Lumos Pharma, Inc. (LUMO) Earnings Call Transcript & Summary

Good morning, and welcome to the Lumos Pharma KOL Event. [Operator Instructions] 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.

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. And 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. So this morning, we issued a press release highlighting the updated interim data from our OraGrowtH210 and OraGrowtH212 trial presented at Endo this past weekend. And before we get to the discussion of these data, I will first introduce the speakers on this call. Our President and Chief Scientific Officer, John McKew, is on, but we will then make a few comments regarding Lumos Pharma's upcoming clinical milestones. So today, we're pleased to have 2 key opinion leaders in the field of pediatric endocrinology on the call, who will review data presented last weekend's Endo meeting. Our first speaker is Dr. Fernando Cassorla, [ Senior ] Investigator of our mechanistic PK/PD or growth 212 trial, 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. And after the discussion, there will be a question-and-answer session with instructions to follow at that time. Mr. Cassorla is currently Chief of Pediatric Endocrinology at the University of Chile and previously served as a clinical director at the National Institute of Child Health, the division of the NIH. He has authored over 200 articles, numerous abstracts in this field has been the 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 his fellowship in pediatric endocrinology in Children's Hospital of Philadelphia. Dr. Tansey is currently a clinical professor Department of Pediatrics and serves as Clinical Director for the Division of Pediatric Endocrinology and Diabetes Department of Pediatrics University of Iowa, Iowa City. Dr. Tansey has been a co-investigator for 1 of 5 clinical centers for the NIH-funded diabetes research and children's network called Direct Net Group since 2001 and has offered numerous scientific publications on brain function and growth in children with type 1 diabetes and has received several awards for his work. Dr. Tansey received his MD from Loyola Stritch School of Medicine, Maywood, Illinois, and completed his residency in pediatrics at the University of Iowa Children's Hospital and is fellowship in pediatric chronology at the University of Iowa hospitals and clinics. But 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 and oral growth hormone stimulating small molecule that works naturally within the into feedback loop and is currently being evaluated in several Phase II clinical trials for moderate and [ hepatic ] pediatric growth hormone deficiency, or PGHD. Prior data suggests that LUM-201 has the potential to address the 10 other growth hormone disorders, representing a total market of approximately $3.5 billion, and this does not include China. Currently, the only treatment for PGHD and tenors hormone disorders consist of either daily or weekly injections of the exogenous growth hormone. If approved by the FDA, we believe LUM-201 has potential to disrupt this sizable injectable recombinant growth hormone market. Our interim data from our Phase II OraGrowtH210 and 212 trial showed the LUM-201 produced growth in line with historical data for moderate PGHD and demonstrated a durability of effect out to 12 months. We look forward to our primary data readout in Q4, while we have 6-month battle on a total of 104 patients called both trials, plus 12, 18 and even 24-month data on a subset of enrollees. And 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. OraGrowtH210 and 212 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 Richmont 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 dose of LUM-201 are enrolled in the study, thereby derisking our trials. 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 recommended growth hormone. The purpose of this trial is to evaluate annualized site velocity or AHV at several LUM-201 doses and determine the optimal dose for a Phase III 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. Again, AHV will be assessed. However, 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 II 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 III trial. That said, in order to set expectations for growth in this moderate PGHD population. We have mined several historical databases where the 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 nanometers per year at 12 months of treatment on growth hormone. The smaller 020 study assessed annualized growth of PEM-positive subjects at 6 months. We believe this 8.3 to 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 historical ranges I just mentioned. The growth hormone cohort demonstrated outsized growth, presumably due to 2 outliers randomized to that arm impacting the mean in the small sample-sized cohort. These 2 outliers were 2 of the 3 youngest patients in the trial with the underage being one of the strongest predictors of faster growth on therapy. Other baseline characteristic imbalances between the growth hormone and the 1.6 mg per kg per day arm at the interim data cut are also suggested growth on an 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, and we would expect this to lead to more balanced AHV