Lumos Pharma - Q1 2024

Executive Summary

• FDA End-of-Phase II meeting was constructive; agency recognized LUM-201 as a novel growth promoter and indicated a placebo-controlled Phase III is an appropriate option, with a proposed double-blind 2:1 randomization (~150 patients) targeting initiation in Q4 2024, pending FDA sign-off.
• Updated Phase II data showed LUM-201 achieved AHV of 8.2 cm/yr at 6 months and 7.6 cm/yr at 12 months at 1.6 mg/kg vs 4.7 cm/yr baseline; combined data suggest durability to 24 months with a smaller YoY AHV decline vs historical rhGH benchmarks.
• Q1 2024 financials: revenue $0.165M, EPS $(1.29), net loss $(10.4)M; cash and equivalents $23.2M with runway through Q3 2024 including Phase III planning; management is confident in financing Phase III via equity and/or regional licensing.
• Catalysts: FDA protocol finalization (Q3), Phase III start (Q4), ENDO poster presentations and full 12-month OraGrowtH212 data release in Q2; focus shifts from non-inferiority vs rhGH to the FDA-suggested placebo-controlled design, a notable strategic pivot.

What Went Well and What Went Wrong

What Went Well

• FDA acknowledged LUM-201’s distinct mechanism and recommended a placebo-controlled Phase III—reduces comparator complexity and may enhance regulatory clarity; “acknowledged the use of a placebo-controlled clinical trial design as an appropriate option”.
• Phase II efficacy durability: AHV 8.2 cm/yr (6m) and 7.6 cm/yr (12m) at 1.6 mg/kg vs 4.7 cm/yr baseline; combined 24-month AHV of 7.3 cm/yr with a ~9.9% second-year decline vs ~19.7% for rhGH historical benchmarks.
• Management reiterated timely Phase III readiness and manufacturing form factor optimization (capsule with mini-tablets) with bridging complete; “moving forward to get our Phase III material ready to go”.

What Went Wrong

• Royalty revenue down year-over-year: $0.165M (Q1 2024) vs $0.691M (Q1 2023); net loss widened to $(10.4)M from $(7.3)M; EPS deteriorated to $(1.29) from $(0.89).
• Cash decreased to $23.2M from $36.1M at year-end; runway only through Q3 2024, necessitating external financing ahead of Phase III.
• Estimates context unavailable via S&P Global (mapping issue), limiting formal beat/miss assessment; investors must rely on company milestones and liquidity disclosures [Attempted GetEstimates—mapping unavailable].

Transcript

Operator (participant)

Greetings and welcome to Lumos Pharma 1st 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. 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. Ms. Miller, go ahead.

Lisa Miller (VP of Investor Relations)

Sir, before we proceed with the call, yes, sorry. Thank you, Operator. Before we proceed with the call, I would like to remind everyone that certain statements made during this call are forward-looking statements under U.S. federal securities laws. These statements are subject to risks and uncertainties that could cause actual results to differ materially from historical experience or present expectations. Additional information concerning factors that could cause actual results to differ is contained in our periodic reports filed with SEC. The forward-looking statements made during this call speak only as of the date hereof, and the company undertakes no obligation to update or revise these forward-looking statements. Information presented on this call is contained in the press release we issued yesterday afternoon and in our Form 8-K, which may be accessed from the investors' pages 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.

Rick Hawkins (CEO and Chairman)

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-of-phase II meeting with the FDA and conducted fresh analyses on updated data from our OraGrowtH212 and OraGrowtH210 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-of-phase II meeting with the FDA where we reviewed the promising data from our phase II OraGrowtH210 and OraGrowtH212 trials and discussed an optimal phase 3 design for a successful regulatory path forward.

Both phase II oral growth trials, as you may recall, successfully met their primary and secondary endpoints, providing robust evidence supporting the potential of oral 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. Now, 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 III 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 III 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 II oral growth trials. As detailed in our press release, we unveiled updated 12-month and 24-month data from these trials, which consistently demonstrate a durable effect and substantial improvement over baseline annualized height velocity. We are confident that the advancements made position Lumos Pharma as a late-stage biopharmaceutical company with substantial growth prospects and continue to support the potential of oral 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 the pivotal phase III trial. John?

