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spk08: Good afternoon and welcome to Lumos Pharma's second quarter 2022 results and clinical update 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.
spk00: Thank you, Operator. Before we proceed with the call, I would like to remind everyone that certain statements made during this call are forward-looking statements under U.S. federal securities laws. These statements are subject to risks and uncertainties that could cause actual results to differ materially from historical experience or present expectations. Additional information concerning factors that could cause actual results to differ is contained in our periodic reports filed with the SEC. The forward-looking statements made during this call speak only as of the date hereof, and the company undertakes no obligation to update or revise the forward-looking statements. Information presented on this call is contained in the press release we issued this afternoon 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. David B. Karp, our chief medical officer, and Lori Lawley, our chief financial officer. I will now turn the call over to Rick.
spk09: Thank you, Lisa, and good afternoon, everyone, and thank you for joining us on today's call. So after the market closed today, we issued a press release announcing our financial results for the 2022 second quarter and detailing our progress advancing our clinical program evaluating room 201 for the treatment of idiopathic or moderate pediatric growth hormone deficiency, or PGHD. On today's call, I'll provide a brief update on LUM201 clinical trials and other developments before turning it over to Lori Lawley for a review of our financial results. Then John and David will join us for our Q&A session. I'm pleased to report that the enrollment trends we highlighted on our last call for our Oral Growth 210 and 212 trials have continued and are able to confirm our intention to announce interim data from both trials in the fourth quarter of this year. Additionally, we expect the primary outcome data readouts for both trials in the second half of 2023, which we expect to include data in 80 subjects from the Oral Growth 210 trial and up to 24 subjects anticipated from our Oral Growth 212 trial. Our interim analysis from the Oral Growth 210 trial will provide an early look at the safety and annualized height velocity or AHV data at three dose levels of LUM201 compared to a standard dose of recombinant human growth hormone in 40 patients at six months on therapy. And as we approach interim data readout, I want to take a moment to explain what we'll be looking for in the data. As most of you know, OroGrow 210 is a global, multi-site, blinded, active control clinical study evaluating oral LUM201 in approximately 80 subjects diagnosed with idiopathic or moderate PGHD. The primary clinical outcome is annualized high velocity at six months on LUM201 for subjects selected by our Predictive Enrichment Marker, or PEM, strategy. compared to the control arm of subjects treated with recombinant growth hormone. So the data signal we will be looking for will be the annualized height velocity in these PEM-positive subjects versus the recombinant growth hormone control arm, not historic comparisons to the height velocity in other trials that typically enroll more severely growth hormone deficient subjects. It's also worth noting that oral growth 210 like all other six-month Phase II trials in the growth hormone space, is not powered to show non-inferiority. The Oral Growth 210 trial is different from all prior PGHD registration studies. This study is enriched to include only PEM-positive idiopathic or moderate PGHD subjects. Our trial does not include individuals with more severe organic PGHD. Now, this is important because it is well known that more severe PGHD subjects respond better to recombinant growth hormone than do moderate PGHD subjects. Therefore, the annualized high-velocity values we would expect in the more moderate idiopathic patient population enrolled in our trial will be lower in all treatment groups compared to, for example, prior long-acting growth hormone studies. You will recall that the overall goals for the Oral Growth 210 trial are one, to identify the optimal dose of BOOM-201 from three dose levels, that is 0.8, 1.6, and 3.2 mgs per kg a day, to be used in a Phase III registration trial, and two, for the annualized height velocity to be numerically comparable to the recombinant growth hormone control arm in this trial, three, to validate our PEM enrichment strategy, And finally, four, to confirm safety and tolerability of LUM201. And as we begin to plan for our single phase three trial required for approval, we expect that its design will mirror prior pivotal trials for growth hormone deficiency therapeutics conducted by our peers. We therefore anticipate enrolling approximately 150 to 200 subjects in our