values and our full readout later this year. Because of these outliers in the small end inherit in any Phase II trial, we believe historical data serve as a better measure by which to evaluate our Phase II data. The learnings from our Phase II trial have proven invaluable and as these Phase II data mature, our confidence in the potential LUM-201 can demonstrate in a well-designed Phase III registration trial growth. Based on recent Phase III trials in PGHD, we anticipate that our registration trial will enroll approximately 180 to 200 subjects who have met our predictive Richmont 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 2 other factors determined by our Phase II data and randomized 2:1, LUM-201 to a standard daily dose of growth hormone. Subjects will be on treatment for 12 months at which point annual height velocity will be measured. The FDA have historically determined success in Phase III trials in this indication by comparing the treatment and control arms, average height velocities at 12 months and requiring a noninferiority margin of approximately 2 centimeters to deem them comparable. We would expect a similar measurement of success expected for our Phase III 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 GH response and IGF-1 and annualized height velocity measured at 6 months in the interim analysis of the OraGrowtH212 study in idiopathic pediatric row hormone deficiency. I present this on behalf of our group, our research the University of Chile and of Lumos Pharma. Now these are by disclosures. And I will move on then to the mechanism of action of this particular drug. LUM-201 is an oral growth hormone secretagogue. It acts as a durable evenness of the growth for incurable receptor, both of the pituitary and the enoftalmus to simulate room release. LUM-201 has been observed to increase the antidote of endogenous pulsatile growth hormone secretion over 24 hours and a very important differentiating feature versus growth hormone is a 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 pulsatile growth hormones secretion in a selective pediatric growth of efficient population. And I emphasize the word selective. These are patients with moderate idiopathic pediatric growth hormone deficiency whose access 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 we have a response to provocative test simulation tests that are intermediate, not really exceeding below as would be the case of severe growth hormone efficiency [indiscernible] responses are showing that the [indiscernible] is actually working in these patients to some degree, but not to the degree to sustain adequate growth. Now our Phase II possibility PK/PD study design is a [ toll ]. We recruited 22 naive idiopathic pediatric growth hormone deficient patients, pretty pubertal 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 at levels that were way above 5, but 20, 25, this is robust response to the acute stimulation with this drug, even though they had a relatively poor response to the classical growth hormone stimulation tests, indicating that they had a responsibility [indiscernible]. At baseline, we measure the height, the silo levels, and they underwent the period of 12 hours of measurements of blood samples every 10 minutes in order to measure growth on pulsatility. They were then 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 the total 22. At 6 months, we measure again height SDS, and we performed another pulsatility study with blood samples obtained every 10 minutes or 12 hours in these patients in order to look at pulsatility or growth of [ hormone ]. The idea is to continue achieving these patients until near adult height. It's an open-label study with a nano 22. These patients are growth hormone treatment-naive, and they have to have the classical characteristics that would make them candidates for treatment, a height below 2 standardizations, delayed bone age, the big response of the 74 to probably a stimulation test between 3 and 10 nanograms. And this was all conducted 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 velocity and to evaluate PK/PD in this shutter. And the goals are to confirm prior PK/PD data in adults of set on the previous study and to support future regulatory filings and commercialization. Now if we look at the questions that we posted 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 2, will increase amplitude of room positivity and increasing IGF-1 serum levels within our range improved height velocity? And number 3, is the effect on annualized high velocity durable out to 12 months. I would show you here the baseline demographics of our patients. This is a subset of the 22 patients at [ OraGrowth ] 15. Here, the age is about the age of 8 for both groups, height about 2.3 [indiscernible] relations below the mean, a [ idea ] of 1 level between minus 1 about approximately minus 0.8% for the 3.2-milligram group. The mid-parental height shown here. The delta [indiscernible] height that is to say the distance that these patients had to their [indiscernible] shown also in this slide. The bone age delay approximately 1.5 years, 1.83 years, the BMI and distribution according to gender with a slight growth in as of more voice in the higher dose group. Even though this was