependently augment endogenous growth hormone pulses in patients with idiopathic pediatric growth hormone deficiency? Number two, will increased amplitude of growth hormone pulsatility and increase in IGF-I serum levels within the normal range improve height velocity? Number three, is the effect on annualized height velocity durable out to 12 months? I will show you here the baseline demographics of our patients. This is a subset of the 22 patients, a total of 15. Here are the ages, about the age of 8 for both groups. Heights, about 2.3 standard deviations below the mean. The serum IGF-I level, between -1, about approximately -1 or -0.8 for the 3.2 milligram group. The mid-parental heights are shown here. The delta, the mid-parental height, that is to say, the distance that these patients had to their midparental height, is shown also on this slide. The bone age delay, approximately 1.5 years, or 1.83 years. The BMI, and the distribution according to gender, with a slight predominance of more boys in the higher dose group. Even though this was a study that is randomized and prospective, there were minor differences between the two groups. There's a slight imbalance in age and gender. There's a slight imbalance also in delta below midparental height, BMI, and bone age delay. We expect that as we complete the study with all 22 patients, these minor differences are gonna be attenuated as the study includes all the 22 patients. Now, these are the annualized height velocities before and after 6 months of LUM-201 administration. You can see that the baseline height velocity is approximately 5 centimeters per year as a mean, and it went up to about 8 centimeters per year after 6 months. In light blue, are the patients that received the 1.6 milligram per kilo dose. In darker blue, are the patients who received the 3.2 milligrams per kilo per dose. It's clear that this drug raised the annualized height velocity from baseline after 6 months on therapy for both the 1.6 milligram per kilo cohort and the 3.2 milligram per kilo cohort. No statistical difference exists between the 2 cohorts at each time point. As expected, greater growth response was observed in patients with lower baseline growth velocity, as shown here in this particular patient, and had the lowest growth velocity at baseline and had a pretty robust response to therapy. If we look at the durable response beyond 6 months up to 1 year, you can see it again in light blue, the patients with the low dose, in dark blue, the patients with the high dose. They tend to increase quite dramatically by six months, and the response remains quite stable at nine months and at 12 months, as shown also on the bar graph shown here on the right, in which you can see that the baseline growth velocities are a little less than five to begin with, go up to about 7.5-8, and remain in that kind of range even up to 12 months, even though the N, the number of patients followed, has obviously been a little lower as the study is still ongoing. We do see a durable response. How does this compare with some of the data that have been shown for growth hormone treated patients? Here are data from the paper published by Dr. Ranke from Germany, a study where patients treated with growth hormone, in which you can divide them into severe pediatric growth hormone deficiency on the upper panels, and moderate pediatric growth hormone deficiency on the lower panels. Those are the ones that are closest to the patients that we see in this particular study. For the less severe patients, during either the first year, particularly the first year, you can see that the age is here on the horizontal axis. For an age of about 8, the mean growth velocity, annualized growth velocity, is approximately 8 centimeters per year, even though some patients grow more and some patients grow less. The mean that we observe in our study is quite comparable to the one that was observed by Dr. Ranke in a cohort that involves a large number of patients treated with growth hormone, indicating that these patients with a severe growth hormone deficiency, just like ours, and at about the age of eight, tend to grow during the first year at about eight centimeters per year, just like our patients. If we look at serum IGF-1 levels, that's another beauty of this study. We see that the baseline IGF-1 levels, for both the 1.6 and 3.2 doses are relatively low. They go up after six months, and a little bit more so with the 3.2 milligram dose, but they essentially increase quite a bit. If you look at it in serum, absolute numbers, or if you look at it in terms of the height, I mean, of the IGF-1 SDS levels, there's again a change from about -1 or close to -1 standard deviation scores below the mean, to approximately the mean for the 1.6, or slightly above the mean for the 3.2 milligrams. Again, we don't see an overshoot of very high IGF-1 levels that might be observed with human growth hormone therapy, because there's preservation here of a natural feedback that allows the system to continue checking and balancing the stimulation of the pituitary by the secretagogue, and therefore, the IGF-1 levels increase but don't go beyond what would be expected as a physiological level. We conclude that there's a significant increase in serum IGF-1 levels that remains within the normal range. We want to emphasize that point. Based on the mode of action of LUM-201, these data support the physiological IGF-1 feedback, as we just indicated. Now, I want to show a couple of representative cases. A patient A, treated with 1.6 milligrams per kilo per day, serum IGF-1 levels, area under the curve, in samples obtained every 10 minutes for 12 hours, and the height velocity at baseline. The change that we observed following the administration of the drug at this particular dose, 1.6 for 6 months, in which you can see that there's a 61% increase in serum IGF-1 level. There's a 33% increase in the Q 10 minutes sampling area under the curve for growth hormone, and there's an increase from 5.6 up to 7.9 centimeters per year on therapy. You can see that the pulsatility, shown in blue, changes quite a bit after 6 months of therapy. If we move on to a patient who received 3.2 milligrams per kilo per day, here are the baseline serum IGF-1 levels, the area under the curve, and the height velocity before therapy. You can see the pulsatile pattern before therapy in this particular patient. After 6 months of therapy, you can see in blue that there is a larger amplitude of these growth hormone pulses following therapy, and the IGF-1 level increases by 131%. The Q 10 minutes sampling area under the curve for growth hormone increases 91%, and the height velocity in this particular case goes up from 4.4 up to 9.4 centimeters per year. Quite a significant increase during this particular period of LUM-201 administration. The interim analysis safety profile shows that there's no treatment-related adverse events, no meaningful safety signals observed in either laboratory values, adverse event data, or in electrocardiogram values. The most common adverse events, transient decreased appetite, 76%, usually a month or two, they show an increase in appetite, not for the full 6 months. Pain or a full year, pain in extremity, 17%, arthralgia, 12%, abdominal pain, and influenza in about 6%, most likely unrelated to the drug. We conclude, therefore, that at the time of interim analysis, LUM-201 was well tolerated and showed no significant safety signals. Now, the questions are: Does LUM-201 dose-dependently augment endogenous growth hormone pulses in patients with idiopathic pediatric growth hormone deficiency? The answer is yes. Will increased amplitude of growth hormone pulsatility, driving increased serum IGF-1 levels, improve height velocity? The answer is yes. Is the effect on adult annualized height velocity durable out to 12 months? The answer is also yes. I would like to conclude with a slide showing the conclusions. Based on this interim analysis, OraGrowtH212 demonstrates that growth acceleration is durable through 12 months in our study