John McKew (President and Chief Scientific Officer)

Thanks, Rick, and good morning, everyone. As Rick mentioned, we recently concluded our end-of-phase II meeting with the FDA to evaluate data from our oral growth trials and explore potential strategies for a phase III pivotal trial. A key highlight from the meeting was its overwhelmingly positive and constructive nature. With approximately 30 FDA staff members present, including senior representatives from pertinent departments, the atmosphere remained collegial and centered on determining the optimal approach for the pivotal trial design of LUM-201 in treating moderate PGHD. The data package we presented to the FDA underscored the outcomes of our phase II oral growth 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 six and 12 months on treatment with LUM-201 at the 1.6 mg/kg/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 6 months of treatment initiation. Furthermore, the trial data provided preliminary confirmation that our predictive enrichment marker, or PEM, strategy accurately identified potential LUM-201 responders and showcased the PEM classification as 100% reproducible, surpassing the predefined statistical margin. Additionally, the safety profile of investigational LUM-201 was further validated. Upon reviewing these data, FDA representatives indicated a shift in their perspective regarding LUM-201's 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 secretagogue 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 somatotropes. By also modulating somatostatin 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 acknowledgment 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 III trial. A significant portion of the meeting was dedicated to exploring different options, culminating in the suggestion by the FDA that we contemplate a placebo-controlled design. Heading into the FDA meeting, we examined historical pivotal trial designs with growth-promoting agents and proposed to the FDA a standard non-inferiority design consisting of, in this case, a 12-month study evaluating 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 2:1 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 6 months, remaining on treatment for the next 6 months. All subjects enrolled in the trial will be PEM positive. This phase III 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 envisioned 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 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 III trial before the end of 2024. Our potential for success in a pivotal trial is bolstered by the evolving data and deeper analysis from our oral growth trials. In yesterday's press release, we unveiled preliminary updated 12- and 24-month growth data from our OraGrowtH210 trial.

The data snapshot from our trials, specifically the 6- and updated 12-month data on LUM-201, 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 deficiency cases. Our updated data consistently demonstrate that we are achieving growth rates similar to those observed in historical data for the moderate PGHD patient cohort. Further analyses compare the 6- and 12-month growth rates on LUM-201 and baseline growth rates. These findings highlight a noteworthy increase in AHV or annualized height velocity from baseline upon treatment with LUM-201. The baseline growth rate of 4.7 cm per year documented in our phase II trial should serve as an indicator of the placebo arm's annualized growth rate in our phase III trial.

The full 12-month data for all cohorts in the OraGrowtH210 trial reinforces our choice to advance the 1.6 mg/kg LUM-201 dose into phase III. Finally, we combine the 1.6 and 3.2 mg/kg/day cohorts from our two phase II 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 Tanner 1 to Tanner 2 to enable a comparison to historical Pfizer/KIGS database. These updated data continue to underscore the enduring efficacy of LUM-201. When comparing Year 1 AHV to Year 2 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 human growth hormone, where the drop-off is closer to 20%.

These findings from our phase II 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 II 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 III study designs. We believe that this placebo-controlled design significantly mitigates our regulatory risk and enhances our potential to introduce the first oral therapeutic for growth hormone deficiency to the market. This innovative oral therapeutic is anticipated to be a welcome treatment option for pediatric endocrinologists seeking to address pediatric growth hormone deficiency in their patients. Earlier this month, analyses of top-line oral growth trial results were presented at three major endocrinology conferences: at the Pediatric Endocrine Society meeting in Chicago by Dr.

Andrew Dauber, highlighting data showing LUM-201 achieved comparable annualized height velocity to daily recombinant human growth hormone in PGHD at the 1.6 mg/kg/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 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 OraGrowtH212 trial with additional analyses from the OraGrowtH210 trial.

The maturing data from our oral 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.

Lori Lawley (CFO)

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 III planning and preparatory activities. With the 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.

Research and development expenses were $7.2 million, an increase of $2.9 million for the quarter ended March 31st, 2024, compared to the same period in 2023, primarily due to increases of $2 million in licensing expense, $0.8 million in clinical trial expenses, and $0.2 million in consulting expenses, offset by a decrease of $0.1 million in personnel-related expenses. General and administrative expenses were $3.8 million, a decrease of $0.6 million compared to the same period in 2023, primarily due to decreases of $0.4 million in licensing expenses, $0.1 million in travel expenses, $0.1 million in consulting expenses, and $0.1 million in other expenses, offset by an increase of $0.1 million in personnel-related expenses. The net loss for the quarter ended March 31st, 2024, was $10.4 million compared to a net loss of $7.3 million for the same period in 2023. Lumos Pharma ended Q1, 2024, with 8,107,121 shares outstanding.