a study that is randomized prospective, there were minor difference between 2 groups. There's a slight imbalance in age and gender. There's a slight imbalance also in delta below midparental high, BMI and bone age delay. We expect that as we complete the study with 22 patients, these minor differences are going to 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. And 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 per dose, in darker blue are the patients who received the 3.2 milligrams per kilo per dose. Now it's clear that this drug raised the annualized high velocity from baseline after 6 months of therapy for both the 1.6 milligram per kilo cohort and the 3.2 million per kilo cohort. No statistical difference exists between the 2 cohorts at each time point. And as expected, greater growth response was observed in patients with lower baseline growth velocity as shown here in this particular location and have the lowest velocity and baseline and had a period robust response to therapy. Now if we look at the durable response beyond 6 months up to a year, you can see it again in light blue, the patient with the low dose, in dark blue, the patients with the high dose. They then to increase quite dramatically by 6 months, and the response remains quite stable at 9 months and 12 months as shown on the bar, graph here on the right in which you can see that the baseline growth velocities are less than 5 to begin with, go up to about 7.5% to 8% and remain in that kind of range, even up to 12 months, even though again, the number of patients followed has obviously been a little lower as the study is still ongoing. So we do see a durable response. How does this compare with some of the data that have been shown for growth hormone-treated patients? Well, here are data on the paper published by Dr. Ranke, Germany, a study for patients treated with growth hormone in which we can divide them into severe pediatric growth on efficiency on the upper panels and moderate pediatric growth on efficiency on the lower panels, and those are the ones that are closest to the patients that we see in this particular study. And for the less severe patients during either the first year, particularly the first year, you can see at the age, you see it on the horizontal axis. So for the age of about 8, the mean annualized growth velocity is approximately 8 centimeters per year, even though some patients grow more and some patients grow less. But that mean that we observed in our study is quite comparable to the one that was by Dr. Ranke in a cohort that involves a large number of patients due to the growth hormone indicating that these patients with a severe growth hormone deficiency, just like ours and about the age of 8 tend to grow during the first year at about 8,000 centimeters per year, just like our patients. Now if we look at CMIDF1 levels, that's another beauty of the study, we see that the baseline at IGF-1 levels for both the 1.6 and 3.2 doses are relatively low. They go up after 6 months and a little bit more so with the 3.2-milligram dose, but they essentially increased quite a bit. And if you look at it in zero absolute numbers or if you look at it in terms of the IGF-1 SDS levels, there's again a change from about minus 1 or close to minus 1, [indiscernible]l below the mean approximately the mean for the 1.6% or slightly above the mean more than 3.2 milligrams. But again, we don't see a overshoot of very high IGF-1 levels that might be observed with human growth hormone volatility because there's preservation here active feedback that allows the system to continue taking and balancing the simulation of the [indiscernible] and therefore, the idea of what levels increase, but don't go beyond what will be expected as a physiological level. In concludes, we conclude that there's a significant increase in 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 I just indicated. Now I want to show a couple of representative cases, Patient A treated with 1.6 megagrams per kilo per day, IGF-1 levels, [indiscernible] obtained the retainment for 12 hours and the high velocity and baseline and the change that you observed following the administration of the drug at this particular goes, 1.6% for 6 months include [indiscernible], there's a 61% increase in serum GH 1 level. There's a 33% increase in the Q10 minutes something to occur for growth hormone, and there's an increase from 5.6% up to 7.9% centimeters per year on therapy. And you can see the positivity 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 baselines. IGF-1 levels, the [indiscernible] or the high velocity before therapy. And you can see the postal patent before therapy in this particular patient. And after in 6 months of therapy, you can see in blue that there is a larger amplitude of these growth hormone pulses following therapy. And the idea 1 level increases by 131% and Q10 minutes sampling [indiscernible] growth hormone increases 91% and high 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 serious adverse events, no meaningful safety signals observed either laboratory values, adverse data or electrocardiogram values and the most common adverse events, transient increased appetite, 76%, usually amounts or 2, they show an increase in appetite, not