Great. Good morning, everyone. Welcome back to the second day of Oppenheimer's 34th Annual Life Sciences Conference. I am Leland Gershell, one of the analysts on the Biotech Equity Research team, and we're delighted to have with us as our next presenting company Lumos Pharma. Lumos is developing an oral therapy for children with growth hormone deficiency and has already shown some very exciting data there and is actually ready to enter a what could be a pivotal study for GHD. On behalf of the company, we have CEO Rick Hawkins. He's joined by John McKew, who's the Chief Scientific Officer, as well as Lori Lawley, who is Lumos's CFO. If you'd like to submit questions for me to ask on your behalf, please do so through Zoom. And with that, I will hand the podium over to Rick. Well, thank you, Leland. It's a pleasure to be part of the Oppenheimer Conference again and really appreciate your coverage. As Leland said, we're solidly in the growth hormone space, which is quite a mature space. A common growth hormone has been approved for about 11 different indications for close to 40 years now. This is a very mature market. The only products that are available are injectable, either daily or weekly, growth hormone products. Our differentiation is the fact that we have a small molecule. That's not a protein, but it's a small molecule that works in a unique way. I'm going to go into the details of that in a second because we really stay within a natural endocrine pathway. Now, it's also a large market. It's about $4.5 billion if you include China. The indication we're going for first is pediatric growth hormone deficiency. And that market is about $1.2 billion. Now, we are in late stage development. We just released the results on not one, but two, phase 2 trials. And I'm really pleased to tell everyone that not only did we meet all of our endpoints, both primary and secondary in both of those studies. We've chosen a dose. This was a dose range finding study, so we've clearly chosen a dose to move forward. And, we're also very pleased with the fact that our growth that we saw in our patients, with our oral product were in line with our expectations that we have been guiding the market for quite some time. In addition to that, we prospectively showed that and validated what we call our PEM or predictive enrichment marker, where we can give a dose of our drug to our patients that they can produce a certain amount of growth hormone and a secondary growth factor, IGF-1. That we know that's a patient we'll likely be our treatment will be effective in. So we de-risk our program by only choosing those patients we believe our drug will be effective in. And we're preparing for an end of phase two meeting with the FDA, and we will have a phase three pivotal trial up and running in the second half of the year, and very excited about that going forward. We have a cash balance of about $43 million at the close of the third quarter of 2023 and a cash runway through the end of the third quarter of this year. But you can imagine with injectable products, especially in children, there's not been much innovation in this space for a very long time. In the first once-a-day oral product, we have a chance to be very disruptive in this large market. I won't go into the details of our staff except to say that we are about 32 full-time people. And the senior staff is all highly experienced with 20 to 45 years of experience in drug development, in particular in the rare disease space. If we go to the next slide. I'm going to concentrate on two studies. The highlight here, and that's the OraGrowtH210 trial. Which was a global multi-center trial in pediatric growth hormone-deficient patients, naïve to treatment. The endpoint is height velocity, annualized at 6 months and height velocity at 1 year. Then, of course, we follow these patients out for a long time, and determine not just their height velocity, but safety over time. The second study I want to emphasize is the OraGrowtH212 trial, which is a single-site study with a highly experienced investigator in Santiago. This is a PKPD study, and the reason for this study is to underscore the very different mechanism of action of this drug. We also have an investigator-initiated study at MGH Harvard. And non-alcoholic fatty liver disease. This investigator, Dr. Dicht el, has presented very positive results in this indication with the injectable growth hormone. So as a first oral, this is a chance to be able to show the same in that disease. If you go to the next slide, please. So I'm going to turn this over to John McKew, who's our Chief Scientific Officer and President of the company. John? Thanks, Rick. So I think we'll start our discussion of the mechanism of LUM-201 by just thinking kind of philosophically about how hormone replacement therapies have been administered in the endocrine space. And so this slide kind of lays out that strategy. You know, in general, all hormones are tightly controlled in their release patterns. And when one tries to replenish or kind of restore hormone levels exogenously. The goal really is to try to replicate the natural secretion patterns. And you can see that in kind of the newer cortisol treatments or thyroid hormone or gonadal steroid treatments. And this is not something that's been able to have been followed in the growth hormone therapy area. You know, the approach has been since recombinant human growth hormone was available to use supraphysiological, much higher doses than would normally occur, and you have to give them kind of in bolus doses, right, which does not replicate