Good afternoon, 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, 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 Rick Hawkins, Chairman and Chief Executive Officer of Lumos Pharma. Please go ahead, Rick. Thank you, Tiara. Good afternoon, and thank you for joining us for our KOL event to review the interim data from our 2 phase 2 trials evaluating oral LUM-201 in moderate idiopathic Pediatric Growth Hormone Deficiency. I'm Rick Hawkins, CEO and Chairman of Lumos Pharma. Will be joined by 2 noted thought leaders in the field of pediatric endocrinology for our discussion. Before we proceed with our program, I'd like to remind everyone that certain statements made during this event are considered forward-looking statements under U.S. federal securities laws and that actual results may differ materially from historical experience or present expectations. I'm gonna begin today's program with a brief overview of Lumos Pharma. Following that, Dr. Dauber will review the mechanisms of actions of LUM-201 and discuss interim results from our Phase 2 OraGrowtH210 trial. Dr. Fernando Cassorla will review interim results from our PK/PD OraGrowtH212 trial, including additional pharmacodynamic data not previously released. I'll make a few final remarks, we'll close the program with a question and answer session with our two speakers, joined by Lumos Pharma's management team, of course. Lumos Pharma is focused on developing therapeutics for rare diseases with our current program targeting growth hormone disorders with our novel oral therapeutic LUM-201. Injectable therapies have dominated this space for over 40 years. We believe that as an oral therapeutic, LUM-201 has the potential to disrupt the $3.4 billion injectable market for growth hormone disorders, not including China, whose market is estimated at around $1.5 billion. Our initial indication targeted is Pediatric Growth Hormone Deficiency or PGHD, which represents approximately $1.2 billion of the injectable market. The interim results our KOLs will review today are from 2 phase 2 trials. OraGrowtH210, a study in moderate, naive to treatment PGHD, is ongoing worldwide at about 45 sites. OraGrowtH212, a single-site PK/PD trial. Prior analyses indicate that the moderate or idiopathic PGHD patients we are targeting represent approximately two-thirds of the total treated PGHD patient population. As we previously announced, our OraGrowtH210 trial was over 80% enrolled at the end of October, with 66 of the targeted 80 patients randomized. At the end of Q3, we had about $74 million as a cash balance, with a cash one runway into Q2 2024, which is beyond the full readout for our two OraGrowtH trials in the second half of 2023. I'd like to introduce our two KOL speakers. Dr. Andrew Dauber is currently chief of endocrinology at Children's National Hospital and specializes in growth disorders. Dr. Dauber has served as the program director and director of Translational Research at the Interdisciplinary Cincinnati Center for Growth Disorders at Cincinnati Children's Hospital Medical Center. Additionally, he was the director of their Genomics First for Undiagnosed Disease program and served as associate professor of pediatrics at the University of Cincinnati. Dr. Dauber also served as Assistant Medical Director for the Clinical Research Unit at Boston Children's Hospital and as Assistant Professor in Pediatrics at Harvard Medical School. He has authored over 100 publications and is an active member of the Endocrine Society, Pediatric Endocrine Society, among others, and has received numerous awards from these organizations. Dr. Dauber received his MD in Masters of Medical Sciences from Harvard University, and he's also an investigator for our OraGrowtH210 trial. Dr. Fernando Cassorla, our second distinguished speaker, is Chief of Pediatric Endocrinology at the Institute of Maternal and Child Research at the University of Chile, position he has held for over 25 years. Previously, Dr. Cassorla conducted research at the NIH, serving as Senior Investigator at the Developmental Endocrinology Branch of the National Institute of Child Health and Human Development, rising to the position of Clinical Director of this institute in 1990. He has authored numerous chapters in pediatric endocrinology and over 200 original articles in peer-reviewed journals, he's presented over 300 abstracts at scientific meetings and has received numerous international awards for his work. Dr. Cassorla received his MD from the University of Chile and completed his pediatric residency at the Albany Medical Center in New York and his fellowship in pediatric endocrinology at the Children's Hospital of Philadelphia. As previously stated, Dr. Cassorla is the principal investigator for our PK/PD OraGrowtH212 trial in PGHD. Now I'm gonna turn the program over to Dr. Dauber. Thank you, Rick. I'm gonna begin by reviewing the interim data from the phase 2 OraGrowtH210 trial. Just to start, I'd like to give you a little bit of background. These are my disclosures. As Rick mentioned, I am a site investigator for the Lumos OraGrowtH210 trial, but I do not receive any personal compensation from Lumos for my participation. I think many of you are aware that this trial is looking at a new agent called LUM-201, and it's an interesting background story to this agent. A number of years ago, actually, Merck was attempting to find molecules that could increase endogenous growth hormone secretion. They did this by, you know, screening a number of drugs in cell-based system and ultimately found this agent, LUM-201, that bound to what's called the GHSR1a receptor, also known as the growth hormone secretagogue receptor. Subsequent to that, it was found that the endogenous hormone that binds this receptor is something called ghrelin. In any case, LUM-201 binds this receptor at the level of both the hypothalamus and the pituitary, and once it does that, it induces signaling, which increases the amplitude of growth hormone pulses made from the pituitary. An important concept to understand that differentiates this from giving exogenous growth hormone is that there is an intact feedback loop between growth hormone and IGF-I. Right? In this situation, the pituitary is releasing larger amounts of growth hormone. Growth hormone goes and works primarily via IGF-I, which is produced both at the liver and directly at the bone. That IGF-I then feeds back in a negative feedback loop at the level of the pituitary and hypothalamus to inhibit further growth hormone secretion. The idea is that this medication can restore growth hormone to a natural normal state, but you won't be able to have excessive IGF-I levels due to that inherent feedback. What we're gonna discuss today is a phase 2 study, which is currently ongoing, comparing three different doses of LUM-201 versus daily recombinant growth hormone. It's a 24-month study in prepubertal individuals with mild growth hormone deficiency. There's another very interesting aspect to the study, which is that in order to enroll in the study, you have to meet what is called a predictive enrichment marker. Where did this idea come from? Well, in looking back at that original study done by Merck, comparing growth hormone to a single dose of LUM-201, it was found that the subcutaneous growth hormone appeared to be more effective in the entire cohort. However, in a subsequent analysis, they divided the group of patients into two groups. One was a group of patients with severe organic growth hormone deficiency, and one was a group with moderate or idiopathic growth hormone deficiency. If you look at these two groups, the severe was around 40% of the population. Those were individuals who had more severe short stature, lower peak growth hormone dose, lower peak growth hormone and stimulation testing, lower IGF-I levels, lower growth velocities. These are likely people who do not necessarily have an intact hypothalamic pituitary axis and therefore were unable to respond adequately to LUM-201. On the other side are the patients with the milder growth hormone deficiency who did actually, in that post-hoc analysis, have just as good of a response with the LUM-201 as compared to growth hormone treatment. When you looked at characteristics that define these two populations, they came up with this term called the predictive enrichment marker, which was looking at the baseline IGF-I level, the people who were better responders had IGF-I levels above 30, and their stimulated peak growth hormone to a test dose of LUM-201 was greater than or equal to 5. Taking advantage of this concept, Lumos has designed the current phase 2 trial, the OraGrowtH210 trial, which is enrolling 80 subjects into the 4 different groups and only including the patients who had a positive predictive enrichment marker. In order to get into the study, you will have to be somebody who will likely respond to LUM-201, presumably with an intact hypothalamic pituitary axis. The patients have to be naive to growth hormone, and you heard about the current enrollment status. There are 3 doses that are being tested, 0.8, 1.6, and 3.2, which is a higher range on the PK/PD curve compared to what had been tested previously, and comparing that to a single dose of daily growth hormone using a dose typically used in children with growth hormone deficiency. Of course, the primary outcome is looking at the annualized height velocity. Before we get to the actual results, I think it's very important to put into perspective the expectation for what types of growth velocity we're expecting in patients who meet those PEM criteria who have moderate growth hormone deficiency. To get to that expectation, there are a number of ways to look at it, but these are 4 different data points. 