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

Rick Hawkins (CEO and Chairman)

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 deficiency 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. 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 the 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.

Operator (participant)

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. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your questions from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, while we pull for questions.

The first question comes from the line of Yasmeen Rahimi with Piper Sandler. Please go ahead.

Lally Johnson (Banking Analyst)

Hi, team. This is Lally Johnson on for Yas. Thanks so much for the update this morning. Just to start, in regard to the upcoming phase III study, I was wondering if you could provide some update on your expected bar for success in connection to growth, and then also any clarity on why you chose a specific dose to move forward with. Further, what is the overall safety database requirement for approval, and have you had any chance to engage with the EMA in regards to the phase III design as well? 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 II and phase III sites.

John McKew (President and Chief Scientific Officer)

Yeah, and that's for now. Okay. All excellent questions. And I think the bar to success question probably should be answered by John. So go ahead, John. Yeah. So as we mentioned, we have to show clinically meaningful growth. And so what we have agreed to in the past with the FDA to define clinically meaningful growth is an agreement with the FDA at the end of 12 months in our phase II trial, subjects have to achieve 6.7 cm 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 III study.

I think just to tackle some of your other questions, the 1.6 mg/kg/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/kg/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. So it's two of your four questions. Yeah, the interaction with the EMA. So the interaction with the 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 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 II site and a phase III? Yes. There we have some phase II sites do continue to participate in phase III, and also we plan to initiate a new site for phase III as well. As you know, the number of subjects that enroll in phase II is much smaller than phase III, 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 increase of awareness of phase II 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 plan initially, 15-18 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 a 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.

Lally Johnson (Banking Analyst)

Okay. Great. Awesome. Oh, and then just one more question. Sorry. How do you plan on funding the phase III beyond year-end 3Q 2024? Are there any details on that?

John McKew (President and Chief Scientific Officer)

Yeah. Lori, go ahead.

Lori Lawley (CFO)

Yeah. 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 III trial as is planned.

Also, as we've said previously, we believe that there is 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.

Lally Johnson (Banking Analyst)

Great. Thank you so much.

John McKew (President and Chief Scientific Officer)

All right.

Operator (participant)

Thank you. Next question comes from the line of Charles Duncan with Cantor Fitzgerald. Please go ahead.

Charles Duncan (Managing Director)

Yeah. Good morning, Rick and team. Congrats on the progress and recent constructive interaction with the FDA. Also, really appreciate all the color you've provided. I did have a couple of questions on the phase III trial design and then one on your perspective regarding FDA engagement. So with regard to the phase III trial design, I'm wondering if you could affirm that the enrollment criteria in phase III will be the same, or if not, how different from the phase II.

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.

Rick Hawkins (CEO and Chairman)

Yep. Yep. Duke, why don't you answer the first part of the phase III design question in terms of enrollment criteria, and then John, if you'll talk about the co-primary.

John McKew (President and Chief Scientific Officer)

Yes. Thank you. That's a very good question. So the majority of inclusion/exclusion criteria are pretty much similar compared to phase III and phase II. The only small changes that we want implemented is, number one, the upper limit of the age enrollment, we're going to lower one year.

The reason behind that is 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 Tanner stage two during the 12-month trial period. We have a bone age criteria that initially, the bone age delay was greater or equal to 6 months, but now we're going to have it greater than 12 months. Other than that, pretty much the same. Again, part of this, the inclusion/exclusion criteria for the PGHD, we do believe that the majority of physicians who actually will participate in this trial will see significant when we have a placebo-controlled trial, the different primary endpoint 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 height velocity coming in in this trial was 4.7, and our trial achieved 7.6 cm 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 III trial. Helpful. And John, the co-primary. Yeah. So Chaz, we do see these as co-primary endpoints, the 12-month growth endpoint and the six-month comparison to placebo, both showing clinically meaningful growth. So that's the plan going in. Obviously, we'll release more details once we have a final sign-off from the FDA on the full phase III protocol. That'll include powering, John. Which of the two do you power to, or does it not matter? No, we'll power 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. 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 a significant change in the first 12 months. So that would not require for this 12-month study.

