This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk07: Good afternoon, ladies and gentlemen, and welcome to the LUMOS Farmers' Year-End 2020 Earnings Conference Call. At this time, 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, Director of Investor Relations, Ms. Miller, please go ahead.
spk05: Thank you. 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 earnings release we issued this afternoon and in our Form 8K, which may be accessed from the investor's page of the company's website. Joining me on today's call are Rick Hawkins, CEO, President and Chairman, John McHugh, Chief Operating Officer and Chief Scientific Officer, Gene Kennedy, our outgoing chief medical officer, and Carl Langren, chief financial officer. Rick Hawkins will provide a corporate update. John McHugh will review the company's lead therapeutic candidate. Gene Kennedy will discuss our clinical trials, and Carl Langren will wrap up the call with a review of the full year 2020 financials and an update of cash guidance. I will now turn the call over to Rick.
spk11: Thank you, Lisa, and good afternoon, and thank you for joining us on today's call. And after the market closed, we issued a press release highlighting our recent clinical and corporate activity, and providing an update on our year-end 2020 financials. Last year marked a period of significant achievement for Lumos Pharma, with the completion of our merger transaction, the monetization of our priority review voucher, and the initiation in the fourth quarter of our Phase IIb or Road 210 trial evaluating our novel therapeutic candidate, Loom 201, for pediatric growth hormone deficiency. Those events put Loomless Pharma on a solid foundation to pursue the development of orally administered Loom 201 with the potential to disrupt the PGHD therapeutic industry where the standard of care consists of daily injections of growth hormone. That momentum continues in 2021 as we move our clinical strategy forward. Our Phase IIb Oral Growth 210 trial continues to advance with data readout anticipated mid-2022. In addition, we expect to initiate our Oral Growth 212 trial shortly. This trial is a small, single-site trial to illustrate the pharmacokinetic and pharmacodynamic effects of LUM201 and PGSD and replicate the pulsatility data that currently exists for LUM201 in adults. Also, today, we introduced our Oral Growth 211 trial, a long-term extension study for eligible PGSD patients who have completed our other LUM201 trials. This extension trial will assess the long-term safety and efficacy of LUM201 in children with growth hormone deficiency. We believe LUM201 is essentially a pipeline and a product with the potential to target up to 11 other indications for which growth hormone has been approved. We're focusing first on PGHD, and once we gather data from our current program, We plan to evaluate LUM201 in a subset of these other indications I just alluded to. Jean Kennedy will review our current clinical efforts in more detail later. We're also pleased by the recent publications of peer-reviewed LUM201 data analyses in the Journal of Endocrine Society. These data from earlier studies of LUM201 in recombinant human growth hormone, or RHGH, demonstrates specific baseline IGF-1 levels and peak growth hormone levels from growth hormone stimulation tests may serve as predictive enrichment markers, or PEMs, useful in identifying the more moderate PGHD patients most likely to respond to LUM201. reviewed data support the approach we are using in our clinical trials. We are also honored to be presenting additional LUM201 data at the Endocrine Society Annual Meeting, also known as ENDO, in late March. As our recently published abstract illustrates, the data being presented at ENDO show a distinction between LUM201 and standard growth hormone secretagogues used to diagnose growth hormone deficiency. These data show that at the lowest dose we are using in our Phase IIb trial, LUM201 elicits statistically higher blood hormone response than standard diagnostic agents. We believe these data further support the potential for LUM201 to be efficacious in the subset of PGAC patients identified by our predictive enrichment markers. John McHugh, our COO and Chief Scientific Officer, will provide more details a bit later on in the call. As you may recall, a priority review voucher was issued upon FDA approval of the Ebola vaccine in which Lumos Pharma had 60% ownership, resulting in a $60 million gross to Lumos Pharma. We received the first payment of $34 million in September and the second and final tranche of $26 million in January of 2021. We continue to look for business development opportunities to expand our pipeline to the acquisition or licensure of another novel therapeutic candidate for rare diseases. These non-diluted funds further strengthen our balance sheet and will be available to support our business development strategy. Carl Langren, our CFO, will discuss our financials in more detail and provide updated guidance regarding our estimated cash use for 2021. So we are excited about the year ahead with the advancement of our oral growth trials in PGHD and the potential expansion of our rare disease pipeline. We believe that LUM201, an orally administered growth hormone secretagogue, offers the potential to disrupt the PGHD market where the current and potential therapies consist only of injectable treatments. Expanding our pipeline would offer an opportunity to reach additional individuals suffering from rare diseases. And we are fortunate to have a solid balance sheet and an experienced management team to execute on this mission. And with that, I will turn the call over to John to review our Oral Growth Pharma and Supretagogue LUM201 and recently published data. John? Thank you, Rick.
