Lumos Pharma Inc (LUMO) 2024 Q1 法說會逐字稿

Greetings and welcome to Lumos Pharma first quarter 2024 financial results and clinical programs update call. (Operator Instructions) 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.

Thank you, operator. Before we proceed with the call, I would like to remind everyone that certain statements made during this call are forward-looking statements under US federal securities laws. These statements are subject to risks and uncertainties that could cause actual results to differ materially from historical experience or present expectations.

Additional information concerning factors that could cause actual results to differ is contained in our periodic reports filed with SEC. The forward-looking statements made during this call speak only as of the date hereof, and the company undertakes no obligation to update or revise 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 investor's 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. Duke Pitukcheewanont, 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.

Thank you, Lisa, and good morning, everyone. I'm pleased to be speaking with you today to provide an update on our progress advancing LUM-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 2 meeting with the FDA and conducted fresh analyses on updated data from our OraGrowtH212 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 end-to-Phase 2 meeting with the FDA, where we reviewed the promising data from our Phase 2 OraGrowtH210 and 212 trials and discussed an optimal Phase 3 design for a successful regulatory path forward. Both Phase 2 OraGrowtH trials, as you may recall, successfully met their primary and secondary endpoints, providing robust evidence supporting the potential of Ora LUM-201 in treating moderate PGHD.

Additionally, the trials demonstrated the effectiveness of our predictive enrichment marker test in identifying patients likely to respond to LUM-201. During our dialogue with the FDA, it was acknowledged that LUM-201 operates distinctly from growth hormone or its mimetics. The FDA recognized LUM-201 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.

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 3 Trial of LUM-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 LUM-201 toward approval as the first oral therapeutic for moderate PGHD.

Our confidence in LUM-201 was further strengthened through our examination of additional data from our Phase 2 OraGrowtH 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 positioned Lumos Pharma as a late-stage biopharmaceutical company with substantial growth prospects and continue to support the potential of oral LUM-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 to our interaction with the FDA and our strategic planning for this pivotal Phase 3 Trial. John?

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 OraGrowtH 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 adversary remained collegial and centered on determining the optimal approach for the pivotal trial design of LUM-201 in treating moderate PGHD.

The data package we presented to the FDA underscored the outcomes of our Phase 2 OraGrowtH Trials. As you may recall, these trials successfully met their primary and secondary endpoints, demonstrating that LUM-201 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 LUM-201 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, LUM-201 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 emergent marker, or PEM, strategy accurately identified potential LUM-201 responders and showcased the PEM classification as 100% reproducible, surpassing the predefined statistical margin.

Additionally, safety profile of an investigational LUM-201 was further validated. Upon reviewing these data, FDA representatives indicated a shift in their perspective regarding LUM-201s distinct mechanism. They acknowledged that LUM-201 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 LUM-201 should not necessarily be directly compared to traditional growth hormone products.

As a reminder, LUM-201 is a small molecule that binds to the growth hormone's receptor 1A in both the pituitary and the hypothalamus. LUM-201 agonizes the receptor, and that signals the release of stored growth hormone in the Somatrogon. By also modulating Somatrogon and growth hormone releasing hormone in the hypothalamus, LUM-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 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 acknowledgement that LUM-201 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 3 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 LUM-201 against the lower-approved dose of growth hormone.

We chose this comparator dose because it more closely mirrors the physiological levels of growth hormone and IGF-1 that LUM-201 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 LUM-201 to placebo.

One arm will receive LUM-201 for 12 months, while the other arm will initially receive placebo and then transition to LUM-201 after six months, remaining on treatment for the next six months. All subjects enrolled in the trial will be PEM positive.

This Phase 3 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 comparison within subject assessing growth on placebo versus growth on LUM-201, 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 LUM-201 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 3 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 OraGrowtH Trials. In yesterday's press release, we unveiled preliminary updated 12- and 24-month growth data from our OraGrowtH210 Trial.

A data snapshot from our trials, specifically the six and updated 12-month data on LUM-201, 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 six- and 12-month growth rates on LUM-201 and baseline growth rates. These findings highlight a noteworthy increase in AHV or annualized site velocity from baseline upon treatment of LUM-201. The baseline growth rate of 4.7 centimeters per year documented in our Phase 2 Trial should serve as an indicator of the placebo arms annualized growth rate in our Phase 3 Trial. The full 12-month data for all cohorts in the OraGrowtH210 Trial reinforces our choice to advance the 1.6 mg per kg, LUM-201 dose into Phase 3.

