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spk12: Good morning, and welcome to Lumos Pharma's Topline Results conference call. Currently, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. As a reminder, this conference call is being recorded. I will now turn the call over to Lisa Miller, Senior Director of Investor Relations.
spk08: Thank you, Operator. Before we proceed with the call, I would like to remind everyone that certain statements made during this call are forward looking statements under US federal securities laws. These statements are subject to risks and uncertainties that could cause actual results to differ materially from historical experience or present expectations. Additional information concerning factors that could cause actual results to differ is contained in our periodic reports filed with SEC. The forward-looking statements made during this call speak only as of the date hereof, and the company undertakes no obligation to update or revise the forward-looking statements. Information presented on this call is contained in the press release we issued yesterday and in our Form 8-K, which may be accessed from the Investors page of the company's website. Speaking on today's call will be Rick Hawkins, CEO and Chairman, John McHugh, our President and Chief Scientific Officer, Dr. Duke Patuk Chuanant, Senior Vice President of Global Clinical and Medical Affairs, and Lori Lawley, Chief Financial Officer. I will now turn the call over to Rick.
spk11: Thank you, Lisa, and good morning, everyone. After the market closed yesterday, we issued a press release announcing top-line results from our Phase II Oral Growth 210 and Oral Growth 212 trials of Oral Loom 201 and Pediatric Growth Hormone Deficiency, or PGHV. I'm pleased to report that all primary and secondary endpoints were met in both trials, and data from these trials provide supportive evidence to... Ladies and gentlemen, please stand by.
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spk00: © transcript Emily Beynon © transcript Emily Beynon
spk12: Ladies and gentlemen, thank you for standing by, and we apologize for the technical difficulty. We will now return to the conference. Please go ahead.
spk11: So after the market closed yesterday, we issued a press release announcing top-line results from our Phase II oral growth 210 and oral growth 212 trials of oral lume 201 and pediatric growth hormone deficiency, or PGHC. I'm pleased to report that all primary and secondary endpoints were met in both trials, and data from these trials provide supportive evidence to advance LUM201 to a Phase III clinical trial. I'm going to commence by offering a summary outlining how we believe these data convincingly establish the validity of LUM201 as a potential oral replacement for moderate PGAC patients. eliminating the need for daily and weekly injections. Subsequently, I'll hand over the discussion to John McHugh, our President and Chief Scientific Officer, who will provide a thorough examination of these results. So, to begin, findings from our Oral Grow 210 study indicate that the LUM201 dosage of 1.6 mg per kg resulted in annualized height velocities, or AHVs, of 8.2 centimeters a year at the six-month mark and 8 centimeters a year at the 12-month mark. These figures align with the historical growth rates observed in the moderate PGHD population. The difference in annualized height velocities at both the 6- and 12-month time periods between the ideal 1.6 mg per kg LUM201 dose and the requirement human growth hormone comparative group falls within the non-inferiority threshold of less than 2 centimeters a year which aligns with the criteria recently employed by FDA approvals. While it's important to note that this study was not designed with the power to establish non-inferiority, we're delighted to observe that the growth outcomes in this study are on par with the recombinant human growth hormone comparator arm, falling within the recent phase three non-inferiority thresholds utilized for FDA approval. Furthermore, The preliminary 24-month 201 data compiled from two sources, and that is a subset of the Orgo 210 participants who met the protocol requirements for an extension beyond 12 months, and the Orgo 212 subjects revealed a sustained effect with no material decrease in annualized height velocity between the 12-month and the 24-month timeframes. In the ORAGO 210 study, we successfully attained our predefined primary endpoint, confirming the validity of our predictive enrichment marker, or PEM test. We also met the secondary endpoint by demonstrating 100 percent reproducibility of the PEM-positive classification. Additionally, data from the ORAGO 212 trial highlighted that LUM201 achieves growth comparable to exogenous injectable recombinant growth hormone while utilizing only 20% of the growth hormone concentration levels. This discovery underscores the significance of LUM201's unique pulsatile mechanism of action and its capacity to restore the natural pulsatile release of growth hormone. And lastly, regarding the safety data gathered from both our phase two trials with paying a well-defined safety profile for LUM201. And at present, there have been no safety concerns associated with its use. And considering that LUM201 induces annualized high velocities in alignment with historical norms for moderate PGSD patients on recombinant human growth hormone that demonstrates a robust and enduring response and validates our PEM strategy for the selection of suitable moderate PGHD patients, and continues to maintain a clean safety record without any signals of concern, we're confident in the strength of our data set for presentation during our end-of-phase two meeting with the FDA and a finalization of our phase three trial plans. So with that, I'm going to now hand it over to John McHugh for a more comprehensive review of our data. John?
