Lumos Pharma Inc (LUMO) 2020 Q4 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Lumos Pharma's Year-End 2020 Earnings Conference Call.

(Operator Instructions) As a reminder, this conference call is being recorded.

I will now turn the call over to Lisa Miller, Director of Investor Relations.

Ms. Miller, please go ahead.

Thank you.

Before we proceed with the call, I would like to remind everyone that certain statements made during this call are forward-looking statements under U.S. federal securities laws.

These statements are subject to risks and uncertainties that could cause actual results to differ materially from historical experience or present expectations.

Additional information concerning factors that could cause actual results to differ is contained in our periodic reports filed with the SEC.

The forward-looking statements made during this call speak only as of the date hereof, and the company undertakes no obligation to update or revise the forward-looking statements.

Information presented on this call is contained in the earnings release we issued this afternoon and in our Form 8-K, which may be accessed from the Investors page of the company's website.

Joining me on today's call are Rick Hawkins, CEO, President and Chairman; John McKew, Chief Operating Officer and Chief Scientific Officer; Gene Kennedy, our outgoing Chief Medical Officer; and Carl Langren, Chief Financial Officer.

Rick Hawkins will provide a corporate update, John McKew will review the company's new therapeutic candidate, Gene Kennedy will discuss our clinical trials, and Carl Langren will wrap up the call with a review of the full year 2020 financials and an update of cash guidance.

I will now turn the call over to Rick.

Thank you, Lisa.

And good afternoon, and thank you for joining us on today's call.

After the market closed, we issued a press release highlighting our recent clinical and corporate activity and providing update on our year-end 2020 financials.

Last year marked a period of significant achievement for Lumos Pharma with the completion of our merger transaction, the monetization of our priority review voucher and the initiation in the fourth quarter of our Phase IIb OraGrowtH210 trial evaluating our novel therapeutic candidate, LUM-201, for pediatric growth hormone deficiency.

Those events put Lumos Pharma on a solid foundation to pursue the development of orally administered LUM-201 with the potential to disrupt the PGHD therapeutic industry where the standard of care consists of daily injections of growth hormone.

That momentum continues in 2021 as we move our clinical strategy forward.

Our Phase IIb OraGrowtH210 trial continues to advance with data readout anticipated mid-2022.

In addition, we expect to initiate our OraGrowtH212 trial shortly.

This trial is a small single-site trial to illustrate the pharmacokinetic and pharmacodynamic effects of LUM-201 in PGHD and replicate the pulsatility data that currently exists for LUM-201 in adults.

Also, today, we introduced our OraGrowtH211 trial, a long-term extension study for eligible PGHD patients who have completed our other LUM-201 trials.

This extension trial will assess the long-term safety and efficacy of LUM-201 in children with growth hormone deficiency.

We believe LUM-201 is essentially a pipeline in a product with the potential to target up to 11 other indications for which growth hormone has been approved.

We're focusing first on PGHD, and once we gather data from our current program, we plan to evaluate LUM-201 in a subset of these other indications I just alluded to.

Gene Kennedy will review our current clinical efforts in more detail later.

We are also pleased by the recent publications of peer-reviewed LUM-201 data analysis in the Journal of Endocrine Society.

These data from earlier studies of LUM-201 in recombinant human growth hormone or rhGH demonstrate specific baseline IGF-1 levels and peak growth hormone levels from growth hormone stimulation tests may serve as predictive enrichment markers or PEMs, useful in identifying the more moderate PGHD patients most likely to respond to LUM-201.

These peer-reviewed data support the approach we are using in our clinical trials.

We are also honored to be presenting additional LUM-201 data at the Endocrine Society annual meeting, also known as ENDO, in late March.

As our recently public abstract illustrates, that data being presented at ENDO show a distinction between LUM-201 and standard growth hormone secretagogues used to diagnose growth hormone deficiency.

These data show that at the lowest dose we are using in our Phase IIb trial, LUM-201 elicits statistically higher growth hormone response than standard diagnostic agents.

We believe these data further support the potential for LUM-201 to be efficacious in the subset of PGHD patients identified by our predictive enrichment markers.

John McKew, our COO and Chief Scientific Officer, will provide more details a bit later on in the call.

As you may recall, a priority review voucher was issued upon FDA approval of the Ebola vaccine in which Lumos Pharma had 60% ownership, resulting in a $60 million gross to Lumos Pharma.

We received the first payment of $34 million in September and the second and final tranche of $26 million in January of 2021.

We continue to look for business development opportunity to expand our pipeline through the acquisition or licensure of another novel therapeutic candidate for rare diseases.

These non-dilutive funds further strengthen our balance sheet and will be available to support our business development strategy.

Carl Langren, our CFO, will discuss our financials in more detail and provide updated guidance regarding our estimated cash use for 2021.

