Q1 2024 Lumos Pharma Inc Earnings Call
Greetings and welcome to new Maus, Fatima first quarter 'twenty 'twenty four 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.
Operator: Greetings and welcome to Lumos Pharma's 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 zero on your telephone keypad.
Speaker Change: If anyone should require operator assistance during the conference. Please press star zero 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. Mccullough you may begin.
Operator: 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.
Speaker Change: Mr. Miller the winter before we proceed with the call yes, alright. 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.
Lisa Miller: 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 these forward-looking statements.
Speaker Change: 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.
Speaker Change: 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.
Speaker Change: [noise] formation 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 at numerous pharma website.
Speaker Change: Speaking on today's call will be Rick Hakan, CEO and chairman.
Speaker Change: John Mchugh, President and Chief Scientific Officer, and Lori Lally, Chief Financial Officer Doctor Do Paducah, Dwana Chief Medical Officer will also join the call for the question answer session. It's now my pleasure to turn the call over to Rick for opening remarks.
Lisa Miller: 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 Lumos Pharma website. Speaking on today's call will be Rick Hawkins, CEO and Chairman, John McKew, President and Chief Scientific Officer, and Lori Lawley, Chief Financial Officer. Dr. Pitukcheewanont, Chief Medical Officer, will also join the call for the question and answer session. It is now my pleasure to turn the call over to Rick for our opening remarks.
Richard J. Hawkins: Thank you Lisa and good morning, everyone I'm pleased to be speaking with you today to provide an update on our progress advancing them to one is the first oral therapeutic for moderate pediatric growth hormone deficiency or P. G H D.
Richard J. Hawkins: Thank you, Lisa, and good morning, everyone. I'm pleased to be speaking with you today to provide an update on our progress advancing Lume 201 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 two meeting with the FDA and conducted fresh analyses on updated data from our Orogro 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.
Richard J. Hawkins: As detailed in our press release, we recently held a collaborative end-of-phase-two meeting with the FDA, where we reviewed the promising data from our Phase 2 oral growth 210 and 212 trials and discussed an optimal Phase 3 design for a successful regulatory path forward. Both Phase II trials, as you may recall, successfully met their primary and secondary endpoints, providing robust evidence supporting the potential of oral LUM201 and treating moderate PGHD. Dishonored, The trials demonstrated the effectiveness of our predictive enrichment marker test in identifying patients likely to respond to LUM201.
Richard J. Hawkins: During our dialogue with the FDA, it was acknowledged that LUM201 operates distinctly from growth hormone or is mimetic. 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 3 trial design. 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.
Richard J. Hawkins: Our recent months have been incredibly productive at la most marked by significant milestones.
Richard J. Hawkins: We've had a constructive end of phase two meeting with the FDA and conducted fresh analyses on updated data from our core ROE to 12 and 210 trials.
Richard J. Hawkins: We are delighted by these developments as we see them greatly enhancing the prospects for a successful phase three trial of WU-201. 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 LUME 201 was further strengthened through our examination of additional data from our Phase 2 Oral Growth Trials.
Richard J. Hawkins: Keep my opening remarks concise before handing over to my colleagues to review in greater detail.
Richard J. Hawkins: We've made so far this year so it's yeah.
Richard J. Hawkins: Hey.
Richard J. Hawkins: 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 velocities. 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 Lume 201 to disrupt the $4.7 billion global market for injectable growth hormone deficiency. Now I'll hand the call over to John McKew for further insights and our interaction with the FDA and our strategic planning for the pivotal Phase 3 trial. John?
Richard J. Hawkins: Press release, we recently held a collaborative and the phase II meeting with the F D. A.
John C. McKew: Thanks Rick and good morning everyone. As Rick mentioned, we recently concluded our end-of-phase 2 meeting with the FDA to evaluate data from our oral growth trials and explore potential strategies for a phase 3 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 adviser remained collegial and centered on determining the optimal approach for the pivotal trial design of LUM2-1 in treating moderate PGHD. The data package we presented to the FDA underlined the outcomes of our Phase 2 Orogrode trials.
Richard J. Hawkins: We reviewed the promising data from our phase two oral rose to 10 to 12 trials and discuss an optimal phase III design for a successful regulatory path forward.
Richard J. Hawkins: Both phase III trials as you may recall successfully met their primary and secondary end points.
John C. McKew: As you recall, these trials successfully met their primary and secondary endpoints, demonstrating that LUM21 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 6 and 12 months on treatment with loop 201 at the 1.6 mg per kg per day dose align with historical recombinant human growth hormone growth rates in similar patient cohorts with sustained efficacy observed at both 12 and 24 months.
John C. McKew: Notably, LUM21 also exhibited the ability to normalize IGF1 standard deviation scores within six months of treatment initiation. Furthermore, the trial data provided preliminary confirmation that our Predictor Merchant Marker, or PEM, strategy accurately identified potential LUM21 responders and showcased the PEM classification as 100% reproducible, surpassing the predefined statistical margin. Additionally, the safety profile of an investigational Loom 201 was further validated.
Richard J. Hawkins: <unk> robust evidence supporting the potential of all Lum 201, and truly modern P. Ghd.
Richard J. Hawkins: Additionally.
Richard J. Hawkins: The trials demonstrated the effectiveness effectiveness of our predictive enrichment marker test identified patients likely to respond to mature one.
John C. McKew: Upon reviewing these data, FDA representatives indicated a shift in their perspective regarding Lutron's distinct mechanisms. They acknowledge that LUM21 is not merely a growth hormone mimetic but rather a distinct growth promoter. The FDA's understanding of these data prompted them to suggest that LUM21 should not necessarily be directly compared to traditional growth hormone products. As a reminder, LUM2O1 is a small molecule that binds to the growth hormone Cretagog receptor 1A in both the pituitary and the hypothalamus.
Richard J. Hawkins: During our dialogue with the FDA. It was acknowledged that loom 201 operate distinctly from growth hormone or it's the medics.
John C. McKew: LUM21 agonizes the receptor, and that signals the release of stored growth hormone in the somatotrope. By also modulating somatostatin and growth hormone-releasing hormone in the hypothalamus, LUMEN 201 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, increasing 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.
Richard J. Hawkins: E F D. A recognized until one is a novel growth hormone promoter with a unique mechanism of.
Richard J. Hawkins: Of action and consequently proposed that we consider a placebo controlled phase III trial design.
John C. McKew: The FDA's acknowledgment that Lumetulin 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 three trial. A significant portion of the meeting was dedicated to exploring different options, culminating in the FDA suggesting that we contemplate a placebo-controlled design. Heading into the FDA meeting, we examined historical PIVL 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 GLUT21 against a lower-approved dose of growth hormone.
John C. McKew: 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.
Richard J. Hawkins: Trial design would not require an active comparator arm.
Richard J. Hawkins: With a non inferiority margin, but would necessitate demonstrating clinically significant improvements in growth compared to placebo.
