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spk01: and welcome to lumos pharma first quarter 2024 financial results and clinical programs update call at this time all participants are in a listen only mode a brief question and answer session will follow the formal presentation if anyone should require operator assistance during the conference please press star 0 on your telephone keypad as a reminder this conference is being recorded It is now my pleasure to introduce your host, Ms. Lisa Miller, Vice President, Investor Relations. Thank you, Ms. Miller. You may begin.
spk07: Ms.
spk00: Miller, go ahead. 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 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 these forward-looking statements. Information presented on this call is contained in the press release we issued yesterday afternoon and in our Form 8-K, which may be accessed from the Investors page of the Loomis Pharma website. Speaking on today's call will be Rick Hawkins, CEO and Chairman, John McHugh, President and Chief Scientific Officer, and Lori Lawley, Chief Financial Officer. Dr. Paduk Chauhanan, Chief Medical Officer, will also join the call for the question and answer session. It's now my pleasure to turn the call over to Rick for our opening remarks.
spk09: Thank you, Lisa, and good morning, everyone. I'm pleased to be speaking with you today to provide an update on our progress advancing LUM201 as the first oral therapeutic for moderate pediatric growth hormone deficiency, or PGHD. Our recent months have been incredibly productive at Lumos, marked by significant milestones. We've had a constructive end to Phase II meeting with the FDA and conducted fresh analyses on updated data from our ORAGRO 212 and 210 trials. I'll keep my opening remarks concise before handing over to my colleagues to review in greater detail the strides we've made so far this year. So let's begin. As detailed in our press release, We recently held a collaborative in the Phase II meeting with the FDA where we reviewed the promising data from our Phase II oral growth 210 and 212 trials and discussed an optimal Phase III design for a successful regulatory path forward. Both Phase II oral growth trials, as you may recall, successfully met their primary and secondary endpoints providing robust evidence supporting the potential of oral LUM201 in treating moderate PGHD. Additionally, the trials demonstrated the effectiveness of our predictive enrichment marker test in identifying patients likely to respond to LUM201. During our dialogue with the FDA, It was acknowledged that LUM201 operates distinctly from growth hormone or its memetics. The FDA recognized LUM201 as a novel growth hormone promoter with a unique mechanism of action and consequently proposed that we consider a placebo-controlled phase three trial design. This trial design would not require an active comparator arm with a non-inferiority margin, but would necessitate demonstrating clinically significant improvements in growth compared to placebo. Now, we are delighted by these developments, as we see them greatly enhancing the prospects for a successful phase three trial of LU201. Pending final FDA approval of this trial design, we plan to initiate this trial by year end 2024. We firmly believe that this refined design significantly bolsters our chances of advancing LUM201 toward approval as the first oral therapeutic for moderate PGHD. Our confidence in LUM201 was further strengthened through our examination of additional data from our Phase II oral growth trials. As detailed in our press release, we unveiled updated 12-month and 24-month data from these trials, which consistently demonstrate a durable effect and substantial improvement over baseline annualized height velocity. We are confident that the advancements made position Lumos Pharma as a late-stage biopharmaceutical company with substantial growth prospects and continue to support the potential of oral LUM201 to disrupt the $4.7 billion global market for injectable growth hormone deficiency. Now I'll hand the call over to John McHugh for further insights into our interaction with the FDA and our strategic planning for this pivotal phase three trial. John?