spk06: Thank you, Rick, and good morning, everyone. Before I review the data, I would first like to remind everyone of LUM201's unique mechanism of action. LUM201 is a small molecule that agonizes a specific receptor on the pituitary and the hypothalamus to stimulate pulsatile growth hormone release over 24 hours, which thereby increases IGF-1 in circulation, and both the growth hormone and IGF-1 then act on the growth plates, enabling a child with growth hormone deficiency to grow. This pulsatile mechanism is very different from injectable growth hormone and the PK curve that its nightly bolus injections produce. Also unique to LUM201 is that this molecule intervenes above the release of growth hormone, so the naturally evolved feedback mechanisms that define physiological levels of growth hormone and IGF-1 are still intact. This prevents LUM201 from overstimulating the pituitary and producing too much growth hormone and subsequently too much IGF-1. This unique mechanism has implications regarding who might respond to our molecule. For analysis of LUM201's mechanism and previous clinical studies in this patient population, we're able to establish cutoff levels for both baseline IGF-1 and LUM201-stimulated growth hormone to determine likely responders to LUM201. We found that patients with a baseline IGF-1 of greater than 30 nanograms per mil and a peak growth hormone stimulation value greater than or equal to 5 nanograms per mil were those deemed likely to respond to LUM201 treatment. These cutoffs represent our predictive enrichment markers, or PEMs, which we use to enroll patients for our Oral Growth 210 trial. Now I'd like to provide a brief overview of the ORA Growth 210 trial results. As many of you may recall, this trial involved a dose-finding study with 82 subjects with the primary goal of assessing the annualized high velocity, or AHV, at six months on treatment. Additional objectives included the confirmation of the pre-specified outcomes, assessing the effectiveness of our PEMS strategy, and the ability to choose an optimal dose for our Phase III trial. It's worth noting that as a Phase II trial, the Oral Growth 210 study is not designed to establish statistical non-inferiority in AHB between lean 201 and the control arm. To begin, I will discuss the baseline characteristics that predict growth for the subjects participating in our dose-finding Oral Growth 210 trial. During our interim analysis, we observed imbalances among the various treatment arms, particularly in terms of age. which seemed to augment the differences in growth rates during treatment. However, as we continue to enroll subjects in the trial with a focus on the 1.6 mg per kg LUM201 arm and the comparator for common human growth in one arm, we have observed the expected narrowing of these imbalances. Consequently, the growth rates in these specific cohorts have started to align. We anticipate that in a fully powered phase three trial, we will likely achieve better balance between the treatment and the control arm, resulting in a more comparable growth rate. We conducted a standard ANCOVA analysis to determine the least square mean of AHVs at both the six-month and 12-month intervals for the study. For the 1.6 Mg per kg dosage of LUM201, Loom 201 achieved an age fee of 8.2 centimeters per year and 8.0 centimeters per year at 6 and 12 months, respectively. It's worth highlighting that the disparity of 1.8 centimeters per year at 6 months and 1.7 centimeters per year at 12 months between the 1.6 mcg per kg dose and the recounted human growth and the comparator arm are within the historical non-inferiority margins commonly agreed to in recent Phase III growth trials. Furthermore, when examining the 12-month AHV data available for 50 out of the 81 subjects, it is clear that the growth rates observed remain consistent and enduring at the 12-month milestone. Allow me to direct your attention to the unexpected increase in annualized height velocity observed in the moderate PGHD population treated with the daily recombinant human growth hormone in the control arm. This outcome deviated from the expectations set by numerous historical trials, which anticipated growth rates in the range of 8.3 to 8.6 centimeters per year for moderate TGH feet. We suspect that this atypical growth in the daily growth hormone arm of this study was likely influenced by the higher recombinant growth hormone dosage administered and the presence of specific growth outliers. PHV aligns with growth rates historically observed in similar patient populations from the Phase IV Eli Lilly Genesis database, the Pfizer-Kiggs database, and a Spanish study of moderate TGHC patients. Furthermore, at the 12-month time point, whom 201 exhibited an annualized height velocity within 1.3 centimeters per year of the daily injectable recombinant human growth hormone arm of the Pfizer Phase III somatrogon trial, for the subset of subjects that are similar to our moderate PGHD population. Now