Finally, we combined the 1.6 and 3.2 mg per kg per day cohorts from our two Phase 2 Trials, since their growth rates were not statistically different. These data include all subjects who were treated to 24 months, excluding those who transitioned from [tender 1 to tender 2] to enable a comparison to historical Pfizer’s KIGS database. These updated data continue to underscore the enduring efficacy of LUM-201. When comparing year one AHV to year two AHV for LUM-201, 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 KIGS database treated with recombinant hemoglobin where the drop-off is closer to 20%. These findings from our Phase 2 studies highlighted how LUM-201 could 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 LUM-201's novel mechanism of action, granting them the freedom to suggest innovative Phase 3 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 OraGrowtH Trial results were presented at three major endocrinology conferences at the Pediatric Endocrine Society meeting in Chicago by Dr. [Andrew Dauber], highlighting data showing LUM-201 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 at two subsequent conferences in Stockholm, the Growth Hormone Research Society and European Congress of Endocrinology, Dr. [Peter Clayton] presented a comprehensive analysis of LUM-201 restoration of growth hormone secretion and the increase in AHV-induced and moderate PGHD patient.

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 OraGrowtH212 trial with additional analyses from the OraGrowtH210 trial.

The maturing data from our OraGrowtH 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.

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 3 planning and preparatory activities.

With the recent developments from the FDA, we are confident that we will be able to finance our Phase 3 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 31, 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 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.

And now I will turn it over to Rick for his closing remarks.

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 LUM-201 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 LUM-201. If approved, we believe LUM-201 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, LUM-201 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 commercial scale production of LUM-201 would be significantly lower than for recombinant growth hormone. And as we've consistently emphasized, we view LUM-201 not only as a singular product, but also as a robust pipeline.

We see the potential for LUM-201 to address 10 additional indications currently treated with recombinant growth hormone, including Prader-Willi syndrome and idiopathic short stature.

With the FDA acknowledging LUM-201 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 LUM-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.

Thank you. (Operator Instructions) The first question comes from the line of Liam Hiester, Piper Sandler. Please go ahead.

Hi, team. This is Liam Hiester on for Yas. Thanks so much for the update this morning. Just 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 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 regard 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. That's for now.

All excellent questions. I think the bar to success question probably should be answered by John. Go ahead, John.

As we mentioned, we have to show clinically meaningful growth. What we have agreed to 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 LUM-201. 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.

Yeah, the interaction with EMA. So the interaction with EMA, we will start that interaction after we have finalized our protocol with the FDA.

Yeah, and Duke, why don't you talk about the enrollment, number of patients, enrollment, and so on.

Yeah, so thank you. So I think answer the first question, do we have overlap of a Phase 2 site and a Phase 3? Yes, there will have some, Phase 2 sites to 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 is 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, kind of like increased awareness of Phase 2 trials at the global scale. We do get significant increase in interest of the KOL around the world as well. So we do believe that with 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, 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, when we increase the number of sites and the number of countries to participate in this trial.

Okay. Awesome. Oh, and then just one more question. Sorry. Just how do you plan on funding the Phase 3 beyond yearend 3Q '2024? Are there any details on that?

Yeah. Lori, go ahead.

Yeah. You know, we've been really busy since we've 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 is planned.

Also, as we've said previously, we believe that there is opportunity to bring in potential strategic or --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.

Great. Thank you so much.

Thank you. Charles Duncan, Cantor Fitzgerald.

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 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 the Phase 2?

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-- call it a step down from the first 12-month AHV to the second? Thanks.

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.

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, since we compare to placebo, we want to make very clear that, no single subject would get into the tender stage 2 during the 12-month trial period.

And we have a bonus criteria that, initially the bonus delay was greater or equal to 6 months, but now we can have it greater than 12 months. And other than that, pretty much the same. And again-- part of this inclusion exclusion criteria for the moderate PGHD. We do believe that majority of physicians who actually will participate in this trial will see significant-- when we have a placebo-controlled trial.

The different primary endpoints 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, we can achieve the clinical significance based on the FDA requirement at the end of this Phase 3 trial.

Helpful. And John, the co-primary.

Yes. So, Charles, 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 3 protocol.

And that will include powering, John? Which of the [two D] you power to? Or does it not matter?

No, we'll pair to both. They'll both be powered. And we do believe right now that we have, -- but the end that we have is more than sufficient to power both of those endpoints.

Okay. Neat design. Is the agency asking for bone mineral density imaging or any bone health monitoring?

Duke?

No, they did not. And actually, most of the trials 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.

Okay. And last question regarding the agency perspective. And 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 LUM-201 being a stimulator, not a simple mimetic? And did you get a sense that they appreciated compliance challenges with the current standard of care with the growth hormone injectables?

Yes, go ahead, John.

So, I think the turning point, Chasles, 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, Ultragenyx rhythm of growth hormone release. And I think that data package was pretty substantial. And as 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 hormone and really open up this whole discussion about kind of creative ways to evaluate the growth potential of LUM-201 in Phase 3.

Good deal. Great to hear. Appreciation of pulsatile mechanism, always a key point of our thesis. Thanks for taking the questions.

Thank you, Charles.