Charles Duncan (Managing Director)

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 LUM-201 being a stimulator, not a simple mimetic?

And did you get a sense that they appreciated the compliance challenges with the current standard of care with the growth hormone injectables?

Rick Hawkins (CEO and Chairman)

Yeah. Go ahead, John.

So I think the turning point, Chaz, just in their viewing of our mechanism was around the extensive data that we've shared publicly and with the FDA about restoration of pulsatile ultradian rhythm of growth hormone release. And I think that data package was pretty substantial. And as you know, we've shown that we can restore normal pulses and levels of growth hormone across a 24-hour period in growth hormone-deficient subjects, which amounts to about 20% of the growth hormone that you need from an exogenous bolus dose. And we're achieving almost the same amount of AHV.

John McKew (President and Chief Scientific Officer)

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 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 III. Good deal. Great to hear appreciation. The pulsatile mechanism, always a key point of our thesis.

Charles Duncan (Managing Director)

Thanks for taking the questions.

Rick Hawkins (CEO and Chairman)

Thank you, Chaz.

Operator (participant)

Thank you. Next question comes from the line of Leland Gershell with Oppenheimer & Co. Please go ahead.

Leland Gershell (Managing Director and Senior Biotechnology Analyst)

Hi. Good morning. Thanks for taking our questions. I also wanted to comment on positive surprise to hear the agency's view on the phase III requirements. A couple of questions from us.

This sort of playing devil's advocate at the same time that we're trying to hear about the placebo control versus inferiority versus daily 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, wanted to ask, given the ancillary but important metabolic benefits of ibutamoren, will you be looking for those potential benefits apart from growth itself in the phase III? Thank you.

John McKew (President and Chief Scientific Officer)

Yeah. Duke, I only heard part of the question, but I think that was really for you. And so why don't you start? You heard the question. Honestly, I cannot hear the question quite well. So if anybody can be.

Rick Hawkins (CEO and Chairman)

Yeah. Go ahead, John.

So I think Leland was asking about the impact of not having comparative treatment data in phase III 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? 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, you know 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.

We do believe that most physicians are fully aware of that, especially the patient who enrolled in this study is prepubertal. Again, pubertal impact with no treatment six months to one month is not going to have a significant impact in final adult height. With that said, we do believe that once we conduct this trial, there will be no issue to enroll the subject. Not to mention that all the patients who 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. I do believe that we incentive to really help for physicians to enroll their patients knowing that in the long term will be beneficial to their patients, especially with the drug getting approved. Mr. Duncan, just a second. Sorry.

Just the metabolic benefits. LUM-201, apart from growth itself, may have other beneficial effects on the body, wondering if you're going to assess for those in phase III. John, do you want to answer that question? So I think we won't be examining that question specifically in this phase III 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 a phase III trial, we're going to focus on the approval endpoints and the path forward in PGHD to get an approval.

Leland Gershell (Managing Director and Senior Biotechnology Analyst)

All right. Thank you.

Rick Hawkins (CEO and Chairman)

But Leland, I think you were also referring to. Thank you. Okay. Go ahead.

Operator (participant)

Thank you. The next question comes from the line of Ed White with H.C. Wainwright & Co. Please go ahead.

Ed White (Managing Director and Senior Biotechnology Analyst)

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 III trial and regulatory filings?

Rick Hawkins (CEO and Chairman)

John, go ahead. Manufacturing readiness.

John McKew (President and Chief Scientific Officer)

Yeah. So thanks for the question, Ed. So yeah, as you know, we recently filed a patent on a new drug product form for phase III, 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 tablets. Smaller kids can open the capsule and take the mini tablets by themselves or in soft food. So that design is in place. The bridging studies are complete, and we're moving forward to get our phase III material ready to go.

So there are no hiccups in the road there. We're well prepared to provide that phase III commercial material to get us through phase III. Okay. Thanks, John. And just a question on the study. As you mentioned, it's going to have some overlap with the phase II. Can you just let us know what you're thinking of as far as a geographical breakdown for the U.S. versus outside the U.S. for sites and the number of patients enrolled? Duke wanted to answer that question. Yeah. So for DSI, what we plan right now is that we plan to enroll about 150 subjects. So 2:1 randomization will be 100 subjects in LUM-201 and 50 subjects in placebo. We plan to include more countries outside the U.S. We're in the process of sending out a site survey to multiple regions around the world.

