Good afternoon, everyone. Thank you for joining our 35th Annual Healthcare Conference here at Piper Sandler. Really excited to be featuring the team from Lumos Pharma. We've lots to discuss over the next 25 minutes and wanna jump right into it. John, great to have you. Congratulations on outstanding data that you reported this month, and we have lots to get through. I think the first question is two strong data sets. Now that the data has become available, how soon can you start? Have you had a chance to engage with the agency to request an End of phase II Meeting, and what's gonna be the cadence on a meeting and coming back and discussing with us sort of next steps? Well, thank you for that, Yas, and thank you for the opportunity to chat with you today. Mm-hmm. So we have two very comprehensive data sets- Mm-hmm that we've generated and released data on. Yeah. We have a mechanistic set and a Mm-hmm dose range-finding study. So we're assimilating all that data, which is more than what we need Mm-hmm to strategize with the FDA and come up Mm-hmm with our phase III study. So we're deep into the process of finalizing our plans that we'll bring to the FDA. And so we will submit our request for an end of phase II meeting soon. I would expect to meet Mm-hmm with them in the first half of next year. Mm-hmm. There's, you know, much to discuss in that meeting. Yeah. There's the phase III design. Mm-hmm. There's our new drug product, right Yeah that we're gonna bring out in phase III. So, we expect it to be a really eventful and Mm-hmm impactful decision meeting Mm-hmm as we go forward. Should really help us very adequately define exactly what we're gonna do in phase III. Okay. And what do you. As we're thinking about broad strokes of the phase III design, what are some of the design elements that you're hoping to propose, or maybe what are elements that are up for negotiation? Yeah. So I think the key pieces that we have to agree with the FDA on, I mean, our data set is gonna help us understand the effect size Yeah of our molecule Mm-hmm the variability in each one of the cohorts. We can use that to propose Mm-hmm the non-inferiority margin Mm-hmm for our non-inferiority trial. We would expect that Mm-hmm to be what other, long-acting growth trials have used, which is about 1.8 to 2 cm. Mm-hmm. So we'll make the case for our non-inferiority margin Mm-hmm and then we'll make sure that we can power it effectively Mm-hmm and agree with the FDA on kind of those broad aspects Mm-hmm of the trial design. Okay. And could you maybe talk to us. Obviously, the PEM strategy was really well conducted across both studies, and you guys highlighted more than 70% of the phase II eligible patients qualified for that, 100% reproducibility. Is there any tweaks that are being made, or is that enrichment, this enrichment protocol gonna be almost identical in the transfer to phase III, or is there anything else Yeah to perfect it further? So I think the data, as you said, there are two key Mm-hmm pre-specified, statistical outcomes in our Mm-hmm phase II study. One of them is an initial validation of our Mm-hmm PEM strategy. Yeah. That is our percent enrichment Yeah that we talked about. So we pre-specified that Mm-hmm we would see enrichment of about, above 70% Yeah of the population, so we met that. So that gives us a very good sense that this strategy of using the PEM tests to identify Mm-hmm responsive patients works. Yeah. We're bringing in the right patients to the trial. Then, importantly, to the FDA and to us, we also wanted to show that every time we test somebody as PEM positive Mm-hmm when we test them three weeks later Yeah they're PEM positive again. Yeah. And so we've got 100% reproducibility- Mm-hmm on that. So those two give us quite a lot of confidence Yeah that we can move forward in phase III with that exact Mm-hmm strategy going forward. I think that where, you know, where there's opportunity to kind of fine-tune things are a little bit in the inclusion criteria Mm-hmm a little bit, you know, all those Yeah baseline characteristics, what are we gonna stratify on? All those pieces, there's still work being done to, to put together the perfect Mm-hmm package of all those variables. Could you maybe talk about when you look historically and across other studies, sort of the translation from a phase II to a phase III study? Like, what is that POS transition, as we have seen obviously with other- Yeah, yeah products? Yeah. So there's, y ou know, as you know, there are four long-acting Mm-hmm growth hormone products that have transitioned from phase II to phase III over the last couple of years. They're different products. They're either prodrugs of Mm-hmm growth hormone, or they're recombinant proteins Yeah that extend the half-life of Mm-hmm growth hormone. All those had phase II studies. Yeah. Now, the things they had to worry about are different than what we have to worry about. They had to worry about antibody titers Mm-hmm high IGF-1 concentrations Yeah extended growth hormone levels. But three out of four of those products did succeed to translate their phase II Mm-hmm data into positive Mm-hmm pivotal trials. So we have, you know, we have a different mechanism of action, but I think what that does show us is that that phase II data is predictive of what Mm-hmm you can expect to see in phase III. If you can build on the design components that are in your phase II trial