spk10: As Rick stated, we are excited to advance our heart growth trials evaluating LUM201 and PGHD patients. We are also pleased about the recent peer-reviewed publications and upcoming endo-presentations of data showing the novel mechanism of action of LUM201 and the potential efficacy of LUM201 and PGHD as compared to standard of care. Given its oral delivery and its mechanism of action that depends on the natural endocrine growth hormone access, we believe that Loon 201 may offer a preferred treatment option for approximately 60% of children suffering from growth hormone deficiency. As a reminder, growth hormone deficiency can be defined by low to absent secretion of growth hormone from the pituitary gland. The current standard of care and other therapeutics in development for children with growth hormone deficiency consists of the delivery of a bolus a growth hormone, or a long-acting derivative to restore growth. All of these therapies are administered by injection and act outside of the body's natural endocrine pathway feedback mechanisms. LUM2-1, on the other hand, is not a growth hormone, but is instead a growth hormone secretion that acts within the body's natural endocrine pathway. LUM2-1 selectively acts on receptors in the pituitary hypothalamus to stimulate the body's ability to release growth hormone at the same intervals and subject to the same Utilizing this endogenous release mechanism should enable the naturally occurring IGF-1 feedback loop to be preserved if needed to help regulate the balance of growth and lunar IGF-1 levels in the body. Given the endogenous nature of loop-to-one activity as just described, individuals able to benefit from the molecule must have a functioning but diminished pituitary axis. For this reason, Lumospharma is targeting the moderate PGHC population of patients who are able to naturally produce some pro-hormone, but in insufficient amounts to attain normal adult height. Based on the analysis of prior clinical data, predictive enrichment markers, or PEMs, identified a moderate PGHC patient group likely to respond to LUM-201 therapy, which represents approximately 60% of the total PGHC population. These data demonstrate that specific PEMs of a baseline IGF-1 level of greater than 30 nanograms per mil and a peak growth hormone level of greater than or equal to 5 nanograms per mil after a single dose of LUM-201 identify this PTHC patient population likely to benefit from LUM-201 and illustrate why these are the PEMs we are using in our oral growth 210 trial. The data analyses recently published in the Journal of Endocrine Society support this PEM strategy. The paper entitled, Development of a Predictive Enrichment Marker for Oral Growth Hormones to Create God's Loon 201 in Children with Growth Hormone Deficiency, is a peer-reviewed analysis of the data from the Merck O20 study we have referred to in prior discussions. Described in detail in the paper, fever operator characteristic, or ROC, curve analysis, and iterative filtering that enabled the determination of specific TEM cutoffs. Also included is our analysis of the growth of children assigned to each treatment arm of the study and their relevant safety data. The second paper, published in the Journal of Endocrine Society, entitled Corroboration between predictive enrichment markers for height velocity to RHGH and an oral growth hormone secretive treatment in children with GHC provides additional support for the use of our predictive enrichment markers to determine those PGHC patients most likely to respond to lumen fuel 1 versus those most likely to respond to standard of care recombinant human growth hormone. This paper describes a data mining exercise of the Eli Lilly Faceboard Legacy Genesis Database. From the database, 514 naive-to-treatment, pre-pubertal children with idiopathic or hormone deficiency whose RHGH treatment data were available for analysis. Genesis was a prospective, open-label, observational research program conducted in 30 countries at more than 800 study sites between 1999 and 2015. The main objectives of genesis was to investigate safety and effectiveness of lilies for common human growth hormone treatment in pediatric patients with growth failure. Baseline IGF-1 assessment and growth hormone stimulation tests were administered and these data were collected in a study. This genesis database, given its size and scope, served as a useful source of real-world evidence for the predictive enrichment marker analysis described in this journal publication. The purpose of the data mining described in the paper was twofold. First, to evaluate if baseline IGF-1 and stimulated peak growth hormone were independent predictors of 12-month high velocity in children with idiopathic growth hormone deficiency. Secondly, to better understand the range of growth hormone deficiency that exists within the PGHC diagnosis and how subsets of the population respond to treatment. Using a correlate of the TBM cut-offs noted above, children with idiopathic isolated growth hormone deficiency, who represent 73% of diagnosed growth hormone deficient patients in the Genesis database, were categorized as severely or moderately growth hormone deficient. Of the 73% with idiopathic GHD, 81 of 514, or 16%, were identified as severely growth hormone deficient, while 433 of 514 patients, 84%, or approximately 60% of the total PGHC population in the database, were determined to be moderately deficient, or what we would term PEM positive. Additionally, these two segmented groups differed significantly in baseline height standard deviation score, height velocity, and change in height during RGH treatment. Further analysis of these groups using the prior work companion study PEM cutoffs showed that the severely deficient group, those with lower