We're waiting for those to receive those site surveys back before making a decision which country we go to. So around the site that we plan is 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.

Rick Hawkins (CEO and Chairman)

And Leland, if you recall, you were in.

Ed White (Managing Director and Senior Biotechnology Analyst)

No, it's Ed.

Rick Hawkins (CEO and Chairman)

Okay. And Leland, if you go ahead.

Ed White (Managing Director and Senior Biotechnology Analyst)

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

John McKew (President and Chief Scientific Officer)

Sure. Absolutely.

Ed White (Managing Director and Senior Biotechnology Analyst)

So we've talked about this before, but out of the 60%-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. So I'm just taking the other side of that. And why wouldn't patients and children want to take your product?

Rick Hawkins (CEO and Chairman)

Well, we do 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 pediatric endocrinologists, if they had a choice between a weekly injection or a once-a-day oral, they overwhelmingly said that they would prefer to take a daily oral. That's sort of a given. And of course, we have a way to identify the patients who our drug will most likely be effective in, and that is our predictive enrichment or PEM strategy. And that further enhances our ability to not only be successful in this trial but also to easily identify those patients that will be effective.

John McKew (President and Chief Scientific Officer)

Yeah.

Ed, I would like to add on top of what Rick just said. As a pediatric endocrinologist, the majority of patients with PGHD 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 4 or 5 years, and we get long-acting approved. But it's not getting rid of injections, which some of the children do not want it, 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 if this drug gets approved, they will offer this LUM-201 to the majority of those patients by using PEM-positive cut-off. If they're 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 patients moving forward. We never really have this option until LUM-201 at this point.

Ed White (Managing Director and Senior Biotechnology Analyst)

Okay. Thanks for taking my questions.

Operator (participant)

Thank you. Next question comes from the line of Catherine Novack with Jones Research. Please go ahead.

Catherine Novack (Director of Healthcare Equity Research)

Hi, guys. Good morning. I just wanted to drill down on the cash position. 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 you might be able to use to bring in new investors? And then just throwing out the possibility of pursuing a 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, are most of the relevant data in hand?

Rick Hawkins (CEO and Chairman)

Yeah. Catherine, that's a good question. I don't think there's any question that investors have enough information at this stage to make a decision. I think, 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. Lori, I don't know if you want to add any more to that or anyone else on the team.

Lori Lawley (CFO)

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 III trial design would look like.

Now that we have gotten feedback from the FDA, they have proposed a placebo-controlled trial as an option. As we finalize that trial design and move forward with FDA approval of that trial design, we do believe that that will instill confidence in the investors and allow us to complete the financing in this near term. As far as looking for regional partners, we've talked previously about looking for ex-U.S. options for regional partners and retaining U.S. rights, of course. And so that is something that we will continue to pursue. And I think what they also were waiting on and the partners that we've talked with have also been waiting on what the phase III 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 the financing in the near term.

Catherine Novack (Director of Healthcare Equity Research)

Got it. And then just, I guess, clarification on the first co-primary endpoint. If you can help me understand the statistical analyses, since placebo is not followed for 12 months, what is the hypothesis testing assumption for the first co-primary endpoint, if you could clarify?

Rick Hawkins (CEO and Chairman)

Yeah. John, go ahead if you want to ask that question.

John McKew (President and Chief Scientific Officer)

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 II 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.

Catherine Novack (Director of Healthcare Equity Research)

Okay. And then just one more, thinking about this down the road, right now, you're focusing on treatment-naive 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?

Rick Hawkins (CEO and Chairman)

Duke, go ahead if you will.

Duke Pitukcheewanont (Chief Medical Officer)

Yeah. So I think that's a very good question. I do believe that most patients will look into that potentially to switch the patient to LUM-201. At this point, we don't have data to show yet. So what we think that moving forward, once we get this phase III trial done, we put that in the registry.

So the majority of those patients are going to get into the long-term extension, especially if the registry is someone who's not in phase II. They can continue to have the phase IV study. Once the drug gets approved, we'll be able to determine some of those, especially when the patient wants to discontinue daily and go into LUM-201. We'll be able to evaluate those efficacy in those trials.

Catherine Novack (Director of Healthcare Equity Research)

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

Operator (participant)

Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.