for the full 6 months, pain over the full year, pain in extremity 17% or arthralgia 12% abdominal pain and influenza in about 6%, most likely unrelated to the truck. We conclude, therefore, that the time of interim analysis, LUM-201 was well tolerated and showed no significant safety signals. So the questions are, does LUM-201 dose-dependently augment endogenous growth hormone in patients with idiopathic pediatric growth hormone deficiency? The answer is yes. Will increase amplitude of growth hormone pulsatility, driving increased IGF-1 levels improve height velocity? The answer is yes. Is the effect of angular head velocity durable out to 12 months? The answer is also yes. And I would like to conclude the slide showing the conclusions. Based on this interim analysis, OraGrowtH212 demonstrates that growth acceleration is durable through 12 months in our study population, pre-pubertal treatment-naive pediatric growth hormone deficiency patients. No statistical difference exists between the boards 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 from a historical growth of 8.3 to 8.6 centimeters per year as shown in the slide from KIGS also GeNeSiS in this moderate 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. So again, this is data that was presented at the recent Endocrine Society Meeting in Chicago, and I think was very well received. So the title of this presentation was Growth Response of Oral LUM-201 and OraGrowtH210 and OraGrowtH212 trials and 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 neural 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. So these are the disclosures that I have there. Next slide. So I also want to make sure that I acknowledge all the contributors that participated and our authors on the OraGrowtH210 data set here. So you'll see a variety of investigators from across the United States as well as from Poland and Australia and at the bottom, again, the members from the Lumos team as well. So next slide, please. So the other, again, data that I presented in terms of OraGrowtH212 abstracts which Dr. Cassorla just presented for his team at the University of Chile. Next slide, please. So the objectives of the presentation are to report the growth response analyzing these combined interim analysis data from each of these 2 Phase II 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. And what we did was we took the interim analysis data from both of these studies, and we combine and analyze that, and we calculated annualized height velocity, which I'll be showing you and also some of the baseline demographic data were analyzed for the 2 combined cohorts as well. And on the top right, you see there, again, we're talking about both combining data for the OraGrowtH210 and 212 trials. Next slide, please. So again, Dr. Cassorla review 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 to secretagogue. This acts on the growth hormone secretagogue receptor, this GHSR1a to actually stimulate growth hormone release. So again, a different drug than growth hormone, which, again, a lot of pediatric endocrinologists have seen that data over many years and are very familiar with growth hormone. So again, this is, I think, something new for our audience there. As Dr. Cassorla highlighted, we know that LUM-201 has been served to increase both the amplitude of endogenous pulsatile growth hormone accretion over a 24-hour period. And again, a differentiating feature versus routine growth hormone, which we prescribed for many patients is that the natural negative feedback mechanisms are intact, so that limits this high IGF-1 levels, which are sometimes seen in traditional recombinant growth hormone therapy. And again, I'm going to highlight here that LUM-201 produces a pulsatile growth hormone secretion in a selective pediatric growth hormone-deficiency population. The slide on the left there just shows the mechanism, again, of action where we see LUM-201, acting on receptors at the level of the hypothalamus in pituitary reduces this pulsatile response in growth hormone secretion, which is very physiologic again, as Dr. Cassorla highlighted. And what we have, again, as a result of this, we see increase in IGF-1, which has the ability to [ negatively ] feedback on the hypothalamus and pituitary. Next slide, please. So 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 identifying who's going to be responding. So what we did was looking at a single dose of LUM-201 as a simulation dose to identify those who we think of as being positive for these predictive enrichment markers or negative for these predictive enrichment markers. So again, we look at that response to a single dose. And on the left side, we see that the PEM-positive group of patients, and those characteristics included a baseline IGF-1 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 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 in pituitary. So if these responders to LUM-201 are positive responders, again, typically have what we call moderate idiopathic pediatric growth hormone deficiency. And that's probably about 50% 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's stimulated. Growth hormone levels of LUM-201 was less than 5%. So again, indicating that they're not responding and a