to shift our focus to the predefined primary and secondary statistical objectives of evaluating our PEM strategy. We met our preliminary validation of the PEM strategy as being effective in enriching our trial for LUM201 responders. Additionally, we achieved 100% reproducibility in the PEM-positive classification of subjects randomized in the OrgGrowth210 trial. These two outcomes reinforce our confidence in using this PEM strategy for our Phase III program. IGF-1, working in conjunction with growth hormone, plays a role in stimulating growth by acting on the open growth plates of the lung bones. Data from the OrgGrowth210 trial revealed that LUM201 successfully restored IGF-1 levels to a normalized state within six months of treatment, and this effect persisted at the 12-month time point. Importantly, we believe that this capacity to normalize IGF-1 is a direct consequence of Loom 201's pulsatile mechanism of action, which operates within the natural endocrine feedback loop, effectively regulating growth hormone and IGF-1 levels to mimic the experience of normally grown children. In summary, the R-Growth 210 trial successfully achieved all of its primary and secondary endpoints. Loom 201 demonstrated annualized height velocity results that are in line with historical benchmarks for moderate PGHD population, meaning our growth expectations. Additionally, LUM201 was shown to restore IGF-1 standard deviation scores to a normalized state within six months of treatment, and this effect was durable to the 12-month time point. Furthermore, the continuing safety profile of LUM201 was reaffirmed. Now I will turn the call over to Duke to discuss our mechanistic PKPD or growth 212 trial. Duke.
spk10: Thank you, John. Transitioning to the outcome from our PKPD Oral Growth 212 study, it is very important to note that this was a single-site trial involving a more uniform patient population compared to our multinational Oral Growth 210 trial. The 212 study was designed to investigate the impact of LUM201 on endogenous growth hormone pulsatility and analyte high velocity, while also assessing the pharmacokinetics and pharmacodynamics of LUM201 in a pediatric growth hormone deficiency population. The demographic of dose enrolled in oral growth 212 highlight a greater degree of youth deformity within this trial, in contrast to what we observed in oral growth 210. However, the baseline characteristics across both trials were comparable enough to permit combining them for further analysis. The analyzed high-velocity fighting at the month-six mark of treatment revealed a substantial growth improvement from pretreatment growth rates for both the 1.6 and 3.2 milligram per kilo dosage of LUM201. These findings were corroborated by the analyte high-velocity data from the 12-month treatment population in this per-protocol analysis, indicating a persistent and lasting impact of LUM201. The IGF-1 standard deviation score data reaffirmed The outcome of the oral growth 210 study illustrating that LUMTO-1 effectively restores IGF-1 level with the sustained impact lasting up to 12 months of treatment and no excursion beyond two standard deviations were observed in this time period. PKPD data demonstrated that LUMTO-1 promotes an elevation in pulsatide secretion of growth hormone, restoring the levels seen in normal physiology. For examining the 24-hour pulsatide secretion, the data revealed that LUM201 achieved growth comparable to exogenous injectable recombinant human growth hormone while utilizing only 20% of the growth hormone concentration levels. These results imply growth hormone secretion generated by LUM201 is potentially more efficient than daily growth hormone in promoting growth. We want to emphasize that LUM201 ability to restore the endogenous pulsatide secretion of growth hormone enables this remarkable increase in growth with significantly less circulating growth hormone, all while maintaining IgE1 level within normal range. In summary, autogrowth 212 achieved all primary and secondary endpoints, with the data providing strong support for this distinctive, novel mechanism of action of LUM201. Now, shifting our focus to the combined data from these two studies, early findings for the 24-month period suggest that LUM2-1 exhibit a more enduring response compared to recombinant human growth hormone. We hypothesized that the small decline in year two annual high velocity compared to recombinant human growth hormone can be attributed to the LUMTO1's ability to bring growth hormone and IGF-1 levels back to normal through its unique pulsatide secretion mechanism. The investigational safety data combined from these two trials indicate the absence of significant serious adverse events. no participant withdrawal due to serious adverse events or adverse events, and no noteworthy safety concern observed to date. With that, I will pass the floor over to Laurie for a brief summary of our Q3 financial results, which we also reported yesterday.