John C. McKew: A placebo-controlled trial would be required to demonstrate clinically significant growth compared to placebo after 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.
Speaker Change: And we're delighted by these developments as we see them are greatly enhancing the prospects for a successful phase III trial of Blu 201.
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 advance England tool one toward approval as the first oral therapeutic for modern P. G H D.
John C. McKew: This Phase 3 trial design serves two strategic objectives. The first is providing the FDA with ample data to evaluate LUM201 for approval and ensuring that all subjects receive treatment with LUM201, the active agent. For this trial, we envisage two co-primary endpoints.
Speaker Change: Our conference.
John C. McKew: First, the 12-month treatment arm must demonstrate clinically significant growth. Second, there will be a pairwise comparison within subjects assessing growth on placebo versus growth on LUM201, which must also exhibit clinically meaningful growth. Following the 12-month trial period, all participants will have the option to transition into long-term safety extension, which will provide room for one 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 decision over the next couple of months, and pending approval from the agency, we aim to initiate the phase three trial before the end of 2024.
Speaker Change: Our confidence in them to a one was further strengthened through our examination of additional data from our phase two oral drug trials.
John C. McKew: 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 6 and updated 12-month data on LUM201, when measured against similar populations from Phase IV 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.
John C. McKew: 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 Lube 201.
Speaker Change: 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.
John C. McKew: 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 ORGROVE-210 trial reinforces our choice to advance 1.6 mg per kg. Lube 2-1 dose into Phase 3. Finally, we combine the 1.6 and 3.2 mgs per kg per day cohorts from our two Phase 2 trials since their growth rates were not statistically different.
John C. McKew: These data include all subjects who are treated for 24 months, excluding those who transition from Tanner 1 to Tanner 2 to enable a comparison to the historical Pfizer-Kiggs database. These updated data continue to underscore the enduring efficacy of Lube 201. When comparing year 1 AHV to year 2 AHV for Lume 201, only a modest drop off of approximately 10% is observed.
Speaker Change: We are confident that the advancements made positioning most pharma as a late stage biopharmaceutical company with substantial growth prospects and continue to support the potential oral lunar two of one does disrupt the $4 $7 billion global market for injectable growth hormone deficiency.
Speaker Change: Yeah.
Speaker Change: Now I'll hand, the call over to Joe Mchugh for further insights into our interaction with the FDA and our strategic planning for the pivotal phase III trial gone.
John C. McKew: This stands in contrast to the published data from the less severe GHD population in the CIGS database treated with recombinant human growth hormone, where the drop-off is closer to 20%. These findings from our Phase II studies highlight 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 2 meeting and were compelling enough to convince the agency of WMT1's novel mechanism of action, granting them the freedom to suggest innovative Phase 3 study designs.
Joe Mchugh: 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 order growth trials and explore potential strategies for a phase III pivotal trial.
John C. McKew: 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 Rheumatoid 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 LUM2-1 achieved comparable annualized height velocity to daily recombinant hemoglobin and PGHD at the 1.6 mg per day dose with a promising safety profile, and the two subsequent conferences in Stockholm, the Growth Hormone Research Society and European Congress of Endocrinology.
John C. McKew: Dr. Peter Clayton presented a comprehensive analysis of LUM201, restoration of growth hormone secretion, and the increase in AHV-induced and moderate PGHD patients. 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 OroGrowth 2.12 trial with additional analyses from the OroG 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.
Joe Mchugh: Key highlights from the meeting was overwhelmingly positive and constructive nature with approximately 30 F. T. A staff members present.
Lori D. Lawley: Thanks, John. We ended the quarter on March 31st, 2024 with cash, cash equivalents, and short-term investments totaling $23.2 million, as compared to $36 million on December 31st, 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.
Joe Mchugh: Including senior Representatives from pertinent departments, the atmosphere remained collegial and centered on determining the optimal approach for the pivotal trial design are linked to one in treating moderate P. G H D.
Richard J. Hawkins: 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 expenses, 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.
Richard J. Hawkins: The net loss for the quarter ended March 31, 2024, with $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. Now I will turn it over to Rick for his closing remarks.
Speaker Change: The data package, we presented to the FDA underscored be the.
Speaker Change: The outcome of our phase two or a growth trials as you may recall. These trial successfully met their primary and secondary endpoints demonstrating that loomed achieved annualized height velocity consistent with predetermined targets drive from historical benchmarks in a moderate P. J H D patient population. Additionally, the growth rates.
Richard J. Hawkins: Thank you, Lori and John. As mentioned earlier in the call, it's 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 anticipate for Oral-Lum 201.
Richard J. Hawkins: 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 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 that as a small molecule, the cost of goods for the commercial-scale production of LUM2O1 would be significantly lower than for recombinant growth hormone.
Richard J. Hawkins: And as we consistently emphasize, we view Room 201 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.
Served at both six and 12 months of treatment with a PD one at the 1.6 Meg per kg per day dose of line with historical where covenant human growth hormone growth rates and similar patient cohorts with sustained efficacy observed at both 12 and 24 months.
Speaker Change: Notably linked to one also exhibited the ability to normalize IGF one standard deviation scores within six months of treatment initiation. Furthermore, the trial data provided preliminary confirmation that our predictive enrichment marker or pen strategy accurately identified potential into one responders and <unk>.
Speaker Change: <unk> case, the Perm classification as 100 per cent reproducible, surpassing the predefined statistical margin.
Speaker Change: Additionally, safety profile of investigational linked to a one was further validated.
Richard J. Hawkins: Now this is truly a pivotal moment in the company's trajectory. With positive guidance from the FDA, we're propelling our late-stage program for oral LUM201 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.
Speaker Change: Upon reviewing these data FDA representatives indicated a shift in their perspective regarding linked one distinct mechanism.
Operator: 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 busy. You may press star 2 if you would like to remove your questions from the chat. For participants using speaker equipment, it may be necessary to pick up a handset before pressing the start key. One moment, please, while we poll for questions. The first question comes from the line of Yasmeen Rahimi with Piper Sandler. Please go ahead.
Liam Huster: Hi team, this is Liam Huster on behalf of YAS. Thanks so much for the update this morning. To start, in regard to the upcoming Phase 3 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 the 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?
Speaker Change: Acknowledged that linked to one is not merely a growth hormone emetic, but rather distinct growth promoter. The fda's understanding of these data prompted them to suggest that linked to one should not necessarily be directly compared to traditional growth from our products.
Liam Huster: 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.
Speaker Change: As a reminder, living through what is a small molecule that binds to the growth hormone secretagogue receptor one in both the pituitary and the hypothalamus I'm too on agonizes, the receptor and that signals the release.
Richard J. Hawkins: Okay, all excellent questions, and I think the Bars to Success question probably should be answered by John, so go ahead.
John C. McKew: Yeah, so, as we mentioned, we have to show clinically meaningful growth. And so what we have agreed in the past with the FDA to define clinically meaningful growth is that 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 LUM201. 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.