spk11: Thanks, Rick, and good morning, everyone. As Rick mentioned, we recently concluded our end of phase two meeting with the FDA to evaluate data from our oral growth trials. and explore potential strategies for a phase three pivotal trial. A key highlight from the meeting was its overwhelmingly positive and constructive nature. With approximately 30 FDA staff members present, including senior representatives from pertinent departments, the atmosphere remained collegial and centered on determining the optimal approach for the pivotal trial design of LIM2-1 in treating moderate PGHD. The data package we presented, to the FDA underscored the outcomes of our phase two oral growth trials. As you may recall, these trials successfully met their primary and secondary endpoints, demonstrating that LUM2-1 achieved annualized height velocity consistent with predetermined targets derived from historical benchmarks in a moderate PGHD patient population. Additionally, the growth rates observed at both six and 12 months on treatment with LUM201 at the 1.6 mg per kg per day dose aligned with historical recombinant human growth hormone growth rates in similar patient cohorts with sustained efficacy observed at both 12 and 24 months. Notably, LUM201 also exhibited the ability to normalize IGF-1 standard deviation scores within six months of treatment initiation. Furthermore, the trial data provided preliminary confirmation that our Predictive Immersion Marker, or PEM, strategy accurately identified potential Allume 201 responders and showcased the PEM classification as 100% reproducible, surpassing the predefined statistical margin. Additionally, safety profile of an investigational Allume 201 was further validated. Upon reviewing these data, FDA representatives indicated a shift in their perspective regarding Allume 201's distinct mechanism, They acknowledge that LUM2-1 is not merely a growth hormone memetic, but rather a distinct growth promoter. The FDA's understanding of these data prompted them to suggest that LUM2-1 should not necessarily be directly compared to traditional growth hormone products. As a reminder, LUM2-1 is a small molecule that binds to the growth hormone secretagogue receptor 1A in both the pituitary and the hypothalamus. LUM2-1 agonizes the receptor, and that signals the release of stored growth hormone in the somatotropes. By also modulating somatostatin and growth hormone-releasing hormone in the hypothalamus, LUM201 restores the natural pulsatile release of growth hormone. The increase in the amplitude or peak of each growth hormone pulse boosts the circulating levels of growth hormone, subsequently elevating the levels of circulating IGF-1. Both growth hormone and IGF-1 then act on the open growth plates in the long bones of children with growth hormone deficiency, stimulating growth. The FDA's acknowledgment that LUM2O1 operates as a novel growth promoter rather than a mimetic of injectable exogenous recombinant human growth hormone enables a more expansive view in considering design approaches for a Phase III trial. A significant portion of the meeting was dedicated to exploring different options, culminating in the suggestion by the FDA that we contemplate a placebo-controlled design. Heading into the FDA meeting, we examined historical pivotal trial designs with growth-promoting agents and proposed to the FDA a standard non-inferiority design consisting of, in this case, a 12-month study evaluating LUM201 against the lower-approved dose of growth hormones. We chose this comparator dose because it more closely mirrors the physiological levels of growth hormone and IGF-1 that LUM201 restores. We engaged in productive discussions with the FDA regarding this non-inferiority approach, but during these conversations, the FDA suggested we could explore a placebo-controlled trial. A placebo-controlled trial would be required to demonstrate clinically significant growth compared to the placebo with 12 months of treatment. Following the FDA's recommendation and drawing from insights provided by our regulatory consultants, clinical and scientific advisory board statisticians, we have designed a placebo-controlled trial featuring a two-to-one randomization of LUM201 to placebo. One arm will receive LUM201 for 12 months, while the other arm will initially receive placebo and then transition to LUM201 after six months, remaining on treatment for the next six months. All subjects enrolled in the trial will be PEM-positive. This phase three trial design serves two strategic objectives. The first, providing the FDA with ample data to evaluate LUM-201 for approval and ensuring that all subjects receive treatment with LUM-201, the active agent. For this trial, we envisage two co-primary endpoints. First, the 12-month