spk03: Thank you, Duke. Lumos Pharma ended the quarter on September 30, 2023, with cash, cash equivalents, and short-term investments totaling $42.7 million, compared to $67.4 million on December 31, 2022. The company expects use of approximately $9 to $10 million in the fourth quarter of 2023. Cash on hand as of September 30, 2023, is expected to support operations through the third quarter of 2024, inclusive of the activities related to planning and initiation of a pivotal Phase III clinical trial. Research and development expenses were $5 million for the quarter ended September 30, 2023, compared to $4.1 million for the same period in 2022, primarily due to an increase of $0.9 million in clinical trial expenses and $0.2 million in consulting expenses, offset by a decrease of $0.2 million in personnel-related expenses. General and administrative expenses were $3.9 million for the quarter ended September 30th, 2023, unchanged as compared to the same period in 2022. The net loss for the quarter ended September 30th, 2023 was $8.3 million compared to the net loss of $7.3 million for the same period in 2022. Lumos Pharma ended the third quarter of 2023 with 7,914,582 shares outstanding.
spk13: Now I'll turn the call over to Rick for some final remarks and forthcoming activities. Rick, I believe you're on mute.
spk11: Yep. Thank you, Lori and John and Duke. As is evident, we're very excited and impressed by the data that we shared today. Both oral growth trials have successfully achieved their primary and secondary objectives. The annualized high-velocity data from the LUM-201 at the 1.6 mg per kg dosage falls within the historical phase III non-inferiority thresholds, and the PK-PD data suggests unique advantages associated with the mechanism of action of LUM-201 for patients with moderate PGHD. In the following stages of this program, We're currently immersed in a careful preparation for a Phase III trial. With our data now available, the initial step involves seeking an end-of-Phase II meeting with the FDA to evaluate the Phase II outcomes and establish the final design of the pivotal trial. We plan to make the request for the end-of-Phase II meeting with the FDA within the first half of 2024, and we expect to kick off the Phase III program in the latter half of 2024. So, in conclusion, we're confident that our findings suggest that LUM201 has the capacity to revolutionize the global growth hormone market, which has been dominated by injectable products for nearly four decades. We're enthusiastic about progressing with this significant program, and we want to thank all of our clinical investigators, their staff, the patients, families who participated in these trials. And we owe each and every one of them our gratitude for the successful realization of these trials. We believe this sets the stage for potential novel oral therapy for moderate PGHD that benefit patients and families worldwide. So thank you for your attention. And operator, we can now open things up for questions.
spk12: Thank you. At this time, we will be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. If at any time you wish to remove your question from the queue, please press star 2. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Once again, to ask a question, please press star 1. Our first question is from Charles Duncan with Cantor Fitzgerald.
spk04: Hey, good morning, Rick and team. First of all, thank you for taking the question. And secondly, yeah, congratulations. Very, very nice results. Good for patients, potentially transformative. I had a couple of questions for Duke, and I'm trying to have him answer this from the perspective of a doctor who used to treat patients, or maybe he still does, with pediatric growth hormone deficiency. I guess I'm wondering if he could provide a little bit more color on the lack of considerable decline over time, not only in terms of, yeah, the effect size in one year, but the effect size over a couple of years. And then I also had a question on the safety observations. Thank you.
spk11: Yep, so go ahead, Duke.
spk10: Yes, so thank you for the question. This is very good, right? As you know, that most of the growth hormone therapy, the dose of the growth hormone that provides for the patient with DIL injection is supra-physiologic. LUM201 have a unique mechanism that basically provides, you know, 24-hour growth hormone secretion. And we do believe that with these drugs, that mimic physiology, you can enhance the growth secretion throughout the growth period. As you know, children, their growing depends on when you start the treatment. The boy will continue to grow until 18 and girl continue to grow about 15. So basically, with the normal physiology, it can match up with the normal growth pattern age appropriate. And that is signaling not just only the safety profile itself, but basically the continued progress of the growth. And we do believe that this type of process dealing puberty, the gloom toll one can help to promote growth alive with a pubertal growth spurt as well.
spk04: That's helpful. I had a question on safety and I'd like you to answer this in the context of potential safety or lack thereof of super physiological growth hormone. I guess I'm wondering, in terms of the 40% treatment-related AEs in the 1.6 arm, can you provide some color, any observations that were maybe greater than 5% of control? And then there was, I think, one patient with transaminase increase. How do you see that, especially relative to the current standard of care?