successfully Mm-hmm in phase III, I think you'll be rewarded with a positive trial. That's very helpful. Maybe the other question that comes up is, maybe could you remind us of similar drugs or other drugs in phase III? I guess the question is: What is the non-inferiority margin that you would want to set up in your phase III? Remind us. Maybe that's a good start. Yeah, so just, you know, this non-inferiority margin, you base it again on Mm-hmm the variability in each one of the cohorts and what your comparators are Mm-hmm right? And so we're building that case right now as part of our, you know Mm-hmm request to meet with the FDA. But all of the, the long-acting growth hormone products Mm-hmm. essentially using similar data sets, right? Had about a 1.8 to 2 cm Mm-hmm. Non-Inferiority Margin, right? So that's the range that your mean has to be in, and your confidence intervals have to be within that range. Okay. And then now, as you guys are also working really towards meeting with the agency, getting ready for phase III, what are other activities that are ongoing that are really, t hat we didn't touch on that, you know, maybe talking about the product, drug formulation aspect, getting the product ready for phase III. So what other activities, phase III readiness? Yeah. So there's a lot going on. Yeah. Right. We still have four clinical trials that we're running. Yeah. Right. So even though we had our primary readout, those trials are extending on, so we're gonna continue Yeah to develop data sets. Mm-hmm. Right? We read out, you know, as a primary readout in our 210 study Yeah 80 subjects had six months on treatment, but they're all continuing on. Yeah. Right? So we'll have a full 80 subjects Mm-hmm 12-month data set, you know, again, in the first half of next year to share. Okay. So that all of those pieces of the clinical data is still accruing, right? We'll continue to have that data. On the CMC front, we've mentioned in the past that we filed a new patent application. Mm-hmm at the end of last year, and it was really focused on some unique properties Mm-hmm of our molecule. It's the, you know, what's unique about this molecule is its compactability and the ability that the compactability Mm-hmm gives us some opportunities Yeah for novel formulation, right? And we're working hard to bring that drug product into Mm-hmm online for phase III. Mm-hmm. That's our plan, that that's what we're going to use. There are a couple of steps that we have to there, but there are a couple of outcomes from that transition that I think are really important. It's gonna give us many more opportunities or different routes of administration Mm-hmm for kids to take this. It'll make it easier Mm for each of these younger children to take it. They could mix our tablets With food with food. They could take it Wow as a capsule, or they could take it in a very small tablet. Oh, wow! So I think it will make it much easier. It'll minimize dose variability. Yeah. We're quite excited to bring that, that part of the strategy forward into phase III and discuss it with the FDA. What would you need to do? Do you need to conduct any bridging studies Yeah. So we to get ready. Yeah, we to then be implemented in phase III? What we have to do is just essentially a bridging study comparing to the Yeah drug product form Yeah that we had in phase II. So, we have those planned, and they'll be done, and the data will be generated in time for our phase III. These are the new mini tablet formulations that you're considering? Yeah. What are some of the little steps that you said are, or needs to be tweaked? What are those steps that are also needs to be done? Is it just like On the drug product or? On the drug product. Oh, yeah. Yeah. So we, we've, you know, we've finalized our formulation Yeah and we're, you know, we're essentially just generating this on a scale and generating the stability data that we need Mm-hmm in order to run our phase III trial. So there's not much mystery left. It's really just about doing the grunt work of drug discovery Right to get ready. Right. And then I guess once you come back, let's say fast-forward, you have the new mini tablet, you did the bridging study, and the bridging study, I assume, would be completed by the time you can initiate the phase III study Absolutely in the second half. Yeah. Then you are in phase III. Is the regulatory agency's view just a single pivotal study is necessary, or is there a chance that they could ask for two? What is the current So our regulatory path, and what's the safety requirement needed? Yeah. So our expectation is that there's one, pivotal study that's needed Mm-hmm from where we are now to an approval. So I think the. Obviously, the negotiations for this one pivotal study are really important to us. Yeah. We understand and can come to agreement with the FDA on a plan Yeah that really is successful. But that should be all that we need, and that is, you know, essentially all that was needed Mm-hmm in the label for many of the other ones, all the other long-acting, so. Okay. And do you think that, I think the next question that comes up is, you know, currently, the company is very much in preparation to phase three and a very desirable product profile. And I'm sure there's definitely strategic interest in the asset. So how are you guys thinking about, partnership interest, partnering this, creating non-dilutive opportunities? So