population, prepubertal, treatment-naive pediatric growth hormone deficient patients. No statistical difference exists between the cohorts at any time points. Due to some baseline imbalance, the optimal dose cannot be determined from this data set. We plan to continue the OraGrowtH212 study until near adult height is reached, and the observed growth is in line with recombinant human growth hormone, historical growth of 8.3-8.6 cm per year, as shown in the slide, from kids and also Genesis in the small idiopathic pediatric growth hormone deficient patient. This is a picture of our group here at Santiago, Chile, and thank you very much. I will turn the podium now over to Dr. Michael Tansey. Well, good morning, everyone. Again, this is data that was presented at the recent Endocrine Society meeting in Chicago, and I think was very well received. The title of this presentation was Growth Response of Oral LUM-201 in OraGrowtH210 and OraGrowtH212 trials in idiopathic pediatric growth hormone deficiency, combined analysis, interim analysis data. The next slide, please. And one highlight on this picture, this is just an example of a girl taking actually a dose of study medication that you see there. I thought that was important to highlight for our audience there at the meeting. Next slide, please. These are my disclosures that you have there. Next slide. I also want to make sure that I acknowledge all the contributors that participated and are authors on the OraGrowtH210 data set here. You'll see a variety of investigators from across the United States, as well as from Poland and Australia. At the bottom again, the members from the Lumos team as well. Next slide, please. The other, again, data that I'm going to be presenting is from the OraGrowtH212 abstract, which Dr. Cassorla just presented for his team at the University of Chile. Next slide, please. The objectives of the presentation are to report the growth response, analyzing these combined interim analysis data from each of these 2 phase 2 clinical trials, which are studying LUM-201 at 2 different doses, including the 1.6 milligrams per kilo per day and the 3.2 milligrams per kilo per day. What we did was we took the interim analysis data from both of these studies and we combined and analyzed that, and we calculated annualized height velocity, which I'll be showing you. Also some of the baseline demographic data were analyzed for the 2 combined cohorts as well. On the top right, you see there again, we're talking about both combining data for the OraGrowtH210 and OraGrowtH212 trials. Next slide, please. Again, Dr. Cassorla reviewed this. I won't go through it in detail, but I wanted to highlight for our recent audience that again, this is not growth hormone that we're talking about. This is a growth hormone secretagogue. This acts on the growth hormone secretagogue receptor, this GHS-R1a, to actually stimulate growth hormone release. Again, a different drug than growth hormone, which again, a lot of pediatric endocrinologists have seen that data over many years and are very, very familiar with growth hormone. Again, this is, I think, something new for our audience there. As Dr. Cassorla highlighted, we know that LUM-201 has been observed to increase both the amplitude of endogenous pulsatile growth hormone secretion over 24-hour periods. Again, a differentiating feature versus kind of routine growth hormone, which we prescribe for many patients, is that the natural negative feedback mechanisms are intact. That limits this high IGF-I levels, which are sometimes seen in traditional recombinant growth hormone therapy. Again, I'm going to highlight here that LUM-201 produces this pulsatile growth hormone secretion in a selective pediatric growth hormone deficiency population. The kind of slide on the left there just shows kind of the mechanism, again, of action, where we see LUM-201 acting on receptors at the level of the hypothalamus and pituitary, produces this pulsatile response in growth hormone secretion, which is very physiologic, again, as Dr. Cassorla highlighted. What we have, again, as a result of this, we see increase in IGF-I, which has the ability to negatively feedback on the hypothalamus and pituitary. Next slide, please. Again, in terms of deciding who we think is going to respond to this medicine, and this I think is very helpful in this study design, kind of identifying who's going to be responding. What we did was looking at a single dose of LUM-201 as kind of a stimulation dose, to identify those who we kind of think of as being positive for these predictive enrichment markers or negative for these predictive enrichment markers. Again, we look at that response to a single dose, and on the left side, we see that the PEM positive kind of group of patients and those characteristics included a baseline IGF-I of over 30. A stimulated growth hormone level of over 5 in response to, again, the single dose of LUM-201, and what we would call kind of a functional but perhaps reduced, hypothalamic pituitary growth hormone axis. Again, noting the method of action of LUM-201 on the receptors at the hypothalamus and pituitary. These responders to LUM-201, or positive responders, again, typically have what we'd call kind of moderate idiopathic pediatric growth hormone deficiency, and that's probably about 60% of our pediatric growth hormone deficiency population. If we look on the right side of the slide at those who are Predictive Enrichment Marker negative, those subjects had a baseline IGF-1 of less than 30. That stimulated growth hormone levels of LUM-201 was less than 5, so again, indicating that they're not responding, and kind of a non-functional hypothalamic pituitary growth hormone axis. Again, not really responding. These are patients who may have what we would consider to be kind of severe organic pediatric growth hormone deficiency, and that may be about 40% of the total pediatric growth hormone deficiency population. Next slide, please. Again, looking at OraGrowtH210, our Phase 2 data for this. Again, these are patients who were all naive, idiopathic, pediatric growth hormone deficiency patients. They all had standard growth hormone stimulation tests. Like I mentioned earlier, for these PEM-positive patients, they had a peak growth hormone of over 5 to the single dose of LUM-201. These subjects were then randomized to 4 different arms, including LUM-201, at a dose of 0.8 milligrams per kilo per day, a dose of 1.6 milligrams per kilo per day, and 3.2 milligrams per kilo per day, and daily growth hormone injections. The study is kind of going on. We're following with height and IGF-1, and then looking at a long-term extension study as well. We have 82 subjects, again, including only those who are PEM-positive, prepubertal pediatric growth hormone deficiency patients, all naive to any growth hormone treatment. Inclusion criteria again, included that LUM-201 growth hormone stimulated response of over 5 and baseline IGF-1 of over 30, had to have that diagnosis of idiopathic pediatric growth hormone deficiency, a height of less than 2 standard deviations below the mean and delayed bone age. We have 45 clinical trial sites across the world, again, this is gonna be a 24-month study. Our primary endpoints are annualized height velocity, with goals of respectively confirming utility of our PEM strategy that I outlined previously, and to help determine our optimal phase 3 dosing for this drug. Next slide, please. Dr. Cassorla kind of reviewed this data. This is the OraGrowtH212, phase 2 trial again, which is looking at pulsatility and PK/PD study. Again, same naive, idiopathic, pediatric growth hormone deficiency patients. You'll see that some of the criteria were similar in terms of having a growth hormone stimulation test and looking at growth hormone response to a single dose of LUM-201. As he mentioned, they're looking at height, IGF-1, and then monitoring growth hormone sampling during the study. These subjects were randomized to 1.6 or 3.2 milligrams per kilo per day of LUM-201, and again, monitoring over