So we're excited about the year ahead with the advancement of our OraGrowtH trials in PGHD and the potential expansion of our rare disease pipeline.

We believe that LUM-201, an orally administered growth hormone secretagogue, offers the potential to disrupt the PGHD market where the current and potential therapies consist only of injectable treatments.

Expanding our pipeline would offer an opportunity to reach additional individuals suffering from rare diseases.

And we are fortunate to have a solid balance sheet and an experienced management team to execute on this mission.

And with that, I will turn the call over to John to review our oral growth hormone secretagogue, LUM-201, and recently published data.

John?

Thank you, Rick.

As Rick stated, we are excited to advance our OraGrowtH trials to validate LUM-201 in PGHD patients.

We are also pleased about the recent peer-reviewed publications and upcoming ENDO presentation of data showing the novel mechanism of action of LUM-201 and the potential efficacy of LUM-201 in PGHD as compared to standard of care.

Given its oral delivery and its mechanism of action that depends on the natural endocrine growth hormone axis, we believe that LUM-201 may offer a preferred treatment option for approximately 60% of children suffering from growth hormone deficiency.

As a reminder, growth hormone deficiency can be defined by low to absent secretion of growth hormone from the pituitary gland.

The current standard of care and other therapeutics in development for children with growth hormone deficiency consist of the delivery of a bolus of growth hormone or a long-acting derivative to restore growth.

All of these therapies are administered by injection and act outside of the body's natural endocrine pathway feedback mechanisms.

LUM-201, on the other hand, is not a growth hormone but is instead a growth hormone secretagogue that acts within the body's natural endocrine pathway.

LUM-201 selectively acts on receptors in pituitary and hypothalamus to stimulate the body's ability to release growth hormone at the same intervals and subject to the same endocrine feedback loops that occur naturally.

Utilizing this endogenous release mechanism should enable the naturally occurring IGF-1 feedback loop to be preserved if needed to help regulate the balance of growth hormone and IGF-1 levels in the body.

Given the endogenous nature of LUM-201 activity as just described, individuals able to benefit from the molecule must have a functioning -- a diminished pituitary axis.

For this reason, Lumos Pharma is targeting the moderate PGHD population of patients who are able to naturally produce some growth hormone but in insufficient amounts to obtain normal adult height.

Based on the analysis of prior clinical data, predictive enrichment markers or PEMs identified a moderate PGHD patient group likely to respond to LUM-201 therapy, which represents approximately 60% of the total PGHD population.

These data demonstrate that specific PEMs of a baseline IGF-1 level of greater than 30 nanograms per mil and a peak growth hormone level of greater than or equal to 5 nanograms per mil after a single dose of LUM-201 identify this PGHD patient population likely to benefit from LUM-201 and illustrate why these are the PEMs we are using in our OraGrowtH210 trial.

The data analysis recently published in the Journal of Endocrine Society support this PEM strategy.

The paper entitled Development of a Predictive Enrichment Marker for Oral Growth Hormone Secretagogue LUM-201 in Children with Growth Hormone Deficiency is a peer-reviewed analysis of the data from the Merck 020 study we have referred to in prior discussions.

Described in detail in that paper is the receiver operator characteristic or ROC curve analysis and iterative filtering that enabled the determination of specific PEM cutoffs.

Also included is our analysis of the growth of children assigned to each treatment arm of the study and their relevant safety data.

The second paper published in the Journal of Endocrine Society entitled Corroboration Between Predictive Enrichment Markers for Height Velocity to rhGH and an Oral Growth Hormone Secretagogue Treatment in Children with GHD provides additional support for the use of our predictive enrichment markers to determine those PGHD patients most likely to respond to LUM-201 versus those most likely to respond to standard of care recombinant human growth hormone.

This paper describes the data mining exercise of the Eli Lilly Phase IV legacy GeNeSIS database.

From the database, 514 naive-to-treatment prepubertal children with idiopathic growth hormone deficiency whose rhGH treatment data were available for analysis.

GeNeSIS was a prospective open-label observational research program conducted in 30 countries at more than 800 study sites between 1999 and 2015.

The main objective of GeNeSIS was to investigate safety and effectiveness of Lilly's recombinant human growth hormone treatment in pediatric patients with growth failure.

Baseline IGF-1 assessment and growth hormone stimulation tests were administered, and they were collected in the study.

This GeNeSIS database, given its size and scope, served as a useful source of real-world evidence for the predictive enrichment marker analysis described in external publication.

The purpose of the data mining described in the paper was twofold: first, to evaluate that baseline IGF-1 and stimulated peak growth hormone were independent predictors of 12-month height velocity in children with idiopathic growth hormone deficiency.

Secondly, to better understand the range of growth hormone deficiency that exists within the PGHD diagnosis and how subsets of the population respond to treatment.