if you could just talk, touch on that, that would be great. Yeah. So I think, the idea of an oral therapeutic coming into a market of daily injectables or weekly injectables is Yeah I mean, I think it's pretty ripe for disruption in that market. Yeah. So there is a lot of interest. You know, we've, as we've said before, you know, we're engaging in conversations. Mm-hmm and have been engaging in conversations about regional partnerships Mm-hmm outside the U.S. primarily. I think, you know, we'll continue to think of that as an option for Mm-hmm non-dilutive financing, as you said Yeah and couple that with other financing opportunities. That's, that's very helpful. Are you planning, I guess, the question here is, is ex-U.S. regional partnerships more interested to occur now at this juncture, or would they want you to, to conduct a phase III and the value would be higher and the partnership post phase III? Well, I think the value may be higher post phase III- Mm-hmm but I think the opportunity to Yeah collaborate with us on phase III Yeah and make sure that we generate the type of data they need for their region or for their marketing Yeah strategy, I think, is an important asset as well. Right. So most people think that this is an appropriate time for many of them to start a phase III Yeah to get involved. What are some of the geographies that have a very high unmet need for, or prevalence of? Yeah, pediatric growth hormone deficiency patients who would really benefit for an oral product that you think, Yeah Could be desirable regions or geographies? If you look at the global market, the U.S. is Mm-hmm the biggest, right? Mm-hmm. China is actually quite a large market as well. Mm-hmm. Korea, another very Yeah large market, right? So I think what we would like to focus on first is ex-U.S. markets, whether it's Korea Right whether it's Japan, whether it's parts of Europe. Yeah. I think those are the ones that I think we would be, you know, we would be open to discussions Yeah about partnering on. So I think those are, that's where we would start. Yeah. Yeah. And also, once the product is approved, do you think it's gonna be in the, w hat would the label language be to say, PEM-positive patients, and how do you implement, you know, PEM enrichment or measurements? How much is that part of the current protocol right now? Yeah, so I can Yeah I can explain a little bit the PEM strategy. Yeah. So the PEM strategy is really a way, as we said, to enrich Mm-hmm in responsive patients. Mm-hmm. Right? It's really based on enriching in subjects with the appropriate physiology to respond to our molecule. Mm-hmm. Our entire phase II and Yeah phase III strategies are gonna be driven in patient populations Yeah who are PEM positive. So we fully expect our label to reflect that. Yeah. And that will be kind of one step towards. So I think it's a good step in a commercial sense in that we will have shown that this test enriches and likely Mm-hmm responders. So you can say to a payer Yeah if they pass this test, there's a very good chance that they're gonna respond to the drug, right? Yeah. It's not like, "Well, let's try it and see if it works," right? Yeah, right. We have kind of a Yeah an analytical way to enrich in Yeah in subjects. Yeah. We do think the label will include Yeah PEM positivity, and that will be part of our strategy going forward. Okay. And in terms of, do docs already do these tests typically in the clinic? So it's not like you're asking any other burdensome, you know, assessment. Yeah. So one, you know, our PEM test is actually two separate tests. One is a baseline IGF-1 value. Okay, yeah. So that test is done by pediatric endocrinologists Mm-hmm to diagnose the disease. Mm-hmm. Our second test is actually, a single dose of our molecule Mm-hmm and we evaluate how much growth hormone we can, Mm-hmm stimulate the release of. Mm-hmm. That is just a growth hormone stim test. The only difference from what is done every day in diagnosin Mm-hmm GHD, is that you're using a single dose of our molecule instead of another agent like clonidine or arginine. Oh, I see. So the tests are run routinely. Each kid in the United States gets- Mm-hmm at least two stim tests Yeah with a different agent, so, you know, we would, we would be adding that. Mm-hmm. I think these aren't. It's not another. Yeah burden, right? Yeah. These kids are being tested this way all along. Yeah. No, that's, that's very helpful. And speaking, I guess, with KOLs and patients and, and, like, who are getting to know that there's an oral drug available for pediatric growth hormone deficiency, could you kind of talk about sort of, while you're doing phase III activity, what's in place to start actually, like, kind of warehousing these patients once your phase III protocol is signed off and you have the mini tablets ready to go? If you could just Yeah. So I think the most important thing is educating people on the mechanism of action of our drug. Yeah. Essentially, what we have shown in our mechanistic study is that we can take growth hormone deficient subjects, treat them, and we can restore their natural pulsatile release Mm-hmm of growth hormone to pretty much what a normal growing child has. Yeah. I think that is one of our most effective marketing tools. Yeah. When you talk to KOLs, when you talk to parents and caregivers Mm-hmm if we can say to them, "Look, you don't have to use Yeah supraphysiological