baseline IGF-1 levels and lower growth hormone stimulated levels, so the greatest one-year high-velocity catch-up growth after treatment with RHTH. Whereas those with higher baseline IGF-1 levels and higher growth hormone stimulated levels, the moderate or PDM-positive group had significantly lower one-year average height velocity on recombinant human growth hormone treatment of 8.3 centimeters per year. Despite growing at different rates, both the severe and moderate groups arrived at the same place compared to their peers after 12 months of treatment, as evidenced by the high SDS scores of minus 2.6 for severe and moderate at minus 2.00. We chose IGF-1 and stimulated growth hormone levels as predictive enrichment markers because multiple regression analyses showed they were independent predictors of high velocity on treatment with or countering human growth hormone. Finally, the data to be presented at ENDO distinguishes LUM201 from standard growth hormone security dogs. The abstract accepted for presentation entitled LUM201 elicits greater growth hormone response than standard growth hormone security dogs and pediatric growth hormone deficiency supports other data suggesting that LUM201 is unique in its ability efficiency to produce higher Cmax values of growth hormone secretion in children diagnosed with PGHD. The difference between the PGHD value upon the LUM2-1 stimulation was even greater in those patients with higher baseline IJF1 values. We look forward to presenting the full data analysis later in March at ENDO and welcome a discussion of that data with the investment community at that time. We believe that they will strongly support our clinical development strategy in PTHD, and I will now turn the call over to Gene Kennedy, our outgoing chief medical officer, to provide an update on our PTHD trials.
spk09: Gene? Thanks, John. I will take some time now to review our Phase IIb ORA Growth 210 trial and provide a few more specifics on our PKPD ORA Growth 212 trial to be initiated shortly. We initiated our Phase IIb or a growth 210 trial in PGHD last quarter, and the trial continues to advance. To review, this trial is a global, multi-site trial involving approximately 80 PGHD patients randomized into one of three dose levels of Wound 201 or a comparator arm of standard of care injectable growth hormone therapy. Only those PGHD patients determined to be PEM positive, as evaluated by our predictive enrichment marker cutoffs, of baseline IGF-1 greater than 30 nanograms per milliliter and a peak growth hormone level greater than or equal to 5 nanograms per milliliter will be randomized in the study. During this Phase IIb study, the repeatability of the PEM classification will be evaluated during screening for randomization. Each potential participant will have two sets of PEM laboratory samples drawn approximately a week apart. Dosing will be administered over six months. with annualized height velocity as the key clinical outcome measure. The main objectives for this Phase IIb study are to prospectively confirm the utility of our predictive enrichment marker strategy in selecting likely LUM201 responders, to assure that the PEM classification is consistent and repeatable, and to determine the optimal dose for a Phase III registration trial. The three dose levels of 0.8, 1.6, and 3.2 milligrams per kilogram of LUM201 were chosen for our Phase 2b trial for patients with PGHD based on supporting data from the Merck study in PGHD patients John mentioned, as well as a prior PK PD study of LUM201 in healthy adults. The Merck study in PGHD showed no statistical difference in average height velocity for PEM positive patients dosed with 0.8 milligrams per kilogram LUM201 versus those dosed with recombinant human growth hormone. The PKPD study in healthy adults shows that the 0.8 mgs per tig dose is only approximately one-third of the way up the growth hormone dose response curve. These data showed that administering increasing doses of LUM201 in healthy adults up to 100 milligrams, the equivalent of 2.8 mgs per tig in children, result in higher plasma concentrations of growth hormone. The three doses chosen for our Phase IIb trial cover that full pharmacodynamic range and suggest the potential for greater growth hormone secretion and potential efficacy in the PGHD patients in our study. The trial is open and enrolling patients currently. We have received strong positive feedback about the potential for an oral therapy for PGHD. We have identified additional experienced clinical sites in Ukraine, Russia, and Israel interested in participating in our study. This should enhance the enrollment process and increases our confidence in our anticipated mid-2022 data readout. These sites and all others were selected based on their prior history of enrolling PGHD patients in clinical trials and the ability to conduct trials in alignment with our standards. While this trial is ongoing, LUMOS expects to initiate a second concurrent trial of LUM-201 for patients with PGHD shortly. This ORA Growth 212 trial is intended to further illustrate the mechanism of action of LUM201 in amplifying the natural pulsatile secretion of growth hormone. The natural secretion of growth hormone in the body is ultradian and pulsatile in nature with 23 to 25 growth hormone peaks over a given 24-hour period. LUM201 stimulates the secretion of growth hormone in a way that maintains this natural pulsatile mechanism amplifying the peaks of these pulses in order to augment growth hormone and IGF-1 levels. We believe this is important as preclinical data illustrate that pulsatile delivery of growth hormone produces greater efficacy than continuous exposure to the same amount of growth hormone. The OraGrowth 212 trial will focus on pharmacodynamic endpoints at two