time and dosing to near adult final height. He has 22 subjects in that study, as he mentioned. Again, all who are have prepubertal pediatric growth hormone deficiency and naive to growth hormone therapy. Inclusion criteria for that part of the study as well, included height, less than -2 standard deviations below the mean, delayed bone age, and peak growth hormone response to clonidine stimulation tests between 3 and 10. Dosing to near adult height and again, only at the University of Chile in Santiago. Primary endpoints for the 212 study include looking at LUM-201 and seeing the effect on endogenous growth hormone pulsatility and annualized height velocity and evaluate PK/PD studies in children as well. Goals are to confirm prior PK/PD data in adults that has been done in adults and the subset of the Merck 020 trial and support future regulatory filings and commercialization. Next slide, please. This is looking at the baseline demographics for both OraGrowtH210 on the left and OraGrowtH212 on the right. Again, all these subjects were about 8 years. They all were kind of less than 2 standard deviations below the mean. You see, they had delays in bone age. BMIs were in normal range and again, about 60/40 male/female. These are the data that represent patient data collected at the time of the interim analysis calculation, and there were no statistically significant differences between cohorts in each trial. Next slide, please. This slide is looking at annualized height velocity. Again, Dr. Cassorla mentioned some of this from the 210 trial. If we look at, the Y-axis of this slide here, we see mean calculated annualized height velocity in centimeters per year, and then we're going in through time on the X-axis. What we're seeing is a change again, which is kind of sustained over time from baseline with response to that annualized height velocity. We think that, our interim data would demonstrate that LUM-201 produces a durable annualized height velocity response, which so again, we're seeing that all the way out to 12 months in our data for these patients with moderate pediatric growth hormone deficiency. We're also seeing that, with both the 1.6 and 3.2 milligrams per kilo per day dosing really produces a clinically meaningful increase in annualized height velocity from baseline. Next slide, please. This is our interim analysis, safety data from the combined trials. Showing you data for both 1.6 and 3.2 milligrams per kilo per day. Really what we saw is that there were no treatment-related serious adverse events. There were no dropouts from our subjects due to SAEs or AEs. We did not see any meaningful safety signals in lab values, adverse events data, or EKG values. Treatment-related AEs we saw in both groups included increased appetite, as Dr. Cassorla mentioned, that was not kind of permanent, but was seen early on. Arthralgias or what people described as kind of growing pains, pain in extremities, occasional abdominal pain and bone pain as well. Next slide, please. In conclusion, again, as growth velocity was comparable for the two different doses, the 1.6 and 3.2 milligrams per kilo per day, the analysis of the combined, again, interim analysis data might suggest 1.6 milligrams per kilo per day is the optimal dosing for a phase 3 trial. G oing to 3.2 milligrams per kilo per day did not really seem to, at least in our, again, our data, so far, did not really offer meaningful improvement or efficacy. Our final dose determination will await full, final dataset analysis for both studies. Again, we did not see any treatment-related Serious Adverse Events, no discontinuation due to Adverse Events, no meaningful safety signals observed in lab values, Adverse Event data or EKG values. I'll kind of wrap up just with a few final kind of notes and kind of highlights. Again, as an investigator in the study, it's been a fun study to be a part of. There's been a lot of interest from families. I think as a lot of people on the call might be aware, people hear about growth hormone and they may be interested, and then they hear about injections, and that gives people pause sometimes about, starting injections on people. We know this from many other studies as well, whether we're talking about diabetes and insulin and, resistant to, start injections of any type, I think is kind of universal among a lot of subjects. People were really interested in having an oral therapy as an option for them. Very excited about that. Very interested, and they're asking me: When is this going to be approved? When can we use this for everybody? W e have to kind of caution them, that's going to take time. o ne of the thoughts I had when we were kind of looking at starting the study, I was like: Well, maybe we're going to have kids, having issues taking these pills. But again, for my part, that has not been an issue at all. I think that, again, is due to probably the size of the pills being relatively small in our study, and we've not had any issues with that at all. That concludes my kind of portion of the data, and I will turn it back over to the rest of the team. Thank you. Thank you, Dr. Tansey. Corey, I think you're gonna open up some questions to our analysts who are on. Tara is going to moderate the live questions from the analysts, and then I'll do the written questions. Okay. Go ahead, Tara. Perfect. At this time, we'll be conducting a Q&A session with our speakers. As a reminder, if you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player or by emailing your questions to questions@lifesciadvisors.com. Please hold for a brief moment while we pull for questions. Our first question comes from Yasmeen Rahimi from Piper Sandler. Please go ahead, Yasmeen. Sorry. First of all, thank you so much, team, for organizing this event. Thank you for our phenomenal KOLs being on the call with us and sharing their thoughts. A few questions. Maybe the first one is, I know you shared the data at month 12. Could you maybe comment on what the IGF levels looks like in month 12? I know it was reported for month 6. That's question 1. Question number 2 is, could you guys maybe speak broadly about translation of studies when we go from a phase 2B study to a larger phase 3, historically speaking, because that's going to be 1 of the key questions for a lot of our investors on the hills of the data in the fourth quarter. Then thirdly, is there an opportunity, given that you're going to have a robust data set, and given what you just said, how much interest exists among families, that there's an opportunity of significant participation into a phase 3 study, and that maybe it could expedite the time of enrolling the study in any way? I know it's premature, but the commentary about significant patient and family interest makes us analysts think that, enrollment could be even expedited. I'll jump back into the queue, and thank you again for organizing it and allowing me to ask my questions. Okay, I think the first question has to do with the IGF-I levels at six months and versus a year. I don't know, Fernando, if you want to start with that? Sure. Your studies. Yes. We have some limited data regarding serum IGF-I levels at 1 year, they remain very similar to what they are at 6 months. The serum IGF-I levels go up. They reach either the mean for age or slightly above the mean for age at 6 months, they remain in that range until 12 months. Some patients are now reaching the 18-month mark, very few. Again, we're looking with a lot of interest in what happens with their serum IGF-I levels. The limited data that we have so far indicates that the serum IGF-I levels remain above the mean or at the mean, compared to about -1 at the time they started. Dr. Tansey, do you want to add anything to that? No, no, I, like I said, I didn't present a lot of IGF-I data at 12 months, but again, I think we're seeing improvements in IGF-I and a good IGF-I response, I would say, is my impression. Yep. I, yes, I think you mentioned how we translate this to a full study. I think the pivotal trust study, the regulatory pathway is pretty clear in