pivotal trial, randomized two to one, LUM201, to a control arm of daily injectable recombinant growth hormone. The subjects will remain on therapy for 12 months at which point height velocity and safety data from both cohorts will be obtained. Again, the LUM201 dose administered in our phase three trial will be determined from our phase two oral growth 210 trial results. These details are obviously subject to the approval of the FDA and other health authorities and we'll engage the agency in discussions about the trial design at the appropriate time. As I mentioned earlier, our upcoming interim data readout will also include data from our Oral Growth 212 trial, our single-site, open-label trial evaluating the pharmacokinetic and pharmacodynamic effects of LUM201 in up to 24 PGHD subjects at the two higher dose levels of 1.6 and 3.2 mg per kg a day. The objective of the 212 trial is to confirm prior clinical data demonstrating the amplified pulsatile release of endogenous growth hormone unique to LUM201 and the potential for this mechanism of action to increase growth hormone secretion across the entire dose response curve in the majority of PGHD patients. The primary endpoint for this trial is six months of PKPD data with additional height velocity data also being assessed at six months and from the extension of this trial to follow subjects to near adult height. We also expect to announce the interim data from the Oral Growth 212 trial in the fourth quarter of this year. For the interim data readout, comparability of baseline characteristics of subjects in each study will determine whether it is appropriate to pool annualized height velocity data from the oral growth 210 and 212 data sets for combined analysis. The primary outcome data readout for oral growth 312 is anticipated around the same time as the primary data readout for the oral growth 210 trial in the second half of 2023 and we expect this oral growth 212 data set to include data in up to 24 subjects. Last quarter we announced the initiation of our Oral Growth 213 trial, or the SWITCH study. This is an open-label, multi-center, phase two study evaluating the growth effects and safety of LUM201 following 12 months of daily recombinant growth hormone in up to 20 PGHD subjects who have completed the Oral Growth 210 trial. Subjects will then be administered LUM201 at a dose level of 3.2 mg per kg a day for up to 12 months. Primary outcome for the 213 trial is annualized height velocity. Secondary outcomes include safety and PK PD measures. This trial continues to enroll subjects from the Oral Growth 210 trial. Now, before turning to other updates, I want to touch on two operational matters related to our clinical trials. We announced last quarter that we had suspended enrollment at our Oral Growth 210 clinical sites in Russia and Ukraine due to ongoing conflict. Fighting in the region has continued, so we have decided to formally close these sites. And as a reminder, no subjects were enrolled at these sites prior to their suspension, so we do not expect these closures to impact our target data timelines. We're adding a few sites in the United States, which should allow us to maintain our original enrollment timelines. And additionally, as many of you probably know, COVID cases continue to have risen again, both in the U.S. and internationally, and the disease continues to be unpredictable. Fortunately, the world continues to adjust to the presence of COVID, and we therefore do not believe that the ongoing pandemic will alter our current clinical development plan. We will, of course, continue to monitor the situation closely. As our clinical trials advance toward data readouts, we're noticing significant interest in the potential of Loom 201 building within the wider PGHD research community. Attendees at both the Endo Conference in June and the Magic Foundation meeting in July advise us that they are following our progress closely and are looking forward to our interim data readout. Last quarter, we announced that renowned pediatric endocrinologist Dr. Pasit Patukchwanat, or Dr. Duke as we call him, joined our medical affairs leadership team. Dr. Duke recently attended the Human Growth Foundation Gala and has been holding investigator meetings in both the U.S. and internationally, and he is observed as growing interest as well. We believe that this reflects the desire among healthcare professionals for an alternative to daily or weekly injections of growth hormone to treat PGHD patients. Feedback, I can tell you, of this nature goes beyond mere buzz. Based on discussions we're having within the broader PGHD community, we believe that the availability of an oral option to treat PGHD has the potential to expand the overall market. Considering the hesitance of some parents have been when faced with the treatment of burden of daily or weekly injections involved with current standard of care, it's not surprising