John C. McKew: 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 in going to that higher dose. We do believe that there is a pharmacodynamic plateau, so we're not getting increased growth hormone secretion at the higher dose, so it would make sense that we would see an increase in AHV. Those are two of your four questions. Yeah, the interaction with the EMA. So the interaction with EMA; we will start that interaction after we have finalized our protocol with the FDA.
John C. McKew: Yeah, and Duke, why don't you talk about enrollment, the number of patients, enrollment, and so on. Yeah, so thank you. So I think.
Speaker Change: Of store growth hormone in the somatic trips by also modulating somatostatin and growth on releasing hormone in the hypothalamus loomed two of one restores the natural pulsatile release of growth hormone. The thing the increase in the amplitude or peak of each growth hormone pulse boost the circulating levels of growth hormone. So.
John C. McKew: Yeah, so thank you. So, to answer the first question, do we have overlap between a Phase 2 site and a Phase 3 site? Yes.
Pisit Pitukcheewanont: We have some, you know, Phase 2 sites to continue to participate 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 is much smaller than in 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 a significant, you know, kind of increased awareness of Phase 2 trials at the global scale.
Speaker Change: Sequentially.
Speaker Change: In elevating the levels of circulating IGF, one both growth hormone and IGF one that act on the open growth rates in the long bones of children with birth of a deficiency stimulating growth.
Speaker Change: The Fda's acknowledgment that lived tool and operates as a novel growth promoter rather than a mathematic of injectable exogenous, where congress human growth hormone enables a more expensive you can consider in deciding to purchase for a phase III trial.
Speaker Change: 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.
Speaker Change: 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 Blu two one against the lower approved dose of growth hormone.
Speaker Change: We chose this comparator dose because it more closely mirrors the physiological level, so growth hormone and IGF, one that linked to a one of our stores.
Speaker Change: We engaged in productive discussions with the FDA regarding this non inferiority approach, but during these conversations the FDA suggested we could explorer placebo controlled trial.
Speaker Change: A placebo controlled trial would be required to demonstrate clinically significant growth compared to the placebo with 12 months of treatment.
Speaker Change: Following the Fda's recommendation and drawing from insights provided by our regulatory consultants clinical and scientific Advisory Board Statisticians, we have decided to placebo controlled trial featuring a two to one randomization of linked to or wanted to placebo.
Pisit Pitukcheewanont: We do get a significant increase in interest from KOL around the world as well. So, we do believe that, you know, with the enrollment timeline as we planned, initially 15 to 18 months should stay intact if we start their enrollment towards the end of this year. So, again, you know, pretty much everything is on track, and we do believe that we'll be able to enroll all those patients in a new placebo-controlled trial in a timely manner, and especially when we increase the number of sites and the number of countries to participate in this trial.
Speaker Change: One arm will receive linked to one for 12 months, while the other art will initially received placebo and then transition to live to one after six months remaining on treatment for the next six months.
Speaker Change: All subjects enrolled in the trial will be P E positive.
John C. McKew: Awesome. Oh, and then just one more question, sorry. Just how do you plan on funding Phase 3 beyond year-end 3Q2024? Are there any details on that?
Speaker Change: This phase III trial design serves two strategic objectives.
Lori D. Lawley: Yeah, Lori, go ahead.
The first providing the FDA [noise] with ample data to evaluate moving to a one for approval and ensuring that all subjects received treatment with them till one the active agent.
Lori D. Lawley: Yeah, you know, we've been really busy since we had our FDA meeting and planning for the upcoming Phase 3 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 3 trial as planned. Also, as we've said previously, we believe that there is an opportunity to bring in 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.
Speaker Change: 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 pair wise comparison within subject assessing growth on placebo versus going with a link to a wall, which must also exhibit clinically meaningful growth.
Lori D. Lawley: Great! Thank you so much.
Charles Cliff Duncan: The next question comes from the line of Charles Duncan with Cantor Fitzgerald.
Speaker Change: Following a 12 month trial period, all participants will have the option to transition at the long term safety extension, which will provide loom to on treatment for up to three years.
Speaker Change: We are confident that the trial size is more than adequate to meet the describe co primary endpoints.
Speaker Change: We anticipate finalizing this deciding 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.
Speaker Change: Our potential for success in our pivotal trials bolstered by the evolving data and deeper analysis from our order growth trials in Yesterdays press release, we unveiled preliminary update at 12, and 24 month growth data from our own growth to 10 trial.
Charles Cliff Duncan: Yeah, good morning, Rick and team. Congratulations on the progress and recent constructive interaction with the FDA. Also, I really appreciate all the detail you provided. I had a couple of questions on the Phase 3 trial design and then one on your perspective regarding FDA engagement. So, with regard to the Phase 3 trial design, I'm wondering if you could affirm that the enrollment criteria in Phase 3 will be the same, or, if not, how different from those in Phase 2.
Charles Cliff Duncan: 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, you know, call it a step down from the first 12-month AHV to the second?
Speaker Change: The data snapshot from our trials specifically the six an updated 12 month data linked to a one when measured against similar populations from phase four studies indicate comparable growth rates.
Speaker Change: Like these historical.
Charles Cliff Duncan: Yeah, Duke, why don't you answer the first part of the phase 3 design question in terms of enrollment criteria, and then, John, if you'll talk about the co-primary. Yes.
Speaker Change: Databases, we are focusing on treating the moderate P. T. H D population, while excluding the more severe growth from a deficient cases.
Pisit Pitukcheewanont: Yes, thank you. That's a very good question.
Pisit Pitukcheewanont: So, the majority of the inclusion-exclusion criteria are pretty much similar compared to Phase 3 and Phase 2. The only small changes that we want to implement are, number one, the upper limit of the age enrollment. We're going to cut it down to one year. The reason behind that is because we want to make sure, since we complied with placebo, we want to make very clear that, you know, no single subject would get into the tenor state, too, during the 12-month trial period.
Speaker Change: Our updated data consistently demonstrate that we are achieving growth rates similar to those observed in historical data for the moderate P. J H D patient cohort.
Speaker Change: Further analyses compare the six and 12 month growth rates I moved to one and baseline growth rates. These findings highlight noteworthy increase in H V or annualized height velocity from baseline upon treatment was alluding to a one.
Pisit Pitukcheewanont: 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.
Pisit Pitukcheewanont: And again, you know, part of this, the inclusion-exclusion criteria for moderate PTSD, we do believe that, you know, the 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 endpoints will be very clear. As you know, I think in the 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 clinical significance based on the FDA requirement at the end of this Phase III trial.
The baseline growth rate of $4 seven centimeters per year documented in our phase two trial should serve as an indicator of the placebo arms annualized growth rate in our phase III trial.
Speaker Change: The full 12 month data for all cohorts in the oil growth to Tetra reinforces our choice to advance the 1.6 make per kick loose.