1 is the patients who are treated with growth hormone from that prior Merck study, and the others are either from other studies of patients with milder isolated growth hormone deficiency or data from the KIGS database, which is a large post-marketing surveillance data set study from Pfizer. You can see that all of these numbers are pretty similar, that historically, for patients who meet the clinical criteria to be in this trial, you would expect them to grow around 8.5 centimeters a year with daily recombinant growth hormone therapy. Approximately that. What did you see? This is the interim data of 41 subjects at 6 months. This looks at the annualized height velocity, and the yellow bar in the middle is the 1.6 milligram per kilogram dose of LUM-201, which showed the best response in the study, exactly at the expectations of around 8.6 centimeters per year for the annualized height velocity. The 0.8 arm was a bit lower. The 3.2 arm was also a bit lower compared to those groups. What stands out as very different from the expectations, though, was the recombinant human growth hormone arm that grew at 11 centimeters per year, which is much higher than one would have expected for daily growth hormone therapy in patients with these types of clinical characteristics. Looking into that a little bit more, there were these differences than expectation. The patients who were treated with the recombinant growth hormone just by chance, by statistical fluctuation with small numbers, ended up being younger, having lower IGF-1 scores, having taller parents, and having higher BMIs. These are all predictors of positive responses to growth hormone therapy. Though that skew in the baseline data may explain some of the improved and higher than expected growth hormone rates in the recombinant growth hormone arm. Just to show you, 2 of the patients, who were really outliers in their growth hormone response, were 2 of the 3 subjects under age 5, and the entire study happened to be randomized to subcutaneous growth hormone. The 3rd was randomized to the lowest dose of the LUM-201. Actually that 1 patient, the star all the way, the highest 1, close to 16 centimeters per year, is actually a patient from my site, 1 of the youngest patients in the trial, who also happened to have pretty significant growth hormone deficiency, just meeting the cut-offs for inclusion in this trial and has had a really remarkable response, to growth hormone therapy. Looking at the results of the LUM-201 across the length of the study, the nine months and 12 months, it appears, as you can see, that this increased growth rate in that 8 to 8.5 centimeter per year range is sustained from six months to nine months to 12 months. It is important to note that the number of subjects at the nine-month and 12-month time points is smaller, six subjects, four subjects in the 1.6 arm. We still need to accumulate the rest of the data of the trial, you know, to be really more confident in where these estimates will lie. From a safety perspective, the safety profile has been extremely reassuring. Data available now for 58 subjects at the time of the interim analysis, there have been no serious adverse events during the ongoing portion of the trial. All of the treatment-related adverse events were quite mild and nothing, no concerning safety signals in the laboratory values either. In summary, the growth of 8.6 centimeters per year on the 1.6 milligram per kilogram arm of LUM-201 is exactly in line with our expectations for what patients should respond to growth hormone in this clinical scenario. The 9 and 12-month data do look encouraging for the LUM-201, but again, the sample size is still quite small. The interim safety data appear very comparable to growth hormone treatment and overall quite reassuring. With that, I'm now gonna turn it over to Dr. Cassorla to tell us about the results from his OraGrowtH212 trial. Thank you, Andy. I will present data on our own study with this particular drug, but looking at pulsatile growth hormone secretion and linear growth in children with moderate growth hormone deficiency. This is another study, phase 2, that's being done with this particular drug, attempting to look at potential mechanism of action for this particular growth hormone security. Here are my disclosures. I've been working with this particular drug now for several months, actually more than a year at the University of Chile. I've acted as consultant for several other pharmaceutical companies on different drugs and different areas. The questions that we would like to ask during this presentation are, which is the potential effects of this particular drug in pediatric patients with moderate growth hormone deficiency by presenting three questions. Does the oral administration of LUM-201 at the doses of 1.6 or 3.2 milligrams per kilo for 6 months increase height velocity? Part of that question has already been answered by Andy. We'll show you our own data. Second, is the change in height velocity correlated with changes in growth hormone pulsatility? That is to say, what is the mechanism of action that this drug appears to have? Third, is the increase in growth hormone pulsatility and height velocity induced by LUM-201 dose dependence. The design of our OraGrowtH212 clinical study is being done in naive pediatric patients with moderate growth hormone deficiency. We have recruited about 21 out of these 24 prepubertal patients between the ages of 4 to 8 years for girls and 4 to 10 years for boys with short stature caused by moderate idiopathic Pediatric Growth Hormone Deficiency and naive to growth hormone treatment that have been randomized to receive LUM-201 at a dose of 1.6 milligrams per kilo per day, an N of 12 or 3.2 milligrams per kilo per day with an N of 12 too. Pulsatile growth hormone secretion has been assessed in blood samples obtained every 10 minutes over 12 hours from 8:00 A.M. to 8:00 P.M. at the beginning and after 6 months of LUM-201 therapy. It's important to indicate that we have done this over the window of the day, 8:00 A.M. to 8:00 P.M. We'll talk about that a little later. The samples are being drawn every 10 minutes in order to get an idea of what is the pulsatility of growth hormone secretion during this period. Height velocity during the 6 months of LUM-201 administration has been compared with a baseline period prior to intervention. In that sense, this study is also a little different because here we don't have a growth hormone arm. We're just comparing two doses, and all patients are being treated, all 24. 12 with one dose, 12 with another dose, and their height velocities are being compared what they were before we started to administer this particular drug. The design of the study shown in this slide, which we've got one arm with 1.6 milligrams per kilo per day, another arm with 3.2 milligrams per kilo per day. All patients have gone through a standard growth hormone stimulation test. We have done the same peak growth hormone to a single LUM-201 administration that Andy was talking about, the PM kind of stimulation test before they are started on therapy with the drug over 12, 6 months. Now, during the baseline period, we measure height, we measure IGF-I, and we establish a protocol whereby we measure growth hormone secretion every 10 minutes over 12 hours in these patients, both before and after 6 months of intervention, measuring again height and IGF-I. The same thing is done with the group that has received 3.2 milligrams per kilo per day. In this particular study, every patient has gotten therapy. All of them have gotten the oral secretagogue at 2 different doses. Their height velocities has been compared with the height velocities that they had before therapy. Here are some details regarding the first 10 patients in which we have data up to a little more than 6 months, and all of them are prepubertal. Here are the ages from 5.2 years, 5 years and 2 months, up to 10 years. 