spk10: Yes, so thank you. So let me separate into two parts, right? So the safety for LUMTO-1 versus supraphysiologic, those treated by growth hormone, right? So in our study, as you can see, the percentage of LUMTO-1, percentage of the adverse event may be a little bit higher, but part of that due to two things. If you can see that part of the PIM strategy, every single patient who came into the trial, regardless they get enrolled or not, if they're exposed to LUM-201, even one dose, we need to document that adverse event. Majority of those adverse events, even though you see the percentage seem on the high side, but none of them related to LUM-201. Come to the treatment adverse events that have been demonstrated related to LUM-201, especially one subject with increased transaminase. So as you can see that that specific subject, when you look into the details, They only mind elevation of liver enzyme and resolve over time when to continue to follow those patients. Now, unlike the superficial dose that treated with daily growth hormone and long-acting, as you know, especially recently approved long-acting growth hormone, you can see significant higher IgA1 SDS and growth hormone concentration. In one week treated with growth hormone, long-acting growth hormone, you can see that the growth hormone in circulation at least the first three to four days after the injection, you can see a very high supraphysiology. However, it comes down towards the optimal or baseline towards seven days. And IGF-1 excursion higher because when you give exogenous daily growth hormone, you shut down a negative feedback loop. which is basically you cannot control how high level IGF-1 will be. That's one of the unique mechanism of LUMTO-1 that differentiates itself from the daily growth hormone therapy because we will not be able to generate IGF-1 high normal because we have intact feedback loop that control the IGF-1 within normal range. And one thing I want to point out as I present earlier, It's very interesting that we only need approximately one-fifth of the growth hormone concentration in order to achieve the comparable growth velocity. This is a very breakthrough information that potentially could be a unique treatment for the patient in the future.
spk04: Got it. One last multi-part question for Rick or John Morris, you know, call it strategic. know that you haven't met with the FDA. So don't expect you to be all that granular on this, but if you contemplate a phase three design, can you give us a sense of, you know, rough size and does the PEM strategy help you to, uh, at least make that more capital efficient, uh, if you will, if not in terms of size, at least in terms of patient population, And then maybe for Rick, are you contemplating partnering this and would that be a geographic partnership or perhaps a broader? Thanks.
spk13: John, why don't you start with that question? Thanks, Charles. So I think, you know,
spk06: As you said, we haven't finalized our phase three plans, but we have been looking towards what the other long-acting molecules in this space have used for their phase three or pivotal designs. And we anticipate a similar sized trial, so something on the order of 200 subjects. many of those studies they did a two to one randomization between the test article and the comparator arm so that is uh that is more that is the direction that we're planning towards but obviously we have to do more work right now finalizing our phase three plans based on the data we just turned over and then negotiate with the fda to agree on that but that's that's the vision we have right now and i'll turn it over to rick to answer the rest yeah
spk11: Thanks, John. You know, Charles, I think we're really fortunate to be at this stage in development as a company as we're looking forward to a global phase three trial. Any company that's at late stage in development, usually a lot of good things happen in terms of potential partners that may show up. I think we've guided in the past that, yes, we've been active in talking to a number of people around the world. We want to keep the major markets for ourselves. And I think many companies at this stage do consider regional partnerships where they can bring in a substantial amount of non-dilutive capital. And that, combined with a typical raise at this stage, would provide a healthy outlook for the company financially. Thank you for taking my questions.
spk13: Congrats on the results.
spk12: Our next question is from Yasmeen Rahimi with Piper Sandler.
spk14: Good morning, team, and congrats on the amazing data. Quick question for you. I guess the first one is really great to see the 12-month data. Could you comment on if moving forward you have any additional time points beyond 12 months to see at the growth charts? has patients continuing treatment? If we don't have it on hand, when do we expect to have that? And then I have a second question as well. Okay.
spk11: Well, good question, Yasmin. I'm going to let John address that.
spk06: So this study is still ongoing. The 210 and 212 studies are both continuing to go forward. So the 12-month data that we've presented as of today is just how many subjects made it to 12 months when we read out the full six-month data package. So, you know, as time goes on and the rest of the cohort makes it to 12 months, that's another very important data set that we'll be sharing when we get to that point.