treatment arm must demonstrate clinically significant growth. Second, there will be a pairwise treatment comparison within subject assessing growth on placebo versus growth on LUM2A1, which must also exhibit clinically meaningful growth. Following the 12-month trial period, all participants will have the option to transition into a long-term safety extension, which will provide LUM2A1 treatment for up to three years. We are confident that the trial size is more than adequate to meet the described co-primary endpoints. We anticipate finalizing this design over the next couple of months, and pending approval from the agency, we aim to initiate the Phase III trial before the end of 2024. Our potential for success in a pivotal trial is bolstered by the evolving data and deeper analysis from our oral growth trials. In yesterday's press release, we unveiled preliminary updated 12- and 24-month growth data from our Oral Growth 210 trial. The data snapshot from our trials, specifically the six and updated 12-month data on LUM201, when measured against similar populations from Phase 4 studies, indicate comparable growth rates. Like these historical databases, we are focusing on treating the moderate PGHD population while excluding the more severe growth hormone deficient cases. Our updated data consistently demonstrate that we are achieving growth rates similar to those observed in historical data for the moderate PGHD patient cohort. Further analyses compare the 6- and 12-month growth rates on LUM201 and baseline growth rates. These findings highlight a noteworthy increase in AHV, or annualized site velocity, from baseline upon treatment with LUM201. the baseline growth rate of 4.7 centimeters per year documented in our Phase 2 trial should serve as an indicator of the placebo arm's annualized growth rate in our Phase 3 trial. The full 12-month data for all cohorts in the R-Growth 210 trial reinforces our choice to advance the 1.6 mg per kg LUM2-1 dose into Phase 3. Finally, we combine the 1.6 and 3.2 mgs per kg per day cohorts from our two Phase II trials, since their growth rates were not statistically different.
spk07: These data include all subjects who were treated to 24 months, excluding those who transitioned from Tanner 1 to Tanner 2 to enable a comparison to historical Pfizer-Kiggs database.
spk11: These updated data continue to underscore the enduring efficacy of LUM201. When comparing year 1 AHV to year 2 AHV for LUM201, only a modest drop-off of approximately 10% is observed. This stands in contrast to the published data from the less severe GHD population in the Kiggs database treated with recombinant human growth hormone, where the drop-off is closer to 20%. These findings from our Phase II studies highlighted how LUM201 can normalize growth hormone secretion and IGF-1 levels, thus restoring normal physiological growth with sustained benefits over time. These data were presented at the FDA end of Phase II meeting and were compelling enough to convince the agency of LUM201's novel mechanism of action, granting them the freedom to suggest innovative Phase III study designs. We believe that this placebo-controlled design significantly mitigates our regulatory risk and enhances our potential to introduce the first oral therapeutic for growth hormone deficiency to the market. This innovative oral therapeutic is anticipated to be a welcome treatment option for pediatric endocrinologists seeking to address pediatric growth hormone deficiency in their patients. Earlier this month, analyses of top-line oral growth trial results were presented at three major endocrinology conferences. at the Pediatric Endocrine Society meeting in Chicago by Dr. Andrew Dauber, highlighting data showing LUM201 achieved comparable annualized site velocity to daily recombinant human growth hormone in PGHD at the 1.6 mcg per day dose with a promising safety profile. And at two subsequent conferences in Stockholm, the Growth Hormone Research Society and European Congress of Endocrinology, Dr. Peter Clayton presented a comprehensive analysis of LUM201
spk07: restoration of growth hormone secretion, and the increase in HIV-induced and moderate PGHD patients.
spk11: We are pleased to announce that we have had two abstracts accepted for presentation at the upcoming Endocrine Society meeting, or ENDO, next month, where we also plan to release the full 12-month data from our Oral Growth 212 trial, with additional analyses from the Oral Growth 210 trial. The maturing data from our org growth trials continue to resonate with the global endocrinology community, and we are encouraged by the growing interest among experts as we finalize our plans for a pivotal trial. With that, I would like to turn it over to Lori for a review of our financial results for Q1.