that an oral option may be more attractive. This is especially true in the more moderate cases that LUM201 is intended to treat for the exact patient population we are rolling in our current trials. We look forward to working with both the healthcare professionals and the PGHD patient community to raise awareness about LUM201 programs and the potential of this drug to be a real game changer in this space. Now turning to the collaboration, we announced last quarter with Dr. Laura Dichtel and Massachusetts General to explore the potential of LUM201 in patients with non-alcoholic fatty liver disease or NAFLD. This investigator-sponsored pilot trial is a single-site, six-month, open-label study of daily oral LUM201 in adults with NAFLD. The trial has been rapidly prescreening patients and should begin enrollment in the near future. Again, this pilot study will evaluate the dose of 25 mgs a day of LUM201 in 10 subjects with non-alcoholic fatty liver disease, or NAFLD, and relative IGF-1 deficiency. Prior studies evaluating growth hormone in this indication have been promising, supporting the potential for oral LUM201 to address this condition. And while we remain focused on our core LUM201 program and PGHD, we are pleased to support Mass General's exploration of LUM201's potential in this indication. The condition estimated to be prevalent in approximately 25% of adults worldwide and which can often advance to the more serious liver diseases and result in need for a liver transplant. As we have mentioned, we continue to explore expansion opportunities for LUM201 and other conditions where injectable recombinant human growth hormone is a standard of care. We believe that LUM201 is a pipeline and a product, and through its unique mechanism of action, may have the potential to be efficacious in indications such as Turner syndrome, Prader-Willi syndrome, idiopathic short stature, and children born small for gestational age. We're actively reviewing potential clinical development plans for LUM201 and several of these indications and believe that interim data from our ORAGO trials should clarify the direction we take. We continue to be judicious in our pursuit of rare disease assets beyond LUM201 with careful attention to shareholder value creation. That said, our priority remains Loom 201 and its development. And with that, I'm going to pass it over to Lori for a review of our second quarter financial results. Lori?
spk01: Thanks, Rick, and good afternoon, everyone. For the quarter ended on June 30, 2022, we had cash and cash equivalents totaling $79.5 million compared to $94.8 million on December 31, 2021. We expect average cash use of approximately $8.5 to $9.5 million per quarter through the remainder of 2022. Cash on hand as of the end of our second quarter is expected to support our operations into Q2 2024. Research and development expenses were $4.6 million for the second quarter, an increase compared to $4.1 million for the same period in 2021, primarily due to an increase of $0.3 million in personnel and stock option expense and 0.3 million in legal and consulting expenses, offset by a decrease of 0.1 million in clinical trial and contract manufacturing expenses. General and administrative expenses were 3.7 million for the quarter ended June 30, 2022, a decrease as compared to 4.6 million for the same period in 2021, primarily due to decreases of 0.6 million in personnel-related expenses, 0.4 million in stock compensation expenses, and 0.3 million in legal and other expenses offset by an increase of 0.3 million in royalty expenses. The increase in royalty expenses were due to fees paid to the Public Health Agency of Canada as a result of royalties earned of 0.4 million from Merck for the sale of Ervivo, the Ebola vaccination. The net loss for the second quarter was 7.8 million compared to net loss of 8.7 million for the same period in 2021. Lumos Pharma ended the second quarter with 8,377,567 shares outstanding. I will now turn it back to Rick for closing remarks.
spk09: Thank you, Lori. And so during our second quarter, we continued to execute on our plans for Loom 201. Enrollment trends for our oral growth trials continues to be positive. This is a very special time in the history of Lumos Pharma. We're excited to be able to announce the results of our interim analyses from two phase two studies evaluating oral Loom 201 in our fourth quarter. The therapeutic potential of Loom 201 continues to garner attention in both clinical and patient communities. Our cash position is solid, sufficient to carry us into the second quarter of 2024 beyond both the interim readouts in Q4 of this year and the primary outcome data readouts for oral growth 210 and oral growth 212 in the second half of 2023. Once again, this is an exciting time for Lumos Pharma as we look forward to providing interim results by the end of this year. Operator, we're now ready to take questions.