6 of them are boys and 4 of them are girls. This is not unexpected in terms of the referral kind of scenario that we get for patients who are short. The doses of the drug administered are shown here according to the randomization schedule. Here are the heights of the patients before therapy, all of them less than -2 standard deviation scores according to the CDC data. Here are the results of the clonidine test. That is the stimulation test to define whether they are or they're not candidates for the study. All of them have levels between at least 3, that's patient 103, and 9.9, 10 essentially for patient 110. The inclusion criteria require that they have a stimulation test between 3 and 10, and all of them have. Here are the results of the stimulation test with LUM-201. I want to stop here for a second or kind of emphasize the fact that the responses to the stimulation test with this oral secretagogue are much higher than what we see with the clonidine test. The patients are way above the cutoff point of 5 nanograms per mL that would be defined as a positive PEM responder. The lowest one was 19.5 and the highest one is 40. Essentially we're getting either a tripling or a quadrupling all the responses that they have to clonidine test, a classical growth hormone stimulation test with this oral secretagogue. This even though the study did not include, I mean, we did not have the exclusion criteria of having patients who would not respond to this drug. In fact, all of our first 10 patients, and in fact all of the second 10 patients going up to 2021, have responded in a very robust fashion to this secretagogue, indicating that the responses to LUM-201, acute responses are much higher than the responses that we see with clonidine, a typical growth hormone stimulation test. Now, here are the height velocities before and after 6 months of administration of this drug. Here are shown the 10 patients before therapy and after 6 months. Each patient is obviously shown with these 2 points that are united by a line. You can see that the slope of the curve is quite similar. That is to say the changes in height velocity that we see with this drug are quite similar for most patients, even though some of them received 1.6 and others received 3.2 milligrams per kilo per day.If we look at the bars for the same kind of data, we have here an N of 5 for 1.6 and an N of 5 with 3.2, and we do see some slight difference in terms of the height velocities over the first 6 months for the group that received the higher dose in this particular small group of individuals who were seen and measured again 6 months later. If we go beyond 6 months and we go to 9 months and then 12 months, we see that the response with a higher dose tends to decrease somewhat. The differences between the low dose and the high dose are less marked at 12 months than what they were at 6 months. Let me caution you that the number of patients that we have at 12 months, 2 patients with a 1.6 dose and only 3 patients with a 3.2 dose, indicate that one should not over interpret this information until we have more data. There seems to be a difference between the two doses in our study, at least at 6 months, that doesn't quite remain in place at either 9 months or 12 months. We then answer the first question by saying, does the oral administration of LUM-201 at the doses of 1.6 or 3.2 over six months increase height velocity? The answer is unequivocally yes. The second question that we posed in this study was: Is the change in height velocity correlated with changes in growth hormone pulsatility? Is the increase in growth hormone pulsatility and height velocity induced by LUM-201 dose dependent? Those are the questions that we'll answer in the next few slides, indicating that from our previous study, we assessed pulsatility in gray before, that is baseline, and in blue, after six months of administration of this drug at a dose of 0.8 milligrams per kilo per day. That's lower than the doses that we are using in our study. We see that the gray pulsatility data is lower than the blue pulsatility data. That indicates that over 24 hours, this is day on the left and night on the right, measured every 20 minutes. We measured in this current study every 10 minutes for 12 hours, so there is a difference there. There appears to be an increase in growth hormone pulsatility in this previous study that measured growth hormone pulsatility over 24 hours, obtaining samples every 20 minutes. What did we see in our study? The current study shows that when we use 1.6 or 3.2 milligrams per kilo per day, the numbers of patients are small, but that we get a mean change in growth hormone area under the curve compared to baseline of 34% with the 1.6 milligram per kilo per day dose and 197% with 3.2 milligrams per kilo per day. There's a major change in growth hormone area under the curve from baseline, whether we use the 1.6 dose, but certainly much more with the 3.2 milligrams per kilo per day. I want to show you a couple of patients in which we show this graphically. Patient 105, who received a dose of 1.6 milligrams per kilo per day. You can see here the baseline pulsatility data over 12 hours during the day with samples obtained every 10 minutes. You can see that the baseline data indicates that the height velocity is below five centimeters per year. The area under curve is about 273, and the serum IGF-I is 110. When we move on to what happened after six months of therapy, you can see that IGF-I goes up from 110 up to 185. The area under the curve essentially triples, going from 273 to 724, and the height velocity increases about 50%, growing from 4.6 centimeters per year up to 6.8 centimeters per year. This is with 1.6 milligrams per kilo dose. You can see here in graphic terms, with the gray data showing the pulsatility before therapy and the blue data showing the pulsatility after six months of growth of LUM-201 administration, that there is a significant change in growth hormone pulsatility, and that's why the area under the curve essentially triples. What happens, we present data on a patient who receives 3.2 milligrams per kilo per day. Again, the baseline IGF-I is on the low part end of the cycle. The area under the curve, very similar to the previous patient, and the height velocity a little lower, 3.4 centimeters per year. When we look at what happens after six months, you can see that we get more than a doubling on our IGF-I. We get almost a 7-fold increase in area under the curve for the growth hormone over 12 hours with samples obtained every 10 minutes. The height velocity increases about 2.5 times, going from 3.4 centimeters per year up to 8.3 centimeters per year, indicating that the blue data that we obtained here after 6 months of therapy is much greater than the gray pulsatility data we obtained during the baseline study period. What happens with serum IGF? Here I show the data from our study indicating that the baseline serum IGFs were about 100, 115, 120, that after 1 month it went up quite a bit with both the low dose in orange and with the high dose in blue. Essentially doubling, almost doubling at 1 month. The differences appear to be a little more clear at 3 months with slightly higher levels with the higher dose. Same thing is true at 6 months, that kind of attenuates the difference after 12 months. Again, the number of patients is quite small at 12 months, we would be cautious about suggesting that actually there is a change in IGF-1 level that is dose dependent. There appears to be a change in growth hormone pulsatility that is dose dependent, but in terms of IGF-1, it's a little less clear. What do we conclude then? That we have documented an increase in the height velocity compared to baseline in this particular study of a group of patients who are pre-pubertal with moderate growth hormone deficiency that were treated with 2 doses of LUM-201. The improved height velocity during LUM-201 administration appears to be correlated with an increase in growth hormone pulsatility after 6 months of therapy with this drug. In this limited sample size, these preliminary findings suggest that the changes in height velocity and growth hormone pulsatility induced by LUM-201 may be dose dependent. I would like to finish by showing a picture of our group here at the University of Chile, all of us pediatric endocrinologists, many of them trained up in the U.S. and Europe. I will turn over the podium now to Rick to give some insight into what these findings mean. Yeah. Well, thank you, Dr. Dauber and Dr. Cassorla. I wanted to spend a few minutes reviewing the data from both trials. Now you can see here on slide 39, the mean annualized height velocity achieved at 6 months on LUM-201 is similar across both trials. Now, we're pleased that the OraGrowtH212 trial corroborated our findings in the OraGrowtH210 trial and anticipate that increasing the sample size from further enrollment of each trial will strengthen these results. We believe that a phase 3 