Good morning. Welcome to Lyra Therapeutics conference call and webcast to discuss top-line results for the BEACON Phase II trial of LYR-220 in chronic rhinosinusitis. My name is Michelle from Notified Conference Call Service, and I will be your operator today. This webcast is being recorded. The webcast will be available on the Lyra website for one month from today's date. Currently, all participants are in a listen-only mode. Earlier this morning, Lyra announced results from the BEACON Phase II trial in a press release. The press release is available on the Investor Relations page of the company's website at www.lyratherapeutics.com. On this conference call today, members of Lyra management will make prepared remarks about the BEACON Phase II trial results with the accompanying slide presentation in the webcast. Today's speakers from Lyra Therapeutics will be Dr. Harlan Waksal, Executive Chairman, Dr. Maria Palasis, President and CEO, and Dr. Richard Nieman, Chief Medical Officer. Following management's prepared remarks, we will open the call for a Q&A session. To ask a question at that time, please press star one one on your phone. During the course of this conference call, we expect to make forward-looking statements, including statements related to the clinical development of the company's product candidates, business strategy, and plan, commercial plans for its candidates. These forward-looking statements are based on the company's current expectations and inherent, inherently involve risk and uncertainties. Lyra's actual results and the timing of event could differ materially from those anticipated in such forward-looking statements. As a result of these risks and uncertainties, factors that would cause results to be different from these statements include factors that the company describes in the section titled Risk Factors in the company's current report on Form 10-Q for the second quarter of 2023. I will now turn the call over to Dr. Harlan Waksal. Please go ahead. Thank you. Good morning. Lyra is engaged in several clinical studies for our 2 product candidates in chronic rhinosinusitis, or CRS, as shown in slide 3. We have LYR-210 for pre-surgical patients and LYR-220 for patients who have undergone prior ethmoid surgery. LYR-210 is currently being studied in 2 pivotal phase 3 studies that we expect will support potential U.S. approval in pre-surgical CRS patients. Today, we are excited to review the positive top-line results from a phase II BEACON trial, the first clinical readout of LYR-220. With me today is the CEO and President of Lyra, Dr. Maria Palasis, and Dr. Richard Nieman, Lyra's Chief Medical Officer. I will now turn the call over to Maria. Maria? Thank you, Harlan, and good morning. We're pleased to share the positive top-line results from the phase II BEACON trial today. LYR-220 is our product candidate for patients who continue to experience CRS symptoms despite having had previous ethmoid sinus surgery. As you can see on slide 4 and in the figure, LYR-220 is an enlarged version of LYR-210 and is designed to accommodate the larger post-surgical anatomy. Both 210 and 220 are formulated to deliver 7,500 micrograms of mometasone furoate, a well-known anti-inflammatory steroid, over 24 weeks. LYR-210 is currently being studied in our pivotal phase 3 ENLIGHTEN program. ENLIGHTEN 1 has completed enrollment, and ENLIGHTEN 2 is actively enrolling. Data for ENLIGHTEN 1 are expected in the first half of 2024. Today is the first time that we're presenting clinical data on LYR-220, an important component of our product portfolio, built upon our proprietary drug- device platform. Our novel technology is an engineered elastomeric matrix, which dynamically conforms to the anatomy of the sinonasal passages and is formulated to provide long-acting, localized drug treatment. In other words, our technology is designed to deliver therapeutics to the right place for the right amount of time. In CRS, nasal steroids are the foundational treatment. However, difficulties arise with safely and effectively targeting the site of disease. Our technology is designed to overcome this delivery problem by targeting therapeutic levels of highly potent steroids directly to the disease tissue, consistently over 24 weeks in a straightforward ENT office procedure. Please go to slide 5. Let me remind you that CRS is a silent epidemic affecting millions of people with no drug approved for the vast majority of patients. It is a chronic inflammatory disease that is not widely recognized despite the millions of people who suffer from debilitating CRS symptoms. 8 million CRS patients in the U.S. seek medical management each year. Roughly half, or 4 million patients, do not receive satisfactory relief from standard medical management. Currently, of the 4 million adult patients, 1.4 million seek the care of an ENT specialist each year for persistent symptoms. While surgery is an option for these patients, it does not directly treat the inflammation. The goal of surgery is to open the airways and allow better access of steroid sprays into the nasal passage. Patients continue to require anti-inflammatory treatment to manage their underlying disease post-surgery. 