Using a correlate of the PEM cutoffs noted above, children with idiopathic isolated growth hormone deficiency who represent 73% of diagnosed growth hormone deficient patients in the GeNeSIS database were categorized as severely or moderately growth hormone deficient.

Of the 73% with idiopathic GHD, 81 of 514 or 16% were identified as severely growth hormone deficient while 433 of 514 patients, 84% or approximately 60% of the total PGHD population of the database were determined to be moderately deficient or what we would term PEM positive.

Additionally, these 2 segment groups differ significantly in baseline height standard deviation score, height velocity and change in height during rhGH treatment.

Further analysis of these groups using the prior Merck companion study PEM cutoffs showed that the severely deficient group, those with lower baseline IGF-1 levels and lower growth hormone stimulated levels, saw the greatest 1-year height velocity catch-up after -- catch-up growth after treatment with rhGH, whereas those with higher baseline IGF-1 levels and higher growth hormone stimulated levels, the moderate or PEM-positive group, had significantly lower 1-year average height velocity on recombinant human growth hormone treatment of 8.3 centimeters per year.

Despite growing at different rates, both the severe and moderate groups arrived at the same place compared to their peers after 12 months of treatment as evidenced by the height SDS scores of minus 2.6 for severe and moderate at minus 2.00.

We chose IGF-1 and stimulated growth hormone levels as predictive enrichment markers because multiple regression analysis showed they were independent predictors of height velocity on treatment with recombinant human growth hormone.

Finally, the data to be presented at ENDO distinguishes LUM-201 from standard growth hormone secretagogues.

The abstract accepted for presentation entitled LUM-201 Elicits Greater Growth Hormone Response than Standard Growth Hormone Secretagogues in Pediatric Growth Hormone Deficiency supports other data suggesting that LUM-201 is unique in its ability among the secretagogues traditionally used to diagnose growth hormone deficiency to produce higher Cmax values of growth hormone secretion in children diagnosed with PGHD.

The difference between the peak GH value upon LUM-201 stimulation was even greater in those patients with higher baseline IGF-1 values.

We look forward to presenting the full data analysis later in March at ENDO and welcome a discussion of that data with the investment community at that time.

We believe these data strongly support our clinical development strategy in PGHD.

And I will now turn the call over to Gene Kennedy, our outgoing Chief Medical Officer, to provide an update on our PGHD trials.

Gene?

Thanks, John.

I will take some time now to review our Phase IIb OraGrowtH210 trial and provide a few more specifics on our PK/PD OraGrowtH212 trial to be initiated shortly.

We initiated our Phase IIb OraGrowtH210 trial in PGHD last quarter, and the trial continues to advance.

To review, this trial is a global multisite trial involving approximately 80 PGHD patients randomized into 1 of 3 dose levels of LUM-201 or a comparator arm of standard of care injectable growth hormone therapy.

Only those PGHD patients determined to be PEM positive, as evaluated by our predictive enrichment marker cutoffs of baseline IGF-1 greater than 30 nanograms per milliliter and a peak growth hormone level greater than or equal to 5 nanograms per milliliter, will be randomized in the study.

During this Phase IIb study, the repeatability of the PEM classification will be evaluated during screening for randomization.

Each potential participant will have 2 sets of PEM laboratory samples drawn approximately a week apart.

Dosing will be administered over 6 months with annualized height velocity as the key clinical outcome measure.

The main objectives for this Phase IIb study are to prospectively confirm the utility of our predictive enrichment marker strategy in selecting likely LUM-201 responders to assure that the PEM classification is consistent and repeatable and to determine the optimal dose for a Phase III registration trial.

The 3 dose levels of 0.8, 1.6 and 3.2 milligrams per kilogram of LUM-201 were chosen for our Phase IIb trial for patients with PGHD based on supporting data from the Merck study in PGHD patients John mentioned as well as a prior PK/PD study of LUM-201 in healthy adults.

The Merck study in PGHD showed no statistical difference in average height velocity for PEM-positive patients dosed with 0.8 milligrams per kilogram LUM-201 versus those dosed with recombinant human growth hormone.

The PK/PD study in healthy adults showed that the 0.8 mg per kg dose is only approximately 1/3 of the way of the growth hormone dose response curve.

These data showed that administering increasing doses of LUM-201 in healthy adults up to 100 milligrams, the equivalent of 2.8 mg per kg in children, result in higher plasma concentrations of growth hormone.

The 3 doses chosen for our Phase IIb trial cover that full pharmacodynamic range and suggest the potential for greater growth hormone secretion and potential efficacy in the PGHD patients in our study.

The trial is open and enrolling patients currently.

We have received strong positive feedback about the potential for an oral therapy for PGHD.

We have identified additional experienced clinical sites in Ukraine, Russia and Israel interested in participating in our study.