our growth hormone space. I think a 180-200 patient study, all patients on drug for a year at least. Annualized high velocity at 12 months is the endpoint. Same patient population using our de-risking the study with our PEM positive patients only. I can tell you that, doing this particular study was really not an easy study to start in the middle of the pandemic. Wouldn't recommend that to anyone, but our enrollment went exceptionally well, I think because of Dr. Tansey just said, and that is the interest of the patient population and the families that participated in it for in oral. To answer your question on a phase 3 study, based on these data, we've already begun our planning for that phase 3 study, and this would be a large multinational study. Obviously, same patient population, PEM positive. I think that, once again, Dr. Tansey's comment about a really keen interest by families in an oral therapeutic, will serve us well. I want to also remind you that, when most of the long-acting growth hormone studies were being done around the world, they were dominated by, three large companies who were competing for the same population. Those studies are over, so we have a very nice, even or clear playing field at this stage in terms of our access to the patient population. Dr. Tansey, I don't know if you want to add anything to that in terms of the interest by the patient population and the families? No, like I said, I think there's a lot of interest, and we're always thinking about, I know, recruitment in clinical trials, and that's a significant factor. We set up goals that we have. T here are other trials, of course, going on now for patients with pediatric growth hormone deficiency. Again, I think there's something very new here, very novel here. I think for, like you mentioned, this select patient population, who have what we kind of call this partial, pediatric growth hormone deficiency, which is a substantial amount, that, I think this would generate a lot of interest and will help with recruitment certainly for phase 3 trials. I think, like you said, I think patients are excited. I think, clinical centers and investigators are always excited to have a new therapy like this to offer patients in their clinics as well. Let me jump in here for a second. I'm old enough to recognize the time when the idea of an oral therapy for pediatric growth hormone deficiency appeared to be like an impossible kind of idea. This has been going on for quite some time. The pediatric endocrine community has had this kind of hope that at some point a drug that would be orally available to produce more growth hormone from the old child would become a possible kind of treatment for this. Now we're beginning to open up the door, now with some clear findings that I think will also help recruitment for phase III. When we were confronted with recruiting patients for Phase 2, the obvious question for the families was: Is this going to work? We had to say, "Well, we're not sure. We think it may work, but we've got hope that this will help your child grow better." Now, we have more than hope. We actually have some numbers. Therefore, when we see patients that may become candidates for the Phase 3 trial, the obvious question is going to be a little easier to answer, because we're going to tell them, "Look, we've got some data." It's over, I mean, it's a little bit over 100 patients altogether. I t's 82 patients in OraGrowtH210 and 22 patients in OraGrowtH212. That's 104. That's a substantial amount of information indicating that these patients grow better on this particular agent. Therefore, when they request some kind of prediction as to what's gonna happen. Mm-hmm. even though we cannot tell them, we cannot guarantee to the families that they will grow better. Showing the data from the phase 2- Mm-hmm. Indicating to them that we have over 100 patients. Mm-hmm. that have grown better on this drug in the initial phase 2 trial, I think will help a lot with the phase 3 trial. Yeah. That's gonna be more clear for them. Thank you so much. That was very helpful. I'll jump back into the queue. Thanks for the questions, Yas. Our next question comes from Pete Stavropoulos from Cantor Fitzgerald. Please go ahead, Pete. Hi, Rick and team. Congratulations on the data presented at ENDO, thank you for taking our questions. First question I have, from Dr. Cassorla's presentation on slide 18, can you help us understand from a mechanistic perspective or perhaps it's just influenced by the baseline demographics? Why the 3.2 mg/kg group in the OraGrowtH212 study, had a sharp rise in AHV in the first 6 months compared to the 1.6 mg/kg group, then there was a drop-off for the 3.2 mg group that came more in line with the 1.6 mg group between months 6 and 12. Yeah. It's a very interesting question. Our interpretation is that the patients who ended up on the 3.2 arm were slightly more growth hormone deficient than the patients who were in the 1.6 and were growing at a slower rate. If you start from a slower growth rate, it's likely that the response will be greater just as it is for growth hormone therapy. I think this has to do more with the slight imbalance in the two groups with the current number of patients that have been evaluated, that may change once we reach all 22 patients getting to the 1-year mark. More than a change, more than a difference than the actual dose, because the other interpretation is that actually the 3.2 dose is better than the 1.6 dose. We don't think that's right, because there's a slight imbalance in the groups at the beginning, and therefore, we ended up having children who were growing worse than children who were growing on the 1.6. This difference in baseline characteristics may be the reason whereby the patients on the 3.2 ended up growing a little better than the 1.6 at 6 months. It's mostly, we think, a question of a slight imbalance in the groups at baseline, rather than an intrinsic difference in the dosing of these particular patients. Okay. You know, with that in mind, you know, can you just sort of speculate if that same phenomenon, you know, would have been observed if the 3.2 was actually given 1.6? Basically what I'm driving at, you know, for those exact patients, you know, would you have left efficacy on the table with a 1.6 mg dose? Yeah, I think so. Again, it's early to say. We're not in a position to say unequivocally that actually one dose is better than the other one. We believe it's not, but we need more data in order to really arrive at that conclusion. As of now, we believe that the differences are mostly related to changes, to differences in baselining for characteristics rather than in the dosing. With the current information available, we are very careful about saying that at this point, we cannot conclude that one dose is better than the other one with the information available at this stage of the game. Okay. Taking into consideration the safety profile and tolerability, you know, would you see a reason not to actually push it to 3.2 versus 1.6? Again, I think we want to use the lowest, most effective dose that we can possibly provide to our patients. In general, as Dr. Tansey was saying, this drug is very well tolerated. The pills are very small, and therefore, when you go up in dose, it's not as if they're taking a huge amount of pills compared to a very small amount of pills with a lower dose. I would say that at this stage of the game, it's early to tell. It's most likely unrelated to dose, the difference that we see, but we cannot exclude for sure that there won't be a slight difference in height velocities once all the group has completed the 12-month period of intervention. We are showing data on 15 out of 22 patients. Even though that's still like, 70% or so, the other 30% may change things a little bit, and maybe there will be a better balance between the two groups. Remember, these patients were allocated randomly to one of the two doses. By definition, the differences should be quite minor once all 22 patients are evaluated at the end of the 12-month