Welcome everyone, and thank you for joining us for LYRA's key opinion leader event. We'll be making forward-looking statements today. Please refer to our current filings with the SEC to review our risk factors. We are very fortunate to have two distinguished guests with us today, Dr. Zachary Soler and Randy Ow. Both are well-known experts in chronic rhinosinusitis. Dr. Soler is Associate Professor of Otolaryngology at the Medical University of South Carolina, and he's a Practicing Otolaryngologist at the MUSC Sinus Center. He is Global Coordinating Principal Investigator for our LYR-210 phase III ENLIGHTEN program. Dr. Ow is a Practicing Otolaryngologist at Sacramento Ear, Nose & Throat, and President and Chief Medical Officer of DaVinci Research. He was the principal investigator in the LYR-210 pharmacokinetics study. Also, we have Dr. Robert Kern here with us today. He is LYRA's Chief Medical Officer and is a key opinion leader and practicing ENT. He is also the Professor and Chair at the Department of Otolaryngology at Northwestern University. Before I turn the call over to our group of experts, I'll take a couple of minutes to introduce our CRS pipeline. Dr. Soler today will review the new six-month follow-up data from the LANTERN phase II study of LYR-210. This data was presented at the Annual Meeting of the American Rhinologic Society earlier this month. Next, Dr. Ow will present the full data from the LYR-210 PK study that he also presented at the American Rhinologic Society. Dr. Kern will then review our plans for the pivotal phase III ENLIGHTEN study, and he'll share the phase II BEACON study for LYR-220. After that, we'll open it up for questions, and we've reserved the majority of the meeting for Q&A today. For those of you participating on the webcast, please submit your questions through the form in the website pane. You may also dial in to the number located on the event page of our IR website. Each year in the United States, 50% of patients treated for chronic rhinosinusitis fail medical management. That's equivalent to about four million patients annually. Their next line of treatment is an invasive surgery or a repeat surgery. In response to that substantial unmet need in patients who fail treatment, LYRA has leveraged our proprietary XTReo platform to develop two product candidates, LYR-210 for surgically naive patients and LYR-220, designed for the post-surgical anatomy. We've now demonstrated in three separate trials both safety and efficacy of our lead product, the LYR-210. We're also pleased to report that we remain on track to initiate two clinical programs very soon. The LYR-210 ENLIGHTEN phase III pivotal program and the BEACON phase II study for LYR-220. Dr. Kern will provide updates on these programs a little later in the presentation. CRS patients who enter an ENT's office fall into two categories, those who have never had a surgery and those who have had a surgical intervention and continue to require medical management. LYR-210 is designed to be used early in the treatment paradigm after topical steroid sprays have failed. We estimate this population to represent about two million patients in the United States each year. The market opportunity for LYR-220 is just as significant at about 1.6 million patients each year who continue to require therapy despite having had a surgery. LYR-220 is designed to fit the larger cavity of a patient who has had an operation. As you can see in the chart here on slide five, the vast majority of these patients do not have a CRS-approved drug. Recent marketed products only target the treatment of polyps. It's a small fraction of the overall CRS market. As a result, there are millions of patients each year that are undertreated and continue to struggle with debilitating symptoms from their CRS. In this disease, the treatment obstacle is not finding an appropriate anti-inflammatory drug. Steroids are the established foundation of treatment for CRS. However, the issue is that to date, there has not been an effective method to deliver the drug deep into the sinuses at the site of the disease and a way to maintain a high dose of drug locally over time such that the disease can be modified. LYR-210 and LYR-220 are designed as small matrix implants that are placed deep in the nasal passage at the central region of the disease, as we show on the figure here to the right. This is done through the nostril in a non-invasive procedure in an ENT's office with just topical anesthetic. Dr. Ow will show you an actual placement in a few minutes. Once in place, the matrix releases a known anti-inflammatory steroid, mometasone furoate, released consistently over a six-month period after just one administration. LYR-210 is designed to sustain a therapeutic dose of the steroid right where it's needed for a period of six months to affect the disease and to improve patients' symptoms. We'll now move to the presentations by the physicians. First, I want to state that neither Dr. Soler or Dr. Ow are employees of Lyra Therapeutics. They have been compensated for their time in relation to this event. All opinions expressed by these physicians belong to Dr. Soler and Dr. Ow, and do not necessarily reflect the opinions of their affiliated institutions. Dr. Soler, maybe you can start off with a bit of your background and an overview of your practice. All right. Thanks, Maria. For the next couple of minutes, I'm gonna focus on data from the LANTERN study with an emphasis on what happens in the six months after the implant's removed. As a bit of background, my name's Zach Soler. I'm an Associate Professor at the Medical University of South Carolina in Charleston. My clinical practice is focused almost entirely on patients with chronic sinusitis. From a research standpoint, my expertise is in outcomes research, specifically in outcomes after sinus surgery. This is an area of real interest of mine. Let's just dive in. I think most are probably have seen results from the LANTERN study. This was the phase II study that looked at LYR-210 compared to a sham control. What I wanted to focus on first is the SNOT-22 data. As a clinician, this is really what's interesting to me and to my patients. For those who aren't familiar, the SNOT-22 is a quality-of-life instrument. It captures how sinus disease impacts a patient and how they feel. It's really what guides decision-making. This is really kind of the core of what's interesting to me. If you look at this graph here, this shows sort of what happens in the six months