Speaker Change: Moving to one dose into phase III.
Speaker Change: Finally, we combined the 1.6 and $3 two makes per kg per day cohorts from our two phase two trials since their group growth rates were not statistically different.
Speaker Change: These data include all subjects, who were treated to 24 months.
Speaker Change: Excluding those who transitioned from tender one to 10 or two to enable.
Speaker Change: A comparison to historical Pfizer King's database.
Speaker Change: Yeah.
Speaker Change: These data these updated data continue to underscore the enduring efficacy of lead to a one.
Speaker Change: When comparing year, one H V to year, two H V for Luna to one only a modest drop off of approximately 10% as observed.
Speaker Change: The stands in contrast to the published data from the less severe ghd population in the kids database treated with recombinant human growth hormone, where the drop off is closer to 20%.
Speaker Change: These findings from our phase II studies highlighted how loomed here, one could normalized growth on its accretion.
Speaker Change: And IGF, one levels, thus restoring normal physiological growth with sustained benefits overtime.
Speaker Change: These data were presented at the FDA end of Phase two meeting and were compelling enough to convince the agency have moved towards novel mechanism of action granting them. The freedom to suggest the antibody in a phase III study designs.
Speaker Change: We believe that this placebo controlled design significantly mitigates, our regulatory risk and enhances our potential to introduce the first oral therapeutic for growth from a deficiency to the market.
Speaker Change: This innovative oral therapeutic is anticipated to be a welcome treatment option for pediatric endocrinologists seeking to address.
Speaker Change: Pediatric growth hormone deficiency and their patients.
Speaker Change: Earlier this month analyses of top line or grow trial results were presented at three major endocrinology conferences at the pediatric Endocrine Society meeting in Chicago by Dr. Andrew Ahlborn, highlighting data showing moved to on a cheap comparable annualized height velocity to daily with common human growth hormone in P. G. H D at one point.
Speaker Change: Six Meg per kg per day dose with a promising safety profile.
Speaker Change: And the two subsequent conferences in Stockholm, the growth of our research Society at European Congress of Endocrinology.
Speaker Change: Peter Cleveland presented a comprehensive analysis of linked to a one.
Peter Cleveland: Restoration of growth from its accretion and the increase in H V induced and moderate P. T H D patient.
Peter Cleveland: We are pleased to announce that we have had two abstracts accepted for presentation at the upcoming Endocrine Society meeting our Endo next month, where we also plan to release the full 12 month data from our Oregon to 12 trial with additional analyses from the order growth to Tetra.
Peter Cleveland: Yeah.
Peter Cleveland: The maturing data from our Oregon gross trials continue to resonate with the global Endocrinology community and we are encouraged by the growing interest in my experts as we finalize our plans for a pivotal trial.
Peter Cleveland: With that I would like to turn it over to Laurie for review of our financial results for Q1.
John C. McKew: and John, the Co-Founder
John C. McKew: Yes, Chas, we do see these as co-primary endpoints, the 12-month growth endpoint and the 6-month comparison to placebo, both showing clinically meaningful growth. So 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 three protocol.
Laurie: Thanks, John we ended the quarter on March 31st 2024, with cash cash equivalents and short term investments totaling $23 2 million as compared to 36 million on December 31st 2023 cash on hand is expected to support operations through the third quarter at this year and close to the phase III planning and preparatory activities with the.
John C. McKew: That will include powering it on, John. Which of the two do you power it on to, or does it not matter?
John C. McKew: No, we'll pair to both. They'll both be powered. We do believe right now that we have but, The end that we have is more than sufficient to power both of those endpoints.
John C. McKew: Neat Design.
John C. McKew: Okay. Neat design. Is the agency asking for bone mineral density imaging or any bone health monitoring?
John C. McKew: No, they did not. And actually, most of the tries to get approved focus on the efficacy in terms of growth velocity. And the bone density tries, in general, you may not see segment change in the first 12 months. So that was not required for this 12-month study.
Laurie: Recent developments from the FDA, we are confident that we will be able to finance our phase III trial for patients with pediatric growth hormone deficiency in the near term.
Speaker Change: 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 point 8 million in clinical trial expenses, and <unk> 2 million and consulting expenses offset by a decrease at point 1 million in personnel.
Speaker Change: All related expenses.
Speaker Change: General and administrative expenses were $3 8 million a decrease of <unk> 6 million compared to the same period in 2023, primarily due to decreases of point 4 million in licensing expenses <unk> 1 million in travel expenses 1 million in consulting expenses and $1 million and other expenses offset by an increase that point 1 million in personnel related expenses and that.
Speaker Change: The 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, when most pharma and at Q1 'twenty 'twenty four with 8 million 107121 shares outstanding and now I will turn it over to Rick for his closing remarks.
Richard J. Hawkins: Thank you Lori and John.
Charles Cliff Duncan: Okay and last question regarding the agency perspective, and you know it's always hazardous to speculate on that, but what do you think was the key shift or driver to the shift in the view of Lume 201 being a stimulator, not a simple memetic, and did you get a sense that they appreciated compliance challenges with the current standard of care with the growth hormone injector?
Lou: As mentioned earlier in the call, it's been an exciting and fruitful time for Lou most.
John C. McKew: Yeah, go ahead, John.
We are steadily progressing towards our objective of unlocking the potential of them 301, as a pioneering oral therapeutic poised to revolutionize the global growth hormone market, which has been dominated by injectable products for nearly four decades.
John C. McKew: So I think the turning point, Chaz, just in their view of our mechanism was around the extensive data that we've shared publicly and with the FDA about restoration of the pulsatile, you know, ultradian rhythm of growth hormone release. And I think that data package was pretty substantial.
Lou: Before opening the call to your questions I'd like to take a moment to discuss the commercial potential we envision for oral Lum 201.
John C. McKew: 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 was really the key to differentiate us away from exogenous growth hormone and really open up this whole discussion about kind of creative ways to evaluate the growth potential of LUM201 in phase 3.
Charles Cliff Duncan: Good deal. Great to hear. Appreciation of the pulsatile mechanism, always a key point of our thesis. Thanks for taking the time to ask the question.
Lou: We are if approved we believe when throw one presents several potential advantages over current injectable recombinant growth hormone products, including sustained growth benefits and the restoration of physiological pulsatile roomies of growth hormone within the natural and welcome feedback loop.
Leland James Gershell: Thank you, Chairperson. Thank you. The next question comes from the line of Leland Gershell with Oppenheimer & Co. Please go ahead.
Lou: As in all therapy mm 301 represents an appealing alternative to daily and weekly injections and has the potential to broaden the pediatric growth hormone deficiency treatment market.
Lou: Particularly among moderately growth hormone deficient patients.
Lou: Additionally, it's worth noting there's a small molecule or costs of goods for commercial scale production of them for one would be significantly lower than for recombinant growth hormone.