different doses, 1.6 and 3.2 milligrams per kilogram, in approximately 24 children with PGHD. Prior data in adults confirm the ability of LUM201 to amplify the pulsatile secretion of growth hormone. The purpose of the study is to replicate these pulsatility data in children with PGHD. We plan to conduct this trial at a single specialized pediatric center with the ability to perform the more frequent sample collection and monitoring required for these types of clinical trials. children will have their baseline levels of growth hormone secretion measured every 10 minutes over a 12-hour period and then start on LUM201 for six months. At the end of the six months, they will again have a 12-hour assessment of growth hormone levels to illustrate LUM201's amplification of pulsatile secretion. Once initiated, the study will run in parallel with our ongoing Phase IIb or a Growth 210 trial with the goal of providing supportive data in future regulatory filings and ultimately in any commercial marketing efforts. We have been advised of a fire at the San Borja Arena Hospital in Santiago, Chile. This location is the planned clinical site for the ORA Growth 212 trial. Our investigator's clinic was not directly involved in the fire. However, limited access to the site as the hospital assesses the impact of the fire might delay our trial start. While we had originally expected to initiate this trial in Q1 of 2021, we now anticipate the initiation of the ORA Growth 212 trial to occur in Q2 of 2021. As we have previously stated, this trial is not on the critical pathway for regulatory approval of Loon 201, and we do not anticipate the fire will cause any delays to our timeline. We continue to work with our local partners to advance the trial, and we are also exploring alternate sites to conduct the trial in the event that the original site is unable to proceed in a timely manner. We are also introducing the ORA Growth 211 trial in PGHD. This study will be an open-label, multi-center, long-term extension study for those who have completed a prior Loom 201 trial, such as ORA Growth 210 and ORA Growth 212 trials. Eligible patients who have completed their six-month treatment in either of those studies Upon enrollment in the ORA Growth 211 trial will be administered the LUM201 or recombinant human growth hormone dose prescribed in the preceding LUM201 trial. Primary objective of this trial will be to evaluate the long-term safety of LUM201. In addition, this study will assess the long-term PK PD effects and growth outcomes in response to LUM201 treatment. We believe that LUM201 may serve as a platform therapy potentially applicable to other indications for which recombinant growth hormone is approved. Petting results from our concurrent oral growth trials just discussed, we plan to evaluate LUM201 in these other indications. Beyond LUM201, we continue to actively pursue business development opportunities to license or acquire other rare disease assets in order to expand our pipeline and our ability to provide innovative therapies to those suffering from rare diseases. I will now turn the call over to Carl Langren, our CFO, to discuss financial results for the year-end 2020 and provide a cash forecast for 2021. Carl?
spk06: Thank you, Gene. We ended 2020 with cash and equivalents of $98.7 million. This year-end cash balance does not include the final $26 million in proceeds from the sale of our PRV, which was received in January. For 2021, we anticipate average quarterly cash use of approximately $8 to $9 million. We also expect that our reported cash balance plus the non-diluted funds from the PRV sale will support our operations through the data readout of our OraGrowth 210 and OraGrowth 212 trials and contribute to supporting the expansion of the company's rare disease pipeline. We reported a net loss of $5.7 million for the year ended December 31st, 2020, compared to a net loss of $9.7 million for the same period in 2019. Please refer to the press release we put out this afternoon for additional details on our financial results. Looking ahead, we hope to speak with many of you participating in the Oppenheimer, H.C. Wainwright, and Roth investor conferences this month. We are also looking forward to speaking with all of you once we present our data at the endo-annual meeting in late March. Now I would like to turn the call back over to Rick before we open up for questions. Rick?
spk11: Thank you, Carl. And so before I offer some closing remarks about our programs discussed above, I first want to say a few words about our outgoing chief medical officer, Gene Kennedy. Gene joined Lumos Pharma management team here by way of our merger with Newling Genetics, which is an oncology-focused company he joined in 2014 and where he also served as chief medical officer. Gene helped us tremendously through the merger, and Loomis Pharm has transitioned to a publicly listed company focused on rare diseases. While we would have loved for him to stay, he will now be returning to his roots in oncology as he joins a privately-owned company in that field. We want to thank you for your service to Lumos Pharma and wish you all the best in your next venture.
spk09: Thanks, Rick, for your kind words. I mean, I really have to say that I've thoroughly enjoyed working with the entire Lumos team. As you said, I'm merely returning to my roots. I am highly confident in the potential for LUM-201 and its ability to be efficacious in the PGHD population identified by the predictive enrichment markers and also in Lumos' team's ability to execute on the clinical plan already in place. I hope to keep in touch with the team, and we'll be watching from a distance and pulling for all of your success as the team advances the Loom 201 program in PGHD and expands beyond that purview.