after LYR-210 is placed. There's a couple of things I wanted to point out. First is just to look at how robust the changes are. If you look at, it's about a 40-point improvement from baseline to about six months. To put that in context, that's a really significant change. Really, that's equivalent or maybe greater than what we see across surgical cohorts and even most of the biologic studies that have been published. That's number one. Number two, just to focus on sort of the durability. You know, you give somebody a burst of oral steroids, you'll see a big improvement for a couple of weeks, and then really by a month or two, that has worn off. But what you see here is really durable improvements up to six months. Then the last thing to point out is just the difference compared to the placebo control. You see a difference of about 19 points. To put that in perspective, that's really twice the minimal clinically important difference. A 19-point difference is quite large. That's something that's both clinically relevant and actually is pretty easy to show statistical change. That's a pretty small sample size that you would need to show that kind of benefit. That's SNOT-22, but let's look at the cardinal symptoms. The three cardinal symptoms are those classic symptoms for chronic sinusitis patients. We're talking about nasal congestion, facial pain and pressure, and nasal drainage. These three are of interest really to the FDA, because the FDA is focused on these kind of symptoms specifically. Really what you'll see here is basically the same thing we saw with SNOT-22. You see a really robust change at six months. You see a durability, and you see a big difference compared to control. The cardinal symptoms really are very similar to what you saw with the SNOT-22 data. That's the LANTERN study. That's what we saw at six months. The question is, what happens once you take it out? Once the implant's removed, what happens in the next six months after that? That's what this follow-up study looked at, looking at safety, rescue treatments, cardinal symptoms. On the left of here is one of the data I just showed you, and on the right is the post-treatment period. If you look at the control group, that's the group that's in gray here, you see what you expect to see, which is worsening over time. Since they didn't have active treatment, their disease worsens over time. Their symptoms start to worsen over that period of six months. If you look at the LYR-210 group, you see durability or even some improvement that happens in the weeks and months that follow implant removal. You know, this is a pretty big distinction compared to something like, DUPIXENT. If you look at the dupilumab data from their study when they took patients off in their open label and followed them for six months, you saw a really significant worsening of those patients and almost back to where they were baseline. You know, once you stop giving them that treatment, basically they're no better. That's really important, and that factors into how I discuss that with patients. When somebody comes in and we're talking about somebody on a biologic, I say, "Look, you know, once this comes off, you're gonna be back to where you are. This is kinda something you have to be on forever or at least for the foreseeable future. Whereas what we see in this data is in the LYR-210 group, it, although the average main patient had durability, it's a mixture, right? There's a group of patients who have about half that have a durable response, and there's about half that actually worsen over time versus controls, where they most all worsen. This really makes sense clinically because we know that chronic sinusitis is a heterogeneous population, and the LANTERN study was fairly lax on who was in there. You had patients with and without polyps, et cetera. It's pretty much a real-world experience. We know there's some patients that have type 2 disease, they have chronic inflammatory. You're not gonna cure those patients. This is about control. They're gonna need you know something like LYR-210 on a regular basis. Then there's a group that are gonna do well, and potentially one device, one implant may be what they need to then have a long durable response. At this point, I'm gonna hand things over to Dr. Ow. He's gonna talk about the PK data. This was actually presented at the ARS really recently. And he's also gonna talk about real-world experience, since he has personal probably the most personal experience of anybody in the U.S. of actually placing this in a patient. Thank you very much, Dr. Soler. My name is Randy Ow, and it's my pleasure to be presenting the LYR-210 pharmacokinetic trial data, a study that I was one of four U.S. sites that participated in. I am a General Otolaryngologist in practice in Sacramento, California. My practice is a full-time ENT practice, seeing patients with cerumen, patients with trauma, cancer, and sinuses. I don't focus on any one area, but what I'd like to say is that I do a lot of clinical research, but 90% of what I do is what my colleagues across the country do. The next slide shows the study design of the LYR-210 study. As I stated earlier, it was done at four U.S. sites, and 24 patients were enrolled to receive either LYR-210 at 7,500 mcg or LYR-210 at 2,500 mcg. They were divided into 12 patients into each group. They all had to meet diagnostic criteria for chronic rhinosinusitis, and they all had never had sinus surgery. Patients were implanted for a total of 56 days, and at nine specified time points, blood was sampled, and mometasone concentrations in their serum was measured. Of the 24 patients, all were successfully and bilaterally implanted, so a total of 48 implants were placed. One patient experienced a premature early extrusion, but that gave a 96% retention rate by day 56. The next slide shows the key data that was obtained from this study. It's quite amazing to me. I didn't know these results until quite recently, but the steady states were achieved very quickly, and they were maintained over the entire 56 days. The upper red line shows the LYR-210 7,500 mcg plasma levels that reached a steady-state concentration of 41 pg/mL. The lower blue line shows the LYR-210 2,500 mcg implant that shows a very tight, steady-state concentration. It is, I think, important for me as a physician to see that the concentration of the drug that's measured in the plasma doesn't fluctuate greatly, and I think that's what these two data plots show very clearly. The next slide shows some of the clinical data or clinical symptoms that we monitored our patients for throughout this study. Again, realizing that we only had 24 patients, it's not a large study, but the SNOT-22 patient-reported outcome survey was applied to these patients at several time points. What we see is an amazing decrease in the disease burden measured clinically by this survey over the 56 days. This is a combined group of both doses, but the p-values are highly significant. You can see them at each time point. 