nonfunctional hypothalamic-pituitary growth hormone axis. So again, not really responding. So these are patients who may have what we would consider to be severe organic pediatric growth hormone deficiency and then maybe about 40% of the total pediatric row hormone deficiency population. Next slide, please. So again, looking at OraGrowtH210, our Phase II data for this. Again, these are patients who were all naive idiopathic pediatric growth hormone deficiency patients. They all have standard growth hormone stimulation tests and last mentioned earlier, for the PEM-positive patients, they had a peak growth hormone of over 5 to the single dose of LUM-201 so these subjects were then randomized for 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 at 3.2 milligrams per kilo per day and daily growth hormone [indiscernible]. And then the study is going on, we're following with height and IGF-1 and then looking at the long-term extension study as well. So 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 drill 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. And again, this is going to be a 24-month study. Our primary endpoints are annualized high velocity with goals of prospectively confirming utility of our PEM strategy that I outlined previously and to help determine our optimal Phase III dosing for this drug. Next slide, please. So Dr. Cassorla reviewed this data, so this is the OraGrowtH212 Phase II trial, again, which is looking at pulsatility in PK/PD study. Again, same naive idiopathic pediatric 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 we mentioned here looking at height IGF-1 and then monitoring growth hormone sampling during the study. The 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. So he has 22 subjects in that study, as we mentioned. And again, all who have prepubertal pediatric growth hormone deficiency and naive to grow hormone therapy, inclusion criteria for that part of the study as well, included less than minus 2 and patients below the mean, delayed bone age and a growth hormone response to economy simulation test between 3 and 10 in 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 effects on endogenous growth hormone pulsatility and annualized height velocity and evaluate PK/PD studies in children as well. And the 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. So 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 less than 2 and aviations below the mean. You see they have delays in bone age, BMIs were in normal range. And again, about 60-40 male, female. So these are the data that representation 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. So this slide is looking at annualized height velocity. So again, Dr. Cassorla mentioned some of this from the 210 trial. If we look at on the y-axis of the 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. And what we're seeing is a change again, which is sustained over time from baseline with response to that annualized height velocity. So we think that our interim data would demonstrate that LUM-201 produces a durable annualized high-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. And we're also seeing that it's both 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. So this is our interim analysis, safety data from the combined trials, again, showing you data for both 1.6 and 3.2 milligrams per kilo per day. And 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 do not see any meaningful safety signals and lab values, adverse events data or EKG values, treatment-related AEs we saw in both groups included, again, increased appetite. And as Dr. Cassorla mentioned, that was not permanent but was seen early on. Orthologist are what people describe as growing pains, paying and extremities, occasional abdominal pain and bone pain as well. Next slide, please. So in conclusion, again, as growth velocity was comparable for the 2 different doses, the 1.6 and 3.2 milligrams per kilo per day, the analysis of the combined, again, interim analysis data might take just 1.6 milligrams per kilo per day to optimal dosing for a Phase III trial because going to 3.2 milligrams per kilo per day did not really seem to, at least again, our data so far did not really offer a meaningful improvement or efficacy. Our final dose determination will await full final data set analysis for both studies. And again, we did not see any treatment-related serious adverse events, no discontinuation due to adverse events, no meaningful safety signals observed and lab values adverse event data or EKG values. And I'll wrap up just with a few final notes and 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 hormones and they may be interested and then they hear about injections. And that gives people pause sometimes about starting injections on people. And 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 universal among a lot of subjects. So 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? And we have to caution then, that's going to take time. One of the thoughts I had when we were 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. And 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. So that concludes my portion of the data, and I will turn it back over to the rest of the team. Thank you.