pivotal trial will support these results even further. On slide 40, we have combined the growth data from the OraGrowtH210 and 212 trials for further analysis to determine an optimal dose for our phase 3 trial. As you can see, the mean annualized height velocities at the 2 higher doses of LUM-201 are similar across the 6, 9, and 12-month intervals and demonstrate a durability of response up to 12 months on LUM-201. With these findings, we believe the combined data from the selection of 1.6 mg per kg a day of LUM-201 dose for our registrational phase 3 trial. Now to summarize. We are very pleased that growth on the 1.6 mg per kg a day dose of LUM-201 met expectations and established by a large data set in our targeted moderate PGHD patient population. Recall, this is for the enriched population we identified through our predictive enrichment marker or PEM strategy for selecting these moderate PGHD patients with the potential to respond to LUM-201. In addition, LUM-201 demonstrated a durable response out to 12 months and showed a favorable safety and tolerability profile. In addition, we believe these data support the selection of 1.6 mg per kg a day of LUM-201 dose for our pivotal phase 3 trial. The company is proceeding with advanced planning for that registrational trial. Finally, I wanna mention again that our molecule's unique mechanism of action and oral administration, we believe these data support the potential for LUM-201 to disrupt the injectable growth hormone therapeutic market worldwide. Now we'd like to proceed to a question and answer session. Great. Thank you, Rick. At this time, we'll be conducting our 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. Thank you so much, team. I hope you can hear me. My question is directed to the fantastic physicians who presented here. Can you maybe allude to us now looking at the totality of the data from 210 and 212 and help us understand, you know, in terms of its utility in the current marketplace for patients with Pediatric Growth Hormone Deficiency. you know, assuming this data could be shown very similarly, and reproduced and strong in the total cohort group, I think we would love to hear your thoughts on the positioning and use in patients and what% of your patients currently on growth hormone injections you would switch over to this oral growth hormone secretagogue, and why. Doc- Try to answer this. This is a very interesting question because it has 2 dimensions to this. One of them is cost, the other one is the simplicity of actually treating the patient. Those are 2 very important issues for most families. Even though, you know, third-party payers will essentially cover growth hormone therapy for patients who have classical growth hormone deficiency, there is a raging controversy as how do we define growth hormone deficiency in different countries. In my country, for example, in most of Latin America, I would say so in large parts of the world, the cutoff points for growth hormone 10 nanograms per ml, kind of growth hormone levels. That means that there is a group of patients who currently, in many countries in the world, have responses of 7 or 8 nanograms per ml, but do not qualify for growth hormone therapy because in these particular countries, that kind of point is not low enough. There's one dimension to this, and that there's a universe of patients out there and third-party payers reluctant to cover, compared to patients who for the most part get this particular drug, growth hormone. This dimension means that there's a universe of patients out there who are partial growth hormone deficient, you wanna call them moderate growth hormone deficient, mild growth hormone deficiency, that we think are the patients who will respond. Some of these patients are either not getting growth hormone, or if they are, they're getting it with the inconvenience of daily injections that growth hormone has. A short answer to your question is yes. I at least believe patients out there who would benefit from this therapy because it's simpler and it's likely to be less expensive than what growth hormone currently costs. The potential for being able to treat patients who have this partial growth hormone deficiency with this drug, in my view, is huge. Yeah. Maybe I can build off that from the U.S. perspective that, you know, in the United more than 50% of patients who are treated with growth hormone would meet the criteria for inclusion in this trial positive, right? In terms of having the milder idiopathic growth hormone. No doubt, the data shows this also, these are not. See, with abnormal brain MRI. Subcutaneous growth hormone is the correct treatment for those. Those are by far the minority of patients who are treated with growth hormone in the United States. Very large percentage of the market who could. The second question, the second part that you asked was about switching. I think that there's a different consideration for starting new patients. You know, with other therapies that come down the line. For. Hesitant or nervous, you know, to start an injection therapy, you know, for obvious reasons alternative, they would clearly prefer an oral alternative. Novo starts would prefer to start on the oral drug. In terms of patients who are already on therapy, the majority of them actually do fine. Like, once they're on it already and they're on daily growth hormone therapy especially those who are having a good response to injection therapy, you know, I don't think that many. For sure, who the kids fight and hate their injections. If given an oral alternative. I think that answered most of the aspects of your question. Yeah. No, no. That was fantastic. If I may ask one last question. After the interim data, I think a lot of investors are just eager to hear that in the remainder of the 20% of patients that Lumos is planning to enroll, we may see an outlier in the growth hormone injectable thoughtfully. You know, now looking at that, as we're at the last stretch of the trial, you know, just your comment at Lumos and how confident you feel that. Well- growth hormone group will perform. Be my question. Yeah. Well, first of all, I think that you have to remember that a phase 2 trial is evidence of superiority or non-inferiority in any one dose or treatment. Many subjects in each arm, that's still not a very large number of people. What Lumos did, and they can probably chime in if they wish, which are based on age as well as based on severity of growth hormone deficiency. How this, the math happens, it will even out over the course of. Now, that, you know, three-quarters of the patients have been enrolled versus half the patients with the interim data or happen mathematically based on stratification. I think that the numbers 6 months, and the growth velocity even in those outliers, like my patient who had the amazing response, the first 6 months is always the best, and by 12 months, it's not going to be as extreme as you saw for the first 6 months. That being said, honestly, important. Like, even if the growth hormone arm in these 20 patients comes out a little bit higher at 12 months, you know, or at, you know. Like, at the final readout. Each arm, like, if the 20 patients in the Lumos arm hit 8 centimeters a year, right? Because now you've got an oral therapy in patients with mild growth hormone deficiency that's giving them around 1 inch extra of height a year, right? Like, I can't tell you how many patients knocked down the doors of my office asking, "Hey, that's a really..." Right? Like, I mean, just think about that, right? That's the reality of what we're dealing with. Yeah. to me, that's still very encouraging. The phase three study will do what it's gonna be designed to do, which is to actually tell us the comparison. Yeah. Yeah. Thanks for the question. Well, I would agree with what Andy said. We are kind of at the very beginning of these 2 trial until final height. After 5 years, that's a lot of additional height. Tons of growth and therapy are very unusual, even for young children. Based upon the data that was presented, the curves. Meters per year with growth hormone appears to be really very good. Some patients will only grow 5 or 6 cm per year during the first year. A spread there in the response. We're seeing patients. On a small group of patients. We'll see how it evens out. We'll see what happens at a year and 2 years. I wouldn't be surprised if during the second year, this patient is growing to maybe less than 10 during the second year. The growth tends to attenuate on all patients. This is likely to happen with both growth hormone and potentially with LUM-201. Cantor Fitzgerald. Please go ahead, Charles. Yeah. Hi. Thanks, Tara. Hi, Rick. Thanks for hosting the call. To Doctors Dauber and Cassorla, thank you for your perspectives today. Said the company has identified in those outliers in terms of the age or parent... Going