1/3 of the patients reached the normal SNOT score by the end of treatment, and almost 2/3s of the patients reached a SNOT score of less than 20. I do wanna point out that in contrast to the LANTERN study that Dr. Soler reported earlier, the entry baseline SNOT score of the LANTERN study was about 68. This study showed a patient population which met with quite a bit less disease burden. They entered at with a SNOT score of 38. It appears to us that even in this small population, LYR-210 at both concentrations can be significantly beneficial for patients even in the mild to moderate amount of disease. The next slide shows a patient that I implanted in my office. I wanna say again, I feel like I have a very average ENT practice, very busy. I do a lot of office procedures, and of all the procedures I do in the office, especially rhinologic, I was extremely pleased that this one was so simple and efficient to perform in the office. I think even without showing or narrating what I just did in this patient, you could see a LYR-210 implant deployed easily, accurately, and what appears to be very comfortably into the space that it's meant to occupy and deliver drug to the tissues and surrounding sinuses over, hopefully, in clinical use, six months of treatment. Going into this study, I had no idea what I was in for or what the patients were, as far as how easy it would be for them to tolerate the implant. I was very concerned as to whether or not an implant that was put into this space would stay in place for 56 days, and I didn't know if I'd be able to find it or retrieve it very easily if it was able to stay in place. What I was surprised to find throughout the study, through all 13 patients that I was fortunate enough to treat, was that they experienced symptomatic improvement in their sinus symptoms, and at the end of the study, all 13 of my patients had all 26 of their implants retrieved without any incident or problem. I was very pleased with the experience I had with LYR-210. Again, this was my first experience and the first experience in the United States. The patients tolerated it very well. I feel that this will be a very successful program. Dr. Kern will now discuss the future plans and the clinical studies that are upcoming. Thank you very much. Thanks, Randy. My name is Robert Kern. I'm the Chief Medical Officer of Lyra Therapeutics, and I'm also the George A. Sisson Professor and Chair of the Department of Otolaryngology at Northwestern University. I've been a practicing rhinologist for 30 years. It means I take care of patients with sinus problems medically and surgically. I also have the pleasure and honor of working with a large team of investigators here at Northwestern. Multiple NIH grants and clinical trials going on at all times. I joined Lyra Therapeutics because I think their products have the potential to really make major changes in the way we treat patients with sinusitis. Let's talk about the LYR-210 phase III program here. As you can see, 350 patients divided between two staggered studies slated to begin later this year. The single primary endpoint of three cardinal symptoms. We're also tracking other endpoints. It's largely similar to the phase II LANTERN study. The LANTERN study was very successful. The change. Sinusitis is a quality-of-life disease, and the change, the improvement in quality of life is similar to what you would see at six months with surgery. It was presented at our spring meeting, and it won the award for best research contribution. In my 30 years as a rhinologist and a member of that society, I can never recall an industry-sponsored project ever winning that award. That's quite an accomplishment. Can I have the next slide? We don't talk very much about LYR-220, at least we haven't so far. If you look at the graph in the middle here, it's about four million patients who fail standard medical therapy. Of those, about 60% have never had surgery before, and that's 2.4 million. Those patients would be candidates for LYR-210. Now, patients who have had prior surgery, the other 40%, they can still fail. Almost all of them need ongoing medical therapy, but sometimes even a combination of surgery and ongoing medical therapy fails. That's about 1.6 million patients, or 40% of our target. Now, those patients, if you used LYR-210, it really wouldn't fit very well. After surgery, there's a large space created. The LYR-220 is really same drug, same dose, but it's a larger matrix to more readily conform to this new size. We can take a look at the next slide, please. This is the BEACON trial, which is slated to begin in November, next month. This is a phase II trial. The primary endpoint here is safety and feasibility at 24 weeks, although we will be tracking all the same endpoints that we are in the phase III for LYR-210. It's three arms, two slightly different matrix designs, and then a control. We're very optimistic that this data, we will be able to leverage the LYR-210 data with the LYR-220 data. We're optimistic that we can achieve an expedited approval for LYR-220. Can I have the next slide? Here's basically the study design here. Randomized trial, three arms, the sham and the two different designs for the product. At this point, I'd like to open it up to any questions. I'd be happy to answer either myself or one of the other KOLs on the call would be happy to address whatever questions you have. Okay, now we will go into the Q&A portion. If you are watching on the webcast and wanna submit a question, please refer to the Ask a Question tab. If you are dialed in, please press star one to raise your hand, and we will call on you to ask a question. The first question we will take is from Tim Lugo. Hey, this is Lachlan on for Tim. Thanks for taking the questions. I just wanted to dig in a bit more on the durability that we're seeing after removal of LYR-210. Should we expect that would be sort of maintained permanently? Would you expect those patients will at some point require another dose, or are we looking at