spk11: Thanks, Gene. And, well, as you can tell, we are excited to advance our oral growth trials in PGHD and look forward to initiation of our PKPD Oral Growth 212 trial. We're pleased about the data recently published and about our upcoming presentation at EMDA. And we are on solid financial footing to execute on our strategy and believe that our clinical trials will confirm the potential for Loom 201 to disrupt the PJC market. We look forward to continuing to provide updates as we progress. And with that, we will open the call for questions. Operator?
spk07: All right. So, as a reminder, to ask a question, you will need to press star 1 on your telephone. To resolve your question, press the pound key. Again, that is star 1 on your telephone. First question comes from the line of Charles Duncan from Cantor Fitzgerald. You are now live.
spk12: Okay. Thank you. Hi, Rick and team. Thanks for taking our questions and congrats on the progress on the 210 trial thus far. I actually had a question on that 210 trial. I imagine it's pretty early days in terms of enrollment, but can you talk at all about the pace of enrollment or the screen failure rate at this time, and would you anticipate the first patient to be through the six-month period, the dosing period, and therefore being able to start with the open label extension trial 211 by the end of the second quarter of this year?
spk11: Well, Chad, that's a good question. We haven't really given any guidance yet on entry into the study, but suffice to say that we're progressing nicely. We haven't initiated all of our sites, but they're coming online in pretty quick order. And as Jean pointed out, there are some new sites with experienced investigators and KOLs in another part of the world that we believe will help us meet our goals of having a readout in 2022, mid-2022.
spk12: Okay, and anything about screen failure or that PEM strategy at all at this point?
spk11: I think it's too early in the game to really address that. I think the publications that John just went over give us a great deal of confidence that the screen failure rate is probably going to parallel what we found in that database. Uh, so I think that's, uh, but as soon as we can, we'll report to you, uh, on, on that data.
spk12: Okay. I appreciate that. And just one follow up, John, um, said a lot and said so quickly, and sorry if I miss this, but I think you mentioned that there might be call it a 60% or so patient population versus say, previous estimates of around 50% that met that positive predictive enrichment marker kind of level that you're looking at. And I guess I'm wondering, could you go over that math again? And then in terms of, you know, for example, what you would expect in terms of average height velocity for, you know, patients that are more moderately Could you compare and contrast what you would expect out of recombinant human growth hormone in the moderate patient population versus the more severely impacted patient population? What kind of numbers are you looking at over the course of an annualized height velocity?
spk10: Happy to answer that, Chad. So we'll start with the numbers for the estimate of the patient population that could be responsive. So essentially we've taken our PEM cutoffs and translated them so that we can use them in the Genesis database and use the standard stint test diagnoses to help us sort patients into the same two groups, you know, kind of the PEM positive group and everybody else that are more severe. And so when you look at the large dataset that's Genesis, the kids we're focusing on are, you know, officially termed idiopathic growth hormone deficient children, and that makes up 73% of the children in the Genesis database with the growth hormone deficiency diagnoses. Of those 73%, 84% meet, you know, our criteria of PEM positive. So multiplying 0.73 by 0.84 gets you to about 60% that could be responsive to our molecule and would fit into this PEM positive category. We feel much more confident about this number just because it's derived from a very large, you know, phase four data set, and I think it really is more of a a real-world number than the estimate we could make from the O2O trial just because that had, you know, several regions that the trial was run in. So we're confident about that number. The second question is about the height velocity that we see. So in the Genesis dataset, the group that is selected with our PEM cutoffs showed 12 month growth rates on recombinant human growth hormone of about 8.3 centimeters per year. And it's very clear that if you include a broader group in an analysis of potential growth, that includes many more severe patients that we would filter out from our trial. That population would have much higher growth. And that's simply because the kids who are more severe grow at a faster rate in those first six months. So that 8.3 centimeters per year for the same population that we're going to isolate in our trial is a pretty good indication of what 12-month growth data would look like in a trial that we're going to have going forward.
spk12: But you wouldn't want to compare apples to oranges with a more severe patient population or sample size or sample?
spk10: Yeah, I think the more severe kids are going to grow significantly more. It depends exactly how you define more severe kids. But, you know, essentially they're going to grow statistically different than the moderate kids. In our Genesis analysis, it was 9.6 centimeters per year. So they're different. They're very different populations.
spk12: Okay, and last question, do you believe that prescribers will understand this or reimbursement authorities in terms of a response rate or annualized height velocity? Does that have any implications in terms of the conduct of the study and keeping patients on for the entire six months, or do you think that's not going to be an issue?