Lou: As we consistently emphasize we view <unk> not only as a single product, but also has a robust pipeline, we see the potential for them to one to address 10 additional indications currently treated with recombinant growth hormone, including product, what we'd syndrome and indeed.
Lou: Pathing short stature.
Lou: With the FAA acknowledging when blue one as a novel growth promoter. We believe this paves the way for a streamline clinical trial design for these other indications as well as for attractive commercial positioning.
Lou: This is truly a pivotal moment in our company's trajectory.
Leland James Gershell: Hi, good morning. Thanks for taking our questions. I also wanted to comment on the positive surprise to hear the agency's view on the PSU requirements. A couple questions from us. Just sort of playing devil's advocate, at the same time that we're trying to hear about the placebo control versus inferiority versus steroid work on injections. I know we're in the early days, but I wanted to hear to what extent those data or the lack thereof of comparable data to psilocybin could impact endocrinologists' view of psilocybin in 2019 as they go to potentially use it Those potential benefits apart from the growth itself in phase 3. Thank you.
Lou: With a positive guidance from the FDA.
Pisit Pitukcheewanont: Yeah, Duke, I only heard part of the question, but I think that was really for you, and so
Speaker Change: Propelling our late stage program for all loan pool, one towards our regulatory pathway with a high likelihood of success.
Pisit Pitukcheewanont: You know what? Honestly, I cannot hear the question quite well, so if anybody can read it, go ahead, John.
John C. McKew: 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. Right, okay. So, Leland, that's a very good question, right?
John C. McKew: This is very important, right? As you know, first of all, FDA fully understands that the mechanism of action of Room 21 is totally different from 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 growth hormone deficiency, such as in moderate PTSD, the only impact with no treatment is only height, no other significant detrimental outcome that could, you know, leave the patient without treatment for six months or one year.
John C. McKew: So we do believe that most patients are fully aware of that, especially the PTSD. Patients who enroll in this study are prepubertal. So again, pubertal impact with no treatment for six months to one month is not going to have a significant impact on final adult height. With that said, we do believe that, when we conduct this trial, they will have no issue enrolling subjects. And not to mention that, you know, all the patients participating in this trial potentially will be able to enroll into a long-term extension study, which we already have in place, and AFD has approved that long-term extension study for three years. So I do believe that we need incentives to really help physicians to enroll their patients, knowing
John C. McKew: [inaudible] you know may have other beneficial effects on the body. Wondering if you're going to accept the donation.
Speaker Change: Additionally, we anticipate some very exciting developments in the coming year and eagerly anticipate sharing updates on our progress with you.
Speaker Change: Thank you all very much listening today and operator, we're ready to take questions will please.
John C. McKew: John, do you want to answer that question? So I think we won't be exa-
Speaker Change: Thank you we will now be conducting a question and answer session. If you would like to ask a question. Please press star one on your telephone keypad.
Speaker Change: A confirmation tone will indicate your line is in the question queue do you remember the start to if you would like to move your questions from the queue.
Speaker Change: For participants using speaker equipment may be necessary to pick up your handset before pressing the stock East one moment. Please poll for questions.
Speaker Change: Our first question comes from the line of Yes mean, Bohemia with Piper Sandler. Please go ahead.
Lee: Hi team. This is Lee in Houston for you guys.
John C. McKew: So, I think we won't be examining that question specifically in this Phase 3 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 3 trial, we're going to focus on the approvable endpoints and the path forward in PGHD to get an approval
Speaker Change: Thanks, so much for the update this morning, just to start in regards to the upcoming Phase III study I was wondering if you could provide some update on your expected bar for success and kind of in connection to growth and then also any clarity on why you chose the specific dose to move forward with them.
John C. McKew: But Leland, I think you were also referring to this. OK.
Edward Patrick White: Thank you. The next question comes from the line of Ed White with HC Wayne White. Please go ahead.
Speaker Change: Further what is the overall safety database requirement for approval and have you had any chance to engage with the E. M. A in regards to the phase III design as well.
Edward Patrick White: 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 3 trial and regulatory filings?
Speaker Change: And then also if you could comment at all on how long you expect it to take to enroll the phase III trial as well as if there's any overlap between the phase two and phase three sites.
John C. McKew: Don, go ahead. Manufacturing readiness.
Speaker Change: Yeah and that for now.
Speaker Change: Okay, but.
Speaker Change: All excellent questions and I think the bar says two success question, probably could be answered by John So go ahead Sean.
Sean: Yeah. So I you know as we mentioned.
John C. McKew: Yeah, so thanks for the question, Ed. So, we, you know, as you know, we recently filed a patent on a new drug product form for Phase 3, which will give us very tight dose variance across the large weight range for children with pediatric growth hormone deficiency and also provide easier routes of administration. So, you know, we have a mini-tablet in a capsule, so larger kids can take the capsule with the mini-tablet.
Sean: You know we have to.
Speaker Change: So clinically meaningful growth.
John C. McKew: Smaller kids can open the capsule and take the mini-tablets by themselves or in soft foods, so that design is in place, the bridging studies are complete, and we're moving forward to get our Phase 3 material ready to go. So there are no hiccups in the road there. We're well prepared to provide that Phase 3 slash commercial material to get us through Phase 3.
Sean: And so what we have.
Edward Patrick White: Okay, thanks, John. And just a question on the study, as you mentioned, it's going to have some overlap with phase two. Can you please 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?
Sean: Agreed to in the past with the F D. A to define clinically meaningful growth is that our agreement with the FDA at the.
End of 12 months in our phase two trial subjects have to achieve $6 seven centimeters per year.
Sean: Growth that was what we defined as the minimal clinically meaningful growth to continue on treatment with live to a one so one of the options that we have is to present that as an option for a clinically meaningful growth in this phase III study.
Speaker Change: I think just to tackle some of your other questions. The 1.6.
Speaker Change: Meg per kg per day dose, we've we've shown throughout the study to be both numerically at the highest H V across the three doses, we don't really see a difference between the $1 six and three point to make per kg per day doses. So I think there's no point to go to that higher dose.
Speaker Change: We do it.
Speaker Change: We 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 would see an increase in H b.
Speaker Change: And John to your for questions like the.
Speaker Change: The interaction with EMA.
Speaker Change: So the interaction with EMA, we will we will start that interaction after we have finalized our our protocol with the FDA.
Speaker Change: Yep and Duke why don't you talk about the enrollment number of patients enrollment and so on.
Pisit Pitukcheewanont: Yeah, so for DSS, what we plan right now is that, you know, we plan to enroll about 150 subjects. So the 2-to-1 randomization will be 100 subjects in Room 201 and 50 subjects in placebo.
Pisit Pitukcheewanont: Duke wanted to answer that question. Yeah, so...
Duke: Yeah. So thank you. So I think I answered. The first question do we have overlap wasn't the phase two sine the phase III, yes. There we have some you know phase two sites do continue to pass it in phase three and also we plan to initiate a new site for phase III as well as you know the number of subjects enrolled in phase II much smaller then phase III.