40% of the patients that an ENT sees have had a previous surgery and continue to have problems managing their CRS symptoms. We hope to provide a new potential treatment for this significant proportion of the CRS population with LYR-220. We're delighted to share the compelling results from the LYR-220 BEACON study. I'm now going to turn the call over to Dr. Richard Nieman, who will share the results with you. Richard? Thank you, Maria. We're very excited to share the top-line results from the LYR-220 BEACON Phase 2 study, which is a multicenter, randomized, blinded, sham-controlled proof of concept study in patients that continue to experience CRS symptoms despite having had previous ethmoid sinus surgery. On slide 6, you'll see that the design was a 28-week study, with 24 weeks on treatment and a 4-week post-treatment follow-up. 42 eligible patients were randomized, with half receiving LYR-220 bilaterally and half undergoing an identical blinded sham procedure. The vast majority of these patients were recruited in the U.S. The primary safety endpoint of the study was the incidence of treatment-related serious adverse events. The study was also designed to evaluate the effects of LYR-220 on key secondary endpoints, including the composite score of the three cardinal symptoms, CRS, and the widely used SNOT-22 total score. The three cardinal symptoms, or 3CS, are nasal blockage, facial pain or pressure, and nasal discharge. The SNOT-22 is a CRS-specific, clinically validated instrument that assesses the symptoms and impact on patients' quality of life. It ranges from 0 to 110. Slide 7 shows some of the key demographic and baseline characteristics of the patients who were enrolled in the BEACON study. Of the 42 patients enrolled, 21 were randomized to the LYR-220 treatment group, and 21 were randomized to the sham treatment group. Patients' average age was 51 years, and approximately 60% of the patients were female. The majority were White, and 3 patients were African American. Importantly, patients had moderate to severe CRS symptoms at baseline, as evidenced by the average baseline SNOT-22 score of 53. This is very representative of CRS patients in the U.S. seeking further treatment. The average baseline 3CS score was 6.6 on a 0-9 scale. Turning to slide 8, this slide shows the results of the 3CS composite score at two key time points, weeks 4 and week 24. At week 4, there was a reduction of 1.81 points in the LYR-220 group, compared to a reduction of 0.94 in the sham group, an improvement of 0.87 points over sham. This difference was statistically significant, with a P value of 0.37. At week 24, in the treatment, there was a reduction of 1.76 points in the LYR-220 group, while the sham group showed a reduction of 0.26 points. This represents a statistically significant difference of 1.50 points between the two groups, with a P value of 0.02. As shown in slide 9, we also observed statistically significant improvements in each of the 3 cardinal symptoms, comprising the composite 3CS score at week 24. Each individual symptom was scored on a 0 to 3 scale. As you can see, improvements in the composite score are made up from equal contributions of the individual scores. On slide 10, the results of SNOT-22 are also shown at weeks 4 and 24. At week 4, there was a reduction of 16.9 points in the LYR-220 group, compared to a reduction of 4.2 in the sham group, an improvement of 12.7 points over the sham. This difference was statistically significant, with a P value of 0.012. At week 24, the end of treatment, there was a reduction of 16.3 points in the LYR-220 group, while the sham group had a deterioration of 0.5 points. This represents a statistically significant difference of 16.8 points between the two groups, with a P value of 0.007.... This improvement in SNOT-22 relative to sham is almost twice the minimally clinically important difference of 8.9 points. On slide 11, the change from baseline in SNOT-22 for the two treatment groups is shown during the course of the 24-week treatment phase. LYR-220 shown in green, while the sham in gray. As you can see, there was early improvement in LYR-220 relative to the sham group, which is sustained throughout the course of 6 months. Statistically significant and clinically relevant improvements in SNOT-22 in the LYR-220 group was evident as early as week 2 and at all the time points through to week 24. So if we turn to the final slide 12 and the conclusions from the BEACON study. Importantly, there were no serious adverse events reported in the study, and the most commonly reported adverse events included sinusitis, nasopharyngitis, bronchitis, and