This should enhance the enrollment process and increases our confidence in our anticipated mid-2022 data readout.

These sites and all others were selected based on their prior history of enrolling PGHD patients in clinical trials and the ability to conduct trials in alignment with our standards.

While this trial is ongoing, Lumos expects to initiate a second concurrent trial of LUM-201 for patients with PGHD shortly.

This OraGrowtH212 trial is intended to further illustrate the mechanism of action of LUM-201 in amplifying the natural pulsatile secretion of growth hormone.

The natural secretion of growth hormone in the body is ultradian and pulsatile in nature, with 23 to 25 growth hormone peaks over a given 24-hour period.

LUM-201 stimulates the secretion of growth hormone in a way that maintains this natural pulsatile mechanism, amplifying the peaks of these pulses in order to augment growth hormone and IGF-1 levels.

We believe this is important as preclinical data illustrate that pulsatile delivery of growth hormone produces greater efficacy than continuous exposure to the same amount of growth hormone.

The OraGrowtH212 trial will focus on pharmacodynamic end points at 2 different doses, 1.6 and 3.2 milligrams per kilogram, in approximately 24 children with PGHD.

Prior data in adults confirm the ability of LUM-201 to amplify the pulsatile secretion of growth hormone.

The purpose of the study is to replicate these pulsatility data in children with PGHD.

We plan to conduct this trial at a single specialized pediatric center with the ability to perform the more frequent sample collection and monitoring required for these types of clinical trials.

Children will have their baseline levels of growth hormone secretion measured every 10 minutes over a 12- hour period and then start on LUM-201 for 6 months.

At the end of the 6 months, they will again have a 12-hour assessment of growth hormone levels to illustrate LUM-201's amplification of pulsatile secretion.

Once initiated, the study will run in parallel with our ongoing Phase IIb OraGrowtH210 trial with the goal of providing supportive data in future regulatory filings and ultimately in any commercial marketing efforts.

We have been advised of a fire at the San Borja Arriaran Hospital in Santiago, Chile.

This location is the planned clinical site for the OraGrowtH212 trial.

Our investigator's clinic was not directly involved in the fire.

However, limited access to the site as the hospital assesses the impact of the fire might delay our trial start.

While we had originally expected to initiate this trial in Q1 of 2021, we now anticipate the initiation of the OraGrowtH212 trial to occur in Q2 of 2021.

As we have previously stated, this trial is not on the critical pathway for regulatory approval of LUM-201, and we do not anticipate the fire will cause any delays to our time line.

We continue to work with our local partners to advance the trial, and we are also exploring alternate sites to conduct the trial in the event that the original site is unable to proceed in a timely manner.

We are also introducing the OraGrowtH211 trial in PGHD.

This study will be an open-label, multicenter, long-term extension study for those who have completed a prior LUM-201 trial such as OraGrowtH210 and OraGrowtH212 trials.

Eligible patients who have completed their 6-month treatment in either of those studies upon enrollment in the OraGrowtH211 trial will be administered the LUM-201 or recombinant human growth hormone dose prescribed in the preceding LUM-201 trial.

The primary objective of this trial will be to evaluate the long-term safety of LUM-201.

In addition, this study will assess the long-term PK/PD effects and growth outcomes in response to LUM-201 treatment.

Finally, we believe that LUM-201 may serve as a platform therapy potentially applicable to other indications for which recombinant growth hormone is approved.

Pending results from our concurrent OraGrowtH trials just discussed, we plan to evaluate LUM-201 in these other indications.

Beyond LUM-201, we continue to actively pursue business development opportunities to license or acquire other rare disease assets in order to expand our pipeline and our ability to provide innovative therapies to those suffering from rare diseases.

I will now turn the call over to Carl Langren, our CFO, to discuss financial results for the year-end 2020 and provide a cash forecast for 2021.

Carl?

Thank you, Gene.

We ended 2020 with cash and equivalents of $98.7 million.

This year-end cash balance does not include the final $26 million in proceeds from the sale of our PRV, which was received in January.

For 2021, we anticipate average quarterly cash use of approximately $8 million to $9 million.

We also expect that our reported cash balance plus the non-dilutive funds from the PRV sale will support our operations through the data readout of our OraGrowtH210 and OraGrowtH212 trials and contribute to supporting the expansion of the company's rare disease pipeline.

We reported a net loss of $5.7 million for the year ended December 31, 2020, compared to a net loss of $9.7 million for the same period in 2019.

Please refer to the press release we put out this afternoon for additional details on our financial results.

Looking ahead, we hope to speak with many of you participating in the Oppenheimer, H.C. Wainwright & Roth investor conferences this month.

We are also looking forward to speaking with all of you once we present our data at the ENDO annual meeting in late March.

Now I would like to turn the call back over to Rick before we open up for questions.

Rick?