period. Okay. Thank you. One question again for Dr. Cassorla and Dr. Tansey. You know, being at ENDO 2023 and other endocrinology-focused conferences, you know, throughout the year, so when you speak to your colleagues about LUM-201, you know, its mechanism of action, you know, how it's differentiated from the standard of care, recombinant growth hormone, you know, as well as having the precision medicine approach, and being able to identify likely responders, using the PEM, you know, what is their reception of this candidate and approach, and the data presented to date? You know, especially compared to recombinant growth hormone. ... Michael, do you want to go first? Sure, I can start. Again, I think there was good discussion about this. You know, there's, I think our presentation was very well attended, I would say, and I thought we had good questions from the audience. I think that there is a high level of interest among our colleagues at other centers. I think people are interested, like you said, in kind of a personalized medicine approach, that this is a new therapy that is different from what they've seen before. I think people are seeing this, the data as being fairly comparable to growth hormone. I'll turn it over to Dr. Cassorla It's interesting, anecdotally, some of the colleagues who actually work for the growth hormone pharmaceutical industry, who we've known for many, many years because they are pediatric endocrinologists, just like we are, expressed a lot of interest and actual, I would say, appreciation for this kind of study. It's not as if we've got, you know, a very skeptical view of this. There's always gonna be people who say, "Well, these patients are not truly growth hormone deficient." We might spend the next 2 or 3 days discussing how to diagnose growth hormone deficiency, but in essence, these patients with what would be called moderate or partial growth hormone deficiency, are the vast majority of the patients that we see in our clinics. Dr. Tansey and myself, we will tell you that actually, out of 10 patients who are short, who may be candidates for growth hormone therapy, more than half of them will not have classical severe growth hormone deficiency. I would say it's less than 40%, maybe 25%. Again, a substantial number of these patients have this partial form of growth hormone deficiency, that according to the assay used to measure growth hormone, according to the test that was performed to stimulate growth hormone release, may or may not pass the cutoff mark to make this diagnosis and to get the insurance company to pay for the drug. These are the vast majority of patients, and I think we all recognize, whether we are investigators of this particular study, or whether some of them work for the growth hormone industry, that actually there is a need to have an alternative. As mentioned by Dr. Tansey, many of these patients and families are reluctant to the injections and to the cost. I might add there's two major factors. In South America, we don't have the luxury of having, you know, third-party payers for this, so families end up paying for this out of their pocket. There's an issue of cost, but there's also an issue of convenience. You put those 2 things together, and it's likely to be very appealing for children who have partial growth hormone deficiency to be treated with a pill rather than to be treated with an injection for many, many years. These are treatments that are not done for 2 or 3 months, but they're done 5, 6, 7 or 8 years, many times. Depending on the age at which you start therapy. My perception is that there's interest in this, that we all recognize there's a need for an alternative, and that they are looking at this with interest. Obviously, we wanna see more data before we arrive at a very firm conclusion, but we have to accept that the data so far looks quite promising. I think that was the impression of most of the people who I talked to after the meeting. As Michael was saying, this was a very well-attended session. The, you know, the hall was totally full, and the people who are there are mostly practitioners, are people who treat patients with short stature, and they want to know about alternatives, and this may be one that is becomes a reality in the not-too-distant future. Just to kind of add another comment to Dr. Cassorla. As he mentioned, this is often a long-term therapy that we're looking at using. Again, right now, our only FDA-approved option for this group that we're talking about, of this kind of mild growth hormone deficiency, is growth hormone. We're talking about keeping these kids on growth hormone, again, it could be 5, 8, 10, 12 years even, so depending upon the age of diagnosis. It's a very long-term therapy. Again, I think that's when we talk to families and patients about this, I think that's part of the burden that they're thinking about, is that, you know, a daily injection for the next 5, 8, 10, 12 years, that's significant and something that they're really considering. I, that's I think adds to this interest in an alternative to our really only therapeutical option that we have right now. Great. Thanks for the questions, Pete. Our next question comes from Leland Gershell from Oppenheimer. Please go ahead, Leland. Yeah, hey, thanks for hosting this event and for taking my questions. A couple of questions for both of our physician experts. With respect to excess IGF-I in response to growth hormone therapies, to what extent is that an issue in clinical practice? To what extent does that limit, you know, perhaps therapy, you know, among some patients? I have a follow-up question. I'll start, then I'll let Dr. Cassorla jump in. You know, I've been prescribing growth hormone for a little over 20 years, not nearly as long as Dr. Cassorla of course, but, you know, we didn't always use to measure IGF-1 with growth hormone therapy. This is kind of a, I wouldn't call it a recent, but a newer development that we monitor IGF-1, and it really is something that we need to do regularly, and it's part of our standard of care right now, and it is something that we pay attention to and are frequently making adjustments to growth hormone dosing based on IGF-1 level. Again. The main reason, again, if we're making an adjustment to our growth hormone dose based on IGF-I level, the vast majority of the time, in my experience, that's because of high IGF-I levels that we're seeing. If we're seeing very low IGF-I level, our first thought is, you know, are they really getting it? Are they taking, or are they having problems giving the injection? Which again, leads back to what we have discussed before. You know, IGF-I monitoring is I'll say it's a little bit of a burden for families, right? Anytime we're getting blood work on these kids, I think they see that as a burden. I think, again, having an alternative therapy which doesn't impact and lead to those elevated IGF-I levels can be helpful. I'll turn it over to Dr. Cassorla as well. Well, I agree with Dr. Tansey. Let me just say that showing high IGF-I levels during growth hormone therapy is not that unusual. Unfortunately, many times the dose of growth hormone is pushed by the physician in an effort to try to improve height velocity. Even in practice, and certainly in the published literature, there's many papers in which IGF-I levels linger about 2 standard deviations above the mean for a given patient on growth hormone, sometimes even higher. Depending on the patient population that you're treating, this may happen particularly with small for gestational age children who are not growth hormone deficient. Many times the temptation there is to use a relatively high dose, and using a relatively high dose will get your serum IGF-I levels at about 2 plus 2, maybe 2 plus 2 and a half standard deviations above the mean. That is something that we do not believe is that kind of acceptable in the sense that it's possible that this will have some kind of long-term effects. The normal ranges occur for some reason, and when you push levels of serum IGF-I levels beyond the 