potentially no longer needing surgery or anything more in the future? For Dr. Kern on the LYR-210 accelerated pathway, given the similarities with the LYR-220 pathway. Given the similarities with LYR-210, would you expect to be able to file based on strongly positive results of BEACON? Or would you still expect to need a phase III, but maybe only one instead of two? Well, I'll answer first. You know, we're obviously not sure, but we're optimistic that given the fact that it's the same drug, the same matrix, that we will be able to label that. You know, it's really just a different size of matrix. But we'll see. I mean, you offered two options there, basically three options there, that we'd have to do two trials, we'd get away with one phase III, or maybe zero. I think we're hoping for zero, but that will depend on many things that haven't happened yet. The other question I think you had was maybe, I mean, we could all give our opinion. Maybe Dr. Soler would wanna go first, if he wants. Sure, I mean, you asked if we anticipate that some patients would need more than one, meaning they would need an implant, say, every six months versus just one. I think the answer is, I think it's gonna depend on the patient and their underlying pathophysiology. You know, chronic sinusitis is not sort of one single disease. We know there's a group of patients who have sort of chronic inflammatory disease, and for those patients, I think a repetitive doses, whether it's every six months or whether they need it, you know, at some period of time, is probably gonna make sense. Where I think there's another group of patients where the data certainly suggests that it may be one sustained treatment gets them to the point where they're controlled such that they don't need any treatment or maybe they just need steroid nasal sprays moving forward. Randy, do you recall any comments from the patients in your study about, you know, when the trial was over, whether they would want another one or what? Or maybe, I mean, you have the real-world experience here, so what do you. Yeah. I had 13 of the 24 patients in the trial, so I got to kinda see how they did through it. You know, what I was impressed with was a lot of them did comment that they were starting to smell or sense things that, you know, I don't typically ask, and even the SNOT-22 doesn't ask for. It is a quality of life disease condition, as you pointed out. They would say things, I feel more open. They sense, you know, a sense of well-being in their head and their sinuses that I think those of us who aren't sufferers may have a hard time grasping. My relation with these patients is I relate to them when I get that viral URI. I feel miserable. I don't like the feeling. I can't wait till I get better. I see these patients as suffering that fluctuating over, you know, months at a time without relief. What I saw in these patients was that, yes, the smell seemed to change or improve. I think, you know, sometimes it wasn't totally pleasant smells. They could smell things that they couldn't smell before. I think as the steroids work on the mucosa high in the nasal cavity where we are afraid to operate because of complications, that the medical treatment kinda gets to that problem quite nicely. You know, small group of patients, but the overall, you know, response was positive. There were a couple patients who, you know, they knew it was a study, but they did say, you know, "Can I come back when this is available?" Because I think from my point of view and their perspective, seeing me or an ENT twice a year for this type of treatment, you know, was a huge positive experience over daily use of nose sprays, daily use of irrigations. We don't know what it's gonna supplant, but this is just early experience that's quite positive and, you know, new. I think that, you know, to try and answer that question more, you know, more globally, I think there's gonna be a range of responses. Some people with milder disease are gonna essentially be cured. They may have. Well, from what we can tell, about half of them will have a durable response. In other words, they'll stay cured. Other people with more severe disease will be improved. Even if it's durable, they're still not quite there. They're not happy. Those people will, you know, they'll want a little bit better. You put another one in, and they'll continue to improve. I think there's a range of responses. The important take-home point for me as a clinician is you don't have to worry about a rebound effect. In other words, when the matrix doesn't have any more drug in it's not like the patients are gonna boomerang back. Which is what you see with certainly the biologic products out there that are $38,000 a year. If you stop giving them, they lose everything. I think that's kinda what you would sort of expect with a steroid. Slow on, slow off. Do we have any other? Oh, wait, I got a question here. Can you please expand on why some patients have durability of response that others don't? Is polyps versus not polyps important? Is disease severity involved? Well, I sort of tried. I think disease severity will be involved because there are people who are better, but they still have symptoms. That's not uncommon. In other words, their SNOT-22, which is sort of a measure, isn't in the normal range. A normal person will have a SNOT-22 less than 10. You know, we started with, in the LANTERN trial, with the average of 68, and we improved to 20 at 48. They're much better, they're very happy, but they're not cured. So yes, disease severity is gonna matter. We don't know exactly why some people have durability and others don't. We did not see a difference between the polyps versus non-polyps, although, you know, we'll be able to weigh in more on that maybe after the phase III. We don't see a distinction there. I don't know. I think that addresses everything. Please, others chime in there if I don't wanna dominate the conversation here. I think you answered it well. It's a heterogeneous, yeah, population. It's impressive results. To me, it's too early to say how durable or long-term the treatment will be, given what we know about these patients. I think they'll need some ongoing treatment, but it was impressive to see lack of rebound and six months after removal, consistent symptom improvement. I believe those patients, Dr. Kern, remind me. I mean, they were on daily saline. They weren't maintenance-free at that point, but they were on pretty standard maintenance therapy that seemed to control