Thank you. Leland Gershell Oppenheimer & Co. I

Hi, good morning. Thanks for taking our questions. I also wanted to comment on a positive surprise to hear the agency's view on the Phase 3 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 serious growth hormone injections.

It may be early days, but I wanted to hear to what extent could those data or the lack thereof of comparability data to growth hormone impact endocrinologists view on LUM-201 as they go to potentially use it in their patients?

And two, I want to ask, given the ancillary but important metabolic benefits of (inaudible) , will you be looking for those potential benefits apart from growth itself in the Phase 3? Thank you.

Yeah. Duke, I only heard part of the question, but I think that was really for you. So, why don't you start?

You know what? Honestly, I cannot hear the question quite well. So, if anybody can read.

So, go ahead, John.

So, I think Leland was asking about the impact of not having, comparative treatment data in Phase 3 for pediatric endocrinologists as they think about how to prescribe this once we're on the market.

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 LUM-201 is totally different than growth hormone, and they make it clear to us that you are not growth hormone. And as a pediatric endocrinologist, that if you participate in the trial, if the patient with growth hormone deficiency, such as in moderate PGHD, the only impact with no treatment is only height.

No other significant detrimental outcome that could, implicate the patient without treatment for six months or one year. So, we do believe that most patients are fully aware of that, -- especially the patient who enrolls in this study is prepubertal.

So, again, pubertal impact with no treatment six months to one month is not going to have significant impact in the final adult height. With that said, we do believe that, when we conduct this trial, they will have no issue to enroll the subject. And not to mention that all the patients participate 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 for physician to enroll their patient, knowing that in the long-term will be beneficial to their patient, especially when the drug is approved.

(inaudible)

John, do you want to answer that question?

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.

Yes, thank you.

Thank you. But, Leland, I think you were also referring to okay, go ahead.

Thank you. Edward White H.C. Wainwright & Co, LLC.

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?

John, go ahead. Manufacturing readiness.

Yeah. So, thanks for the question, Ed. So, yeah, we-- 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, we have a mini tablet in a capsule. So, larger kids can take the capsule with the mini tablet. 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 3 material ready to go.

So, there are no, -- 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.

Okay. Okay. Thanks, John. And just a question on the study, as you mentioned, it's going to have some overlap with the Phase 2. Can you just let us know what you're thinking of as far as a geographical breakdown for the US versus outside the US for sites and the number of patients enrolled?

Duke, why don't you answer that question?

Yeah. So, for this, as we plan right now, is that-- we plan to enroll about 150 subjects. So, two to one randomization will be 100 subjects in LUM-201 and 50 subjects in placebo. We plan to include more countries outside the US. We're in the process of sending out a site survey to multiple regions around the world.

We're waiting to receive those sites survey back before we make a decision which country we go to. So, around the site that we plan, it's about 90 sites ish. So, again, 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.

Okay. Thank you. Leland, if you recall, you were in? -- (technical difficulty)

I'm sorry, Rick. I'm sorry for interrupting you, Rick. My last question. Can I ask another question?

Sure, absolutely.

So, the, 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 take your product?

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 repeat dose, 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.

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 at will be effective.

Yeah, Ed, I would like to add on top of what Rick just said. As a pediatric endocrinologist, majority of patients with PGHD 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, five years, And we get long-acting approved, but just not get rid of injection, which is some of the children do not want it, especially not only treatment for a month or so, not a year or so, but much longer period of time.

So physician in general, I do believe that their perception was if this drug get approved, they will offer this LUM-201 to mature those patients by using PEM positive category. The PEM positive, they potentially can be on the treatment. So I do believe that-- this is extremely important, right, to have this option for the treatment for patient moving forward. We never really have this option until LUM-201, you know, at this point.

Okay. Thanks for taking my questions.

Thank you. Catherine Novack JonesTrading Institutional Services, LLC.

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 3. Do you see any inflection points between now and the start that might be where--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?

Yes. Catherine, that'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, we're very 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.

Yeah, I think, Catherine, I think, 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 the placebo control 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-US options for regional partners and retaining US 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.

So 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.

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?

Yeah. John, go ahead if you had a question.

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 6.7 centimeters per year representing 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 we already have with the FDA. So that is the first option that we'll pursue.

Okay. And then just one more. 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?

Duke, let's go ahead, if you will.

Yeah. So I think that that's a very good question. I do believe that most physicians will look into that potentially because we patient LUM-201. At this point, we don't have data to show yet. So what we think that moving forward, when we get this Phase 3 trial done, we put that in registry. So majority of those patients going to get into the long-term extension, especially registry is someone who's not in Phase 2.

They can continue to, have the Phase 4 study when the drug get approved, we'll be able to determine some of those, especially when the patient want to discontinue daily and go into LUM-201. We'd be able to evaluate those efficacy in those trials.

Okay. Got it. That's helpful. Thanks.

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