the natural hormone release patterns that are out there. And so I think the unique facet of our molecule is to be able to restore for the first time this growth hormone access, kind of restore the natural pulsatility patterns, and to do that with an oral therapy. So the next slide kind of gives a visual picture of the differences in these therapies. So the solid black line on the graph to the right is what a normal pituitary secretion pattern would look like for an adult. The dotted line is someone with growth hormone deficiency who would need therapy. And then the blue line is what that pattern looks like from a daily injection. So essentially, it's a very different pattern. It's, you know, supraphysiological throughout most of the day, and then it drops off over time. And really, I think by the time we go through the mechanism and the data that we can share with you about restoring pulsatility, you'll see that we're actually replicating the natural pulsatile release patterns, which are very distinct from the blue line that's shown here. So if we go on to the next slide, we can talk through the mechanism. So the way that we can achieve these goals of restoring natural secretion is because we do have a completely different target, right? We're not just giving growth hormone back. We are actually taking a small molecule that is stimulating a specific receptor. When our molecule binds to that receptor across the hypothalamus and the pituitary, we get an ability to increase the natural pulses of growth hormone across the day. So the yellow box is kind of a schematic representation of a normal, you know, a normal, growth hormone secretion pattern and ultradian rhythm. Later on, I'll show you some actual traces of these at baseline and after treatment with LUM-201. But as we increase the amplitude of each one of these peaks in a growth hormone deficient child, we increase the amount of growth hormone that's circulating. And that increases the amount of IGF-1 that's produced, and then the IGF-1 and growth hormone act on the open growth plates of children with growth hormone deficiency and help them restore their normal physiological growth. So one other important differentiating factor for our molecule, besides the restoration of natural pulsatility, is that there are natural feedback mechanisms that are still in play with our mechanism. These feedback mechanisms have evolved to define what physiological circulating levels of IGF-1 and growth hormone are. And when they exceed those levels, they feed back and they slow down further release of growth hormone until those levels come down. And this is another aspect that's unique to our molecule, and it's a safety valve to prevent any hyperstimulation of the pituitary and, you know, supraphysiological levels from being attained. So these are the two key differentiating factors, and we have to take the mechanism of our molecule into account when we think about the best way to develop it clinically. So what's represented here is kind of a patient selection strategy. The reason that we have to take this approach is because there is a full continuum of growth hormone deficiency that fall under the same disease diagnosis. They're a very severe group of kids, who are termed, in general, organic growth hormone deficient subjects. Those subjects came to their growth hormone deficiency either by a genetic mutation that doesn't let them, say, make growth hormone or some other physiology that prevents them from having a sufficient number of somatotropes to store the growth hormone that's made endogenously. Or there's, you know, a disconnect between the hypothalamus and the pituitary, and you can't regulate release well. This can happen from head trauma, from a radiation of a brain tumor. Or a genetic defect. So these subjects are not going to be able to respond to our molecule because they can't make and store enough growth hormone for our molecule to stimulate the release of. The majority of patients, though, have more of a hypothalamic disease. And they do make sufficient amounts of growth hormone and store it. They just don't release it effectively. So as a way to focus in on that part of the population, we developed two laboratory tests that we call predictive enrichment markers. One is to look at baseline IGF-1. The other is to look at the amount of growth hormone that an individual subject can release when they take a single dose of our molecule in the first 60 minutes after that dose. We developed the cutoffs that are described on the bottom left of the slide after evaluating some previous clinical data in this patient population. So with this strategy, before anyone comes into our trial, we can put them in the category of a likely responder, and we call those kids PEM-positive subjects. Let's go on to the next slide. So this is just a quick summary of actually a huge amount of both non-clinical and clinical research that was generated by Merck when they first developed this molecule. So they were very interested in age-related sarcopenia at the time. So they studied more than 1,000 adults in a variety of different indications, hip fracture recovery, just sarcopenia in healthy adults, even did a trial in Alzheimer's disease. What's remarkable is that in every one of these patient populations, this molecule reproducibly increased growth hormone and IGF-1 levels, which are the, you know, downstream pharmacodynamic markers of its effect. In adults, when you don't have open growth plates, the most visible signs of LUM-201's clinical action is in improvements in body composition. It increases