their symptoms much better than they were pre-treatment. Yes. They all stayed with the nasal saline, or not all. I think it was, like, 70% or 80%, but it was extraordinarily high percentage. You know, that's also part of it. Okay, the next question will come from Bert Hazlett with BTIG. Bert, please ask your question. Yeah, thanks. I've got one or two. Thank you for doing this. Just with regard to the procedure itself, the implant and the procedure. Could you describe how long the procedure took, kinda soup to nuts, preparation to actually insertion? And then do you have any. You know, we have the data from LANTERN with regard to how the outcomes were with regard to the SNOT score and the 4 CS and 3 CS. Do you have any anecdotal evidence about the patients, how they, how well they tolerated the implant itself? Either polyp patients or non-polyp patients. Any feelings or sensations that were out of the ordinary? Randy, why don't you take the first one there? Okay. The question, f irst question was, you know, I guess practically speaking, how long does this procedure take? You know, run through it. First of all, in clinical research, there's so much data being captured. It's not, w e're not speeding through as we would in a day-to-day practice. I think your question probably leads more to how do I see this applying, assuming FDA approval, and it's out there for these patients. I would say I do all the sinus procedures that are, you know, on the market in office, and this is the simplest and I would say quite frankly, you know, the easiest. It would take 10 to 15 minutes to get this done in a patient that you had scheduled that you thought needed it. That's, you know, whether or not you needed prior authorization to have the product in your office. As far as doing the procedure, it's a very simple topical anesthetic in the middle meatus. I would do this. I did not use any needles or injections, and that implant that you saw, I mean, it actually was slow. It looked like it was in slow motion. It could be done, you know, in just a few seconds. Numb them up, decongest them, place it. This is, you know, a 10-minute office visit. I'll just chime in that, you know, with sort of the shift that's happened in ENT to office-based procedures, just the average person is very comfortable with this type of thing of having somebody come in, spraying their nose, putting some topical. You maybe go see one patient, you come back 10 minutes later, they're all numbed up, you put it in, out, and they leave. So when it comes to, you know, comparing this to in-office balloon surgery or, you know, the, you know, LATERA implants or whatever, this is, you know, pretty straightforward on the simple side, and I think would be something that pretty much all general ENTs would be comfortable doing. Yeah, I would agree. I mean, it's pretty straightforward and pretty easy. 15 minutes, 10 to 15 minutes is a typical office visit. It really would not slow down office management. I think the other question was more about tolerance from the LANTERN trial, and this was a question that I had at the very beginning when I became involved with LYRA. It wasn't even called LYRA back then, in 2015, 2016. How well tolerated this product would be for six weeks, and it's extraordinary. I'm sorry, six months. It's extraordinarily well tolerated, and the patients are unaware. Even in the control patients just thought they had the product. So there really wasn't, and they couldn't tell the difference. This product is very well tolerated, and there doesn't appear to be a difference in the polyp or the non-polyp patients. That isn't an issue. You know, patients are unaware that they have this thing in their nose. Well, thank you for that. I have one other question maybe for the company, but just with regard to 220, just kinda given the successful data that you have with 210, could you go in a little bit more about why what you're thinking about in terms of the matrix design differences, what you're trying to accomplish there. Is it really trying to maintain the implantation in the patients with the larger area you're trying to cover? Or is it something with the delivery or distribution of the active? Just a little more about the dual matrices that you have and with regard to 220 and how you're exploring those. Well, you know, there may really be no difference between the two products. The differences are relatively subtle. You know, placing the product in an unoperated patient is pretty straightforward. In an operated patient, every one of their sinus cavities is gonna be a little bit different, and this is an attempt to see which is easier to place, whether they have the same performance, and, you know, tolerance. There's a lot of unknowns with regard to that. Giving us two different devices that are a little bit different in the way they're structured, we may see some differences. My personal bias is that they're not gonna be much difference. We'll see. That's really the reason, the main reason to do it. Okay t errific. Thank you for that. You know, I might add one comment. I remember, you know, realizing I wasn't positive, but I had a sense that the first patient we had in the PK study was the first patient in the U.S. to be implanted. The engineer, obviously, the company was here. We got everything ready. We had the patient anesthetized. I put the delivery device in the middle meatus, and I slowly delivered it and, you know, very quickly it was in the correct place. You know, I remember turning to the engineer and smiling at her and saying, you know, "What a beautiful design." I mean, it was easy. You know, Dr. Soler and Dr. Kern are rhinologists. I am a General ENT, and what Dr. Soler said, this is something that all ENTs can do and probably will adopt. It conforms to that cavity in a way that I think you... When you see it's just intuitively perfect for the cavity. That's can be different with other, you know, experiences that you've probably heard. I have had patients who've had other products that have asked after you put in devices, say that, "You know, it's uncomfortable and, you know, even though I want to see the end result, kinda, I'd like you to remove it." That would. I don't ever see that happening with this product because of how, you know, how comfortably it fit. That's why my first fear was it's sitting in there so comfortably, is it gonna fall out when they irrigate or sneeze? You know, again, 26 of the implants that I implanted were there. I was, you know, expecting, this is