spk04: Thanks, John. We ended the quarter on March 31, 2024, with cash, cash equivalents, and short-term investments totaling $23.2 million, as compared to $36 million on December 31, 2023. Cash on hand is expected to support operations through the third quarter of this year, inclusive of phase three planning and preparatory activities. With the recent developments from the FDA, we are confident that we will be able to finance our phase three trial for patients with pediatric growth hormone deficiency in the near term. Research and development expenses were $7.2 million, an increase of $2.9 million for the quarter ended March 31st, 2024, compared to the same period in 2023. primarily due to increases of $2 million in licensing expense, $0.8 million in clinical trial expenses, and $0.2 million in consulting expenses, offset by a decrease of $0.1 million in personnel related expenses. General and administrative expenses were $3.8 million, a decrease of $0.6 million compared to the same period in 2023, primarily due to decreases of $0.4 million in licensing expenses, $0.1 million in travel expenses, $0.1 million in consulting expenses, and 0.1 million in other expenses offset by an increase of 0.1 million in personnel related expenses. The net loss for the quarter ended March 31st, 2024 was 10.4 million compared to a net loss of 7.3 million for the same period in 2023. Lumos Pharma ended Q1, 2024 with 8,107,121 shares outstanding. And now I will turn it over to Rick for his closing remarks. Thank you, Lori and John. As mentioned earlier in the call,
spk09: been an exciting and fruitful time for Lumos, and we are steadily progressing towards our objective of unlocking the potential of LUM201 as a pioneering oral therapeutic poised to revolutionize the global growth hormone market, which has been dominated by injectable products for nearly four decades. Before opening the call to your questions, I'd like to take a moment to discuss the commercial potential we envision for oral LUM201. If approved, we believe LUM201 presents several potential advantages over current injectable recombinant growth hormone products, including sustained growth benefits and the restoration of physiological pulsatile release of growth hormone within the natural endocrine feedback loop. As an oral therapy, LUM201 represents an appealing alternative to daily and weekly injections and has the potential to broaden the pediatric growth hormone deficient treatment market, particularly among moderately growth hormone deficient patients. Additionally, it's worth noting there's a small molecule, the cost of goods for commercial scale production of LUM201 would be significantly lower than for recombinant growth hormone. And as we've consistently emphasized, we view LUM201 not only as a singular product, but also as a robust pipeline. We see the potential for LUM201 to address 10 additional indications currently treated with recombinant growth hormone, including Prader-Willi syndrome and idiopathic short stature. With the FDA acknowledging LUM201 as a novel growth promoter, we believe this paves the way for a streamlined clinical trial design for these other indications as well as for attractive commercial positioning. Now, this is truly a pivotal moment in a company's trajectory. With the positive guidance from the FDA, we're propelling our late-stage program for Oral Loom 201 towards a regulatory pathway with a high likelihood of success. Additionally, we anticipate some very exciting developments in the coming year and eagerly anticipate sharing updates on our progress with you. Thank you all very much for listening today. And operator, we're ready to take questions. Will, please.
spk01: Thank you. We will now 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. You may press star 2 if you would like to remove your questions from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the start keys. One moment, please, while we poll for questions. The first question comes from the line of Yasmin Bahimi with Piper Sandler. Please go ahead.
spk05: Hi, team. This is Liam Heaster on for Yaz. Thanks so much for the update this morning. Just to start, in regard to the upcoming phase three study, I was wondering if you could provide some update on your expected bar for success in connection to growth, and then also any clarity on why you chose a specific dose to move forward with. Further, what is the overall safety database requirement for approval? And have you had any chance to engage with the EMA in regards to the Phase 3 design as well? And then also, if you could comment at all on how long you expect it to take to enroll the Phase 3 trial, as well as if there's any overlap between the Phase 2 and Phase 3 sites. Yeah, and that's for now.
spk07: Okay, bye. All excellent questions.
spk09: And I think the bar to success question probably should be answered by John. So go ahead, John.