spk14: So, could we envision multiple readouts into 2024 from those data cuts?
spk06: major conferences if you could just maybe talk about the cadence of data in the next 12 months that could be helpful yeah so we we will uh fully enroll but or the you know the full cohort at 12 months will absolutely come out next year in the first half of next year and I think we have several key endocrine conferences that happen in the springtime with Pediatric Endocrine Society and the ENDO meeting. And then later in the year, we'll have the DSP meeting outside the US. So I think those are going to be the three key time points for scientific presentations on our full data set. We are also hosting, more currently, a KOL session on December 6th where we'll explore this current data set in much more detail.
spk14: Wonderful. And then maybe a last question is, could you maybe talk about what are areas of discussion in regards to phase three design? You talked a little bit about, you know, the potential size, but maybe what are areas where maybe you may have sort of a negotiation with the agency in regards to pivotal photographs? And I'll jump back into the queue, and thanks again, and congrats.
spk11: Thank you for that question, Yaz, and I'm going to turn that back over to John, too.
spk06: Yeah, I mean, I think the data package we just turned over has the pieces that we need to have this discussion with the FDA, right? We have to look at the effect size, the variability in each cohort, and we have to take that and plan for the size trial that I think is going to be appropriate to run for phase three. So there are lots of pieces of data that are still kind of slowly coming out. One of those is the PK data from our 212 study. We're still waiting for that whole data package to come out. And those are all some of the pieces that we'd like to have in hand before we finalize our phase three study.
spk13: Thank you very much. Thank you, Jeff.
spk12: Our next question is from Leland Gershell with Oppenheimer.
spk09: Hey, good morning, Rick and team, and adding my congratulations as well on this terrific readout. Also great to see the 100% reproducibility in the PEM testing element. And to that end, I wanted to ask, maybe early days, but I wanted to ask with respect to the criteria for the PEM test, did you see, with the benefit of these prospective data, did you see any correlation between the magnitude of either of the two elements in terms of the IGF-1 baseline or the growth hormone response and what a particular, the degree to which a particular patient, you know, increased their height velocity?
spk11: Excellent question. And, John, would you please address it?
spk06: Sure. So, Leon, that's something we're interested in. We're digging into that individual kind of subject by subject data yet. We don't have a, you know, we haven't done enough work on that to draw firm conclusions yet. But it is obviously something of interest that we're excited about and, you know, just exploring how much information we can get out of the current data set. That is one of the pieces that we're still working through.
spk09: Okay. And also with respect to the AHV data, it looks like from the data that you show here that the error bars are tight. But I wanted to ask with respect to AHV across the 1.6 milligram per kig cohort, could you kind of describe the range of AHVs that you saw, and particularly with respect to those who were responders, you know, the 70-30 breakdown responder rate? what the AHVs looked like in those who qualified as responders. Thank you.
spk13: Yes, John, why don't you address that?
spk06: So we haven't broken it down on an individual subject-by-subject basis yet, but I think, you know, clearly the standard errors that mean that we have in the graphs that we released is very tight, right? So this is very tight for the 212 study. So it's a very homogeneous population at baseline, and their growth response is very homogeneous to 201. And I think we see a very similar thing in the 210 study, very tight error bars. So all of those subjects are growing very well at a very similar rate.
spk09: Great. And then just lastly, with respect to seeing a fuller breakout of these data, would we have to wait for the endo? conference next June, or could we see these presented maybe at an earlier conference?
spk13: John?
spk06: So there will be this KOL presentation that I spoke about earlier on December 6th, where we'll have three of our clinicians in the trial discussing the results, hopefully in a more fulsome manner as we continue to dig through the data. But PES Pediatric Endocrine Society is in May, and that's the first big meeting that we'll have the opportunity to present that next year.
spk09: All right, terrific. Well, again, congratulations, and thank you. Thank you, Leland.
spk12: Our next question is from Ed White with HC Wainwright.
spk05: Good morning. Congratulations on the data, and thanks for taking my questions. I just want to get your thoughts and perhaps more information on the growth hormone control that reached the 10 centimeters per year in growth. You had said that the higher dosage in the presence of outliers was the reason that it was above the range. I just want to get, if you can, the numbers of patients that you consider the outliers. What was their recorded growth? and what was the increased dose and, you know, why the higher doses were seen in the study?