2 standard deviation mark, it's possible that your patients will pay, end up paying a price later on in life. There's any of a number of possible possibilities there. I won't get into that. This does happen quite frequently with growth hormone treatment because there's a tendency to push the dose a little higher, and if that happens, the patient may or may not grow a little better, but the serum IGF-I levels are gonna be hovering around the plus two standard deviation mark, and sometimes a little more. This is a real problem in practice. It's not as if it never occurs. And it does occur, and we are not absolutely certain what the meaning of this represents for the patient, for a growing child who has another 60 or 70 years to live, and having gone through relatively high serum IGF-I levels during a long period of infancy and potentially adolescence may not be all that innocuous. All I'm saying is that this is a real problem. Most physicians are gonna be very careful, and once they reach that level, they may cut back a little bit the dose, but this doesn't happen all the time. The short answer to your question is yes, this does happen. It's not that infrequent, and we're not absolutely certain what this means, but it may have some negative consequences later on in life. Okay, that's helpful. thank you. My, my next question is, you know, in Dr. Tansey's presentation, we saw the baseline, demographic information for the studies for both doses. With respect to those data, and particularly with the baseline height, you know, SDS, you know, how well does that represent, you know, patients with true GHD versus perhaps another cause of short stature, with respect to those patients who've been enrolled in the 201 studies? Sure. Both physicians. Thank you. I think, you know, what we have seen, you know, in both the 210 and 212, you know, trials that, you know, our baseline data showed, I think, an initial height SDS of around -2.1 to -2.3, which is pretty common. That is, I would say, pretty consistent with a lot of the kind of expected heights that we may see families coming in with who are diagnosed with growth hormone deficiency. Again, I think if, you know, for patients who have severe growth hormone deficiency, depending upon when they are caught in that process, they may be a little bit even smaller, have a lower height SDS. I think this is pretty typical for what we would see, you know, in terms of kids coming in with growth hormone deficiency, in terms of that height SDS. Okay. Thank you very much. Sure. Thanks for the questions, Leland. Our next question comes from Catherine Novak, from Jones Trading Institutional Services. Please go ahead, Catherine. Hi. Congrats on the presentation. Thanks for taking my question. My question is for Dr. Tansey and Dr. Cassorla. Can you both comment on what% of the patients in your practice would fall into this moderate idiopathic PGHD category? You know, from a physician's perspective, do you anticipate any additional burden to screen patients for these positive enrichment markers? Or do these tests fall under the scope of how you currently diagnose PGHD? Thanks. Yeah, go ahead and start with Dr. Tansey, if you will. Sure. Sure, I'll go ahead and start. I think, you know, in terms of testing that are done compared to the clinical trial that we did. Again, we typically are doing growth hormone stimulation tests for all these patients. That's often required for insurance by us. It also gives us good information about, again, are we dealing with what we would kind of call, you know, the severe growth hormone deficiency or the moderate? We would determine that based upon those stimulated growth hormone values for the growth hormone stimulation test. I mean, the rest of the things that we're doing in terms of study, you know, kind of data that we're capturing, bone age X-ray and height measurement, IGF-I measurement, those are all very routine. I don't think this adds any extra burden. I think the only thing that was a little, you know, unique and that would not be done clinically now, of course, is looking at a test dose to LUM-201, right? Looking at a growth hormone-stimulated response to LUM-201. That is not part of our kind of standard clinical practice at this time, and would be additional. Otherwise, like I said, I think a lot of the parameters and things that we're looking at are part of our kind of clinical care for our patients. In terms of% of patients in your practice, you think would be PEM positive, I think was the question. Yeah. Sure, to answer that as well, you know, I'd probably say we're 60%-70% is my guess. You know, just kind of thinking about the patients, and I, and I say that, based upon, growth hormone stimulation test results, right? In terms of kind of categorizing them into kind of what I'd call kind of severe and moderate. I'd probably say probably between 60% and 70% of our patients would fit probably these criteria and be in that kind of PEM positive group for us. Yeah. Thank you. Dr. Cassorla? Yeah, well, let me put this into perspective. % of your patient population, do you believe it would fit, the PEM positive criteria? Yeah, I know. I know. Let me just say to begin with, that in most pediatric endocrine practices around the world, the child who is short and is seeking medical attention for that reason, is more than half of the population of the patients that we see. Whether you, whether you think about thyroid disease or adrenal disease or puberty abnormalities, disorders or whatever, the children who are short are more than half of the population of patients that we see in any pediatric endocrine clinic. We start with a very large number of patients that we see. How many of them are gonna be candidates for the study? I would say a substantial number, because the number of patients who are short because of severe growth hormone deficiency are relatively few. That means that they will go through the standard provocative tests and, potentially a head MRI and the rest of the pituitary function and a bone age. The patients with severe growth hormone deficiency are going to be very few. There's gonna be a substantial number of patients who end up in this gray zone, that some people would call growth hormone deficient, partial growth hormone deficient, some other people would call idiopathic short stature. This is an ongoing kind of controversy that has taken place and has occurred over the last several years in all over the world. In that group of patients, this gray zone, of patients who are short but do not have classical growth hormone deficiency, we will have, I think, the target population for this drug. Many of them will have a provocative test that is between 3 and 10 nanograms per ml to a clonidine or a glucagon test, so therefore they would be candidates for the study. They might be candidates for growth hormone therapy, but then the question of daily injections and insurance gets into the equation. If you get that out of the equation, and you say there's an oral drug that may help your child grow without the injections, and potentially at a lower cost, I think that the appeal for that would be great all over the world. I'm thinking that in the U.S., you know, it's likely that the patients will consider growth hormone therapy if they have all the characteristics that will enable the insurance to cover that cost. They will balk at the injection part of the whole equation. In the rest of the world, they will consider an alternative, not only because it's not a question of injections, it's a pill, but actually, potentially, it's gonna be a simpler therapy. I believe that there's substantial... I cannot give you a number. I can tell you it's a substantial number. Out of that, over 50% of patients who consult a pediatric endocrine clinic, for any reason at all, who are short, I would say out of that 50%, a substantial number of them would be candidates for the study. If I were to look at this, I would say that the market, the target for growth hormone therapy is, you know, a certain number, but that this