Welcome to Verona Pharma's conference call. At this time, all participants are in a listen-only mode. Earlier this morning, Verona Pharma issued a press release announcing top-line results from its phase III ENHANCE-1 trial evaluating nebulized ensifentrine for the maintenance treatment of COPD. A copy can be found in the investor relations tab on the corporate website, www.veronapharma.com. Before we begin, I'd like to mention. Excuse me, I'd like to remind you that during today's call, statements about the company's future expectations, plans, and prospects are forward-looking statements. These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees and involve known and unknown risks, uncertainties, and other important factors that may cause our actual results, performance, or achievements to be materially different from our expectations, expressed or implied by the forward-looking statements, including our regulatory plans for ensifentrine and the timing of those plans, the treatment potential for ensifentrine, and its potential impact on patients. Any forward-looking statements represent management's estimates as of the date of this conference call. While the company may elect to update such forward-looking statements at some point in the future, it disclaims any obligation to do so, even if subsequent events cause its views to change. As a reminder, this call is being recorded and will remain available for 90 days. If you require operator assistance, please press Star then zero. I'd now like to turn the call over to Dr. David Zaccardelli, Chief Executive Officer. Good morning, everyone. Thank you and welcome to today's call to discuss the positive top-line results from our phase III ENHANCE-1 trial. With me today are Mark Hahn, our Chief Financial Officer, Dr. Kathy Rickard, our Chief Medical Officer, Chris Martin, our Senior Vice President of Commercial, and Dr. Tara Rowe, our Senior Vice President of Research and Development. In addition, we are very pleased that Dr. Antonio Anzueto, professor of medicine and section chief of pulmonary at South Texas Veterans Healthcare System, is joining us today to share his thoughts on the exciting study results and will be available during the Q&A part of the call. Note, the slides we are showing today will be available on our website after this call. Today is a momentous day for ensifentrine, Verona Pharma, and most importantly, the millions of patients suffering from COPD. The ENHANCE-1 results confirm the impressive results from the ENHANCE-2 trial earlier this year. Patients and physicians are in need of an effective new therapy. ensifentrine, with its novel mechanism as a selective PDE3 and PDE4 inhibitor, providing increased lung function, improved symptoms and quality of life measures, and remarkably reduced rate and risk of exacerbations are groundbreaking for the field of COPD management. Along with its favorable long-term safety profile, ensifentrine provides a compelling benefit to risk profile. To be clear, we believe ensifentrine will change the treatment paradigm for COPD by providing bronchodilation and non-steroidal anti-inflammatory pharmacology with one compound. Before we discuss the exciting results, let's briefly review the ENHANCE program. As a reminder, the ENHANCE-1 and ENHANCE-2 trials replicated measurements of efficacy and safety data over 24 weeks, and ENHANCE-1 also evaluated longer-term safety over 48 weeks for a subset of patients. The trials are designed to enroll approximately 800 moderate to severe symptomatic COPD subjects for a total of approximately 1,600 subjects across sites primarily in the U.S. and Europe. Subjects received ensifentrine or placebo as either monotherapy or added on to a single long-acting bronchodilator, with approximately 50% of subjects receiving either a long-acting muscarinic antagonist or LAMA or a long-acting beta-agonist or LABA. Additionally, approximately 20% of subjects receiving inhaled corticosteroids or ICS with their concomitant LAMA or LABA. In summary, ensifentrine successfully met the primary endpoint and key secondary endpoints in the ENHANCE-1 trial, demonstrating statistically significant improvements in lung function, symptoms, and quality-of-life measures. In addition, ensifentrine treatment resulted in substantial reduction in both the rate and risk of exacerbations. Ensifentrine was well tolerated over 24 and 48 weeks. Now let's walk through these exciting results. First, let's review the types of subjects enrolled in ENHANCE-1. Overall, the demographic and disease characteristics were very well balanced between the ensifentrine and placebo groups. The COPD patients enrolled had compromised lung function with a predicted post-bronchodilator FEV1 of approximately 52% in both groups. The study population included approximately 66% of patients on background therapy, including either LAMA or LABA, and approximately 21% of subjects received ICS in addition to their bronchodilator medication. On the next slide, let's review in detail each of the lung function endpoints by looking at serial FEV1 curve over 12 hours at week 12. The primary endpoint of average FEV1 AUC 0-12 hours post-dose at week 12 demonstrated a placebo-corrected, highly statistically significant and clinically meaningful improvement at week 12 of 87 milliliters, P < 0.001. We are also pleased the secondary endpoints evaluating lung function were met. Statistically significant and clinically meaningful increases in placebo-corrected peak FEV1 of 147 milliliters, P < 0.001, and morning trough FEV1 of 35 milliliters, P < 0.05, were observed at week 12, supporting a twice-daily dosing regimen. As noted on the next slide, all subgroups, including gender, age, smoking status, COPD severity, background medication, ICS use, chronic bronchitis diagnosis, FEV1 reversibility, and geographic region demonstrated consistent improvements in the change from baseline in average FEV1 AUC 0-12 at week 12 with ensifentrine. We are very pleased to show on the next slide that subjects receiving treatment with ensifentrine had a substantial 36% reduction in the rate of moderate or severe COPD exacerbations compared with placebo over 24 weeks with a P value of 0.05. As a reminder, an exacerbation was defined in the protocol as a worsening of symptoms requiring either a minimum of 3 days of treatment with oral or systemic steroids and/or antibiotics or hospitalization. On the next slide is the Kaplan-Meier graph, which displays the exacerbation events in each group over the study period. The occurrence of exacerbations separated early, and the ensifentrine treatment group continued to demonstrate a reduced rate of exacerbation events over 24 weeks. Treatment with ensifentrine significantly decreased the risk of an exacerbation as measured by time