back to Yasmeen's question, do you feel like those are variables that will be reconciled within a larger study of phase 3, or would you recommend to the company that they keep track of any? I think in a larger trial Those variables will even out much better, for sure. You know, I think that you're kinda asking like, how many different stratification factors would you want in a big trial? Yeah. Like, would you necessarily want to stratify by age and by peak growth hormone level, which are probably the two best predictors. I think that in a big... You're gonna be fine. Yeah, I think that this was just a chance... Like a chance occurrence, you know. Like that we showed you so far, or two of the 10, you know, happen to be very good growth hormone, you know. Got it. Dr. Cassorla, anything to add? I'm all in favor. With the current growth hormone therapy. That is to say, there are these parameters that are important. The BMI, the midparental height, how growth hormone deficient are they? We take into consideration these things when we decide the dose of growth hormone that we're gonna use on a particular patient. I'm not surprised by the fact that there are differences in the response. Make sure that we don't have kind of a uniform approach to all patients who have partial growth hormone deficiency. Some of them will be quite severe. Classical growth hormone deficiency. To stimulation tests already close to the cutoff point of 10. I would say that we look at these, like, characteristics of patients in order to decide what do we do with current doses of growth. It's possible. We have to look certainly. LUM-201. We want patients who have a robust response, like we. On the best, and we don't want the patients who have a tiny response to... Yes. Yes, I think that some of these criteria are considered. We have right now, and it's possible in the future, we will have to decide when if this drug becomes available, which gonna be, the patients that will respond the best. The patients who are slightly... With, with very, hypofunctioning pituitaries are not the patients that will respond to this drug. Out of the large population of short children who will ask Andy and myself about, what are the chances of increasing the height of my child by giving them an oral medication. Targeted by this every day. It's likely that in this particular group, the patients who have, this partial or micro hormone deficiencies who... Benefit from this drug. Yeah. If I can add to that. Obviously a number of years down... Pathway where it, you know, identify patients with mild growth hormone deficiency. Those who, like, as a first step therapy, those who responds well, great, you keep them on that. Those who don't, then fine, maybe you. I think some of this will, as Dr. Cassorla alluded to... I don't think it always has to pose as an either/or as much as also a, you know, a stepwise progression. I really could see a role... A trial of growth hormone therapy. Additional question. I'll hop back in the queue, that is related to the mechanism. I'm quite intrigued with the pulsatility of the secretagogue. I guess I'm wondering if you see there being any inherent value in that versus just, I guess, flooding the system with growth hormone. Would you... Obtained over time. I think that you, Dr. Cassorla. I understand there may be a, call it denominator function, and that growth kind of settles out over time. Would you anticipate there to be any like tachyphylaxis with the pulsatile mechanism versus, say, the daily injection? There's two. Before you answer. Two questions there. You know, with patients who. Decreasing response over time. The pulsatility data that is to say that we are saturating the system. Feedback mechanism ends up shutting off response, and the pulsatility becomes quite attenuated at 6 months. We haven't seen it yet. We may see it in the future. Some data that we show there is a tendency for a slight decrease in IGF-I serum levels after 6 months. Slightly too high. I would be very cautious about interpreting in that sense. It's possible. We understand that in this particular setting, the feedback loop remains active. Therefore, if you have more growth hormone, it's possible that you will shut off, eventually IGF-I production and that your IGF-I levels will go down. Regarding the kind of the concept behind giving a growth hormone secretagogue as opposed to giving growth hormone, I think there is a clear advantage of trying to reproduce physiology. Yeah. When we give growth hormone, we give a huge amount of the, of this hormone that remains circulating in the blood for a period of time with levels that are supraphysiological and that then come down to essentially nothing before the next dose is given on the following day. If one had to think about the least physiological way of trying to reproduce growth hormone secretion, this would be the one. Yeah. Flooding the system with a huge amount of growth hormone and then essentially having levels that are gonna be very low over several hours of this 24-hour interval. In answer to your question, it may make sense to me. That's, like, why I think we practicing pediatric endocrinologists are interested in this field, is that we are attempting to reproduce physiology. Certainly, giving this drug tends to magnify growth hormone pulsatility that remains quite pulsatile in fashion. That is to say it doesn't remain as a huge plateau that then goes down to essentially nothing, as you would see with injectable growth hormone. We all think that nature, you know, has designed a system in the somatotropic axis that includes pulsatility as a key component of growth hormone secretion and then potentially of action. This is no accident. This happens for some reason, and certainly by giving growth hormone, we abolish that. Now, with this drug, we are attempting to reproduce physiology. We seem to have data up to now that indicates that pulsatility remains quite robust with the higher dose and even with the lower dose after six months, suggesting that the potential tachyphylaxis doesn't seem to be that clear, at least with pulsatility study that we performed up to now in this small number of patients. Allow me just to add that, as you also know of, Dr. Cassorla, in the Merck studies, which went out in adults for 2 years, even after 2 years of dosing with the essentially the 0.8 dose, there were still increases from baseline in both growth hormone and IGF-I, really putting the tachyphylaxis issue to rest pretty much. If I may, though, give just a slightly different perspective, though. You know, while I agree, and in general, I'm a big fan of trying to mimic human physiology, I would note that, you know, daily growth hormone, the way we've been doing it does work well. Even now, long-acting growth hormones that you give once a week, which are even far less physiologic, are showing equivalent responses, you know, to daily growth hormone in terms of response. While I don't disagree with Dr. Cassorla said, I wouldn't make too much out of that, you know, in that, non-physiologic ways of growth hormone replacement still are effective. The last point is, while I think this comes back to the point of who's gonna respond or not respond, I could see that there are some patients, as Dr. Cassorla alluded to, in this spectrum who are, let's say, less growth hormone deficient than others, right? One of the benefits of growth hormone therapy is that you can push the dose and push the IGF-I level to maybe a supraphysiological range, and some patients will respond better to that. Probably for those patients, LUM-201 might not be as ideal. Just to give a little bit of a, you know, the other side, I think that this all has to do with the right patient selection, you know, who's gonna respond, and that it's good to have more than one option out there. That's helpful. Thank you for taking my question and the added color, Dave. Thanks for the questions, Charles. Our next question comes from Leland Gershell from Oppenheimer. Please go ahead, Leland. Looks like Leland is joining now. Hi, Leland. Please go ahead. Leland, you may be on mute. Why don't you go to the next question, Tara, until we get this resolved? Okay, great. Our next question comes from Ed White from H.C. Wainwright. Please go ahead, Ed. Hi. Thanks for taking my questions. sorry, I had some connectivity issues, so, I hope this question wasn't already asked. Perhaps both the doctors can talk about, compliance in their practices and the impact of patients, for non-compliance, and then also your expectations for compliance with an oral. Well, let me go first, Andy. This is a major issue with all therapies, whether they be injectable, parenteral or oral. This has been studied at length, and we know that patients, particularly children and a little worse for adolescents, may have poor compliance, particularly with drugs that are injectable. On our