a first trial, first design here. We're not gonna find some come out. I mean, some of the other products did, but this was there. When I found them there, I worried that some would be kind of overgrown or stuck in place. I've used some, you know, some malleable nitinol metal implants, and those are. They're very strong springs, and removing those from a patient after they've been in, you know, two months was extremely difficult for, you know, me as the surgeon and also the patient. You could tell it wasn't gonna move 'cause you had to wiggle it a little, and then it just slid out. I wish we had an explant, but, you know, it to me, it's doing what it's meant to do. To see the clinical data, the PK and the clinical improvement, you know, I'm really happy to be involved, and I look forward to seeing how this is gonna change the way we treat our patients. Okay. The next question we have comes from Chris Howerton from Jefferies. Chris, please ask your question. Great t hank you very much. I think Dr. Kern, I had a little bit of a webcast problem, but you read one of my first questions. The second and third question that I had, if you would indulge me, is, you know, how do you think about treating a patient on the severe end of CRS with either LYR-210 in the situation where it would be commercially available versus surgery? You know, what are the features or clinical presentation of that patient that would shift you one way or the other? And then I guess, you know, just from a very kinda like crass modeling perspective, can each of the physicians estimate what percentage of their CRS patients they would use LYR-210 on? Well, okay. Well, I'll go first. You know, I don't think severity in terms of. Yeah, I mean, how do you measure severity? Well, the most common way is SNOT-22. If their numbers, we've already treated 68, is very high. That's much higher than the biologic trials. They're, you know, at least 10 points lower and more in some cases. You know, we can reach into the far end of this. As long as we can insert it without a problem, there's nothing wrong with trying. Now, that doesn't mean it's gonna work in everybody, but it just means that severity would not dissuade me. You know, it's, I think the majority. To answer your second question, I think the majority of CRS patients would be a candidate. The vast majority would be a candidate for one of these two products. four million, that's the number that we presented, is a conservative number. The number could actually be larger. Just going with that, I think the majority of them would be candidates. The only patients that really would not be those patients with massive nasal polyps that you can't readily insert the. That's, you know, maybe of the four million, that's maybe 100,000. The rest of them, you know, it's obviously a discussion between the doctor and the patient, et cetera, et cetera, et cetera. I think that it's conceivable that all of them would be candidates. Then there's an unknown number which I alluded to that maybe we're not capturing with the analysis, the one that comes up with four million. I don't know. Please, again, the others, KOLs should chime in. Sure, I'll just chime in. You know, I think sometimes people think about, you know, like, let's say you have somebody with cancer or something. You know, you basically say, "Look, this is what you need to do. You need surgery followed by chemotherapy or whatever." The vast majority of chronic sinusitis is a quality of life issue. It's not life-threatening. You don't technically have to do anything. So really, patients have options. You know, when you talk about someone who's failed medical management, who is potentially at a point where they might be a candidate for surgery or something, that's where you get to the point where you say, "Look, you know, we've tried the basic stuff. You were on some antibiotics and some steroid sprays, and you maybe did an oral steroid course, and that's not working." You say, "All right, you know, we can, we can put an implant in, like 210. We could do surgery, et cetera." You lay those options out to people, and through shared decision-making, people come to the option that fits them. You'd be surprised, you know, there are certain patients who are so against surgery, they almost live their life miserably. Then there's other patients who, you know, they're like, "I wanna do surgery tomorrow." You know, I think LYRA- 210 is gonna fit. It's gonna be one of these tools in your toolbox, and I think it's gonna appeal to a lot of patients because, one, the results are positive, are really significant. It's so easy to do in the office, and it's a six-month thing. I think it's positioned right there at that point where I'm about to have that surgery discussion, and I say, "Hey, you know, you're a candidate for surgery. There's one other thing that you could think about. It's this implant." I think there's gonna be a lot of patients who that makes a lot of sense to. You know, it isn't like I'm gonna tell them exactly what to do. I'm gonna present this to them, and then, you know, based on their life and circumstance and their goals, et cetera, they're gonna choose one pathway or the other. I agree with everything that's been said. I guess the one caveat that I see in my practice is, you know, if patients who are presented with that surgical option, what do you have to lose by trying LYR-210? You don't have much at all. The one thing I think that would probably sway my guiding a patient is, of the four cardinal symptoms that they come in complaining of, obstruction is probably the one that drives most of their desire for treatment. If they had a severely deviated septum or very large turbinates, I think I know that surgery would help that, and I might be inclined, you know, if they're really someone who's struggling with obstruction, unilateral, you see the structural problem. I don't feel that LYR-210 would address that. I would probably lean towards, you know, saying we can get the obstruction with surgery. The question then is, you know, do we just straighten out the septum and, you know, not do sinus procedures, or do you kinda get them through that surgery, including a sinus procedure at the same time? Is, you know, what I see. I think it's gonna be a great offer or option for us to discuss with patients, you know, if all the trials are successful. Well, I really appreciate the answers, and thanks for hosting this event and taking my questions. Okay. The next question comes from Ashwani Verma