COVID-19. Despite this being a relatively small phase 2 study, statistically significant and clinically relevant improvements in the key efficacy endpoints were demonstrated. For both 3CS and SNOT-22, there was early statistically significant improvements, which was sustained out of the 24-week end of treatment time point. At 24 weeks, there was a 1.5 statistically improvement in 3CS and a statistically significant improvement in SNOT-22 relative to sham. Taken together, we are really thrilled to demonstrate this early and durable efficacy in this proof of concept study. We believe these results demonstrate not only efficacy and safety of LYR-220 in the BEACON study, but also validate Lyra's technology with the same dosage of mometasone furoate being used in our LYR-210 ENLIGHTEN program. And now I'd like to turn the call back over to Maria for her concluding remarks. Maria? Thank you, Richard. We are really excited about these results as they support the robustness of our drug device technology platform to treat the full spectrum of CRS patients. These results provide additional confidence in the ongoing ENLIGHTEN pivotal Phase 3 program of LYR-210 in presurgical CRS patients. We look forward to sharing the ENLIGHTEN 1 top-line data with you in the first half of 2024 and presenting these top-line results from the BEACON study at the American Rhinologic Society annual meeting later this month. We will now open it up for Q&A. Operator? As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. The first question comes from Louise Chen with Cantor. Your line is open. Hi, congratulations on the really strong data, and thank you for taking my questions here. So I wanted to ask you if there was any read-through from the BEACON study to your ENLIGHTEN trial results, which are coming up in the first quarter or first half of 2024. And then I wanted to ask you if you could please give an update, post your end of phase two meeting with the FDA. Is that something that you're gonna, you know, get, provide a press release or host a call on? And then lastly, are you gonna plan on marketing these products if approved, LYR-210 and LYR-220, on your own, or may you seek a commercial partner for it? Thank you. Thank you, Louise. I will start off, and I'll have Richard also add his commentary. Let's start first with read-through on the ENLIGHTEN trial. We are, you know, we're very pleased with the results that we see here. These results give us a lot of confidence in our platform. Let me first mention that in our LANTERN study, the changes that we saw in our both SNOT-22 at 24 weeks and our cardinal symptoms at 24 weeks are very consistent with what we see in BEACON. We saw a change of 16.8 points, as Richard mentioned, in SNOT-22 and in LANTERN, we saw 19 points in the SNOT-22, and then in the cardinal symptom, three cardinal symptom composite score, we saw a change of 1.5 and a 1.6 in LANTERN. So absolutely, these results give us a lot of confidence in our ENLIGHTEN program, that we'll be reading out in later 2024. Just quickly, post the FDA question. When we get all the results from the BEACON study, we will be having an End of Phase 2 meeting with the FDA and getting aligned with the FDA in terms of next steps for a pivotal program. I wanna mention that the way that LYR-220 was designed, with the same dose of drug and very similar release kinetics to LYR-210, it allows us to leverage the data from LYR-210. So that's our strategy here. We intend to leverage the safety from the ENLIGHTEN program. That'll be a supplemental NDA for LYR-220. After we have the meeting with the FDA and have clarity, we will update you on that. And then finally, your third question on whether we're going to market this drug. Yes, we believe that this is a very focused patient population. They're seen by an ENT specialist. It's a concentrated group of physicians, and our plan is to commercialize and market this on our own. And I'm gonna turn it over to Richard to add some commentary, too. Thanks, Maria. So, just very briefly, and Louise, thanks so much for your question. Just in terms of the read-through, you know, I think we really think that this now de-risks even further our ENLIGHTEN program. As Maria said, same dosage of mometasone furoate in both programs. Although this, in the BEACON study, is a post-surgical group, and ENLIGHTEN is a pre-surgical group, there's serious overlap in those conditions. So you know, both sets of patients have CRS. We're using a similar device with the same amount of mometasone. So I think we really have been able to de-risk this further. The other thing I think is really important is that, you know, from an executional excellence perspective, I think we've been able to recruit this study, getting quality data, in a really very timely manner. I think that really bodes well as we report out our first ENLIGHTEN study, which we've completed enrollment in at the beginning of 