daily practice, and I'm gonna speak for myself, my experience at the NIH and then in Chile over the last decade, couple of decades, is that some families are very disciplined and the children follow the kind of Indications of the parents, and they're very compliant with therapy, in this case with growth hormone therapy. Many, unfortunately, are not. Many. There are several studies published in the literature, Wayne Cutfield from New Zealand and others, that have shown that a substantial number of patients miss their daily injections with growth hormone. This has an effect on growth hormone velocity, on height velocity. This has been published, several groups. There's a nice review by Acerini and others that indicates that actually this is a problem. Now we cannot exclude that there will be compliance issues related to an oral medication, because there are. When we have patients with hypothyroidism in which we need to give them a small little pill of levothyroxine, some of them don't get the pill as frequently as they should. Remember that we are treating children, and children tend to be a little less compliant than adults, particularly during the adolescence period. The short answer is that compliance is an issue with injectable growth hormone right now, as extensively published in the literature. This affects height velocity. Therefore, one can have the best intention of treating a family and a patient with growth hormone during several years. Remember, these are very long periods of treatment, and the responses tend to decrease over time. You start measuring IGF-I levels, and they are lower. Then this information is very hard to come by. As you ask questions about compliance, most patients and families will say, "No, no, he gets the hormone every day. We're very careful," whatever. The fact is that many patients do not. From a theoretical point of view, it would seem that an oral medication would have a slightly better chance of improving compliance compared to an injectable drug. That is something that is intuitively kind of easy to accept. We will still have some patients who will not take the oral medication as planned. That is going to happen. My perception, my kind of guess is that there will be less issues of compliance with an oral medication compared with an injectable medication. That may be one of the advantages of actually providing this form of therapy for children with partial growth hormone deficiency. I agree. I have nothing to add. I completely agree. Okay, thank you. Rick, perhaps a question for you. I'm just curious as to why not wait for the full data to inform the phase 3 dosing instead of calling the dose now at the 1.6. You know, just looking at the 212 data, you know, that appears to favor the 3.2 dose. It's a good question, Ed. You know, I think we still have lots of flexibility here and time to make a final decision. As you know, there's, there are a lot of advanced issues that have to, you know, come into not only designing but preparing for a registration trial. Doesn't make any difference whether that's the 1.6 or 3.2. We're gonna be in the middle of all that planning. But we will be closely looking at the data as we get closer to this period of time. Okay, in other words, the 1.6 isn't the definitive phase 3 dose yet? Well, it looks like it could be if we wanted it to be. You know, there is a, on the 210 trial, a dose response from 0.8 to 1.6, but the 3.2, I think, is bumping up against the feedback mechanism. I think- We would feel quite comfortable. Let's put it that way. Yeah. Yeah. going into all of these trials, we were looking at the PK/PD study that Merck & Co., Inc. did. we chose these doses to provide good separation of doses and PK exposure. And we already knew that in the PK study that the top of the dose response curve, above which you get no more growth release, is right around 2.8 milligrams per kilogram. 3.2 was chosen to be above that. given that the combined data... First of all, I would say that there are some differences in growth hormone responsiveness between the 1.6 and 3.2 milligram groups in Carrascosa study, and that may partially underlie why 3.2 looks better in that study. I'm heartened by the fact that when you combine the data, the high velocities look to be totally comparable. In that situation, it's much wiser decision to go with the lower of the two doses because you have much greater safety exposure from having two or three or four years with a higher dose when you're planning for phase 3 and talking to the agencies. I think at this point in time, if I had to pick a dose between 1.6 and 3.2, as someone who has designed a number of phase 3 studies, I would clearly favor 1.6 at this time. As Rick says, we will have some time, not a huge amount of time, because there are some decisions you have to make long in advance at phase 2 as far as getting your final drug product. We will use all of the data to make the decision. I'll also say that what this, what this data show is that we can go up to a dose of about 3.2. You know, I'll just remind folks that You know, when phase 2 studies with the transcutaneous hormone, phase 2 used 0.21 and 0.30 and 0.18 mgs per kg per day. There was no 0.24 mg per kg per day in phase 2. That was a dose which is standard dose in phase 3. We have the ability to pick a dose that is 1.6 or higher, up to probably around 2.8, I think, as the optimal dose. If it was a solitary decision right now based upon the data at hand between these two doses, I think it comes down on the 1.6 dose. Okay. Ed, any more questions? No. Thank you for taking my questions. Okay. Tara? Yes. Our next question comes from Leland Gershell from Oppenheimer. Please go ahead, Leland. Thanks, Rick and team for this very detailed discussion. This had a lot of good points in the review of the data from both studies. My question really is, maybe it's directed to Dr. Dauber, since this product is available where you are but I don't believe where Dr. Cassorla is, but Skytrofa the once-weekly injectable for Pediatric Growth Hormone Deficiency. You know, just wondering, you know, as we get kind of, you know, past the clinical development of LUM-201 and, you know, presume this will be approved and will be on the market as a once daily, if you look at the example of that once weekly injectable, it's taken some time to kind of get pickup in the marketplace. You know, obviously, you have a particular practice setting, in an academic environment, you know, versus others who may be kind of in community practice. I'm just wondering if you can kind of reflect to us, you know, what maybe some of the challenges have been with respect to that once weekly, and what you would take away from that experience and, you know, advise if you were to sort of be an advisor to Lumos on its strategy for LUM-201, you know, what things you might do differently than what we're done with Skytrofa. Thank you. Sure. That's a great question. I hope people like my answer. Skytrofa, in my experience, because I've tried to prescribe it a number of times now and have maybe one patient or two patients who have successfully started on it, and it's been really hard to get approved by insurance companies. As a practicing pediatric endocrinologist in the U.S., you know, it's interesting. Like, patients think that we have all these, like, decision-making capacity over what growth hormone they get. Honestly, it's all determined by their insurance companies, right? It really, I decide I wanna start somebody on growth hormone, it gets approved or not approved based on their insurance company, and then which growth hormone is also totally based on their insurance company, unless the people are, you know, independently wealthy and wanna pay out of pocket whatever they wanna pay. I don't know the behind the scenes what happens with, you know, Ascendis and Skytrofa, but whatever they did, a lot of the insurance companies are not approving it, or are only making it as a second more expensive tier after failure of a daily growth hormone therapy. You know, most people don't actually fail a daily growth hormone therapy. What I would recommend to Lumos, because that's what you asked, is that you wanna position whatever you do, whether it's pricing, whether it's, I don't know, you wanna position this as not a second tier to growth hormone therapy, right? This should be, in my opinion, a first tier, potentially even before growth hormone therapy. If that means that you need to price it to make it cheaper for the right population, this is not my area of expertise. You guys know more about this. Yeah, that's my basic advice, is like, don't do something that makes it hard for the doctors to access it, because what's happening in practice is people are just stopping prescribing it or they're getting too frustrated with the process that, you know, it's becoming less likely. You know, we have