from Bank of America. Please ask your question. Thanks for taking our question. I just had a quick one. Just trying to understand from a retention standpoint 220. We know that when surgery is done, the nasal cavity is enlarged. You are using a bigger matrix size here for 220. Just like does that fit on the contours of the enlarged nasal cavity? Or how can we be sure that the retention would not be an issue similar to 210? Well, let me answer or take that first. I mean, the nose, the nasal cavity is not enlarged, the sinus cavity is enlarged. The middle meatus will still be there. So there's a space, and we're putting the product in that enlarged space. When it hasn't been operated, it's just a slit. When you take the ethmoid sinuses out, there's a larger space. It would be basically the way to look at it if you think of an egg crate, when you do surgery, you take out the partitions between the eggs. So if you were to put one egg in there, it might flop out, but if you put something large in there, it would fit more snugly and be retained. It would touch all the surface area so that it can deliver the drug. I mean, this is where the competitor device, SINUVA, what they do, they put it in a cavity and it's a fairly large device. Our device will be much more how should I say? Space-friendly and but it's a similar idea. You need a larger product to fill the space. The other KOLs could please feel free to weigh in. Yeah. No, I mean, my understanding is the two different designs have you know slightly different. They're sort of more spacing you know between the edges. One has a bit more surface area to contact the edges, one has a bit less. You know, it's not 100% clear which one if there's a difference in retention between one versus the other. But I think to me, I don't think it's gonna be a major issue. I think there are some patients who structurally have had such severe surgery. They've had so much middle turbinate resections, et cetera, where it's not gonna be an option. But for most people, most surgeons do a relatively conservative surgery the first time. For the most part, the middle turbinates are intact, et cetera. I think at least, you know, for my patient population, I think the large majority would be still candidates for something like LYR-220. I'm gonna mention one thing that I thought about when I was implanting these patients. I see my wife and women in the family wear clothing that they seem to love. I don't own Lululemon, but they seem to love to buy Lululemon, and they say it feels great. I think, "Oh, that costs a lot." They say, "No, it feels great." Last Christmas, I get my first Lululemon. I put it on and I'm like, "This feels great." It feels comfortable, it feels snug, it's not tight. I love the way that feels, and I don't know how to explain it, but that's when you see the implant go into the LYR-210. I only have experience with LYR-210, that's what happens in the middle meatus. You could tell that it's touching comfortably, gently, not too much. I mean, they didn't dislodge at 1 out of 46, and not too hard. I was able to remove it, so it's a comfortable fit. My understanding of this XTReo, you know, this, you know, the engineering behind the polymer is that it self-expands to fit spaces. Expanding, what it does is it expands. I think for those of us who have used other products, they disintegrate fairly quickly, and there's no expansion to them. They either stay, or they fall out, or they fragment. This, you know, it was completely intact at two months in the study I was at. It's meant to go six, but overseas it was removed at six months. I could not tell that there was a change in the integrity of the device. I mean, it almost looked like I had just placed it. It was snug. I did have to tug it a little, but I'm sure that the design of the 220 is meant to be something that will stay in place comfortably for six months and deliver drug to that operated sinus for six months. Maybe I misunderstood the question whether it was if you wanted us to try to differentiate the two implants. I think that for the 220, I think that again, my bias is that they're not gonna be much difference, but one may be a bit a little easier to insert, it may conform to the spaces more readily, it may be better tolerated. There may be a, you know, it gives us essentially two bites at the apple, but they're very similar. The drug dose is similar. The weave pattern is a little more dense in one versus the other. So, you know, it's really how should I say? To give us a little broader experience that there might be some distinction that may make us like one versus the other. I think that the efficacy results will, again, I'm not a betting person, but I think they're likely gonna be very different, very similar. Got it. Thank you. Okay. That concludes our audio questions. I will hand it over to Maria for any of the webcast questions. Thank you, Macy. Yeah so w e do have a question here. I'll start with this one right here. We have a few minutes left. There are many treatments for polyp patients. Can you comment on how you manage the non-polyp patients, the nature of the unmet need in these patients, and how LYR-210 can address the non-polyp? Yeah. I mean, I'll start real quick. I mean, non-polyp group has been the one that's been ignored. I think the reason is it's a bit, you know, polyps are. They're easier to identify. The CRS group without is a little more heterogeneous, but the reality is that, you know, most of the treatments for polyps were basically co-opted from something else, right? They weren't designed for polyps. They were just designed for something else, and people realized that they might work for polyps. It's been a group that's been ignored, but it's by a much larger group than the polyps. I mean, people estimate, you know, you can argue about these numbers. 