Thank you, Carl.

And so before I offer some closing remarks about our programs discussed above, I first want to say a few words about our outgoing Chief Medical Officer, Gene Kennedy.

Gene joined Lumos Pharma management team here by way of our merger with NewLink Genetics, which was an oncology-focused company he joined in 2014 and where he also served as Chief Medical Officer.

Gene helped us tremendously through the merger and Lumos Pharma's transition to a publicly listed company focused on rare diseases.

While we would have loved for him to stay, he will now be returning to his roots in oncology as he joins a privately held company in that field.

Gene, we want to thank you for your service to Lumos Pharma and wish you all the best in your next venture.

Thanks, Rick, for your kind words.

I mean I really have to say that I've thoroughly enjoyed working with the entire Lumos team.

As you said, I'm really returning to my roots.

I am highly confident in the potential for LUM-201 and its ability to be efficacious in the PGHD population identified by the predictive enrichment markers and also in Lumos team's ability to execute on the clinical plan already in place.

I hope to keep in touch with the team and will be watching from a distance and pulling for all of your success as the team advances the LUM-201 program in PGHD and expands beyond that purview.

Thanks, Gene.

And well, as you can tell, we're excited to advance our OraGrowtH trials in PGHD and look forward to initiation of our PK/PD OraGrowtH212 trial.

We're pleased about the data recently published and about our upcoming presentation at ENDO.

And we are on solid financial footing to execute on our strategy and believe that our clinical trials will confirm the potential for LUM-201 to disrupt the PGHD market.

We look forward to continuing to provide updates as we progress.

And with that, we will open the call for questions.

Operator?

(Operator Instructions).

First question comes from the line of Charles Duncan from Cantor Fitzgerald.

Congrats on the progress on the 210 trial thus far.

Actually, I had a question on that 210 trial.

I imagine it's pretty early days in terms of enrollment.

But can you talk at all about the pace of enrollment or the screen failure rate at this time?

And would you anticipate the first patient to be through the 6-month period, the dosing period and therefore being able to start with the open-label extension trial, 211, by the end of the second quarter of this year.

Well, Chaz, that's a good question.

We haven't really given any guidance yet on entry into the study.

But suffice to say that we're progressing nicely.

We haven't initiated all of our sites, but they're coming online in pretty quick order.

And as Gene pointed out, there are some new sites with experienced investigators and KOLs in another part of the world that we believe will help us meet our goals of having a readout in 2022, year 2022.

Okay.

And anything about screen failure or that PEM strategy at all at this point?

I think it's too early in the game to really address that.

I think the publications that John just went over gives us a great deal of confidence that the screen failure rate is probably going in parallel of what we found in that database.

So I think that's -- but as soon as we can, we'll report to you on that data.

Okay.

I appreciate that.

And just one follow-up.

John said a lot and said so quickly, and sorry if I missed this, but I think you mentioned that there might be, call it, a 60% or so patient population versus, say, previous estimates of around 50% that met that positive predictive enrichment marker kind of level that you're looking at.

And I guess I'm wondering, could you go over that math again?

And then in terms of, for example, what you would expect in terms of average height velocity for patients that are more moderate, could you compare and contrast what you would expect out of recombinant human growth hormone in the moderate patient population versus the more severely impacted patient population?

What kind of numbers are you looking at over the course of an annualized height velocity?

Happy to answer that, Chaz.

So we'll start with the numbers for the estimate of the patient population that could be responsive.

So essentially, we've taken our PEM cutoffs and translated them so that we can use them in the GeNeSIS database and use the standard stim test diagnosis to help us sort patients into the same 2 groups, kind of the PEM-positive group and everybody else that are more severe.

And so when you look at the large data set that's GeNeSIS, the kids we're focusing on are officially termed idiopathic growth hormone deficient children.

And that makes up 73% of the children in the GeNeSIS database with the growth hormone deficiency diagnosis.

Of those 73%, 84% meet our criteria of PEM positive.

So multiplying 0.73 by 0.84 gets you to about 60% that could be responsive to our molecule and would fit into this PEM-positive category.

We feel much more confident about this number just because it's derived from a very large Phase IV data set.

And I think it really is more of a real-world number than the estimate we could make from the 020 trial just because of the several regions that the trial was running.

So we're confident about that number.

The second question is about the height velocity that we see.

So in the GeNeSIS data set, the group that is selected with our PEM cutoffs showed 12-month growth rates on recombinant human growth hormone of about 8.3 centimeters per year.

And it's very clear that if you include a broader group in an analysis of potential growth, that includes many more severe patients that we would filter out from our trial, that population would have much higher growth.

And that's simply because the kids who are more severe grow at a faster rate in those first 6 months.

So that 8.3 centimeters per year for the same population that we're going to isolate in our trial is a pretty good indication of what 12-month growth data would look like in a trial that we're going to have going forward.