spk11: Yeah. So, you know, as we mentioned, you know, we have to show clinically meaningful growth. And so what we have agreed to in the past with the FDA to define clinically meaningful growth is an agreement with the FDA at the end of 12 months in our Phase 2 trial, subjects have to achieve 6.7 centimeters per year growth. That was what we defined as the minimal clinically meaningful growth to continue on treatment with LUV201. So one of the options that we have is to present that as an option for clinically meaningful growth in this Phase 3 study. I think just to tackle some of your other questions, the 1.6 Mg per kg per day dose we've shown throughout the study to be both numerically the highest AHV across the three doses. We don't really see a difference between the 1.6 and 3.2 Mg per kg per day doses, so I think there's no point to go to that higher dose. We do believe that there's a pharmacodynamic plateau, so we're not getting increased growth hormone secretion at the higher dose, so it would make sense that we wouldn't see an increase in AHV. Two of your four questions. Yeah, the interaction with EMA. So the interaction with EMA, we will start that interaction after we have finalized our protocol with the FDA.
spk09: Yeah, and Duke, why don't you talk about the enrollment, the number of patients, enrollment, and so on?
spk06: Yeah, so thank you. So I think to answer the first question, do we have overlap of a Phase 2 site and a Phase 3? Yes. There we have some, you know, Phase 2 sites do continue to pass it in Phase 3, and also we plan to initiate a new site for Phase 3 as well. As you know, the number of subjects that enroll in Phase 2 much smaller than Phase 3, which is nearly double. We want to increase the number of countries and number of sites around the world. At this point, we have significant, you know, kind of like increased awareness of Phase 2 trial at the global scale, we do get significant increase in interest of the KOL around the world as well. So we do believe that, you know, with enrollment timeline as we planned initially 15 to 18 months to stay intact if we start, you know, their enrollment towards the end of this year. Again, you know, pretty much everything on track, and we do believe that we'll be able to enroll all those patients with the new placebo-controlled trial at the timely manner, and especially, you know, when we increase the number of sites and the number of countries to participate in this trial. Okay.
spk08: Good.
spk05: Awesome. Oh, and then just one more question. Sorry. Just how do you plan on funding the phase three beyond year end 3Q 2024? Are there any details on that?
spk09: Yeah. Lori, go ahead.
spk04: Yeah. You know, we've been really busy since we've had our FDA meeting and planning for the upcoming phase three trial design. Now that we have some of the details finalized, we are confident that we can go out to the investment community and finance the phase three trial as is planned. Also, as we've said previously, we believe that there is opportunity to bring in potential strategic, potential partners for regional licensing deals, which would also allow for non-dilutive financing in some of those territories that we would not necessarily go out and commercialize on our own.
spk07: Great. Thank you so much. All right.
spk01: Thank you. Next question comes from the line of Charles Duncan with Cantor Fitzgerald. Please go ahead.
spk10: Yeah. Good morning, Rick and team. Congrats on the progress and recent constructive interaction with the FDA. Also, really appreciate all the color you provided. I did have a couple of questions on the phase three trial design and then one on your perspective regarding FDA engagement. With regard to the phase three trial design, I'm wondering if you could affirm that the enrollment criteria in phase three will be the same, or if not, how different from the phase two? And then the second question I had with regard to that is if you could provide a little more color on the co-primaries. Is it a true co-primary, or is there a, you know, call it a step down from the first 12-month AHB to the second? Thanks.
spk09: Yep. Yep. Duke, why don't you answer the first part of the phase three design question in terms of enrollment criteria, and then, John, if you'll talk about the co-primary.
spk06: Yes. Thank you. That's a very good question. So the majority of inclusion-exclusion criteria are pretty much similar compared to Phase 3 and Phase 2. The only small changes that we want to implement is, number one, the upper limit of the age enrollment. We're going to lower one year. The reason behind that, because we want to make sure, as soon as we compare to placebo, we want to make very clear that, you know, no single subject would get into the 10th state, too, during the 12 months. trial period. And we have a bonus criteria that, you know, initially the bonus delay was greater or equal to six months, but now we're going to have it greater than 12 months. And other than that, pretty much the same. And again, you know, part of this, the inclusion-exclusion criteria for the moderate PTSD, we do believe that, you know, majority of physicians who actually will participate in this trial will see significant, you know, When we have a placebo-controlled trial, the different primary endpoint will be very clear. As you know, I think in majority of those patients, as you see the data John presented earlier, the baseline high velocity coming into this trial was 4.7. And our trial achieved 7.6 centimeters at 12 months. So basically, we see very clearly that, you know, we can achieve the clinical significance based on the FDA requirements. at the end of these phase three trials.