lean body mass. That really is the anti-sarcopenia outcome that Merck was looking to. Merck had also run studies in the healthy elderly population out to 24 months and showed that we, you know, maintained growth hormone and IGF-1 level increases throughout that period. Merck also studied about 200 kids with growth hormone deficiency. They ran three trials, one small PKPD study and two efficacy trials. That is the data that we mined very effectively to help us get ready for our trial and to develop our cutoffs for predictive enrichment markers. We do have data from an early PKPD study that Merck did that helped us set doses for our phase III study. And essentially, or a phase II study, excuse me. And essentially, what we're doing is we're going to span the entire pharmacodynamic range of the molecule. So there is a plateau, that falls in between, we think, in between the 2 top doses that we're using. And we'll explore, how this dose response curve translates into kids with growth hormone deficiency. The last thing I'll say on this slide is just that Merck gave up its development of age-related sarcopenia primarily because they couldn't convince the FDA that there was a path forward in that space, for essentially healthy elderly people to prevent, you know, frailty and sarcopenia that hadn't arisen yet. And Merck didn't pursue the growth hormone deficiency in kids for a variety of reasons. I think primarily because they just weren't interested at the time in doing rare disease, small market drug development. Okay, but let's move on. So this is the trial that we read out recently at the primary readout. Just as a note, everybody passed, everybody to come in had to pass our PEM strategy. So they're all likely responders. This was a multinational study, across the U.S., about 45 sites. The primary readout was at six months. That's the data we'll see today, full enrollment at 6 months. The study does go out to 24 months. We can also share data for longer-term treatment. As I said, 3 doses of our molecule that span and actually exceed the pharmacodynamic plateau that we talked about. We'll run that against the daily injectable growth hormone arm. Let's go on to the next slide. Here is the annualized height velocity data. This is on the y-axis. How high these kids were growing per dose. What you see at 6 months and at 12 months on treatment. The 12-month data is just the number of kids who had made it to 12 months when we read out the full cohort at 6 months. You'll see reproducibly that the middle dose, the 1.6 mg/kg/day dose gives the best height velocity. Actually, there's really no statistical difference between the 1.6 dose and the 3.2 dose. You also see a very flat growth decline between 6 months and 12 months for our molecule, showing the durability that Merck had already seen in the adult population. Then you are able to see that there's a small 1.7 cm difference between the growth we're seeing at 12 months and the comparator growth hormone arm. So the 12-month data is quite important to look at because that is the duration of the study that we'll be running in phase III as a non-inferiority study. So because we're running this study longer than 6 months, we can use both the predictive data at 6 months and the actual data at 12 months to go through all this data and be predictive for our choices for phase III. So what you see here is a little bit of an assessment of the subjects who did enroll in our growth hormone arm. So unfortunately, 2 of the kids who were randomized into our growth hormone arm were the 2 youngest children in the study. And they turned out to be also 2 of the fastest growing kids in the study. So the red stars here are their 6-month growth rates. And the grid is less severe growth hormone deficiency subjects, similar to the subjects that we would pick that we picked for our PEM study, PEM-positive kids. It's kind of charted across the standard, first-year response to recombinant human growth hormone. So you see the centiles there. These two children grow, you know, essentially above the 97th percentile at six months. So they have probably pushed up the growth rates in the growth hormone arm a little bit more than one would expect based on historical data. If we go on to the next slide, we can see some of that historical data here. We have our six- and 12-month growth rates in the gold bars. The darker gray are three phase 4 studies that focus in on the moderate end of the population that are similar to the population we selected for our study. You'll see the expectations there in those phase 4 studies are between 8.3 and 8.6 centimeters per year. And the graph on the right is, or I'm sorry, the bar in the lighter gray is the daily injectable Genotropin arm from a long-acting growth hormone trial. And it's filtered by the standard STIM test above 3 nanograms per mil, which is, again, similar to our population. You'll see those kids grow a little bit more, 9.3 centimeters. So this is really we're sitting kind of in line exactly where we historically, you know, based on the historical data expected we would be at the end of this 6- and 12-month study. Let's go on to the next slide. This is the two pre-specified statistical outcomes for this phase 2 study. They are based on the efficacy and reproducibility of the predictive enrichment marker. So the bar chart on the left is how we showed that our predictive enrichment marker strategy brought in children who could respond to our molecule. So essentially, the no enrichment bar is a group of PEM-positive and PEM-negative kids who were in Merck's 020 trial, previous