spk10: So I think that most of the prescribing clinicians understand that the most severely growth hormone deficient kids grow the most in those first six months. And once they understand that the tools that we're using to select our patients are going to select for moderate growth hormone deficiency, I think they will understand the, you know, they will have expectations set for how much those kids will grow. And it's not just that they're going to grow less on our molecule. They're going to grow less whether they're given recombinant human growth hormone or a different molecule, right?
spk12: It makes sense. Thanks for taking my questions.
spk07: Next one on the queue is Ed White from AC Wainwright. You are now live.
spk10: Good evening, everyone. Thanks for taking my questions. And so just to be clear on the enrollment for the sites, I think you previously had said you're expecting to enroll patients at 40 sites in the US, Poland, Australia, and New Zealand. And now you have interest in these other areas, the Ukraine, Russia, and Israel. Can you give us any idea of the number of sites that are currently enrolling patients or what we would expect to see, say, by the end of the year? Should they all be up and running by then?
spk11: Gene, do you want to take that?
spk09: Yeah, certainly. By the end of the year, definitely. Well, I think we expected them to be up before the end of the year. But, no, we have, you know, many of our U.S. sites are up and running. The few that aren't will be coming up in the next, you know, weeks to months. And then the international sites, again, shortly thereafter. So we're announcing our intentions to open sites in these countries today. It's not that we are starting the work today, if you understand what I'm saying. We've been preparing this for a while. So we expect these sites to all be able to contribute pretty soon.
spk10: Okay, thank you. And then on the core growth 2012 study that was affected by the fire. How long will you give the site to open before you start thinking about moving that study to a different location?
spk02: Gene?
spk09: Yeah, certainly. I mean, thinking, we're already obviously exploring options. But the report we have is that they're likely to be back up and running very soon. I mean, it's a major pediatric hospital. It serves a large portion of the population of Santiago de Chile. And they're optimistic they'll be finished with their repairs in other parts of the building, but it's had some consequences in the part where the clinic are. So I think we're all optimistic this is going to be a short delay. If it proceeds beyond our guidance into Q2, then obviously we'll have to consider other options.
spk11: Yeah, and I think a sound business procedure here is to, no matter what, even though we're confident this site is going to be a viable site going forward, we want to hedge our bets and make sure that we have a backup plan. That's what it's all about.
spk10: Okay, thank you. And then my last question is just on the Extension Study 211. Once those patients are enrolled, how long do you expect them to continue to be followed? I mean, are these patients eligible to continue through the end of puberty or would they just, would you follow them until 210 is completed and perhaps a short time after that? Thank you. Go ahead, Gene.
spk09: Yeah, I mean, our intention would be to allow those kids access to the therapies and to follow them as long as we believe and their physicians and families believe that it's beneficial. That's sort of the answer in a nutshell. But no, 211 would be expected to live beyond the end of the ORGROVE-210 or ORGROVE-212 trials, clearly.
spk07: Okay, thank you for taking my question. Next one on the line is Yoon Young from Jefferies. You are now live.
spk04: Hi, this is Suzy Dowling for you. Thanks for taking our question. Our first question is on the Phase IIb. What's going on? Just wondering if you plan to do an interim look of the study and maybe adjust the number of patients based on that. And the second question is kind of relevant to the first question, but based on the PKPD study data, do you expect to adjust the Phase IIb trial design. Thank you.
spk11: John, you want to take that first?
spk10: Yeah, I'm happy to answer that. So we don't think that an interim look at the data will be necessary for Phase 2b, 210 trial. We also do not think that the PKPD study results will influence in any way the design of the 210 trial. The PKPD study is really about understanding more about the pulsatile nature of release. And it's going to be a separate study that's going to go along in parallel with the 210 trial.
spk04: I see. And my last question is the ENDO 2021 presentation. Has this data been presented before? Just wanted to make sure.
spk10: No, that specific data has not been presented. previously, that's in the abstract of the poster.
spk11: And we would be more than pleased to circle back with you and go over.
spk04: Yeah, that would be great. Thank you.
spk07: Next one on the line is Lena Kaminski from Jones Trading. You are now live.
spk03: Hi, guys. Thank you for scooching me in. So I guess this one may be for John. So you talked about the recent publication, so I really appreciate that. So I guess maybe you can elaborate a little bit further kind of what gives you the confidence and the support for the ongoing 210 trials for LUMES 201. And then also maybe just a little bit on the predictive enrichment marker strategy. I'm specifically kind of trying to understand the relationship between the standard growth hormone stimulation test and the stimulation test with Zoom 201, the difference between the two nanograms per ml versus the five, and then I have a follow-up.
spk02: John?