to push so many appeals or denials, you know, to try and get Skytrofa. It's frankly annoying, like, from a prescriber's perspective. Yeah. That's my perspective. Your comments are well taken. Believe me, we've studied this pretty carefully. Yep. We hope not to make this the same mistake in the market. No. Thank you. That's been very helpful. I guess just one kind of corollary question to that is in your observation that there's this pattern that, you know, that product has been regarded by some as kind of a second line for those who failed, you know, daily growth hormone, which as you say, is not really, you know, a drug that one fails. I mean, would that be a risk at all to LUM-201, presuming that in its phase 3 studies it, you know, shows, you know, non-inferiority to daily and has all the right, you know, kind of, you know, safety, clean tolerability and so forth? Would there be any reason that a clinician, even if it's not from a pharmacoeconomic or, you know, reimbursement standpoint, that a clinician, given the long history of established growth hormone, you know, in his hands and so forth, would regard, you know, LUM-201 as still being relegated to some kind of a second-line sense? Thanks. Yeah, good question. I have two parts to the question. First, let me be clear. I don't think that from a physician prescriber's perspective, that Skytrofa was thought of as the second line as people who failed, right? I think when all the data was coming out in the phase 3 trial, the doctors were really excited about giving a weekly, and lots of us were like, "Yeah, I'm gonna prescribe this all the time instead of daily." It was only after whatever decisions happened that made it not become an equivalent price as easily and approved just as easily as daily, that it became the second line. That was more I was trying to speak from the insurance company's perspective, not from the doctor's perspective. I don't want it any misinformation that I'm, you know, dissuading people from a medical perspective in Skytrofa, which I think is a lovely medication. Similarly, I just think that if LUM-201 in its phase 3 trial shows non-inferiority to growth hormone, right? It doesn't need to be superior. It just needs to be non-inferior. If it's non-inferior to daily growth hormone, I think lots of doctors will think about this as a first-line option. As long as there's no insurance barriers to it, I think we'll start saying, "Hey, do you want a pill or do you want a shot?" You know, the shot's been around for longer, but the pill seems to work just as well. You know, I mean, there are a lot of people who are gonna be like, "I'll take the pill." You know, now that being said, there is one thing I do think this is worth mentioning, and that I assume the Lumos people are thinking about this. I honestly haven't talked to them about this. The one thing that is gonna have to figure out is the streamlining of the indication. If we're still gonna need to do classic growth hormone stim tests on patients and then bring them back again for a stim test with LUM 201 to show that they hit the predictive enrichment marker, that's a little bit more complicated of a, you know, approval, like clinical process, you know, for people. Mm-hmm. Like, I just had a patient in clinic today who just went through a growth hormone stim test, which is not a pleasant experience. The LUM stim test actually is much easier. Far, far easier than giving a kid arginine glucagon. If I still have to do both, some people are gonna be a little like, turned off by having to come back for another IV, you know. I honestly think that there are parameters that we're gonna learn from these studies that may obviate the need for that. Because I'll tell you, every person I stimmed with their LUM-201, they all pass with flying colors, as Fernando just showed you. Like anyone who, you know, who meets these other criteria, they's gonna have a very high peak, you know. Perhaps in the design of phase 3 or the data mining before you get to a label, you can figure out a way to not have to do extra stim tests. That could be a little bit of a access barrier, but it's not insurmountable. Andy, very, very, very good point. Based upon the data we have in phase 3, it won't be a stim test per se. It'll be taking the single dose of LUM-201 and getting a single blood draw an hour later. No IV. That's much better. Yep. Got it. Thank you, David as well for that. Just so, just to be clear, it sounds like, Dr. Dauber, the novelty of this small molecule would not be a reason for physicians to not embrace LUM-201. It's, I don't think so because it's also it's like there's an endogenous hormone that stimulates the same receptor, you know. Also I think along with Dr. Cassorla's data showing the increased pulsatility, if anything, as he said, it's much more physiologic than what we're already doing. I'm not and the safety profile is so benign, like I'm not really worried that the novelty is gonna scare people away. Got it. Let me make a point here about the injection once a week. It's still an injection, and it's true that it's much, much less invasive than every day growth hormone injection. This is gonna mean four injections a month. You know, we're talking about 48 injections a year. It's not as if this is gonna be nothing compared to what it means to actually take a pill. I would assume that beyond the regulatory and insurance issues that Andy was talking about, that may relate more to the U.S. compared to other parts of the world. There's other reasons whereby some families will see, well, even though it's once a week, it's still an injection and potentially at a much higher price. I would suggest that that may be reducing the injections from once a day to once a week is gonna help some patients to make that choice. There will be others who will still prefer an oral medication every day compared to once a week injection. Let me just add that in South America, and particularly in my country, we already have an oral kind of placebo that people use in order to stimulate growth based upon very old studies that were performed when our country had malnutrition and for socioeconomic reasons. That's zinc. When I see patients in my, in my office, essentially most of them have been on zinc for several months with no results of any sort because the studies that were performed many, many years ago, indicated that in malnourished children, supplementations with zinc would help them grow a little better. I'm just giving this historical information to indicate that in parts, some parts of the world, the first line of intervention is an oral medication. In this particular case, it doesn't work. We have to tell them, "Look, it's a good try, but actually zinc is not gonna make a difference." They come to see you because the child is not growing any better. Keep in mind that that sequence of decision-making by families and by patients, it tends to go through the oral medication first. Whether it's a placebo like zinc that doesn't work or hopefully with LUM-201 that may work. Keep in mind that there's an historical kind of sequence of events that suggests that for some families, an oral medication is the first line of intervention, whether they have or they don't have access to injectable growth hormone, either daily or once a week. Thanks, Dr. Cassola. Thank you, all. Great. Thanks for the questions, Leland. Our next question comes from Catherine Novac from JonesResearch. Please go ahead, Catherine. Hi. Afternoon, everyone, thanks so much for taking my question. You know, Dr. Cassorla, you mentioned, you know, the importance of looking at personalized regimen and PGHD in the future. I'm curious for both Dr. Cassorla and Dr. Dauber, if for LUM-201, you know, if AHV stays in this range, let's say it shows non-inferiority in phase 3, what% of your patients do you think would really benefit from oral therapy like LUM-201. Just a rough estimate. It's tough to say. I think I wouldn't venture a guess that that would be too solid, but I think a substantial number, at least 50% or more, are likely, and I emphasize the word likely, to respond to long-term LUM-201 therapy. Just based upon the categorization of patients who we see in clinic, that most of them have either idiopathic short stature, that is to say, no growth hormone deficiency of any sort, or mild growth hormone deficiency. These are the largest population of patients that we see in our clinics on a daily basis. There's a small number of patients with classical growth hormone deficiency, whether it's associated with other pituitary deficiencies or not. These patients indicated before are not candidates for LUM-201. This is a relatively small number of patients. I think we wouldn't even consider treating them with this particular drug if they have, you know, a response to a growth hormone stimulation test below 2 and with a really essentially an