Speaker Change: It's nearly double what we want to increase the number of countries and number of sites around the world. At this point, we have signaled Ken you know kind like increase a van is a phase two trial at the global scale, we do get significant increase in interest of the came out around the world as well so.
Pisit Pitukcheewanont: We plan to include more countries outside the U.S. We are in the process of sending out a site survey to multiple regions around the world. We are waiting for those to receive those surveys back before making a decision on which country we go to. So around the site that we plan is about, you know, 90 sites-ish. So again, you know, so potentially about 14 countries. However, the final number and number of sites in the country will be finalized when we receive the survey back.
Speaker Change: We do believe that you know with enrollment timeline as we planned initially 15 to 18 months since the intact it'd be start you know their enrollment towards the end of this year. So again, you know pretty much everything on track and we do believe that we'd be able to be able to enroll those patients with anemia placebo controlled trial.
At the time, the manner, and especially you know when we increase the number of sites and number of country to participate in this trial.
Speaker Change: Okay.
Speaker Change: Good.
Speaker Change: Awesome, Oh, and then just one more question sorry, just on how do you plan on funding the phase three beyond here and <unk> 2020 four are there any other.
Speaker Change: Details on that.
Laura: Yeah, Laura go ahead.
Laura: Yeah, and you know we've been really busy since we've had our FDA meeting and planning for the upcoming phase III 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.
Laura: C III trial as as planned also as we've said previously we believe that there is opportunity to bring and potential strategic potential partners for our regional licensing deals, which would also allow for a non dilutive financing them and some of those territories that we would not necessarily go out and commercialize on our own.
Speaker Change: Great. Thank you so much.
Alright.
Speaker Change: Thank you.
Speaker Change: Next question comes from the line of Charles Duncan with Cantor Fitzgerald. Please go ahead.
Charles Cliff Duncan: Yeah, Good morning, Rick and team congrats on the progress some recent constructive interaction with the FDA also really appreciate all the color you provided I did have a couple of questions on the phase III trial design and then one.
Charles Cliff Duncan: On your your perspective regarding F D. A engagement so 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 did.
Charles Cliff Duncan: Right 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. It is it a true co primary or is there are you know call. It a step down from the first 12 months of age.
Charles Cliff Duncan: The to the second.
Charles Cliff Duncan: Yeah.
Charles Cliff Duncan: Yep.
Speaker Change: Yep, Duke once you answer the first part of the Phase III design question in terms of our enrollment criteria and then John If you would talk about the co primary.
John: Yes. Thank you that's a very good question. So the majority of inclusion exclusion criteria are pretty much similar compared to phase II and the phase two the only small changes that we want to implement it is number one the upper limit of the age enrollment we can a logo one year the reason behind that because we <unk>.
John: Want to make sure I shouldn't be compared to placebo, we want to make very clear that you know no single subject would get into the tender stage two dealing the 12 month trial period, and we have a bonus criteria that you know initially the ammonia delay with greater equal to six months, but now we can have a greater than 12 months and.
Speaker Change: Other than that pretty much the same and again you know part of this the inclusion exclusion criteria for didn't moderate PTSD. We do believe that you know majority of physician, who actually will participate in this trial was sees significant you know when we have a placebo controlled trial.
Speaker Change: This the different primary end point will be very clear as you know I think in majority of those patients and Youll see the data John present earlier, the best lie high velocity coming into these try but full priced seven and I would try ashish seven quite sick and they made or at 12 months. So basically we see that.
Speaker Change: Very clearly that you know we can achieve the clinical significant based on the FDA requirement at the end of this phase III trial.
Speaker Change: And John the co primary.
John: Yes, so Chad we do see these as co primary endpoints the.
John: 12 month growth endpoint in the six month comparison to placebo.
Speaker Change: Both showing clinically meaningful growth so that that's the that's the plan going and obviously, we will release more details once we have a final sign off on the from the F. D. A.
Speaker Change: A full phase III protocol.
John: That that'll include powering, John which which of the two D or power to or does it not matter.
Speaker Change: Yeah.
John: No well pair to both they'll both be they'll both be powered and and.
John: We do believe right now that we have.
John: <unk>.
Speaker Change: And that we have is more than sufficient to cover both of those endpoints.
Speaker Change: Okay. Neat design is the agency asking for bone mineral density imaging or any any bone health.
Speaker Change: Monitoring.
Duke.
Speaker Change: No that did did not and actually most of their.
Speaker Change: <unk> tried to get approved are the focus on the efficacy in terms of good velocity and the bone density try in general you may not see stigma and change in the first 12 months, so that would not required for these 12 months study.
Speaker Change: Okay and last question regarding the agency perspective, and you know always hazard for for that speculating on that but what do you think was the key shift or driver to the shift in in the view of this of our lunar 201 being a stimulator.
Speaker Change: Not a simple mathematic and did did you get a sense that they appreciate it.
Speaker Change: Compliance challenges with the current standard of care with the with the AR growth hormone are injectables.
Speaker Change: Okay.
John: Yeah go ahead John.
John: So I think.
John: Turning point Chez just in their viewing of our mechanism was around the extensive data that we have shared publicly and with the F. D. A about restoration of pulsatile.
John: Old trading rhythm of growth hormone release, and I think that data package was pretty substantial and that as you know we you know we've shown that we can.
John: Restore normal pulses and levels of growth hormone across a 24 hour period.
Speaker Change: From a deficient subjects, which amounts to about 20% of the growth that you need from an exogenous bolus dose and we're achieving almost the same amount of HB and I think that level.
Speaker Change: Of understanding and <unk>.
Speaker Change: Realizing that our growth of our 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 Perth them and really open up this whole discussion about kind of creative ways to.
Speaker Change: <unk> the growth potential of Blu two one in phase III.
The deal great to hear our appreciation and pulsatile mechanism always a key point of our thesis thanks for taking the questions.
Speaker Change: Okay.
Speaker Change: Yeah.
Chip: Thank you chip.
Pisit Pitukcheewanont: And Leland, if you recall, you were... Nope, it's it. Okay, and Leland, if you...
Leland James Gershell: Thank you next question comes from the line of Leland <unk> with Oppenheimer <unk> co. Please go ahead.
Operator: I'm sorry, Rick. Sorry for interrupting you, Rick. Operator.
Speaker Change: Oh good morning, Thanks for taking.
Leland James Gershell: Our questions.
Speaker Change: Also one third coming from pricing going forward.
Speaker Change: Suffice to say.
Speaker Change: Okay.
Speaker Change: Couple of questions from us that sort of things, which I'll just say, it's the same thing.
Speaker Change: So we feel about the placebo control versus inferiority or whole foods.
Speaker Change: So both of those as.
Speaker Change: Maybe early days, but once a year.
Speaker Change: Yeah, what extent.
Speaker Change: Those data or the lack thereof of.