should expand the kind of the target population, because there's gonna be patients who are gonna be in this gray zone, that might not get accepted into a program of growth hormone therapy by the insurance, but would be candidates for this particular drug. Keep in mind that the target population for this is slightly larger, and potentially much larger, than would be for growth hormone therapy in patients with short stature. Thank you, Dr. Cassorla. That's very helpful. Thanks so much for taking my questions. Okay. Thanks, Leland. Our next question comes from Matt Schanzler at Jefferies. Please go ahead. Hi, Rick and team. Thank you for taking my questions. I'm on for Yuen-Uen Yang. Just to start for Dr. Tansey and Dr. Fernando Cassorla, what percentage of your patients have switched to SKYTROFA, the weekly injections from the daily growth hormone. I guess, what is the main reason why your patients are not able to switch or don't choose to switch to the weekly injections? I can start and kind of give the U.S. perspective, and then maybe Dr. Cassorla will give us kind of a different, more international perspective. We've had more of our patients switch to SKYTROFA. I mean, growth hormone, and I don't know how familiar everyone is with kind of the growth hormone industry and the mess that it has been in over the last year with kind of shortages of growth hormone and suppliers. That is actually what's driven more of a switch to SKYTROFA than anything else for a lot of our patients, is just the ability to have some form of growth hormone therapy with the shortages that we've had over the last year. In terms of what's why people aren't going to SKYTROFA or why people are, again, for us in practice in the U.S., this is driven by insurance more than anything else in terms of what we're prescribing and what options are for patients. I think there is interest in weekly therapies. It's kind of a different topic than what we're on today, but related certainly. Like I said, the growth hormone industry has been, I would say, quite dynamic over the last year. That's kind of what's driving, I think, some of the changes more than anything else, has been availability of any product, weekly or daily. Certainly there is interest in weekly. Again, that's not universal. It's not that weekly therapy is what all of our patients are asking for. We've actually had. You know, clinically, I can tell you know, we've had patients who are getting weekly. They don't like it. They want to switch back to daily for various reasons, volume of injection, pain, things like that. Again, it's kind of a changing market. I'd say it's been a very interesting year in terms of growth hormone options for us. Well, let me just add that, having alternatives is exactly what families want. Yeah. Therefore, having the possibility of switching over to a longer-acting growth hormone therapy becomes interesting. South America, unfortunately, doesn't have available many of these, some of these long-acting forms at this stage of the game. They may become available later on. Again, if they become available, then there's an issue of cost, that I understand is quite substantial, compared to daily growth hormone, at least for SKYTROFA. Michael may correct me if I'm wrong, but my impression is that it's actually significantly more costly than daily growth hormone. In addition to that- Right. Yes. There's still going to be an injection. That's correct. Is that... Yeah. There's an issue, of course, that is not a little bit, but it's a whole lot more, and that's always an issue for insurance and for some of the families. That's number 1. Then number 2, they're still getting an injection. It's not as if they're going to get an injection once a year or whatever. This is happening every week, and therefore, it's much less than every day. We understand that, and it's more convenient, but it's not as if there's no injections. There will be injections, and some of them are painful and that's why some patients want to go back to the daily injections. The other point that is important is that you have to measure IGF-I levels following the injection of long-acting growth hormone, and there it's a little more tricky than when you measure IGF-I levels following a daily injection, because if you measure it at 2 days, it's likely to be the peak serum IGF-I levels, and at 4 days, it's likely to be the kind of the mean. At 2 days, the levels tend to be quite high. The question then becomes, again, are we having patients during part of the week, when they are treated with this weekly dose, having a relatively high serum IGF-I levels during the first 2 or 3 days after the injection? Does that have any potential impact on their health later on? How physiological is this? That's even worse because with a daily injection, you get a bolus of growth hormone that actually circulates in your body, very different from the exquisite pulsatility that comes up with the pituitary with a normally growing child. In the case of daily growth hormone, that's true. In the case of weekly growth hormone, it's even worse because you're going to have very high levels of growth hormone for a couple of days, and then they will go down, really in no way reproducing what's normal physiology. We think that there is interest in long-acting growth hormone, but the jury is still out regarding cost, the inconvenience and the potential pain with the drug and how to monitor therapy. How are we going to make sure that the patient gets the right dose and doesn't get too much of a dose that will increase serum IGF-I levels, at least for a couple of days following an injection, way beyond what they should? Reproducing physiology, in my view, is important, and an oral growth hormone, ibutamoren, has a vast advantage over the daily growth hormone and certainly over the weekly growth hormone injections, because in that case, you get a huge amount of growth hormone for a short period of time, and then they go down to relatively low levels before the next injection. That's not physiological at all. Great. Thank you. You know, recognizing that the idiopathic short stature patients might be a target for this drug later on, but right now, I guess, how many KIGS or what% of your growth hormone deficient children who may benefit from growth hormone therapies are not taking it because of injection issues? Dr. Tansey, would you answer the question? Sure, I can go ahead and start. I don't know how to answer that easily. For one thing, we are only referred a subset of KIGS who are short. There are a lot of KIGS out there in the community with heights, you know, less than minus 2.3 standard deviations below the mean. They never even get in the door, because maybe someone, you know, maybe their doctor says, "Maybe you got a growth hormone problem." The family says, "Oh, we don't want to do that." Right? Like Dr. Cassorla mentioned, I think there's a probably a bigger group than we realize, we don't know the full extent, I don't think, of the patients kind of coming in. You know, I like we've said, I think already, I think for the patients that we are seeing and diagnosing with growth hormone, we think probably the majority, a little over a majority of them probably would be eligible for this. It's hard to say like if your question is really, you know, how often do we get a patient who comes in, we diagnose with growth hormone deficiency, and then the family says, "I don't want growth hormone." That's a pretty small percent. I'm probably gonna say less than 5%, and sometimes we see this in some other particular populations that we tend to use growth hormone in, whether it's Turner syndrome, Prader-Willi syndrome, some other kind of conditions, sometimes we see that as well. It's a minority, I would say, of the patients who turn down growth hormone because of injections or issues like that, I would say. Yeah. Dr. Cassorla? Well, I still think that the issue of expanding a target population is one that is particularly important for this drug in the future. I would envision that if we're looking at