spk09: Helpful. And John, the co-primary.
spk11: Yes, so Chas, we do see these as co-primary endpoints, the 12-month growth endpoint and the six-month comparison to placebo, both showing clinically meaningful growth. So that's a That's the plan going in. Obviously, we'll release more details once we have a final sign-off from the FDA on the full Phase 3 protocol.
spk10: That will include powering, John? Which of the two do you power to, or does it not matter?
spk11: No, we'll pair to both. They'll both be powered, and we do believe right now that we have... the end that we have is more than sufficient to power both of those endpoints.
spk10: Okay. Neat design. Is the agency asking for bone mineral density imaging or any bone health monitoring?
spk07: Duke?
spk06: No, they did not. And actually, most of their... the trial to get approved, the focus on the efficacy in terms of growth velocity. And the bone density trial in general, you may not see significant change in the first 12 months. So that would not require for this 12-month study.
spk10: Okay. And last question regarding the agency perspective. And, you know, always hazard for that, speculating on that. But What do you think was the key shift or driver to the shift in the view of this, of LUM201 being a stimulator, not a simple mimetic? And did you get a sense that they appreciated the compliance challenges with the current standard of care with the growth hormone injectables?
spk07: Yeah. Go ahead, John.
spk11: So I think the turning point, Chas, just in their viewing of our mechanism was around the extensive data that we've shared publicly and with the FDA about restoration of pulsatile ultradian rhythm of growth hormone release. And I think that data package was pretty substantial. And as you know, we've shown that we can restore normal pulses and levels of growth hormone across a 24-hour period. in growth hormone deficient subjects, which amounts to about 20% of the growth hormone that you need from an exogenous bolus dose. And we're achieving almost the same amount of AHV. And I think that level of understanding and realizing that our growth hormone delivery is significantly more efficient because we're doing it in a pulsatile 24-hour period. I think that was really the key to differentiate us away from differentiate us away from exogenous growth. I'm going to really open up this whole discussion about kind of creative ways to evaluate the growth potential of LUM2A1 in phase three.
spk10: Good deal. Great to hear. Appreciation of the pulsatile mechanism, always a key point of our thesis. Thanks for taking the questions.
spk01: Thank you, Chad. Thank you. Next question comes from the line of Leland Kershaw with Oppenheimer & Co. Please go ahead.
spk02: Hi, good morning. Thanks for taking our questions. I also wanted to comment on a positive surprise to the agency view on the PSU requirements. A couple of questions from us. Just for playing devil's advocate, at the same time, I would like to hear about the placebo control versus inferiority versus theoretical injection. maybe early days, but want to hear to what extent could those data or the lack thereof of comparability data to those women impact endocrinologists' view in 201 as they go to potentially use it in their patients. And two, want to ask, given the ancillary but important metabolic benefits of And will you be looking for those potential benefits apart from the scope itself in the phase three? Thank you.
spk09: Yeah. Duke, I only heard part of the question, but I think that was really for you. And so why don't you start?
spk06: You know what? Honestly, I cannot hear the question quite well. So anybody can read.
spk11: So yeah, go ahead, John. So I think Leland was asking about the impact of not having, you know, comparative treatment data in phase three for pediatric endocrinologists as they think about how to prescribe this once we're on the market.