2024. Great. Thank you. Please stand by for the next question. The next question comes from Tim Lugo with William Blair. Your line is open. Thank you for taking the question, and congratulations on the impressive data. I was kind of struck between the durability of response between week 4 and week 24. Are you following patients beyond week 24? It seems like potentially maybe the response could be more durable at a later time point as well. Are these patients being, you know, continuing to be followed or maybe rolled into some sort of a something where you can capture that data? Thank you, Tim. Good morning. We have seen... You're, you're correct. We're seeing very durable responses here, starting as early as 2 weeks in this SNOT- 22. So our response is rapid, and it's very durable through the 24 weeks. In this study, we're gonna be going out to 28 weeks, and we'll be reporting that out in the when we report out the full data set. I also wanna mention that we have looked at durability in our LANTERN study. If you recall, after removal, we studied those patients for an additional 24 weeks, and in half those patients, we saw that they did not worsen over those 24 weeks. So in BEACON, we'll get some data for a month after removal. Then in addition to that, I wanna remind you, in our ENLIGHTEN program, we have an extension study where we're gonna be studying the durability after treatment out to 52 weeks. Understood. Thank you. You know, it seems like placebo response was managed particularly well in BEACON. Can you talk how is there a significant overlap between sites, between BEACON and ENLIGHTEN, or, you know, maybe how you know how you looked at placebo responses in this study versus LANTERN? Yeah, I will have Richard address that question. Thanks. Tim, thanks for the question. Yes, we're very satisfied with the placebo response for the sham that we saw in the BEACON study. The BEACON study was conducted almost exclusively in the U.S., and we think that the quality elements in the study that we put in place were really put to good effect in this particular study. Patients in the U.S., I think, are well used to coming up to see their physicians, and we managed that, I think, extremely well with support at the sites. In terms of the overlap, as you recall, the LANTERN study was predominantly conducted in Europe with slightly different standards of care, and we saw a slightly different sham control response in that study. But we believe that the sham control response that we're seeing in BEACON is really something that we expect to see moving forward. There is some overlap in the sites between BEACON and ENLIGHTEN, so we're really very happy that we'll be seeing similar results, or we expect to see similar results in ENLIGHTEN. Fantastic, and congratulations on the data. Thank you. Thank you. Please stand by for the next question. The next question comes from Jason Gerberry with Bank of America. Your line is open. Hey, guys. Thanks for taking my question, and congrats on the data. So couple for me, maybe first, commercially, how you'd see LYR-210 and LYR-220 coexisting in the marketplace. You know, would you see one potentially getting, you know, greater utilization, knowing what you know now about the evolving clinical profiles of the two? Can you comment at all, secondly, about implants? Were there any issues reported in the trial for any patients in terms of implants coming out, or was that pretty consistent that there were no issues there? And then lastly, realize we're talking about kind of small numbers here in the trial, but it looks like there was a greater proportion of female subjects in the LYR-220 treatment arm. Got me wondering, like... You know, we've seen in some other symptomatic diseases with PRO endpoints like depression, you know, females tend to be better subjects to re-recruit in clinical trials. So do you think that had any impact either on the trial or could be a factor in future trial enrollment? So those are my questions. Thanks. Thanks, Jason. I'm going to hand it over to Richard. Commercially, this is when a patient goes to see a specialist for their symptoms. They will either be surgically naïve, have not had ethmoid sinus surgery, or they have had previous surgery. And so the difference is really anatomical. 