spk10: Yeah, so let me take the last one first. So in the Bright Manuscript, In Table 4, you'll see a correlation between the standard diagnostic STIM test results and the Loom 201 STIM test results. So we ran a receiver-operator characteristic curve analysis on those datasets, and that's essentially the different stint tests in the same patient, right? And then we correlated what their response would be. And we're able to come up with this correlate that, you know, greater than or equal to five is similar to greater than two with a standard stint test. And then that's the PEM values that we applied to the Genesis data set, simply because they have standard diagnostic STIM test data in the database, and none of those patients had taken the LUM201 STIM test. So that's the connection between those two papers, table four of the Brighton manuscript. So in terms of how do we feel, how do these two publications make us feel more confident about our potential success? I think first, we've enjoyed the results of the analysis for quite some time, but I think the scientific rationale and the approach that we took to derive the cutoffs is important to get out in all of its glory, so to speak. We took a very scientific approach to do that, and I think it's very evident now in the bright manuscript how deeply we thought about the data and how we worked very hard to find the right cut-offs, the right breakpoints in these two different parameters. And I think one way the Bloom manuscript supports our PEMs is first, in this patient population, it was shown very clearly that both baseline IGF-1 values and the growth hormone stimulation values were independent predictors of growth on recombinant human growth hormone. So that means essentially what we want to do with these PDM markers is be able to predict how a child is going to grow. we know that if we can put them in a moderate group or a more severe group, they're going to grow at different rates. And the moderate group with a partially functioning axis is really the group that has the physiology to respond to our LUM201 product, right? Because as a secretagogue, they have to be able to make some growth hormone, and then we're going to help them release it by continuing to stimulate that receptor. And because we can show that they're independent predictors of growth, they turn out to be very good markers to combine and use to separate patients into this PEM positive or moderate category versus the severe category that are less likely to respond. So we like that aspect of that publication. It supports the choices we've made to direct cutoffs from. I hope that answers your question, Lena.
spk03: Got it. Okay, yeah, thank you. That's really helpful. And I guess the last question I have is just more on kind of your strategy and how you're thinking about this patient population. So, you know, do you think, obviously, you're enrolling naive patients, but how are you thinking about maybe which population, maybe patients that were previously treated with growth hormone? Do you think that they might for the benefit from room till one? And are you thinking of conducting this study like that?
spk11: Lee, that's a good question, and I think that anyone who has a product in this space eventually has to get around to that type of switch study. And we certainly will at the right time. Most important goal and objective in front of us is to get this dose to go into a registration trial after this study is over. And then the timing afterwards for that study we will focus in on. I think, John, the second part of our question, I think maybe whether there's any prediction on our part, whether scientifically we would feel that those patients who've been on long-term treatment and switched to our drug would also gain benefits.
spk10: So I think there is a history of exploring those switch patients with some of the long-acting growth hormones. And I think what is known is that the longer a patient stays on, we're commenting the growth hormone therapy, Their growth is maintained, but it's not the same level of growth you see in those first six to 12 months. So you would expect that you would take a patient on recombinant human growth hormone, kind of wash them out from their daily injectable for a while, and then put them on treatment. And I would expect if they meet our PEM criteria that they would be able to respond to the drug. You're going to get a slightly different growth rate from somebody who's been on recombinant growth hormone for five years than you will at 90 patients. It's important to understand that. And that's, again, the same with our molecule or any molecule that you put these kids on. But yes, I do think that if a switch patient meets our criteria, they will be able to respond to our molecule.
spk02: Okay. Operator, any other questions?
spk07: Yes, we do have a question from Yasmin Rahimi from Piper Sandler. You are now live.
spk01: Thank you, Tim. First, before I ask my question. I just want to say thank you, Gene. It's been a pleasure working with you and my team wishes you the best of luck in your next adventure. So it's been wonderful working with you. I have a set of questions. Maybe the first one I would like to start off is just discussing maybe the size of the open label study, you know, meeting with regulators. Is there a certain safety data set that you require and therefore this there's a certain requirement of patients to have an open-label extension. The second question is around the 211 study. Maybe highlight to me what the reason was for not running recombinant growth hormone is one of the groups rather than just two doses of Lumo 201. And then I have a third pipeline question.
spk11: John, you want to start?
spk10: So you asked, I think, about the 212 trial, and you asked why isn't there a common human growth hormone comparator in that trial. Is that correct?
spk01: Yes, that's one of the questions. Yep.