Speaker Change: Comparability data and so some of them.
Speaker Change: Endocrinologists are you.
Speaker Change: 201, as they as they go to essentially use it.
Speaker Change: And to wanted to ask you know given the ancillary but important metabolic benefits.
Speaker Change: Argued them more and would you be looking for.
Speaker Change: Those essential benefits apart from the source itself in the phase III.
Speaker Change: [laughter], Duke I only heard part of the question, but I think that was really for you and.
Speaker Change: So when do you start.
Speaker Change: You know honestly I cannot hear the question quite well so if anybody can tell you so.
John: Yeah go ahead John.
So I think Leland was asking about the impact of not having.
John: Comparative.
Speaker Change: Treatment data in phase III for pediatric endocrinologists as they think about how to prescribe. This once we're out of the market.
Speaker Change: Right. Okay. So leland that's a very good question right. I think this is very important right. As you know first of all if D. A fully understood that mechanism action that room to one totally different than growth hormone and did make it clear to us that you are not going to tell them on and as a pediatric endocrinologists you know that.
Speaker Change: If you participate in the trial at the patient with Goldman deficiencies, such as in moderate P. J D. The only impact with no treatments only height no. Other significant detrimental outcome that could you know indicate the pace should be how treatment for six months or one year. So we do believe that most efficient fully aware that especially.
Speaker Change: The piece.
Speaker Change: Patients who enrolled in this study in prepubertal. So again people don't impact with no treatments six month to one month is not going to have a stigma impact in final adult height with that said, we do believe that you know when we conduct these trial. They will have no issue to enrolled this subject and not to mention that all the <unk>.
Speaker Change: <unk> participated in this trial potentially will be able to enroll into long term extension study, which is we already have that in place and FDA approved that long term extension study for three years. So I do believe that we incentive to really help flow physician to enroll their patient knowing that and the long term.
Speaker Change: We'll be benefit to a patient, especially when a drug get approved.
Speaker Change: Understood.
Speaker Change: Second.
Speaker Change: It was.
Speaker Change: Metabolic benefits linked to Alon.
Speaker Change: Apart from from gross itself.
Speaker Change: They have other.
Speaker Change: Beneficial effect on.
Speaker Change: Nobody wanted to African Festival.
Speaker Change: John do you want to answer that question.
Speaker Change: So I think we won't be examining that question specifically in this phase III study, we do have.
Speaker Change: An investigator initiated study going on in asphalt, where where some of that data is being collected in the context of examining the impact of liver fat. So it's being run at M. G H, but for a phase III trial, we're going to focus on the approvable endpoints and the path for the N P. J H D to get an approval.
Speaker Change: Thank you.
Speaker Change: But I don't think you were also referring to.
Speaker Change: Go ahead.
Speaker Change: Oh, thank you.
Speaker Change: The next question comes from the line of Ed White with H C. Wainwright. Please go ahead.
Speaker Change: Good morning. Thanks.
Speaker Change #100: Thanks for the update this morning, so I'm just a couple of questions for me.
Speaker Change #101: Can you comment on your manufacturing readiness for the phase III trial, and our regulatory filings.
Speaker Change #102: John go ahead.
John: Fashion readiness.
Edward Patrick White: Yeah. So thanks for the question Ed. So yeah. We you know as you know we recently.
Speaker Change #104: <unk> filed a patent on a new drug product form for phase III.
John: Which will give us great tight dose variance across the large weight range for children with pediatric growth hormone deficiency and also.
John: Provide easier routes of administration of them. So you know we have a mini tablet.
Speaker Change #105: In a capsule.
Speaker Change #105: Larger kids can take the capsule with the mini tablet smaller kids can open the capsule and take the many tablets by themselves or in a soft food.
Speaker Change #105: So that design is in place the bridging studies.
Speaker Change #105: Our complete and we're moving forward to get our.
Speaker Change #105: Our phase III material ready to go so there are no Ah you know there there are no hiccups in the road there, we're well prepared to provide that phase III slash commercial material ticket get us through phase III.
Speaker Change #107: Okay. Thanks, John and just a question on the study as you've mentioned, it's going to have some overlap with the phase two.
Speaker Change #106: Can you.
Speaker Change #108: Just let us know what you're thinking of as far as the geographical.
Speaker Change #109: The geographical breakdown for the U S versus outside the U S, where states sites and the number of patients enrolled.
Speaker Change #109: Duke wants to answer that question.
Speaker Change #110: Yes, so part D is that we plan right now is that you know we plan to enroll about 150 subjects. So two to one randomization will be 100 subject loom to one and <unk> 50 subject placebo. We plan to include more country outside the U S. We in the process of setting our sights so.
Speaker Change #111: A two month multiple region around the world, we waiting for those to receive those sites they way back before make decision, which country would go to so around the site that we plan is about and you know.
Speaker Change #112: 90 site ish. So again, you know so potentially above 14 country. However, the final number numbers cited the country will be finalized when we received a survey back.
Speaker Change #113: Okay mainland if you recall you wear them well.
Speaker Change #113: Ted.
Leland: Okay Leland.
Speaker Change #115: Well yeah.
Speaker Change #115: Yeah.
Speaker Change #115: Yeah.
I'm, sorry, Rick sorry for interrupting you Rick operator.
Richard J. Hawkins: My last question can I ask another question.
Edward Patrick White: My last question: did I ask another question? Absolutely, absolutely. So, the, um... You know, we've talked about this before, but out of the 60 to 62% of the patient population that's eligible, I just want to get your thoughts on why children who are eligible wouldn't want to be on the oral solution versus the injectable, especially since, as you mentioned, the cost will be lower. But the ease of use is apparent, and so I'm just taking the other side of that, and why wouldn't patients and children want to use your product?
Richard J. Hawkins: Sure absolutely.
Richard J. Hawkins: So the.
Speaker Change #116: We've talked about this before but out of the 60% to 62% of the patient population that's eligible.
Speaker Change #117: I just wanted to get your thoughts on why children, who are eligible wouldn't want to be on the oral solution versus the injectable, especially since as you mentioned the cost will be lower but the ease of use as a parent and so I'm just taking the other side of that and why wouldn't.
Speaker Change #118: Patients in children want to take your product.
Speaker Change #118: Well.
Richard J. Hawkins: 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 Indos, if they had a choice between a weekly injection or a once-daily oral, they overwhelmingly said that they would prefer to take a daily oral. That's sort of a given. So, 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. Yeah, I-
Edward Patrick White: We were just employment research Leland and no. This is this is Ed excuse me and.
Speaker Change #119: It's pretty clear when we ask for the families. But also the the Pete N does because they had a choice between a weekly injection or a once a day oral they own overwhelmingly said that they would prefer to take a daily oral that's a sort of a given so and of course we.
Speaker Change #119: We have a way to identify the patients who are our drug will most likely.
Speaker Change #119: Be effective and that is our predictive enrichment Oh.