spk11: Thanks for your question, Ed, and John, if you'd begin to answer that.
spk06: Sure. So, Ed, you know, at the interim analysis data presentation last November, we talked about the two outliers that we had in the growth hormone arm. These were the two two of the three youngest subjects that enrolled in our trial. And we had some really strong growth. One of them grew at about 16 centimeters per year annualized at the six-month time point. The other one was, I think, 13 or 14. So these subjects were growing very, very well for their age. And they were 20% of the data set at interim with 10 subjects per cohort. And now they're down to 10% with 20 subjects. But they're still there. And so I think the good news is we didn't have any other very high-growing subjects enrolled between interim and now. So those two subjects are still the largest outliers. They still exist. And the comment around the growth hormone dosage is really that there is a wide range of growth hormone dosages that are approved on the label, right? And the 34 microns per kick per day is at the upper end of the doses that are approved for nortotropin and genotropin. So we're just pointing out that that, you know, that has been the convention to use that dose going forward, and it is at the higher end of the approved dose on the label. I think it's a combination of both those two very young subjects who were given the higher end of the dose response and responded enormously well.
spk13: That is the outliers we're speaking to.
spk05: Okay. Thanks, John. And another question was just if you can break out the number of patients treated in the U.S. versus international. Any thoughts you have on what phase three enrollment will look like geographically? And were there any differences in the different geographic areas between the U.S. and outside the U.S.?
spk11: Thanks for the question, Ed. And Duke, if you would begin to answer that. And John, jump in. I think I can hear your own questions.
spk10: Yeah, thank you for the question. That's very good. As you know, the Global Phase III trial, right, what we plan moving forward, it can be Global Phase III, not only in the U.S. However, the U.S. will be the number one enrollment site, right? We can have majority of the site in the U.S. and we have some sites outside the U.S. as well. However, in the meantime, We try to do feasibility survey to looking at, because all of this is not only about enrolled subject. We need to think about CMC, the drug supply of each of the country, so how we can provide the drug to each different country, because each country requires regulatory requirements. So with that said, we're still working on the details. And clearly, when we have those data available, we will share publicly.
spk13: Okay, thank you.
spk12: Our next question is from Catherine Novak with Jones Trading.
spk02: Hi. Morning. Congrats on the data. Thanks so much for taking my questions. The first question is for Rick and team. I just wanted to ask a little bit more about the enrollment dynamics. You know, given the time required to fully enroll the Phase IIb study, Do you think there's anything you can do to accelerate enrollment of a potential phase three, you know, thinking about additional geographic regions or a potential partnership? And then, you know, as a follow-up, do you see competition for treatment-naive patients based on the recent approval of long-acting injectable growth hormones? Thanks.
spk11: Thanks for the question, Catherine. I think it's a really good one. We've really thought quite a bit about this. I think as we are in the planning process here, historically, you look at the competition for patients that was in the marketplace for quite some time with three companies. conducting, you know, large global, you know, phase three trials, there was a great deal of competition for those patients. There's a lot less at, you know, currently. So, I think that's going to help us. But I also believe that, you know, we chose some very interesting and connected, but investigators who are really keenly interested in what we're doing because These are mainly very highly experienced investigators, but they've worked with all injectable products for their entire career. So having the first chance to work with a daily oral certainly got their interest. And I believe the results from these two trials is going to pique their interest that much more. And it's going to go directly to, I think, even a really good enrollment in phase three. I think I, was that, did I answer all of your questions there?
spk02: No, yeah, thanks. That was helpful. And I have, you know, one additional question thinking about this from a prescriber's perspective. You know, you showed that, you know, patients on LUM201, they maintain IGF-1 levels within one standard deviation, which, as you mentioned, is not the case with injectable growth hormone. You know, Thinking about this from a prescriber's perspective, what are some of the negative outcomes of having consistently elevated IGF-1? How compelling is this from a commercial standpoint when prescribers are making these decisions in a more moderate population?
spk11: Maybe I can start with an answer, and Duke, if you would jump in right afterwards. But I think we've got some additional insight. Very recently, we had a KOL event. These were a set of five clinicians not attached as investigators to our development program, but independent of us. And I think the consensus of the concern that they had about especially long-acting growth hormone and excursions of IGF-1 over different periods of time especially for a patient who's going to be on drug for perhaps six or seven years of their lives, definitely came out as a concern. And a couple of investigators said, essentially, our goal is to, you know, normalize the growth hormone production and normalize their growth. And as they put it, this is exactly what this drug does. So that part, you know, to us and hearing that from independent investigators was really exciting to hear. And, Duke, if you want to add anything to that, please.