spk08: Thank you. We'll now begin the question and answer session. To ask a question, you may press star then 1 on your touchtone phone. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then 2. At this time, we'll pause momentarily to assemble our roster. Our first question comes from Charles Duncan from Cantor Fitzgerald. Please go ahead.
spk07: Hi. Good afternoon, Rick and team. Congratulations on the progress, and thanks for taking our questions. I had a couple of questions about the Orr Growth 210 study. I guess I'm wondering if, as you characterize enrollment patterns in second quarter, can we assume that those are continuing roughly the same into the third quarter despite some of the kind of usual summer slowdown? And then you mentioned the height not studying highly severe PGHD and really looking at moderate levels. So could you let us know what you would anticipate as a good result out of those particular patients, even just responding to recombinant growth hormone?
spk09: David, why don't you proceed with that question?
spk04: Here, Charles. Both great questions. So to the first question, as far as the enrollment, your assumption is correct. There does not appear to have been any slowdown in enrollment, and that is why we can really report that the enrollment is still going very, very well. And again, it's really important to understand that PGHD writ large is primarily combined of two subsets. 35 to 40 percent of the kids have organic GHD, which is indicated by an abnormality, an MRI involving the pituitary usually or occasionally can result from a brain cancer and radiation therapy knocking off all the growth hormone-producing cells. About two-thirds, 60%, 65% of the population has so-called idiopathic GHD, which means non-organic. Idiopathic basically means you don't know why they have GHD, although it's felt now to be probably a hypothalamic dysregulation because the hypothalamus controls the pituitary. And that's tailor-made, really, for a compound with the mechanism of LUM201, which really binds to the growth hormone-decreting hormone receptor in the hypothalamus as well as pituitary, and also suppresses somatostatin. So by both those actions, it enhances hormone release of growth hormone. So as far as the question about what kind of growth we expect, when we look at the studies that have been done in the past that have evaluated this, And we've looked at a cut of the Genesis database that we've reported previously and has published where we have kids that basically meet the requirement for our studies. And also we look at a study that was published actually in a Spanish group where they enrolled 100 kids with idiopathic GHD. The response to the standard dose of growth hormone really are aligned in both of those analyses. And it's right around 8.3 centimeters per year. which is somewhat less than what you see in the more severe GHT kids who can grow 10, 10 and a half, et cetera, centimeters per year. So many, many studies over the past 30, 40 years have demonstrated that the more severe the GHT, the better response to growth hormone. So kids that are severely GHT, you can basically wave the bottle over them, they'll grow. They grow perfectly well on, much less than standard doses of growth hormone, doses as low as 0.16 to 0.18 mg per kg per week, whereas the standard in the trials is 0.24, and the average in the U.S. is probably 0.28, 0.30 mg per kg per week. And so all these studies show that if you are younger, if you have more lower growth hormone peak response stimulus, like less than 3, which is exclusionary for our study, the lower your IGF-1, SDS, the farther away you are from mid-parental height, the lower your baseline high-velocity, all of these factors predict a greater response to growth hormone. And so because we're really identifying the bulk of the population with idiopathic, we don't think that they have exactly the same growth potential as the more severe subjects who were studied, for example, in the height study that I ran when I was at Ascendus, for example, and all the other long-acting growth hormone studies which tend to favor enrollment of the more severe organic subjects over the less severe subjects. Does that answer your question?
spk07: I think it absolutely does. Very thorough, and I appreciate that. And then when you look at, on a blinded basis, at some of the phenotypic variables that you can easily see, such as age, et cetera, and other measures, do you feel that your sample is enrolling the patients that you really want to have in this study?
spk04: Yes. We're doing a very good job of excluding organic subjects in the trial, and that's pretty key because a subject with organic GHD is not going to respond to our PEM test because they can't respond. nor are they likely to respond to Loom 201. And that's part of the reason why our screen failure rate is actually lower than we had anticipated. Because if the investigators were just enrolling any kid, we'd expect about, you know, two-thirds of the population to be PIM positive. And we have to be excluding one-third of the kids that are screened. But because they're really identifying kids with a diagnosis of idiopathic GHD, we're experiencing a much lower screen failure rate than we had put into the protocol.