But you wouldn't want to compare apples-to-oranges with this more severe patient pop or sample size or sample?

Yes.

I think the more severe kids are going to grow significantly more, right?

Depends exactly how you define more severe kids.

But essentially, they're going to grow statistically different than the moderate kids.

In our GeNeSIS analysis, it was 9.6 centimeters per year.

So they're different and very different populations.

Okay.

And last question.

Do you believe that prescribers will understand this or reimbursement authorities in terms of a response rate or annualized height velocity?

Does that have any implications in terms of the conduct of the study and keeping patients on for the entire 6 months?

Or do you think that's not going to be an issue?

So I think that most of the prescribing clinicians understand that the most severely growth hormone deficient kids grow the most in those first 6 months.

And once they understand that the tools that we're using to select our patients are going to select for moderate growth hormone deficiency, I think they will understand the -- they will have expectations set for how much the kids will grow.

And it's not just that they're going to grow less on our molecule.

They're going to grow less whether they're given recombinant human growth hormone or a different molecule, right?

It makes sense.

Next one on the queue is Ed White from H.C. Wainwright.

So just to be clear on enrollment for the sites, I think you previously had said you're expecting to enroll patients at 40 sites in the U.S., Poland, Australia and New Zealand.

And now you will have interest in these other areas, the Ukraine and Russia and Israel.

Can you give us any idea of the number of sites that are currently enrolling patients?

Or what we would expect to see, say, by the end of the year?

Should they all be up and running by then?

Yes.

Gene, do you want to take that?

Yes, certainly.

By the end of the year, definitely.

Well, I think we expected them to be up before the end of the year.

But no, we have -- many of our U.S. sites are up and running.

The few that aren't will be coming up in the next weeks to month and then the international sites, again, right -- slightly shortly thereafter.

So we're -- and these aren't -- we're announcing our intentions to open sites in these countries today.

It's not that we are starting the work today if you understand what I'm saying.

This has been -- we've been preparing this for a while.

So we expect these sites to all be able to contribute pretty soon.

Okay.

And then on the OraGrowtH212 study that was affected by the fire, how long will you give the site to open or before you start thinking about moving that study to a different location?

Gene?

Yes, certainly.

I mean we -- thinking, we're already obviously exploring options.

But the report we have is that they're likely to be back up and running very soon.

I mean it's a major pediatric hospital.

It serves a large portion of the population of Santiago, Chile.

And they're optimistic they'll be finished with their repairs in other parts of the building, but it's had some consequences in the part where the clinics are.

So I think we're all optimistic that this is going to be a short delay.

If it proceeds beyond our guidance into Q2, then obviously, we'll have to consider other options.

And Ed, I think the sound business procedure here is to -- no matter what, even though we're confident that this site is going to be a viable site going forward, we want to hedge our bets and make sure that we have a backup plan.

That's what it's all about.

Okay.

And then my last question is just on the extension study, 211.

Once those patients are enrolled, how long do you expect them to continue to be following?

I mean are these patients eligible to continue through the end of puberty?

Or would they just -- would you follow them until 210 is completed and perhaps a short time after that.

Go ahead, Gene.

Yes.

I mean our intention would be to allow those kids access to the therapies and to follow them as long as we believe and their physicians and families believe that it's beneficial.

That's sort of the answer in a nutshell.

But no, the 211 would be expected to live beyond the end of the OraGrowtH210 or OraGrowtH212 trials clearly.

Next one on the line is Eun Yang from Jefferies.

This is [Soo Jang Min] on for Eun.

Our first question is on the Phase IIb.

I'm just wondering if you plan to do an interim look of the study and maybe just the number of patients based on that.

And then second question is just kind of relevant to the first question, but based on the PK/PD study data, do you expect to adjust the Phase IIb trial design?

John, do you want to take that first?

John, I think...

Yes.

I'm happy to answer that.

So we don't think that an interim look at the data will be necessary for Phase IIb 210 trial.

We also do not think that the PK/PD study results will influence in any way the design of the 210 trial.

The PK/PD study is really about understanding more about the pulsatile nature of release.

And it's going to be a separate study that's going to go along in parallel with the 210 trial.

I see.

And my last question is the ENDO 2021 presentation.

Has this data been presented before?

Just wanted to make sure.

No, that specific data has not been presented previously.

That's in the abstract of the poster.

No.

And Eun, we would be more than pleased to circle back with you to go over.

Next one on the line is Lina Kaminski from JonesTrading.

So I guess this one maybe for John.

So you talked about the recent publication.

So I really appreciate that.

So I guess maybe you can elaborate a little bit further kind of what gives you the confidence and the support towards the ongoing 210 trial for LUM-201?

And then also maybe just a little bit on the predictive enrichment marker strategy.