levels of growth hormone- Yeah you don't have to hit this with a hammer. You can just restore your natural levels Yeah “and get growth,” and I think that is a really helpful way to recruit. Yeah kids into the trial. And we do have.. You know, our current trial has 45 sites Yeah worldwide. Yeah. All of those clinicians now understand the type Yeah of subjects who can respond to our drug Mm-hmm because they've helped us recruit. Yeah. I think it's, that's a great core Yeah group of people to start to think about Mm-hmm you know, which patients Yeah Can they quickly pull in from their practice? No, that's good. That's great, and I think it's also important to understand, sometimes I get this question, you know, the timing of enrollment. I think you guys enrolled during COVID, and it was challenging Painful. painful as these kids, obviously, you know, were not in schools, were not being measured, were not seen Yeah routinely. So, like, have you been able to, like, model out how much faster when you enrolled into the study, like, what will be the natural. How much faster is the absence of COVID Yeah Expediting the enrollment? Yeah. Yeah, so I think we would expect Yeah You know, there are a couple things. We would expect much better enrollment this time. Yeah. But it's not just the absence of COVID, it's also having these 45 sites Yeah who know exactly which patients. Right. Right? We can look at the enrollment curves Yeah from our current trial, and we know once, you know, once the sites are educated Yeah and kids are coming in Yeah and getting referred to ped endos, we actually got quite good enrollment. So we feel comfortable, especially Yeah there are no competing Yeah growth hormone trials Right right now, so I think we have a good opportunity to Opportunity to quickly enroll. No, that's. And then another question that comes up is: Have you guys started the competitive landscape? Like, obviously, this is the only oral product in development, but there are other in, you know, long-acting injectables Yeah that are available. What market research have you guys done to understand sort of, you know, the appetite for an oral versus maybe, like, a once-a-month injection, potentially? Yeah, so I think, you know, what our competition Mm-hmm is out there now is the daily injectable or weekly injectable. Yeah. And I'm sorry, weekly. Yeah. Yeah. So right there, we've done a little bit of market research, looking at both clinicians and Mm-hmm and, caregivers and Yeah it's very clear, you know, more than three-to-one, that they're gonna prefer to take an oral therapeutic than Yeah than an injectable. You know, again, we're not gonna treat the entire market, right? Yeah. 'Cause the more severe kids, the PEM-negative kids Yeah are gonna need, an injectable, but I think we're gonna offer a great opportunity Yeah for kids. You also have the opportunity for the families that come in, they get diagnosed by Yeah A pediatric endocrinologist, and the endocrinologist says, "I'm sorry, your child has growth hormone deficiency, but there is a therapeutic for that. Yeah. The therapeutic is that you're gonna get a daily injection for the next Mm-hmm Six years." A lot of those people walk out of the office, right? Yeah. There is an opportunity to kind of expand that market Yeah based on people who might not walk out of the office Yeah If there's an oral opportunity. Yeah. No, that's great. Have you guys also been able to connect with payers to get an understanding on, like, what could be the additional incremental cost flexibility for an oral product versus, you know, the burden and the compliance associated for patients who, you know, do the daily injection or the weekly injection? Yeah. So the market is interesting. Obviously, the daily injectables have been on the market for 35 years Yeah and they're, you know, about $40,000 a year. Yeah. The weekly injectables are about double that Yeah which seems like a big jump to save Yeah Six injections a week. Yeah. Yeah. The most important thing about our molecule is it's a small molecule. Yeah. It's not a recombinant protein. Yeah. It's not a complicated prodrug, right? And so the cost of goods for our molecule is going to be significantly lower than any of those other competing products Yeah which gives us opportunities, to work with people. I think, you know, even, even setting Mm-hmm our price at something like Yeah the daily injectables, right? Yeah. It's still significantly lower Yeah than the long-acting that are out there. So I think we have a lot of freedom to Yeah work with payers. And the other piece with payers that I think should make them quite happy is the PEM test, right? Mm-hmm. Like we talked about. So we can give them some indication that their kid, you know Yeah this kid is actually gonna respond to the drug, and they're not gonna waste six months. Yeah of treatment Right with no response. No, that's great. John, you did a great job. You've literally, like, went very efficiently through all my questions related to next steps, regulatory, commercial, payers, phase III design, tablet formulation. So what an incredible, you know, execution we have seen and really excited for you guys as you go out into 2024. And just wanna say thank you on behalf of all of us here at Piper Sandler for great, you know, great successful studies to be conducted in a very challenging COVID environment. I wanna say thank you and congrats. Thank you.