Speaker Change #120: Our perm strategy.
Speaker Change #120: And 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.
Pisit Pitukcheewanont: Yeah, I would like to add on top of what Rick just said. As a pediatric endocrinologist, the majority of patients with PTSD fall into the PEM positive category. As you know, over 40 years, we don't have an option but just give injections to those children, right? Just until about four or five years, when we get long-acting approved.
Speaker Change #120: Yeah.
Speaker Change #121: Would like to add on top of what Rick just said as a pediatric endocrinologist majority of patients with PTSD falling two payment policy of category. As you know over 40 years, we don't have option, but just keep injection to dose children right just until about four or five years, then we get long acting approved but.
Speaker Change #121: Not get rid of injection, which is someday children do not want it, especially not only treatment for mondo, so not a year or so but much longer period of time. So physician in general I do believe that the perception was if this drug get approved they will offer a D has room to run to mature those patients.
Pisit Pitukcheewanont: But just not get rid of injections, which some of the children do not want, especially not only treatment for a month or so, not a year or so, but a much longer period of time. So physicians, in general, I do believe that their perception was that if this drug gets approved, they will offer Lumetroban to mature those patients by using PEM positive cutoff. With the PEM positive, they potentially can be on treatment. So I do believe that, you know, this is extremely important, right, to have this option for treatment for patients moving forward. We never really had this option until Lumetroban, you know, at this point.
Speaker Change #121: I used in Perm policy cut off the dividend policy that 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 patient moving forward. We never really have this option until loom to when you know at this point.
Speaker Change #122: Okay. Thanks for taking my questions.
Edward Patrick White: Okay, thanks for taking my question.
Speaker Change #122: Yeah.
Speaker Change #123: Thank you next question comes from the line of Catherine Novak with John's Research. Please go ahead.
Catherine Clare Novack: Thank you. The next question comes from the line of Catherine Novack with Jones Research. Please go ahead.
Speaker Change #124: Hi, Good 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 III do you see any inflection points between now and the start that might be.
Catherine Clare Novack: Hi guys, good morning. I just wanted to drill down on the cash position. You know, you need to bring in additional funding before you start Phase 3. Do you see any inflection points between now and the start 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? Are there more analyses that you think partners or investors would be interested in? Or, at this point, is most of the relevant data in hand?
Speaker Change #124: You might be able to use to bring in new investors and then just staring at the possibility of pursuing strategic partnerships. For example, what do you think they'd want to see before stepping 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.
Catherine Clare Novack: Yes Catherine.
Richard J. Hawkins: Bye. Bye.
Richard J. Hawkins: Catherine, it's a good question, and 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, really confident that the FDA gave us this trial design with a placebo arm, and 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 anything more to that or anyone else on the team. Yeah.
Catherine Clare Novack: I don't think there's any question that.
Catherine Clare Novack: That investors have enough information at this stage.
Catherine Clare Novack: To make a decision I think we're as Lori said, we're very confidence that the FDA gave us.
Speaker Change #126: This this this trial design with a placebo.
Lori D. Lawley: The 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.
Speaker Change #128: And Laurie I don't know if you want to add any more to that or anyone else on the team.
Lori D. Lawley: Yeah, I think Catherine, you know, when we've talked with investors, I think a lot of investors have just been waiting to determine what the Phase 3 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 move forward. That is why we are confident we will be able to move forward and complete a financing in the near term.
Speaker Change #128: Yeah, I I think Katherine I think you know when we've talked with investors and I think a lot of investors have just been waiting to determine what the phase III trial design would look like and now that we have gotten feedback from the FDA them. They have proposed a placebo controlled trial as an option as we finalize that trial design and and move forward with F. D. A.
Catherine Clare Novack: Got it. And then just, I guess, clarification on the first co-primary endpoint. If you could 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 end point, if you could clarify?
Speaker Change #128: All at that trial design, we do believe that that will instill confidence and their investors and allow us to.
Speaker Change #128: We did a financing in the near term as far as you know looking for regional partners. You know, we've 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 all.
Speaker Change #129: I've been waiting on you know what the phase III trial design will look like so now that we have that information in hand, and we have more of those details that I think that is why we are confident we will be able to move forward and completed a financing in the near term.
Speaker Change #130: Got it and then just I guess clarification on the first co primary endpoint.
Speaker Change #131: If you could help me understand the statistical analysis.
Speaker Change #132: He was not followed for 12 months what does the hypothesis.
Speaker Change #132: For the first co primary.
Speaker Change #134: And if you could clarify.
Speaker Change #133: Yep Yep.
Speaker Change #135: Yeah. John go ahead, if you didn't ask a question.
John C. McKew: Yeah, John, go ahead if you didn't have a question. Sure, so.
John C. McKew: Sure. 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 6.7 centimeters per year, which represents minimal clinically meaningful growth. So, we're using that to transition essentially from our Phase 2 study into our long-term safety extension. And that is an agreement that we already have with the FDA. So, that is the first option that we'll pursue.
John: 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 F. D. A on 6.7 centimeters per year, representing minimal clinically meaningful growth. So we're using.
Speaker Change #135: That.
Speaker Change #135: 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 a that is the the first option that we'll pursue.
Speaker Change #135: Okay.
Catherine Clare Novack: 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?
Speaker Change #136: And then just one more you know thinking about this down the road right now you're focusing on treatment naive patients, but it seems like it.
Speaker Change #137: Does this make sense to us after an initial year or two with growth hormone for people, who are maybe interested in having daily injections indefinitely.
Speaker Change #137: Duke loads will hit if you will.
Pisit Pitukcheewanont: Duke, let's go ahead, if you will.
Speaker Change #138: Yeah. So I think that that's a very good question I do believe that motivation will look into.
Pisit Pitukcheewanont: Yeah, so I think that that's a very good question. I do believe that most patients will look into that and potentially could switch the patient room to one. At this point, we don't have data to show yet. So we think that moving forward, when we get this phase three trial done, we will put that in the registry. So the majority of those patients are going to get into the long-term extension, especially the registry. If someone who's not in phase two, they can continue to, you know, have the phase four study.
Speaker Change #139: Into that potentially could switch a patient's room to one at this point, we don't have data to show yet so what we think that moving forward. When we get these phase III trial done we put them in registry. So majority of those patients going to get into the long term long term extension, especially rich history is someone who is not in <unk>.
Speaker Change #139: <unk> too. They can continue to you know have the phase four study when the drug get approved would be able to determine some of those especially when the patients want to you know discontinued daily and going to live to a one we'd be able to evaluate dose efficacy in those trials.
Pisit Pitukcheewanont: 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 its efficacy in those trials.
Catherine Clare Novack: Okay, I got it. That's helpful. Thanks.
Okay got it that's helpful. Thanks.
Speaker Change #140: Thank you.
Operator: Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.
Speaker Change #141: This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.
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Speaker Change #141: Okay.
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