trial. The dotted line is their mean height velocity on treatment. Because it's the mean, that means 50% of those kids are above and 50% are below. What we did is say if we're only going to bring in PEM-positive subjects, we should increase the number of kids who are above that responsive line. That is what we did. If you look at our 1.6 and 3.2 dose cohorts, we shifted up to the point estimate that we had pre-specified in our protocol in the SAP. So we beat the 70% enrichment goal that we set for ourselves. So that's exciting. It's good validation of the strategy to select responsive patients. The second, pre-specified outcome that we agreed to with the FDA is to show reproducibility of the PEM classification. So that's the middle box. So every subject who tested PEM-positive on screening was retested on day one of the study and found to absolutely repeat their PEM positivity. So we had a 100% reproducibility rate. Okay, let's go on to the next slide. We're going to dive into our mechanistic study here. There was lots of really fascinating mechanistic information that came out of this that we're still digging through, but there's lots we can share with you today. Every subject here was also a PEM-positive subject. This was done at a single site. So it is not a multinational study. It was kind of at a specialized, clinical site in Santiago, Chile. The reason we needed a specialized site is because we are going to accurately track growth hormone secretion patterns. In order to do that, we have to put an indwelling catheter in these subjects and sample, take blood samples every 10 minutes for 12 hours. We do that at baseline. We do that at six months on treatment. That will give us an enormous amount of information about the pharmacodynamic effects as well as the PK of our molecule. We did this at the top two doses in our last study, 1.6 and 3.2. Again, this is the key readout is at six months. But we will continue this study until the subjects reach near adult height. On the next slide, you see six and 12-month data. Again, these cohorts are a little bit smaller than what we saw in the 210 study. The percentage of them that reached 12 months when we read out the full 6-month data is shown on the right. Here we have their baseline data. We're looking at the change from baseline. You see essentially the same thing. The 1.6 and 3.2 cohorts are about the same, slightly higher for 3.2 this time. They're not statistically different. You also see the flat drop-off of annualized height velocity between 6 and 12 months. So very reproducible with the effects that we saw from our larger 210 study. The next slide will show us this pulsatility data that is quite exciting. So if you look at the graph on the right, the gray line is the baseline. That's how much growth hormone was being secreted by this child pre-treatment. And then if you look at the blue line, that's how much growth hormone they're secreting in 12 hours at six months on treatment. So visually, it's as I've told you, we were able to increase the amplitude of peaks across an entire day. This is 12 hours. If we looked at 24-hour data, we would see this effect last all 24 hours. If you look at the table, it's exciting to see the changes from baseline for the two key growth-promoting hormones, IGF-1 and growth hormone. And you'll see that there's a substantial increase from baseline in both of those. And that results in more than doubling the height velocity of the subject in six months. So this is an absolute validation of the mechanism that we have, restoration of pulsatility. That restoration of pulsatility has a dramatic impact on height velocity in this child. The next slide is a summary slide. In this case, we took the 1.6 and 3.2 cohorts and combined them because they aren't different in AHV. It turns out they're not different in the amount of growth hormone they secrete at six months. We took essentially what was on the last slide, which is just concentration of growth hormone. We ran it through an algorithm that turns that into pulses of secretion events, basal secretion, and total secretion of growth hormone in physiological units of micrograms per kg per day. We have that data for 12 hours. We are able to calculate 24-hour data from that data set we have. That's what this is showing. What you see here is our data in blue. You can look at baseline and you can look at six months on treatment. The gray on the left is actually published data that was collected similarly to ours and also similarly run through the same algorithm that we used. What you'll see is that our growth hormone deficient kids at baseline are very similar to the published growth hormone deficient kids who are untreated. You'll also see that our treated kids are very similar and overlap with the amount of growth hormone that a normal, healthy, growing child releases. That's very exciting. Again, you know we talked about our goal being to restore normal growth hormone secretion patterns. If you compare that again to our comparator arm, which is the far right column, again, this is like the blue line in the graph I showed you in the very beginning. Those kids are receiving, you know, when they take exogenous growth hormone, a significantly higher dose, right? 