spk10: Yeah, so that's a very good question, right? I am a pediatric endocrinologist myself. I treat a lot of patients. And we know that since the growth hormone recombinant growth hormone had been approved in 1985, We are somewhat concerned about the long-term effect of the growth hormone, especially if it's IgA1 very high. As you know, high IgA1 theoretically could increase the cancer risk. But so far, more than 30 years, we have a large registry, multiple companies follow those patients with growth hormone. It's very clear that IgA1 is good. growth hormone dose-related. If you increase the growth hormone, the higher the dose, IGR1 go up higher. The concept of daily, at this point, we feel quite comfortable after 30 years. However, the new drug therapy, which is long-acting, the mechanism of action is different because a half life is longer. So the patient, during one week period, you expose higher growth hormone as a daily basis and higher IGR1 in general. But again, each drug of the long-acting have different mechanism of action. But in general, that's what you can see. However, the drug get approved, we don't see significant safety signal at 12-month period. But I think as a practitioner, we want to see a long-term data, a safety profile. As you know, growth hormone, we're not treating only a few months or a few years. It could be five to 10 years, depending where the patient received the treatments. With that said, I think long-term follow-up should be continued to see is that any issue with the high excursion IGF-1. As a physician of a cell, if we have the drug that we can provide efficiency, promote growth with the clear safety profile, IGF-1 within normal range, that would be ideal, especially if it's oral therapy versus injection.
spk02: Got it. No, that's very helpful in that. Congrats again on the data. Thanks for taking my questions.
spk13: Thank you, Catherine.
spk12: Ladies and gentlemen, we are showing no further questions. Thank you for participating.
spk08: Apologies, operator. I believe there is a follow-up from Cantor. They're trying to get into the queue.
spk12: Okay. And what is the name?
spk08: Anyway, you could assist them on the other end.
spk12: Yes.
spk13: Stand by, please. Mr. Duncan, are you there? Yeah. Can you hear me?
spk12: Yes, please proceed, sir.
spk04: Okay. Thank you for taking the follow-up. I had two brief questions. Wondering, since we did this diligence a while back, can you remind us of the dosing paradigm, given that Sometimes children have trouble swallowing pills. I guess I'm wondering, I think these are micro tablets. Did you have any issues with regard to compliance? And then second question is regarding intellectual property. Again, I apologize, but I have forgotten this. Can you give us a sense of the IP behind Loom 201? And should it be approved? What do you think the kind of the life of the IP is with regard to that approval. Thanks.
spk11: Okay. The first question, Duke, I want you to answer that, if you will, on compliance.
spk10: So far, the compliance that we see is on the subject compliance, but not related to the taking pill, right? Because I think that some of those issues could be drug shipping delay, et cetera. But so far, as you may or may not know, right, the pill is very small. And even the youngest children in these trials, four years old, will have no problem with swallowing the pills. So I think that, you know, the size of the pill is not an issue with the compliance in terms, in regards to this trial.
spk06: And if I may add to that, we do have, you know, as we spoke about, we do have a new patent where we're focusing on even smaller mini tablets for our phase three and commercial plans moving forward. So we expect that to make it even easier for children to take our drug.
spk11: And Charles, that was a patent that was filed earlier this year. We hope to hear something back very soon. from the Bureau and that patent will go out to 2042. We believe that that will be an Orange Book listed patent and it has to be around composition of matter of the formulas of unique properties of the formulation itself. We found in the process a novelty around the compatibility of the chemicals. So it's really an important patent for us that will go out to 2042. And remember, our method of use patent is around the diagnosis and treatment of growth hormone across the board, not just PGHD, is by the use of our PEM strategy. And that has been issued in the U.S. and many other parts of the world, and it continues to be so in new countries almost every few months. That goes out to 2036. And then, of course, we have orphan drug designation in U.S., Europe, and we'll file for that in other parts of the world as time goes on.
spk04: Very good. Thanks for taking the follow-up.
spk13: Thank you.
spk12: Thank you. Ladies and gentlemen, there are no further questions at this time. Thank you for participating. This ends our call for today.
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