spk10: So I think in that case, we're working on a study at a single site in Chile. We wanted to make sure that we could recruit enough patients into that single site to enable us to really explore the two different doses of LUM201 that are there. There is a decent amount of background or historical data on growth for kids with chronic human growth hormone. We also know what the PK of recombinant human growth hormone looks like in kids, right? So the PK effect of recombinant human growth hormone is the same thing as the PD effect that we're going to look at in that trial. So because that PK curve is so well characterized and it's a single bolus dose, right, that is given at night and within 8 or 10 hours goes away, we know very clearly what the difference in the look of growth hormone being released is going to be for the comparator. So we didn't think that it was necessary, and we would rather focus on enrolling as many kids as we can in our treatment arms. Does that part make sense?
spk01: Yeah, no, that's helpful. And then in regards to the size of the open-label study that is needed for submission,
spk10: Yeah, so the open-label study, I mean, we're going to roll any kid who's interested in continuing from any of our trials, from the, you know, the Phase 2B trial, the 212 trial, or any upcoming Phase 3 study into that, right? We'd like to get as much long-term data as we can. You know, Gene, it was mentioned earlier that, you know, that we want kids on there as long as possible, you know, potential for kids to go through puberty while on that study. So we'll collect a lot of data there. We don't have a fixed number in mind of how many we'd like to have. We'd like to be as inclusive as we can. Anybody who is enjoying benefits from Room 201 should certainly be able to have the opportunity to switch into that and stay on their treatment.
spk01: I just wanted to make sure that's very clear that there is no requirement of safety or additional safety data needed that prompted the open label extension.
spk10: No, no. I mean, the open label extension is pretty common in all of these, in most rare disease studies, right? You want to build a database of kids who have, you know, multiple years of experience on the therapeutic when you get to an NDA file. But there's no requirement upon us to do it. It just makes good sense. And it also is good for the patients. If they are, you know, if they feel like the therapy is working for them, it makes a lot of sense to enable them to continue to take it.
spk01: Great. Thank you for the clarity. And then the question on the pipeline-wise, maybe you can comment on where you are in your licensing discussions and whether this is, you know, we expect to see over the next quarter or two, or whether, you know, expansion of the pipeline with LOMO 201 could be happening ahead of in licensing opportunities. So if you could just give us a little bit more granularity would be helpful. And thank you for taking our questions.
spk11: Yes, also it's a good question. And the minute we can let you know, we will. We haven't given any guidance on where we are right now, but I can tell you this whole process, it's a robust one. and it's led by an industry veteran with over 25 years of experience, Aaron Schuhart. And, you know, I'm pleased with the... Let's say the number of opportunities, yet we are taking our time and being as cautious as we possibly can to find the right asset for this company. Obviously, we would like to stay in the endocrine space, but we're willing to throw a broader net and to look at other compounds or assets outside of endocrine. But I think it's a little too early to give any guidance right now.
spk01: Thank you, Ray. Thanks for the call.
spk07: Next one on the line is Elmer Tyrus from Realty Capital Partner. You are now live.
spk08: Yes, hello. Thank you for allowing me for a couple of questions. Coming back to the thought experiment of using Loom 201 in previously treatment experience populations, Would it also make sense, at least theoretically, that these children, where there is a high degree of noncompliance with injections, and therefore there is subpar growth, and now suddenly if there is an oral therapy available, daily oral pill, that their growth might catch up under that sort of regimen? John?
spk10: Yes, I think that's a very good point. You'll note in some of the publications about compliance that compliance tends to go down as kids get older and start to take more control of their own, you know, they self-administer the drug instead of having their parents give it to them. So I do agree in general. I think especially out in the real world, that's very true. A lot of times the kids that you enroll in a clinical trial tend to just be very compliant because they seem to be the ones most interested in their growth because they're willing to sign up on a trial five years after their big growth peak or years after they started the therapy. But I do agree there's quite an opportunity there for that population, which is most susceptible for low compliance.
spk08: And, John, just to follow up on the genesis data set, the analysis that you performed, there appears to be in the moderate population that there is a 8.3 centimeter per year growth velocity. and more severe patients respond more robustly, perhaps. Isn't it also true that at the end of the year, they would come to the same sort of normalized height, so the end result, so to speak, would be very similar?
spk10: Yes, that's very true. And you can see that in the height SDS values after 12 months of treatment. There's no statistical difference between the severe group and the moderate group. So really, the severe group starts further behind. They grow faster. And then after 12 months, they're in about the same place as the moderate group. So even though the moderate group is growing at a different rate, they're both progressing in relation to their peers at the same rate.
spk08: Okay. Thanks for confirming that.
spk07: Operator? Thank you. I'm showing no further questions in the queue at this time. I'll hand the call over back to Mr. Hawkins for closing remarks.
spk11: Okay. Well, thank you for your interest, everyone, and we look forward to speaking with investors at the investment conferences this month and other venues in the coming year. Thank you very much.
spk07: Ladies and gentlemen, this concludes today's conference call. You may now disconnect.
Disclaimer