spk07: Okay, very good. Last question quickly on the SWITCH study. Rick mentioned that you are enrolling patients. Can you be at all quantitative or at least qualitative with regard to the percentage of patients who complete the 210 study who decide to switch over to the SWITCH study, 213?
spk04: Yeah, we can right now because it is only subjects who completed their 12-month visit, so the sample size is really too small to comment, I think, right now. It's fair to say that all the subjects who have completed to date have desired to continue on in lieu 201.
spk07: Okay, very good. That's helpful. Thanks for taking the question.
spk08: The next question comes from Jasmine Rahini from Piper Sandler. Please go ahead.
spk02: Hi. This is Emma on for Yaz. Thank you for taking our questions. We have two. First, could you please comment on how many total sites are active at this junction, providing us some insight on how enrollment has picked up in the last three months? Specifically, do you notice if certain geographies have greater uptake versus others? And second, what is your expectation regarding annualized height loss being in the upcoming interim data readout such as what is the expected range and what could be drivers of potentially different data outcomes?
spk04: Yeah, it's fair to say that we have about 40 or 45 percent enrollment from five sites in Poland and the bulk of the other ones come from the U.S. with some enrollments in Australia and New Zealand so it's um I I don't you don't recall like that being because of the recent changes I Can't quote you exactly of sites.
spk09: Well, you know close to 50 distributions They may have half a patients of the patients in the US and half the patients and the rest of the world is the distribution right now right and as far as
spk04: As the anticipated growth, I answered that question when Charles asked it. But again, I can say that based upon the published data in this population, we would expect the mean response to be something around 8.3 centimeters per year. There will obviously be variability around that, as there is with all treatments. And the predictors are really quite well known. So the shorter kids grow better than taller kids. Lower IGF-1 SDS value grows more than higher IGF-1 SDS values. Lower baseline height velocity grows more to growth hormone than higher baseline height velocities. Age, younger kids grow more than older kids. So there's a lot of parameters, bone age delay, that are well known by Renge and others to predict the response to growth hormone. So this is very well described in about 30 years of publications. Okay.
spk02: Thank you.
spk08: The next question comes from Ed White from HC Wainwright. Please go ahead.
spk12: Good afternoon. Thanks for taking my question. First, just a little clarification on the Orr Growth 212 study. you said that you're going to follow patients to near adult height. Can you clarify a bit what that means?
spk04: Sure. The pediatric dosing of growth hormone for both the organic and the idiopathic population usually extends until one of several things happens. Either they complete puberty or they have demonstrated closed epiphyses or Growth velocity falls to less than two centimeters per year. All of those indicate basically that you've basically, that the epiphyses are either closed or very close to being closed, and you've basically consumed all the time when you can treat with growth hormone to add to their adult height. And so the way the protocol's written is they're treated to near adult height, and that's widely understood by the pediatric enterological community to mean one of those things. It's either when a high velocity falls very, very low or there's evidence of epiphyseal closure or Tanner stage three or four, basically. So completion of puberty. Does that answer your question? If you're organic, then you should, not always happens, but you should transition to adult GHD doses. But many of the idiopathic kids, once they complete puberty, now test normal and no longer need to take growth hormone as adults.
spk12: Okay, great. Thanks. That does answer my question. Sure. We've gone into this a few times, you know, that the human growth hormone has been approved for about 11 different indications, and you mentioned several today that might be of interest to the company. I think that Rick had mentioned today that once you see interim data, that should clarify what actions you can take. So should we be anticipating to hear your next steps for different indications sometime at the end of this year or next year? And how do you think about How is this data going to impact what indication you pick? Is there something in particular that you're looking for from the data?
spk09: Sure, sure. We haven't given any guidance about what indication we're going to go to next.