4 times higher than what they would get normally and about 4 or 5 times higher than what we're able to restore with our mechanism. So it is pretty fascinating to think about the impact of pulsatility on growth. So we're able to capture almost all of the growth that a giant exogenous dose of growth hormone can deliver with much less growth hormone because we're giving it impulses. All right, let's go on to the next slide. Just a quick snapshot on the combined data. In each one of these cases, IGF-1 is being taken from a deficient state to zero. And zero is the mean for the normal range for these children. So we're able to restore their IGF-1 levels. The next slide is durability of effect. We have a small subset of kids. Can we go to the next slide, Lisa? If we can look at this slide, this is all the kids in the 1.6 and 3.2 arms combined who made it to 24 months on treatment. And what you see here is a very flat decline in growth between year one and year two. That's the green bar. There's only about a 6% decline. And you'd compare that to published data for this, you know this less severe population. And in general, those kids are dropping off between year two compared to year one about 20%. So I think this shows we have quite a durable effect on growth that will be long-lasting. Finally, this molecule has been in the clinic for a number of years. The next slide shows the combined safety data. And what it really shows, this is combined from all the trials that we're running right now. Essentially, our biggest AEs are increased appetite and some pain in the extremities. So the increased appetite, we would align, I think, with the mechanism of action of inducing growth. And you could say the same about the pain in the extremities. So with the data that we've seen, we don't see a safety signal. And the data that Merck has generated in kids doesn't give us any worries about a path forward for safety here. I think this won't be an issue as we move forward. So with that, I'll turn it over to Rick and he can give us a summary. Yep. Everyone, as we've stated earlier, we're very pleased to have run these trials, these global trials, and very pleased to tell everyone that we've met all of our endpoints, both primary and secondary in both of these studies. We have reproducible results and durability of effect that goes out beyond a 2 years or 2 years. This turns out to just natural return of natural physiology, the pulsatile release of growth hormone really does matter, and especially when it comes to durability. As John said, if clinicians want to return hormone levels to a normal range, that's exactly what this drug does. With comparable growth to recombinant growth hormone. And as we've said also, we're going to take the 1.6 mg/kg arm forward into a phase III. And we're also very pleased to say that just as we predicted, based on all of the large databases that have been kept for about these patients, mild growth hormone deficient patients for a long period of time, we were right in line with the growth of these historical trials. Once again, FDA meeting coming up and a phase III program that will be initiated before the end of this year. And I don't need to say, I think, a whole lot about the fact that if you go to the next slide, Lisa, or the next slide, I should say, that in this space, it's a mature space. Once again, $4.5 billion revenue a year space that we have a chance to be completely disruptive with a once-a-day oral. Not just in PGHD, but there are many other indications that we can move towards. And right now we have about $43 million end of the third quarter in our treasury. We're burning about $9 to 10 million a quarter cash runway out to the end of the third quarter. And I think with the right partners, we have a chance to make a big impact in this space. - Great. Thank you, Rick. I think we have just maybe a minute here just for a question, which is, you know obviously very good to see the, I think it was 100% rate of reproducibility in the PEM testing data. And you know, just to be clear, you know, this, the drug may not serve every patient with GHD. And I think you know we know that. But for those for whom it you know could be used, you know, even if for some reason there was, you know, in particular patients, maybe less efficacy than one might expect, this is not a commitment to using LUM-201, correct? One could always go to an injectable growth hormone in the case that, you know, growth from 201 was less than one might expect, right? So one is not locked into using your drug in the event that certain patients, you know, may not be getting to what could be the expected rate of growth. Is that right? - Well, that's right. But as you know, the durability of effect of our compound, restoring the natural physiology, turns out to be really important as our clinicians tell us. You know, all patients are pre-programmed to reach a certain adult height by their genetics. This, you know, the year one to two data, year two data shows only a 6% drop-off on height velocity versus what everyone understands historically is almost 20% with growth hormone. So you have to get that with growth hormone, that catch-up growth that first year with growth hormone. We're going to have a much better durability of effect over time, we believe. John, I don't know if you want to add anything. - Nope, you did a great job, Rick. All right. Yeah, well, I think as we've seen, you know, the weeklies are doing very well in a market that, again, is already very mature with the dailies. And I think, you know, as the direction of therapeutics kind of becomes, you know, more convenient and easier for patients to take, an oral, you know, would be, you know, the next advancement for the space. So, looking forward to seeing 201 get into pivotal. Thanks very much, team, for joining us today. And thanks, everybody, for dialing into the session with Lumos Pharma. Have a great day. Thank you, everyone.