60% of the patients that they see, according to our research, are surgically naïve. LYR-210 will be used in those patients. For patients who have had a prior surgery, that represents about 40% of the patients at an ENTC. They will be using LYR-220. So essentially, we'll be providing with these two product candidates a therapy for the full spectrum of patients at an ENTC. Now, in terms of what we see great utilization, I think it's important to note that those patients who had surgery are very motivated, and they're making a repeat surgery. So as people being that, they're going to be very, very motivated to be looking for alternatives rather than an additional surgery. With respect to implant dislodgement, that's something that we don't see as an issue in this study. In fact, our rate of bilateral dislodgement is zero. So then let me just have Richard add some more color on that and the next question. Thanks. Good morning, Jason. Thanks very much for the questions. So as Maria has just started to say, we had 0 bilateral dislodgements in the BEACON study, which we're very excited to see. So there was really very good handling of the device. In terms of your question about demographics, it's a very good question. We look at the graphics, which shows you know, differences between the two treatment groups. But we think overall, there was no significant or many meaningful differences between the two treatment groups. You know, as you intimate, you know, female patients are often more likely to get into clinical trials, particularly in the U.S. But we don't believe that any of the results are affected by any of the demographic characteristics, and we've looked at that. So we feel pretty comfortable with the demography and with the patient group that we've enrolled. And we again think, with our overlap with sites into the ENLIGHTEN program, that we'll be recruiting a very similar and appropriate patient group in that particular study. So I hope that answers your questions. Yep. Thank you. As a reminder, to ask a question, please press Star one one on your telephone. Please stand by for the next question. The next question comes from Justin Zelin with BTIG. Your line is open. Hi, good morning, and congrats on this really nice data set. Very impressive, considering it's a small patient population here in the study. I just had a quick question on the safety side of things. I know you said there was no serious adverse events observed, but could you comment? Was there any imbalance in the other adverse events, sinusitis, nasopharyngitis, bronchitis, et cetera? And if you could comment just what grade those were, that'd be helpful. Thank you. Thank you, Justin. Richard will address your question. Thanks for the question, Justin. As you say, no serious adverse experiences, adverse events in the study, which was the primary safety endpoint. We did see, you know, adverse experiences that we would counter, that we would call nuisance, adverse events, across the two treatment groups. Incidences of sinusitis, bronchitis, COVID-19. Numerically, there were some differences between the two treatment groups, but looking across that, nothing again, that we would think was, was relevant. Particularly no concerns of any sorts of, of, of signal. We didn't see any cataracts, anything like that. So very exciting to see that result. You know, looking across, we believe that the safety profile is very consistent with a very known, you know, mechanism of mometasone furoate, and nothing that we were concerned about in regards to the study adverse experience. Great, thanks. And maybe just on the efficacy side of things, obviously they're quite statistically significant. Maybe if you could just put into context how you view this from a clinically significant bar. You know, I think, you know, this might have been twice what was deemed clinically significant. That would be helpful. Thanks so much. Yeah. So, no, thanks again for that question. So again, particularly pleased with the results that we've seen. As we know, the SNOT-22 is an extremely well-characterized and well-studied efficacy outcome with a well-known, minimally clinically important difference, the difference that patients can perceive. And in our results at the 24 weeks, we saw almost twice that minimally clinically important difference, which is really, really very exciting. And in fact, you know, puts us very much in very similar territory to some of the biologics and what they've shown in slightly different treatment groups, but very similar to that, to those effects on SNOT-22, which is really very exciting.... Moreover, the SNOT-22 improvements were statistically significant and clinically relevant as early as week two, which really is exciting because patients will be able to experience an improvement in their symptoms really very early on in the course of treatment. So this, this combination, very early clinically relevant improvement, which increases, and then is sustained right through the course of the study, I think is really very impressive, both from the statistical perspective, but to your point, very much from the clinically important perspective. And then finally, just very briefly, our improvements in the three cardinal symptoms, where at the end of treatment, we had a 1.5 difference in the symptom score. You know, again, very clinically relevant. So very, very happy to see this combination of statistical significance and clinical relevance, which, as I say, I think puts us well into the territory of what biologics see for efficacy, but with the