spk04: But it's logical to assume that before you can write a protocol for another indication, you kind of need to know what the optimal dose is. So that's really what is gating now really with our discussion of next indications is the interim data showing what the optimal dose is. So it would be reasonable to expect that sometime after that we may be in a position to discuss other indications, but we have not given guidance on that as of yet. The timing.
spk12: Okay. Okay, great. I guess the last question that I have is just on the tentative phase three trial design. Have you received any input at all from the FDA on this potential trial design, or are you going to wait to talk after the phase two?
spk04: Well, okay, yeah. So we have not yet had our end of phase two meeting, but having had the experience of getting a growth hormone approved by FDA and EMA, this does not actually rocket science, so Our Phase III program will likely look like everyone else's Phase III program. Novo's with somopacitin, Ascendus' with Skytroph, et cetera. So the actual sample size will be confirmed after end of Phase II meeting. I will say that the... What's widely misunderstood is kind of why Ascendus added the switch pivotal phase three trial, because they didn't actually add it to broaden the indication to include non-naive subjects. They added it because we switched from an older formulation in phase two to a newer formulation in phase three, and so the phase two trial was truncated at six months, maximum six month data. So in order to reach the required safety database for a BLA filing, they had to increase the sample size above and beyond the high trial. And the switch trial was considered to be, and it was, the fastest way to get other subjects into the program ahead of the BLA filing. Here at Lumos, we have the advantage of having 24 months in our main trial. We have like three or four or five years in the 210 trial. And so that's going to be increasing our safety database. And also, if it should turn out, for example, let's say that 1.6 milligrams per kilogram per day turns out to be the optimal dose, it means we'll have up to two years of treatment with twice that dose, which will add tremendously to the safety database, which is a key box check for an NDA filing. So my assessment, based upon my past experience, is that given our phase two population, the single pivotal phase three trial will be sufficient for NDA. We'll confirm that at the end of phase two meeting, and if we have to add more subjects for any reason, We may do a switch study, but I don't think that will probably be necessary. But we'll see after we discuss with the health authorities. So that's why the guidance is between 150 to 200. 150 to 160 would be my best guess unless we need to get more safety data. But there isn't a good rationale for that because Phase 2 is providing a tremendous amount of safety data. Okay.
spk08: Any other questions, Ed? Our next question comes from Catherine Novak from Jones Research. Please go ahead.
spk03: Hi. Thanks for taking my question. I'm wondering, given that the oral growth study is not powered to show efficacy, can you give us a sense of, from your standpoint, what Numerically comparable means, both from a go-forward perspective and a dose selection perspective, and what other factors are going to play into the Phase III design?
spk04: Yeah. So, first of all, I will state categorically that no Phase II study is ever powered if it was powered to be a Phase III study. And so, the Phase II study done with Transcon-Glutamone was also not powered for non-inferiority. But you can look at the data, and if you get a consistent response that looks basically the same as growth hormone, you can say it's comparable. So if any of the three doses of Loom 201 produces high-velocity curves that basically overlap growth hormone, I would say that if the mid and the top dose look very, very similar and overlap growth hormone, that would push us to choosing the lower of the two doses as the optimal dose, whereas if there is a dose response, then given the good safety, we'd go with the highest dose. But it'll be based upon a numerical assessment of the curves, but not actual statistics, because the study is not actually powered for proving non-inferiority, statistically.
spk03: Does that make sense? Yeah, thank you for that clarification.
spk04: It's kind of a qualitative assessment,
spk03: It's proven to be successful in the past with other... And then I wonder if you can talk just briefly about the NAFLD study, about how this fits into the company's overall strategy, and from your perspective, what differentiation does Loom 201 bring to this landscape?
spk09: John, why don't you answer that question then?
spk11: So NAFLD is just an interesting opportunity for us to look at other applications of Loom 201 and its effect more broadly. And I think the important thing here is that we've connected with a really talented researcher who is very interested and has done multiple studies in the NAFLD space, including studies with injectable growth hormone. And I think she brings a lot of experience to the table to help us understand what the impact of a daily oral molecule that stimulates growth hormone and has an impact on lipids and on body composition and all the other parameters that can really have an impact in NAFLD. This is a small exploratory study, but I think it's going to have quite an interesting impact that we can learn more about how the mechanism of action of LUM201 can have a broader application outside of the pediatric endocrine indications we're looking at now.