spk06: Right. Okay. So Leland, that's a very good question, right? I think This is very important, right? As you know, first of all, FDA fully understood that mechanism of action of room to one totally different than growth hormone. And they make it clear to us that you are not growth hormone. And as a pediatric endocrinologist, you know that if you participate in the trial, if the patient with Goldman deficiency, such as in moderate PTSD, the only impact with no treatments, only height, no other significant detrimental outcome that could, you know, implicate the patient without treatment for six months, for one year. So we do believe that most physicians are fully aware of that, especially the piece Patients who enroll in this study are prepubertal. So, again, pubertal impact with no treatment six months to one month is not going to have significant impact in final adult life. With that said, we do believe that, you know, when we conduct this trial, they will have no issue to enroll the subject. And not to mention that all the patients participating in this trial potentially will be able to enroll into long-term extension study, which is we already have that in place, and AFD approved that long-term extension study for three years. So I do believe that we incentive to really help for physician to enroll their patient, knowing that in the long term will be benefit to their patient, especially when the drug get approved.
spk02: Just the metabolic benefits, you know, LIM201 apart from growth itself, you know, may have other beneficial effects on the body wondering if you're going to assess the risk.
spk09: John, do you want to answer that question?
spk11: So I think we won't be examining that question specifically in this phase three study. We do have an investigator-initiated study going on in NAFLD where some of that data is being collected in the context of examining the impact on liver fat. So it's being run at MGH. But for our phase three trial, we're going to focus on the approvable endpoints and the path forward in PGHD to get an approval.
spk07: Thank you. But Leland, I think you were also referring to, okay, go ahead.
spk01: Thank you. The next question comes from the line of Ed White with HCVN White. Please go ahead.
spk12: Good morning. Thanks for the update this morning. So just a couple of questions from me. Can you comment on your manufacturing readiness for the phase three trial and regulatory filings?
spk07: John, go ahead. Manufacturing readiness.
spk11: Yeah. So thanks for the question, Ed. So yeah, we, you know, as you know, we recently filed a patent on a new drug product form for phase three, which will give us very tight dose variance across the large weight range for children with pediatric growth and deficiency and also provide easier routes of administration. So we have a mini tablet in a capsule. So larger kids can take the capsule with the mini tablets. Smaller kids can open the capsule and take the mini tablets by themselves or in soft food. So that design is in place. The bridging studies are complete and we're moving forward to get our phase three material ready to go. So there are no hiccups in the road there. We're well prepared to provide that phase three slash commercial material to get us through phase three.
spk12: Okay, thanks, John. And just a question on the study, as you mentioned, it's going to have some overlap with the phase two. Can you just let us know what you're thinking of as far as a geographical breakdown for the U.S. versus outside the U.S. for sites and the number of patients enrolled?
spk09: Duke, why don't you answer that question?
spk06: Yeah, so for DS, as we plan right now is that, you know, we plan to enroll about 150 subjects. So two-to-one randomization will be 100 subjects in room 201 and 50 subjects in placebo. We plan to include more countries outside the U.S. We, in the process, have sent out a site survey to multiple regions around the world. We're waiting for those to receive those site surveys back before we make a decision which country we go to. So around the site that we plan is about 90 sites-ish. So again, you know, so... potentially about 14 countries. However, the final number and number cited in the country will be finalized when we receive the survey back.
spk07: Okay, thank you. And Leland, if you recall, you were in... Nope, it's Ed. Okay. And Leland, if you... Go ahead. I'm sorry, Rick. Sorry for interrupting you, Rick. Operator? My last question. Could I ask another question? Sure, absolutely.
spk12: So the, you know, we've talked about this before, but out of the, you know, 60 to 62% of the patient population that's eligible, I just want to get your thoughts on why children are who are eligible wouldn't want to be on the oral solution versus the injectable you know especially since as you mentioned the the cost will be lower but the ease of use is is apparent and so i'm just taking the other side of that and why wouldn't patients and children want to take your product
spk09: Well, we did some preliminary research, Leland, and no, this is Ed, excuse me, Ed. And it's pretty clear when we asked both the families, but also the Pete Endos, if they had a choice between a weekly injection or a once a day oral, they overwhelmingly said that they would prefer to take a daily oral. That's sort of a given. And, of course, we have a way to identify the patients who our drug will most likely be effective in, and that is our predictive enrichment or PEM strategy. And that further enhances our ability to not only be successful in this trial, but also to easily identify those patients that will be effective.