patients who have a responsive pituitary, it's very likely that the patients with idiopathic short stature are gonna be the patients who will respond better to this drug because they will have, for the most part, an intact pituitary. I understand that the regulatory steps and everything else indicate that we have to go through a growth hormone deficient population first in order to demonstrate the safety and efficacy of the drug. If I were to leap forward and to think of what would happen in another 10 years or so, I wouldn't be surprised if this drug ends up being available and of interest to families that don't have any real problem with their somatotropic axis, but they have an insufficient production of growth hormone for their age. That most likely would not be called growth hormone deficiency at this stage of the game. This gray zone that I keep on coming back to is one that I think is likely to produce a large number of patients who will be interested in this drug. I may actually give you an anecdote. I'm coming back from the meeting in Chicago just over the weekend, you know, and I've got a member of my team who is very short and who has a very short child. She works in more in pediatric gynecology than pediatric endocrinology. At the airport, she tells me, "Well, Fernando, when is this stuff gonna be available? Because I've got this little girl who's the shortest one in her class, who comes home and tells me, 'I'm the shortest one, Mom. I don't really feel very good about this.'" The mother says, "Well, I was the shortest one in the class, too. Look at me, I'm a doctor. I'm doing pretty well." Here's an example of what may happen in the future, and that patient is unlikely to have growth hormone deficiency, even partial growth hormone deficiency. Again, if we have to leap forward and to think what may happen in the future, at this stage of the game, we are focusing on partial, moderate growth hormone deficiency. Down the line, I think it's very likely that there's gonna be an expanding target population for this drug that is simpler to use. If it proves that it's really effective, as it is up to now, and it continues to have no side effects that are important, I can envision that this expanding target population will become a reality in the not-too-distant future. I would just kind of add in, this population that Dr. Cassorla is talking about is at least a magnitude higher than what we've kind of been talking about previously with idiopathic pediatric growth hormone deficiency. Now you're getting into a much larger population of kids with familial short stature, idiopathic short stature. Again, there's a lot of patients out there who are coming to us and do not receive growth hormone, though that's, I think, an important point. They are not receiving growth hormone, but, you know, with future studies, could this medicine be beneficial to these patients? I think there's a good possibility for that. I think that's what the community would get very excited about, both the professional pediatric endocrinology clinic and patients, you know, who are dealing with this and want to improve growth. Understood. Thank you for answering my questions. All right. Very, very good, thorough answers, no question about it. I think that I'm gonna remind everybody, we're talking about two ped endos who operate out of a university setting. A private practice pediatric endocrinologist may answer that question a little differently, Matt. Certainly a pediatrician who talks to a family that may have PGHD, or as Dr. Cassorla says, this gray area, sometimes when they opt out of further treatment, because of the burden of injectable for seven, eight years of their lives. All right. In the interest of time.... A bunch of written questions, but I just want to ask one question, and then we can wrap it up after that. Most of these questions have been asked and answered, but this one gets to the clinical relevance of the data that we've seen so far and how that would relate to enrollment in Phase 3. The question for both Dr. Tansey and Cassorla would be: Do you think that that change that you showed, the change of a baseline age to be around 5 going to 8, represents a clinically meaningful increase in growth for these kids? Is that the kind of statement you feel comfortable providing to families that is something that they should expect if they enroll in the Phase 3? Sure. I can start. I feel that that's a meaningful change in annualized height velocity. I mean, if just mathematically, if a patient came to me and asked that question, you know, we're not just talking about a year of therapy. We're talking about, you know, years of therapy. If we're going to have a child on therapy for 4 years, and you have a, you know, height velocity difference of 3 centimeters a year, well, you know, that's 12 centimeters. I mean, that's, you know, 4 or 5 inches. That makes a significant impact to me on final adult height. Is that a meaningful difference? Absolutely. You know, if that annualized height velocity continues at that level over time, that adds up to a significant improvement in final height. I think especially when we think about where kids are coming in at, right? If you're coming in and you know you're a male and you're at -2.3 SD for height, and we can improve your height velocity like that, I mean, your final adult height is going to be significantly improved. My answer would be yes. I think this is a meaningful clinical difference. Sorla? Just to add my comments to this. It will depend whether we can start early in some of these children. Obviously, we start treatment when they're already teenagers. All of our studies, 210 and 212, include only pre-pubertal children, so they're likely to get this drug for many, many years. Even a delta of 2 centimeters per year, if it's sustained, is likely to be quite significant after several years of therapy. It all depends on whether it is sustained or it is not. Up to now, we've seen it is sustained, but we're only at the year and a half mark. If that remains the way it is now, that delta of, let's say, 2 centimeters per year, not even thinking about 3, it might be quite significant after several years of therapy. I might add here a little comment. When I was at the NIH, I worked on the study that led to the approval of growth hormone for idiopathic short stature, that paper is published. I'm author on that paper, co-author, that went through the FDA. Ultimately, the FDA gave approval to this particular drug, growth hormone, for idiopathic short stature with a change. There were two groups there, one treated, one untreated, placebo-controlled, the difference was less than 4 centimeters of mean gain in height after several years of therapy. This was a total mean gain over several years of therapy, this led to the approval of that particular drug by the FDA for idiopathic short stature. Don't underestimate the effect of having a delta of maybe 2, 3 centimeters per year over several years if it is sustained. Even lower net gains than that have been approved by the FDA for the use of other medications for idiopathic short stature. My perception is that the key thing is sustainability. If it remains sustained, it's likely to be quite significant. Wonderful. Rick, back to you for thanks and closing remarks. Well, thanks, everybody, for participating. This is really important. I think that, as we gain momentum and as we are on the podium at all the major endocrine meetings around the world, I think there are a growing body of interest by the endocrine community, but also by everyone in the growth hormone community, to now begin to believe that there's actually a possibility of an oral therapeutic, as Dr. Cassorla said earlier, and that's translated into another level of enthusiasm that we found. I think that bodes well for us in terms of our Phase 3 pivotal trial that's coming up, and getting the community all together. We are excited that to make that happen. I want to thank our esteemed investigators in helping us get to this point. We appreciate you very much.