spk09: And of course, Catherine, we filed a patent for this indication, too.
spk03: Got it. Thanks. Thanks very much.
spk08: Sure. The next question comes from Leland Gershow from Oppenheimer. Please go ahead.
spk10: Hey, guys. Good to see the progress, and thanks for taking my questions. A couple from me. First, if you could just review for us how you're going about measuring the 10 markers in the 210 study, and how frequently, and times a day in relation to the, you know, the dosing of fuel one in that study and also the biomarkers themselves. And also have a question with respect to the yeast and dendro meeting. Just your experience here, if you could elaborate, you know, with that having occurred after Ascendis already has Phytophthora in the market, you know, clearly, you know, there's a new option that's perhaps more convenient than the other growth hormone. you're offering an even more convenient one. I know your market research has suggested that there'd be great interest in a once daily oral or once or twice daily oral versus a LBC injectable. But now that that's in market, I just wanted to see if you could share any further perspectives. You may have gotten from physicians who have been prescribing Cyclofa and there's some huge interest in room 201, how that may have changed or not. given that some patients who may be coming onto your candidate may have already switched once from daily to weekly and then be switching again if that poses any hurdles. Thank you.
spk09: Okay, let me start and then maybe anybody else can jump in. But the company has done an exploratory market research study and we queried both pediatric endocrinologists and caregivers. And we've asked the question if they would prefer a weekly injection or a once-a-day oral. And both groups, the pediatric endocrinologist and parents, overwhelmingly chose an oral. So we, based on that preliminary independent market research, we believe that we have really a market shifter, kind of a game changer in this space. it's pretty obvious that kids don't like injections, whether that's once a day or even once a week. And we have a mini tablet. It doesn't make any difference whether you give it morning or evening or with or without food. There's a great deal of flexibility here. So we think we're going to have – it's going to be impactful. Let's put it that way.
spk11: And then I think you wanted a definition of our predictive enrichment markers. So these are predictive enrichment markers that fell out of Merck's or that we derived from Merck's existing clinical data on kids with growth hormone deficiency. So we published on this previously in the Journal of Endocrine Science in 2021. But just to reiterate, basically for PEM positive kids, they have to from a single dose of our molecule, they have to make greater than or equal to 5 nanograms per mil of growth hormone as Cmax, so within an hour of taking a single dose of our drug. And their baseline IGF-1 values, unstimulated, have to be greater than 30 nanograms per mil.
spk10: Great, thank you.
spk09: Does that answer your question, Leland? Questions?
spk10: Yes, that's great. Thanks very much.
spk08: Okay, thank you. The next question comes from Elmer Pyrus from Roth Capital Partners. Please go ahead.
spk06: Yes, good afternoon, gentlemen. I would just like to maybe confirm a couple of things. I want to make sure that I understand it correctly. So combining the 210 and the 212 trial would make sense to you if the baseline parameters are similar in those cohorts. Is that correct to assume?
spk04: Yes, it's exactly right.
spk06: Finish your question, Elmer, I'm sorry. This was the first one, Rick, so I can wait with the other one. Okay, then go ahead.
spk04: Based upon the breadth of the data showing that the baseline characteristics predict the response to growth hormone, it would make sense to combine them if the populations look very, very similar. as far as the degree of GHD. And if they look different, it would argue against combining them.
spk06: Okay.
spk04: And... So if... Yeah.
spk06: Yeah. And also about the PEM strategy. So as you mentioned, there is about two-thirds of the patients who are idiopathic. But in your trial, you find that the screen failure rate is less than the one-third. So you actually... finding patients that are higher in percentage that would fit your strategy. How do you explain that?