spk06: Yeah. I would like to add on top of what Rick just said. As a pediatric endocrinologist, majority of patients with PTSD fall into PEM-positive category. As you know, over 40 years, we don't have option but just give injection to those children, right, just until about four or five years, and we get long-acting approved, but just not get rid of injection, which is something that children do not want, especially not only treatment for a month or so, not a year or so, but much longer period of time. So physicians in general, I do believe that their perception was if this drug gets approved, they will offer this Lumto-1 to mature those patients by using PEM-positive cutoff. With the PEM-positive, they potentially can be on the treatment. So I do believe that, you know, this is extremely important, right, to have this option for the treatment for patients moving forward. We never really have this option until Lumto-1, you know, at this point.
spk07: Okay, thanks for taking my questions.
spk01: Thank you. Next question comes from the line of Catherine Novak with Jones Research. Please go ahead.
spk03: Hi, guys. Morning. I just wanted to drill down on the cash position. You know, you need to bring in additional funding before you start the phase three. Do you see any inflection points between now and the start that might be that you might be able to use to bring in new investors? And then just throwing out the possibility of pursuing strategic partnership, for example, what do you think they'd want to see before stepping in? You know, are there more analyses that you think partners or investors would be interested in? Or at this point, are most of the relevant data in hand?
spk09: Catherine, that's a good question. I don't think there's any question that Investors have enough information at this stage to make a decision. I think we're, as Lori said, we're really confident since the FDA gave us this trial design with a placebo comparator arm that we are fully confident we're going to be able to raise the capital needed to get this drug across the finish line. And Lori, I don't know if you want to add any more to that or anyone else on the team.
spk04: Yeah, I think, Catherine, I think, you know, when we've talked with investors, I think a lot of investors have just been waiting to determine what the phase three trial design would look like. And now that we have gotten feedback from the FDA, they have proposed a placebo-controlled trial as an option. As we finalize that trial design and move forward with FDA approval of that trial design, We do believe that that will instill confidence in the investors and allow us to complete a financing in this near term. As far as looking for regional partners, we've talked previously about looking for ex-U.S. options for regional partners and retaining U.S. rights, of course. And so that is something that we will continue to pursue. And I think what they also were waiting on and the partners that we've talked with have also been waiting on what the phase three trial design will look like. Now that we have that information in hand and we have more of those details, I think that is why we are confident we will be able to move forward and complete a financing in the near term.
spk03: Got it. And then just, I guess, clarification on the first co-primary endpoint. If you can help me understand the statistical analysis, since placebo is not followed for 12 months, what is the hypothesis testing assumption for the first co-primary endpoint, if you could clarify?
spk09: Yeah. Yeah, John, go ahead if you have a question.
spk11: Sure. So as we mentioned, we just have to show clinically meaningful growth. And so we talked a little bit about one approach to show that, which is the agreement we already have with the FDA on six point seven centimeters per year representing minimal clinically meaningful growth. So we're using that to transition essentially from our phase two study into our long-term safety extension. And that is an agreement we already have with the FDA. So that is the first option that we'll pursue.
spk03: Okay. And then just one more, you know, thinking about this down the road, right now you're focusing on treatment night use patients, but it seems like Does this make sense to use after an initial year or two with growth hormone for people who aren't maybe interested in having daily injections indefinitely?
spk07: Duke, let's go ahead, if you will.
spk06: Yeah, so I think that's a very good question. I do believe that most patients will look into that potentially could switch the patient room to one. At this point, we don't have data to show yet. So what we think that moving forward, When we get this phase three trial done, we put that in registry. So majority of those patients are going to get into the long-term extension, especially registry is someone who is not in phase two. They can continue to, you know, have the phase four study. When the drug gets approved, we'll be able to determine some of those, especially when the patient wants to, you know, discontinue daily and go into room 201. We'll be able to evaluate those efficacy in those trials.
spk07: Okay, got it. That's helpful. Thanks.
spk01: Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.
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