10%-15% of the U.S. population has chronic sinusitis, but only 1%-3% has nasal polyps, so it's a much larger group. In my mind, this is what's exciting about it is that we actually have a product or potentially will have a product for this patient population. You know, I mean, it is the real unmet need, completely unmet need is for the non-polyp group. It's larger, and there are no FDA-approved drugs for it. We still give a lot of antibiotics for this problem. They don't work well. They have side effects. This is where the game could potentially really be affected, the CRS paradigm. You know, the link of sinusitis even if, even in the non-polypoid one that's kind of heterogeneous as Dr. Soler alluded to, it's all inflammation. That's the common pathway. Steroids are the best, most effective, broadest anti-inflammatory agent, safest anti-inflammatory agent we have out there. Delivering them locally makes perfect sense. I guess I just reiterate. There are no, you know, for all the patients that come in with chronic sinusitis without polyps, there are no FDA-approved treatments. Everything we do is off-label, is well-studied, widely studied, but there is nothing out there. You know, doing lots of research like my co-presenters, I mean, there is a lot of research being done. A lot of companies looking for that indication. There's a lot of sufferers, and we need things studied, indicated, and out there for us to use. Thank you, Randy. There's one other question here. We have a couple minutes, so why don't we take this one too? How does the efficacy data from the PK study which shows the benefit in patients with more mild disease, what does that mean in terms of positioning the product? Can you see LYR-210 moving even earlier in the treatment paradigm? Okay. I guess the first thing I would say is I realize that is a small group of patients, 24 patients. But the responses were remarkable. It was a group that had less disease, but this PK study wasn't designed to, you know, look at an effect on a severely diseased patient. It was to look at the, you know, serum levels, are they safe? Which they are. You know, it does show a broader, you know, effect that does hint or clue in that this product could be used potentially in patients with lesser amounts of disease. I think there are so many factors that will come into play. You know, what's the cost of the product? Again, a 10, 15 minute procedure that's cost-effective twice a month in the office, I think could move way up in the treatment paradigm of these patients. It's like, you know, you think of what else we use off-label. You know, once every six months, come into our office and have a quite simple procedure done, easier than going to the dentist. I think, you know, it needs a lot more study, though. I mean, this was a small group of patients. I mean, I think of it less about where it is, where it fits in the paradigm and which patients will then choose that. I mean, there are definitely a group of patients who have disease but, you know, at this point in time with, you know, your options if you fail basic medical treatment is surgery or nothing or just continuing what you're doing. There is a group of patients who, what you said, they're not they're not bothered enough, or they're not bothered severely enough that, you know, a $15,000 surgery and the recovery and all that sort of stuff makes sense to them, where something like this definitely would. I think there is a group of patients who aren't being treated. I mean, for example, when we hang up here, I have to call somebody who very much has had disease for a year, but she's had a bad experience with another surgery, not for sinuses, but for something else, and she can't bring herself to do it. She has no other options. This would be an option for somebody like that. Yeah. I mean, I agree. I mean, the point, the take-home from that PK study clinically is that we can treat the full range of the problem. In other words, even when people have lesser degree of disease, we're still seeing a measurable, substantial response. If really this is a way of asking, could we see the product being quote-unquote first-line therapy? Now first-line therapy is nasal steroid sprays, even though they're off-label, and saltwater rinses. Could this position ahead of that? You know, if costs were not an issue, and if I wore my patient hat, and I do have sinusitis, as a matter of fact, I would prefer the product rather than using nasal sprays or saltwater rinses, you know, once or twice a day. And I see my dentist every six months, so why wouldn't I do that? But, you know, that's not really we're not at that point of having that discussion. Right now, we're trying to establish, in a phase III, how effective this product is. I think we have every reason to be extremely enthusiastic about our prospects. I mean, you actually bring up something that we haven't really talked much about, which is patients who are controlled on a certain regimen, whether it's a steroid rinse or a nasal spray on a regular basis, but either don't like doing it, can't be compliant or whatever, and would potentially prefer to switch to something like this every six months. I mean, we haven't even talked about that, but I just know from experience that is a group of patients that I have that something like this would be because it's a quick, easy one-time thing, and I need to see those people every six months anyway, that it would make sense rather than them, you know, not ever using their medications and then becoming uncontrolled repetitively. Yeah, nasal sprays, and I'm sure many on the call have used them. They're unpleasant. They cause bleeding sometimes. You have to remember to use them. There's a lot of negatives. You know, that's maybe beyond where we're really focused right now. Well, it is beyond where we're focused right now. It's an interesting discussion. Great, t hank you, Robert. It's a little after three, and I do wanna make one comment about LYR-220. There were some questions around the two designs and how they may work. You know, as a company, we're really careful to not make too many assumptions around you know which design will work in the patients. I think we have to put them in the physician's hands, and we have to see. Our objective here is to make sure that with LYR-220, we don't make assumptions, that we have two what we think are really good options. Perhaps they both will be shown to be effective. I think that'll be great. But there may be one that physicians like more. It really speaks to the versatility of our platform that, you know, we can make it more open cell or more closed cell. I think we're really excited to see in the BEACON study how each design will perform, and then we'll move forward with the one that we get the best feedback from. I know we've gone a little over. I want to thank Dr. Ow. I want to thank Dr. Soler and Dr. Kern. This has been a great discussion. We're looking forward to your involvement also in the ENLIGHTEN pivotal program and continue to help us as we continue to develop products in the CRS space. I'd like to thank the audience for participating, and please enjoy the rest of your afternoon. Thank you. Bye-bye.