spk04: Well, yeah, it's pretty easily explainable. If we told the investigators just to screen for our study any subject they diagnosed with GHD, we would expect that basically about two-thirds of them would be PEM positive, and one-third would be screen failed for being PEM negative. But they're They're not doing that. They're doing the smart thing, which is they're screening subjects who are already identified as having idiopathic GHD. So they're self-selecting to not screen subjects with organic GHD. Don't get me wrong. There's many reasons why a subject can fail, can be screened failed in a study. They can have a conditioned baseline. They can be taking a drug that's prohibited. They can lack a bone age delay. There's lots of reasons. But the sum total of all the possible screen failure reasons is much lower than we had predicted in the protocol, because in the protocol we modeled a somewhat greater screen failure rate on the basis of failing the PEM test. And it turns out because they're screening the appropriate patients, subjects, or patients and similar subjects, we're seeing a much lower screen failure rate because of the PEM test. Does that make sense?
spk06: It does. Thank you. Thank you very much.
spk08: Okay. The next question comes from Suji Jeong from Jefferies. Please go ahead.
spk13: Hi. Thanks for taking my question. So I understand that choosing Phase III dose based on the Phase II result is going to be qualitative. But my question to you is approximately how many centimeters difference would be considered as a comparable to growth format? And I have a follow-up question.
spk04: Yeah, it's a hard question to answer because in Phase 3, when you have an agreed-upon with agencies non-inferiority margin, you can accurately state what the lower boundary of the 95% confidence interval is. But Phase 2, we'll be doing it the same way the doses are selected by NOVO, by Ascendus, et cetera, by looking at the data and deciding, does the balance of the data support this dose or that dose? So it will be largely driven by the high-velocity response. It will probably be partially supported by the IGF-1 response. It will be supported by the safety. I mean, it's kind of a thumbs-up, thumbs-down kind of assessment, kind of how Phase II selects doses for lots of different indications and drugs, but especially in the growth hormone deficiency space.
spk13: I see. So if you look at historically other phase three trials for growth hormones for PGHD, what is the non-inferiority margin used?
spk04: I can tell you categorically that the one used for scitropho was 1.8 centimeters. For Sardis was 2 centimeters. For Sardis was 2 centimeters. So in that range, 1.8 to 2 centimeters. But the non-inferiority margin is based upon the growth hormone response in your trial. So the variability of the response to growth hormone. So we'll have a much better sense of what the non-inferiority margin we would propose would be once we see the final data in all 80 subjects. Well, the 20 subjects on growth hormone, actually, in our trial.
spk13: Yeah. Yeah, and then expanding on that, because LUM201 trial for phase 3 or even phase 2, you mentioned that the patient population is more moderate compared to growth from trials, which tend to enroll more severe patients. Do you think the variability in the trials for LUM201 might be greater than what other trials for GH have seen in the past?
spk04: do I think the potential for growth is greater?
spk13: Yeah, well, variability in growth.
spk04: Oh, is it variability? You know, I've looked at all the published data studies that have looked at this population, and I have been impressed with somewhat less growth. I haven't been impressed with greater variability, but I can say that I've looked at that specifically.
spk11: And even the difference, you know, between Versardis and And the ascendance is only 0.2 centimeters. There's not a huge number in the other studies.
spk04: You're saying in the growth or in the non-inferiority margin?
spk11: No, in the variability determines the non-inferiority margin. Oh, correct. Very similar variabilities. Our population will be different, but like David said, I think it's a little hard to guess because all the studies that are published, I think, on idiopathic aren't exactly, you know, they're observational trials.
spk04: Yeah, and I'll just comment that whereas at Ascendus, the non-operator margin was based upon the Phase II glucomine response, Brassardus, because it lacked a glucomine control in Phase II, I'm not sure how they arrived at the non-operator margin.
spk09: Yeah, historical. Thank you for the question, Suzy. Do you have another one?
spk13: No, I think I'm good. Thank you.
spk08: Thank you for the question. Thank you. I'm showing no further questions in the queue at this time. Thank you for joining us and enjoy your afternoon.
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