safety profile that we think is really very, very benign. So a very exciting set of results. Great. And maybe last question for me, and I'll jump back in the queue. Just, just viewing the results here from BEACON, how do you view these results in light of LANTERN and, and, 210? Do you, do you view the efficacy results to be fairly similar as, as showing the, the effect of the drugs, or do you see any differences in the data that you've noted? In terms of the two studies, obviously slightly different populations. I think really we're very excited to see now that we have two phase 2 studies that are very strongly positive, and so we're very excited to see that. You know, we've run four studies now with our program, and I think consistently we see across the program this balance of a very safe product with no, you know, significant adverse events coupled with the efficacy that I think now in the BEACON study, really from across the 3CS and the SNOT-22, we see these very early improvements that are sustained right through the treatment phase. You know, similar to LANTERN, slightly different population. But again, I think this really builds on the confidence that we have to abandon and move very far now as we move forward to get the ENLIGHTEN data at the beginning of next year. Justin, I, I just want to add to what Richard said. I totally agree with everything that he mentioned. I think the thing that impressed me the most when I looked at these BEACON results was just the consistency in the change that we saw in both the SNOT-22 and in the three cardinal symptoms. In the SNOT-22, the change of 16.8 was so similar to the 19-point change that we saw in LANTERN over control. And then the three cardinal symptoms, the 1.5 change we saw in BEACON at 24 weeks nearly identical to that 1.6 change that we saw in this LANTERN. And the other thing I want to note that in BEACON, it wasn't one of the cardinal symptoms that was driving the response, it was all three, as Richard shared with you. Each one showed a statistically significant improvement at 24 weeks. So we were really thrilled to see this and to see the consistency, and this is why we feel very confident about our ENLIGHTEN program. Great. Thanks for taking my questions, and congrats once again. Thanks. Thanks, Justin. Please stand by for the next question. The next question comes from Dennis Ding with Jefferies. Your line is open. Hi, good morning. Thanks for the question. Maria, you mentioned, you know, the consistency of effect on SNOT-22 and 3CS being, you know, generally consistent between the two Phase 2s. Should we be expecting a similar magnitude of change in the upcoming phase 3? And, you know, what are some of the pushes and pulls on that efficacy number? Specifically, you know, what baseline characteristics do you see moving that delta smaller versus bigger? And, can you also, lastly, remind us of your powering assumptions as well? Thank you. Thank you, Dennis. So I will, I'll have Richard first address this, and I can comment as we go. Yeah. Thanks for the question, Dennis. I mean, I think without getting into the specifics of demographics across, you know, the different programs, I think the real benefit of these results is this de-risking of the program through to phase three. You know, that the ENLIGHTEN program of LYR-210 is conducted across Europe and the U.S., with a lot of overlap of sites that we have in the BEACON study in the U.S. So we do expect similar levels of care between the two programs. We, you know, we think that the demographics that we recruited in BEACON really represents the entire population, and the expectation that the demographics in my program will similarly represent the population that will take us to benefit. You know, we obviously will have to wait for the results of the ENLIGHTEN program, but we certainly think that now this validates our treatment paradigm and the executional excellence of running these studies, you know, in Europe and the U.S. I don't know, Maria, if you want to add anything to- Yeah, there is one thing I definitely want to add here, and that is, you know, we saw a baseline SNOT on average of about 53. It's very consistent with other large CRS studies in this space. So as Richard said, these are patients that are impacted, they're moderate to severe, and very consistent with other large studies. So we believe this bodes well for our U.S. ENLIGHTEN program that is mostly enrolling patients in the U.S. and some in the EU. Thank you. I show no further questions at this time. I would now like to turn the call back to Dr. Maria Palasis for closing remarks. Thank you, Michelle. I want to thank everyone again for joining the call this morning. We look forward to sharing our next data readout in the first half of 2024 from our ENLIGHTEN-1 pivotal program. Thank you very much. This concludes today's conference call. Thank you for participating. You may now disconnect.