Thank you, Fernando and Tansey. And Corey, I think you're going to open up some questions to our analysts who are on.

Sarah is going to moderate the live questions from the analysts, and then I'll do the written questions. Go ahead, Sarah.

[Operator Instructions] So our first question comes from Yasmeen Rahimi from Piper Sandler.

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. So that's question one. And then question number 2 is, could you guys maybe speak broadly about translation of studies when we go from a Phase IIb study to a larger Phase III historically speaking, because that's going to be one of the key questions for a lot of our investors on the [ halt ] of the data in the fourth quarter. And 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 III study in that maybe it could expedite the time of enrolling the study in any way. And I know it's premature, but the commentary about significant patient and family interest makes us analysts think that enrollment could be even expedited.

Okay. I think the first question has to do with the IGF-1 levels at 6 months and versus a year. So I don't know, Fernando, if you want to start with that in your study.

Yes. We have some limited data regarding serum IGF-1 levels at the year, and they remain very similar to what they are at 6 months. So the serum IGF-1 levels go up. They reach either the mean for age or slightly above the mean for age at 6 months, and they remain in that range until 12 months. Now some operations are now reaching the 18-month mark, very few. And again, we're looking with a lot of interest in what happens with the serum IGF-1 levels and the limited data that we have so far indicates that the serum IGF-1 levels remain about the mean or above the mean compared to about minus 1 at the time they started.

And Dr. Tansey, if you want to add anything to that?

No, like I said I didn't present a lot of IGF-1 data at 12 months. But again, I think we're seeing improvements in IGF-1 and a good IGF-1 response, I would say, is my impression.

So 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 online space. And so I think 180 to 200 patients study, all patients on drug for a year at least and [ noise ] high velocity at 12 months is the endpoint, same patient population using our -- derisking the study with our PEMs patients only. And I can tell you that doing this particular study was really not an easy study to start in the middle of the pandemic, I wouldn't recommend that to anyone. But our enrollment might exception well, I think, because of the – Dr. Tansey just said, and that is the interest of the patient population and the families that participated in oral. And then to answer your question on Phase III study, based on these data, we've already begun our planning for that Phase III study. And this would be a large multinational study, obviously, same patient population, PEM-positive. And 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 3 large companies who are 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. And 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 recruitment in clinical trials, and that's a significant factor and goals that we have. There 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. So I think for -- like you mentioned, this select patient population who have what we 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 III trials. So I think patients are excited. And 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 [indiscernible] for pediatric growth hormone deficiency appear to be an impossible idea. And this has been going on for quite some time. The pediatric endocrine community has had this hope that at some point, a drug that would be orally available to produce more growth hormone from the [indiscernible] would become a possible treatment for this. And now we're beginning to open up the store now with some clear findings and I think we also had recruitment of Phase III. When we were confronted, we're recruiting patients for Phase II, the obvious question for the families was is it going to work. And we have to say 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. And therefore, when we see patients that may become candidates for the Phase III 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 a little bit over 100 patients altogether. It's 82 patients in 210 and 22 patients in 212 plays at 104. And that's a substantial amount of information indicating that these patients grow better on this particular agent. And therefore, when they request some predictions as to what's going to happen, even though we cannot guarantee to the families that they will grow better, showing the data from the Phase II indicating to them that we have over 100 patients who have grown better on this drug in the initial Phase II trial, I think will help a lot with the Phase III trial because that's going to be more clear for them.

Our next question comes from Pete Stavropoulos from Cantor Fitzgerald.

Congratulations on the data presented at Endo. So first question I have from Dr. Cassorla's presentation, 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 per kg group in the 212 study had a sharp rise in AHV in the first 6 months compared to the 1.6 mg per kg group, and then there was a drop off for the 3.2 mg group that came more in line with the 1.6 group between month 6 and 12?

Yes, 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 that were growing at a slower rate. So if you start from a slower growth rate, it's likely that a response will be greater, just as it is for growth hormone therapy. So I think this has do more with the slight imbalance in the 2 groups with the current number of patients that have been evaluated with not may change when we reach all 22 patients getting to the 1-year mark. But more than a difference than the actual dose because the element interpretation is that actually the 3.2 dose is better than the 1.6. 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 are growing worse and children who are growing on the 1.6. And 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 group's baseline rather an intrinsic difference in the dosing of these particular patients.

Okay. With that in mind, can you just speculate if that same phenomenon would have been observed if the 3.2% was actually given 1.6? And basically, what I'm driving at for those exact patients, which you have left efficacy on the table with a 1.6 mg dose.

Yes, I think so. Again, it's early to say. We're not in a position to say and equitably, 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 baseline characteristics rather than in the dosing. But 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. And then taking into consideration the safety profile and tolerability, would you see a reason to have 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 of those compared to a small amount of those with the lower dose. So I would say that at this stage of the game, it's early to tell. It's most likely unrelated to those, the difference that we see, but we cannot exclude, for sure, that there won't be a slight difference in high velocities once all the group has completed the 12-month period of intervention. We are showing data on 15 out of 22 patients. And 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 because the 2 dose. Because remember, these patients were allocated randomly to dose. So by definition, the differences should be quite minor once all 32 patients are evaluated at the end of the 12-month period.