I'm specifically kind of trying to understand the relationship between the standard growth hormone stimulation test and the stimulation test of LUM-201, the difference between the 2 nanogram per mL versus the 5. And then I have a follow-up.

John?

Yes.

So let me take the last one first.

So in the Bright manuscript, in Table 4, you'll see a correlation between the standard diagnostic stim test results and the LUM-201 stim test results.

So we ran a receiver operator characteristic curve analysis on those data sets.

And that's essentially the different stim tests in the same patient, right?

And then we correlated what their response would be.

And we're able to come up with this correlate that greater than or equal to 5 is similar to greater than 2 with a standard stim test.

And then that's the PEM values that we applied to the GeNeSIS data set simply because they have standard diagnostic stim test data in the database, and none of those patients have taken the LUM-201 stim test.

So that's the connection between those 2 papers in Table 4 of the Bright manuscript.

So in terms of how do we feel -- how do these 2 publications make us feel more confident about our potential success.

I think first, we've been showing the results of the analysis for quite some time, but I think the scientific rationale and the approach that we took to derive the cutoffs is important to get out in all of its glory, so to speak.

We just took a very scientific approach to do that.

And I think it's very evident now in the Bright manuscript how deeply we thought about the data and how we worked very hard to find the right cutoffs, the right breakpoints in these 2 different parameters.

And I think one way the Blum manuscript supports our PEMs is first, in the -- in this patient population, it was shown very clearly that both baseline IGF-1 values and the growth hormone stimulation values were independent predictors of growth on -- for recombinant human growth hormone.

So that means essentially, what we want to do with these PEM markers is be able to predict how a child is going to grow.

We know that if we can put them in a moderate group or a more severe group, they're going to grow at different rates.

And the moderate group with a partially functioning axis is really the group that has the physiology to respond to our LUM-201 product, right?

Because as a secretagogue, they have to be able to make some growth hormone, and then we're going to help them release it by continuing to stimulate that receptor.

And because we can show that they're independent predictors of growth, they turn out to be very good markers to combine and use to separate patients into this PEM-positive or moderate category versus the severe category that are less likely to respond.

So we like that aspect of that publication.

It supports the choices we made to derive cutoffs from.

I hope that answers your question, Lina.

Got it.

Okay.

Yes.

That's really helpful.

And I guess the last question I have is just more on kind of your strategy and how you're thinking about the patient population.

So do you think -- obviously, now you're enrolling naive patients.

But how are you thinking about maybe switch population?

Maybe patients that were previously treated with growth hormone, do you think that they might further benefit from LUM-201?

And are you thinking of conducting a study like that?

Yes.

Lina, it's a good question, and I think that anyone who has a product in this space eventually has to get around to that type of switch study.

And we certainly will at the right time.

Most important goal and objective in front of us is to get this dose to go into a registration trial after this study is over.

And then the timing efforts for that study, we will focus in on.

I think, John, the second part of her question, I think maybe the -- whether there's any prediction on our part whether scientifically, we would feel that those patients being on long-term treatment and switch to our drug would also gain benefit.

So I think there is a history in -- of exploring those switch patients with some of the long-acting growth hormones.

And I think what is known is that the longer a patient stays on recombinant human growth hormone therapy, their growth is maintained, but it's not the same level of growth you see in those first 6 to 12 months' frame.

So you would expect that you would take a patient on recombinant human growth hormone, kind of wash them out from their daily injectable for a while and then put them on treatment.

Then I would expect they -- if they meet our PEM criteria that they would be able to respond to the drug.

You're going to get a slightly different growth rate from somebody who's been on recombinant human growth hormone for 5 years than you will at naive patients, right?

It's important to understand that.

And that's again the same with our molecule or any molecule that you put these kids on.

But yes, I do think that if a switch patient meets our criteria, they will be able to respond to our molecule.

Operator, any other questions?

Yes, we do have a question from Yasmeen Rahimi from Piper Sandler.

First, before I ask my question, I just want to say thank you, Gene.

It's been a pleasure working with you, and my team wishes you the best of luck in your next adventure.

So it's been wonderful working with you.

The -- I have a set of questions.

Maybe the first one I would like to start off is just discussing maybe the size of the open-label study, meeting with regulators, is there a certain safety data set that you require, and therefore, there's a certain requirement of patients to have an open-label extension?

The second question is around the 211 study.

Maybe highlight to me what the reason was for not running recombinant growth hormone is one of the groups rather than just 2 doses of LUM-201.

And then I have a third pipeline question.

John, do you want to start?

Sorry.

I think -- so you asked, I think, about the 212 trial.

You asked why isn't there a recombinant human growth hormone comparator in that trial.

Is that correct?

You said 211, I think, that's the trial.

Yes, that's one of the questions.

Yes.

Yes.