IGF-1 level at the detection level of the assay. We're not even gonna consider. At least I wouldn't consider treating them with LUM-201. Those are the patients that I seldom see in my clinic and in my office. I see mostly patients who are either idiopathic short stature, as defined by peak responses above 10 nanograms per ml to a growth hormone stimulation test with a lowish IGF-1 levels who are slightly below 2 standard deviations in height and who are really desperate, and I would emphasize this word, to become a little taller, so they're not bullied at school. This sometimes is a big problem. Many times the parents have gone through the same thing, so the last thing they want is for their child to go through the same thing. If they can help the child in any way, they're likely to really proceed. In summary, my answer is, I think it's a substantial number. I would venture probably more than 50%, but more than More precisely than that, I wouldn't venture a number. Yeah. I don't have a specific number. I definitely think it's more than 50%. Probably in the 60%-70% range, but I don't have a specific number. Got it. I just wanted to follow up sort of on, you know, how meaningful what we the AHV that we saw with LUM-201 is in this study. You know, albeit it's a small sample size. But given, you know, that we touched on how the low compliance potentially for injectable growth hormone in real-world setting, you know, how meaningful would you say the results of LUM-201 in the phase two study are for patients with idiopathic short stature or moderate PGHD? I think that, you know, while I've been very positive so far, I think that one of the key data points that we don't have is what happens really at 12 months and at 24 months, right? Like, I mean, we, you know. I think if you sustain the growth velocity over 8 centimeters a year for 2 years, that's really good, right? Then, you know, you've just given somebody a pill and gotten at least an extra 2 inches or so, like, in these milder patients, and if that's sustained, that's very, very good. You know, just on 6 months alone, seeing a growth velocity in the 8 centimeters per year, I'm like really encouraged. Like, that's why I'm positive about this. Like, look, it seems to be working. Before making a definitive statement that, like, yeah, this is gonna be really clinically impactful, I think we just need longer term data, which is, you know, forthcoming. I would fully agree with that. Let me say that the purists, the clinicians, the pediatric endocrinologists who are in the outside world will look at six months data with a little bit of hesitancy. That is to say that depending on the part of the world in which you work, I can tell you that now in Chile, we're in the middle of the summer, so for us, you know, we've got over 90 degrees temperatures. I know it's very different right now up in the U.S. That's a concept that becomes important when you look at patients who live very far away from the equator at higher latitudes. keep in mind that the height velocity that is more likely to convince the academic community and the parents and the FDA are the data that we will get over at least 12 months and hopefully over 2 years. I would fully agree with the concept that these data are encouraging, but they are preliminary. Therefore, we wanna make sure that these increases in height velocity remain in place over at least 12 months and hopefully 24 months. That ultimately, these interventions make a difference in terms of final height. Our study is supposed to continue until final height is reached, and we would hope that there will be a difference with this particular drug after several years of administration. The jury is still out. We don't know for sure. We're only showing data for a limited period of time. I kind of agree with Andy's view of this that we need a little longer period of time before we can really say for sure that over 12 months this is holding up. Got it. Appreciate you taking my questions. Thanks so much to both of you. Thanks to the Lumos team for hosting this call. Great. Thank you for the questions, Catherine. Our final question comes from MacCaleCale Chandler from Jefferies. Please go ahead, MaCale. Thank you. Thank you Doctors Kisoila and Dauber for answering our questions today. I guess the first one is really for Dr. Kisoila, and I was just wondering if you could expand on how you interpret the relationship between what appears to be better growth velocity in the 1.6 dose level in OraGrowtH210 versus a significantly greater growth hormone area under the curve in the higher dose in OraGrowtH212. Is this attributable to the feedback mechanism that you've talked about? I guess it also appears that the baseline characteristics are again different between the dose levels for OraGrowtH210 and OraGrowtH212 that might have impacted the AHV as well. Yeah. Well, yeah. I think that we have a slight imbalance in the two groups of five patients in each group with 1.6 and 3.2. The 3.2 patients are more growth hormone deficient. They may therefore respond to this drug in a slightly better way than the patients who are less growth hormone deficient. I believe that these differences may be to the slight imbalance in the two groups that we have studied up to now. This happens to be true also for the OraGrowtH210 study, which there's a slight imbalance there in the four groups. Remember when we are analyzing data, at 12 months with only 2 patients in my study, at 12 months and 3 patients in the other with the other dose, we are decreasing the number of observations quite a bit. We need to be particularly careful about concluding that actually there is a true difference between these two groups. We'll have to see. We've got hopefully 24 patients that are gonna be studied with the 2 doses, and we will see hopefully after 1 year whether it's true that they grow better with a higher dose compared to the lower dose. I think the jury is still out for that. I would only suggest that the difference that we're seeing up to now may be related to 2 facts. The first one is that the numbers are very small. The numbers of patient studies is very small at 12 months. Number two, that actually the baseline characteristics of the two groups are slightly different and therefore we shouldn't conclude that actually one of the doses is much better than the other one until we have a data in a larger population of patients. Great. Thank you. I guess also, how can you use the pulsatility data to help potentially inform a different dose between the 1.6 and the 2.8 ceiling for a phase 3 trial? Is that something that is possible or that you're thinking about? Well, again, I'm not involved in that decision, but I would think it's possible and that we should use these data to try to come up with the best possible base for the phase three trial. I think that the beauty of our study is that it includes pulsatility data obtained. Remember, we've got six-year-old, seven-year-old children who are have a butterfly in their arm for 12 hours and in which our star nurse can get a sample, a minute sample of blood every 10 minutes for 12 hours. These children are obviously reading or watching TV or moving around a little bit, not a lot and having their meals during the 12 hours. This is a major kind of undertaking that's being done. Fortunately, our group has a lot of experience with doing this. As I say, our star nurse has done this in the past with other studies. We feel confident that these data are a true picture of what happens in terms of pulsatility or growth hormone. I would hope that this information is gonna be taken into account by Lumos to decide which is gonna be the best possible dose for the phase 3 trial. I'm not totally convinced that the 1.6 is equivalent to the 3.2, but again, I've got a little bias because I'm involved in our study. In our study up to now, we're seeing a little difference, but I have to be the first one to accept that this is based upon a very limited number of patients. I wouldn't dare to say that these are definite data. It's suggestive preliminary data. In our hands at least, the 2 doses are not quite the same, whether in terms of growth hormone pulsatility or growth velocity. Understood. Thank you. Thanks for the questions, MacCale. This concludes our question and answer session for today. I'll now turn it back to Rick for closing remarks. Yes. I'd like to thank everybody for participating in our KOL event. This is a really important discussion. I would say overall, Lumos is really grateful for the participation from our investigators, the endocrine community at large, in particular our patient population and their families, and of course, the investor community that came to us today. The Lumos team would be really more than pleased to answer any additional questions you might have on a follow-up call. Thanks again for your participation.