Okay. And then one question again for Dr. Cassorla and Dr. Tansey, being at Endo 2023 and other endocrinology-focused conferences throughout the year. So when you speak to your colleagues about LUM-201, its mechanism of action, how it's differentiated from standard of care recombinant growth hormone as well as having the precision medicine approach and being able to identify likely responders using the pens. What is their reception of this candidate and approach and the data presented to date, especially compared to the company growth hormone?

Michael, do you want to go first?

Sure, I can start. So again, I think there was a good discussion about this. I think our presentation was very well attended, I would say. And I thought we had good questions from the audience. So 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 a personalized medicine approach that is a new therapy that is different from what they've seen before. And I think people are seeing this, the data as being fairly comparable to growth hormone. But I'll turn it over to Dr. Cassorla.

Well, it's interesting. Anecdotally, some of the colleagues will actually work for the growth hormone pharmaceutical industry, who we know for many, many years because they are pediatric oncologists 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 a very skeptical view of this, there's always going to be people who say, well, these stations are not truly growth hormone efficient, 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 as the vast majority of the patients have been seen in our clinics. Dr. Tansey and myself would 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 [ plastic out severe ] growth hormone deficiency. I would say it's less than 40%, maybe 25%. But again, a substantial number of these patients have this partial form of growth hormone deficiency. But according to the assay used to measure growth hormone, according to the test 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. So 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 are families are reluctant to the injections. And to the cost, I might add there's 2 major factors. In South America, we don't have the luxury of having third-party payers for this. So families end up paying for this out of their pocket. So there's an issue of cost, but there's also an issue of convenience. So 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. So depending of the age which you start therapy. So my perception is that there's interest in this, that we all recognize as a need for an alternative and that they are looking at this with interest. And obviously, we want to see more data before we arrive at a very firm conclusion, but we have to accept that the data so far looks quite promising. And I think that was the impression of most of the people who do I talk after the meeting. And as Michael was saying, this was a very well-attended session. The hall was totally full. And the people who are there are mostly practitioners, are people who keep patients with [indiscernible], and they want to know about alternatives, and this may be one that becomes a reality in the not-too-distant future.

And just to add another comment to Dr. Cassorla. As he mentioned, this is often a long-term therapy that we're looking at using. So again, right now, our only FDA production for this group that we're talking about of this mild growth on deficiency as growth hormone. And 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. So it's a very long-term therapy. And again, I think when we talk to families and patients about this, I think that's part of the burden that they're thinking about is that a daily injection for the next 5, 8, 10, 12 years. That's significant and something that they're really considering. So that I think adds to this interest and alternative to our really only therapeutical option that we have right now.

Our next question comes from Leland Gershell from Oppenheimer.

A couple of questions for both of our physician experts. With respect to excess IGF-1 in response to growth hormone therapy, to what extent is that an issue in clinical practice? And to what extent does that limit perhaps therapy among some patients? And then I have a follow-up question.

I'll start, and I'll let Dr. Cassorla jump in. So I've been prescribing growth hormone for a little over 20 years, not nearly as long as Dr. Cassorla, of course, but we didn't always use to measure IGF-1 with growth hormone therapy. So this is 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 upon IGF-1 level. And again, the main reason – again, if we're making an adjustment to our growth hormone does based on IGF-1 level, the vast majority of the time, in my experience, that's because of high IGF-1 levels that we're seeing. If we're seeing very low IGF-1 level, then our first out is, 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? So IGF-1 monitoring is -- I'll say it's a little bit of a burden for families. Any time we're getting blood work on these kids, I think they see that as a burden. So I think, again, having an alternative therapy, which doesn't impact and lead to those elevated IGF-1 levels can be helpful. But I'll turn it over to Dr. Cassorla as well.