So I think in that case, we're working on a study at a single site in Chile.

And we wanted to make sure that we could recruit enough patients into that single site to enable us to really explore the 2 different doses of LUM-201 that are there.

There's a decent amount of background or historical data on kids on growth -- or kids with recombinant human growth hormone.

We also know what the PK of recombinant human growth hormone looks like in kids, right?

So the PK effect of recombinant human growth hormone is the same thing as the PD effect that we're going to look at in that trial.

So because that PK curve is so well characterized and it's a single bolus dose, right, that is given at night and within 8 or 10 hours goes away, we know very clearly what the difference in the look of the growth hormone being released is going to be for the comparator.

So we didn't think that it was necessary, and we would rather focus on enrolling as many kids as we can in our treatment arms.

Does that part make sense?

Yes.

No, that's helpful.

And then in regards to the size of the open-label study that is needed for submission?

Yes.

So the open-label study, I mean we're going to enroll any kid who's interested in continuing from any of our trials from the Phase IIb trial, the 212 trial or in an upcoming Phase III study into that, right?

We like to get as much long-term data as we can.

Gene -- it was mentioned earlier that that's -- we want kids on there as long as possible.

There's potential for kids to go from puberty while on that study.

So we'll collect a lot of data there.

We don't have a fixed number in mind of how many we'd like to have.

But we'd like to be as inclusive as we can.

Anybody who is enjoying benefits from LUM-201 should certainly be able to have the opportunity to switch into that and stay on their treatment.

So I just wanted to make sure that's, sorry, clear that there is no requirement of safety or additional safety data needed that prompted the open-label extension.

No.

No, I mean the open-label extension is pretty common in all of these -- in most rare disease studies, right?

You want to build a database of kids who have multiple years of experience on the therapeutic when you get to an NDA filing.

But there's no requirement upon us to do it.

It just makes good sense, and it also is good for the patients.

If they are -- if they feel like the therapy is working for them, it makes a lot of sense to enable them to continue to take it.

Great.

And then the question on the pipeline one.

Maybe you can comment on where you are in your licensing discussions and whether this is -- we expect to see over the next quarter or 2 and/or whether expansion of the pipeline with LUM-201 could be happening ahead of in-licensing opportunities.

So if you could just give us a little bit more granularity, it would be helpful.

Yes.

Also, it's a good question.

And the minute we can let you know, we will.

We haven't given any guidance on where we are right now, but I can tell you, this whole process, it's a robust one.

And it's led by an industry veteran with over 25 years of experience, and that's Aaron Schuchart.

And I'm pleased with the -- let's say, the number of opportunities, yet we are taking our time and being as cautious as we possibly can to find the right asset for this company.

Obviously, we want to -- we would like to stay in the endocrine space, but we're willing to throw a broader net and to look at other compounds or assets outside of endocrine.

But I think it's a little too early to give any guidance right now.

Next one on the line is Elemer Piros from Roth Capital Partners.

Yes.

Coming back to the thought experiment of using LUM-201 in previously treatment-experienced populations, would it also make sense, at least theoretically, that these children where there is a high degree of noncompliance with injections and therefore, there is subpar growth, and now suddenly, if there is an oral therapy available, daily oral pill, that their growth might catch up under that sort of regimen?

John?

Yes.

And I think that's a very good point.

You'll note in some of the publications about compliance that compliance tends to go down as kids get older and start to take more control of their own -- they self-administer the drug instead of having their parents do it to them.

The -- so I do agree.

In general, I think especially out in the real world, that's very true.

A lot of the times the kids that you enroll in a clinical trial tend to just be very compliant because they seem to be the ones most interested in their growth because they're willing to sign up on a trial 5 years after their big growth peak or years after they started the therapy.

But I do agree, there's -- and there's quite an opportunity there for that population, which is most susceptible for low compliance.

And John, just to follow up on the GeNeSIS data set, the analysis that you performed.

So there appears to be in the moderate population that there is a 8.3 centimeter per year growth velocity, and more severe patients respond more robustly perhaps.

Isn't it also true that at the end of the year, they would come to the same sort of normalized height, so their end -- the end result, so to speak, would be very similar?

Yes, that's very true.

And you can see that in the height SDS values after 12 months of treatment.

There's no statistical difference between the severe group and the moderate group.

So really, the severe group starts further behind, they grow faster, and then after 12 months, they're in about the same place as the moderate group.

So even though the moderate group is growing at a different rate, they're both progressing in relation to their peers at the same rate.

I'm showing no further questions in the queue at this time.

I'll hand the call over back to Mr. Hawkins for closing remarks.

Okay.

Well, thank you for your interest, everyone.

And we look forward to speaking with investors at the investment conferences this month and other venues in the coming year.

Thank you very much.

Ladies and gentlemen, this concludes today's conference call.

You may now disconnect.