to first exacerbation when compared with placebo by 38%, P < 0.05. We are extremely pleased by the reduction in exacerbations as seen in ENHANCE-1. When pooled with ENHANCE-2 data, as pre-specified in the protocol, subjects receiving treatment with ensifentrine had a 40% reduction in the rate of exacerbations compared with placebo over 24 weeks, P = 0.0012. In addition, in the pooled analysis, treatment with ensifentrine decreased the risk of an exacerbation as measured by time to first exacerbation when compared with placebo by 41%, P = 0.0008. We believe this magnitude of reduction in exacerbation rate and risk further highlights the importance of this new mechanism, including non-steroidal anti-inflammatory activity, in addition to bronchodilation for the treatment of patients with COPD. On the next slide, let's review the secondary endpoint measurements of symptoms and health-related quality of life measures. ensifentrine significantly improved daily symptoms as measured by the Evaluating Respiratory Symptoms, or E-RS, total score in the ensifentrine group, exceeding the minimally clinically important difference, or MCID, of - 2 units, with a statistically significant improvement compared to placebo at week 24. The improvement in health-related quality of life as measured by the St. George's Respiratory Questionnaire, or SGRQ, total score in the ensifentrine group exceeded the MCID of minus 4 units with a statistically significant improvement compared with placebo at week 24. The improvements in both measures were early and sustained, with statistical significant versus placebo at weeks 6, 12, and 24. Turning to safety results on the next slide, ensifentrine was well-tolerated, with very few events occurring in more than 1% of subjects and greater than placebo over 24 and 48 weeks. The next slide summarizes the top-line data from ENHANCE-1 trial. We are delighted with the highly positive results that also includes meeting key secondary endpoints. Finally, when evaluating the results of both the ENHANCE-1 and ENHANCE-2 trials, we note the consistency of the positive results between the trials. The totality of the data from the ENHANCE trials, including improvements in lung function, symptoms and quality-of-life measures, and exacerbation reductions, coupled with the consistent favorable safety profile of ensifentrine, confirm the strong benefit to risk and support our belief that ensifentrine will change the treatment paradigm for COPD. Our next steps are to submit a new drug application to the FDA in the first half of 2023 for inhaled ensifentrine for the maintenance treatment of COPD, and to continue preparations for our planned U.S. commercial launch through the NDA submission, so we are fully prepared for the potential U.S. launch of ensifentrine in 2024. We expect to release additional information from the ENHANCE trials at upcoming scientific conferences. I will now turn the call over to the operator for the Q&A. We will now begin the question-and-answer session. To ask a question, you may press star then one on your touch tone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. The first question comes from Yasmeen Rahimi with Piper Sandler. Please go ahead. Good morning, team, congrats to the outstanding data set from ENHANCE 1. Couple questions for you. Maybe the first question is there an opportunity to conclude that if you combine ENHANCE 2 and ENHANCE 1, you're able to also pick up statistical separation in the patient-reported questionnaires and instruments that were used in the ENHANCE 1? That would be really helpful in what the importance of getting that data into the label means in terms of commercial preparedness. The second question for you is now, how much of the NDA filing or the process has been completed? How soon can you get it done? The third question is, how are you thinking about partnerships here in the US and ex-US? Thank you again for taking all of our questions. Great. Thanks, Yas. Good morning. Maybe I'll just start with the NDA filing and turn it over to Dr. Rowe for her comments about patient-reported outcomes. We are very well progressing on the NDA, which I'm very pleased to report. We talk about clinical, of course, enormous amount, but as everyone knows, an NDA comprises many aspects, including non-clinical, CMC, and those sections are proceeding very nicely. We're quite confident in our progress. As we mentioned, we do plan to file in the first half of 2023. I think for practical purposes, that probably lands us in Q2. We look forward to updating everybody on our progress in upcoming calls. I'll just touch on partnerships. Of course, you know, I think many partners were looking to see the ENHANCE 1 data, which is, as you know, just announced today. I expect that activity to pick up very quickly and be very well informed on our next steps on partnerships in Q1. With that, I'll turn it over to Dr. Rowe on patient-reported outcomes. Sure. I think, you know, as part of any NDA, the pooling of efficacy measures across pivotal studies is an important aspect of the assessment of efficacy for NDA submissions, and we will be doing that for symptoms and quality of life in our NDA submission too. We don't have the pooled data yet. Of course, we just received the ENHANCE 1 data readout, but we do intend to do that. Certainly, with both studies showing an improvement favoring ensifentrine, already I think we're positioned very well to look at that pooled analysis. If I may just ask one more quick follow-up. Can you maybe put into context what this additional statistical separation and a pooled analysis of exacerbation means for physicians? Is there a magnitude that's considered clinically meaningful, or is it just the ability to explain to a patient that you should be able to see exacerbation reductions? Any commentary on the statistical significance of the pooled analysis from a commercial positioning perspective would be really helpful for us. Thanks, I'll jump back into the queue. Thanks, Yas. Maybe have Dr. Anzueto comment on the exacerbation data, and then Chris can comment on commercial aspects of it. Dr. Antonio Anzueto? Good morning. Thank you for your question. Certainly it's very exciting to see more than 30% reduction in the rate of exacerbations. Remember that if you look at a couple of miles across, the separation starts occurring early in the course around 4 weeks. This is a 3-month study that shows the separation. I think it's more exciting when you put it all together and also the reduction in the time to the first exacerbation. Those are endpoints that we have recognized, and we have done large clinical studies over 1 year. The fact that we're seeing early in the course of the therapy, I think is very encouraging and very exciting for us as a clinician and for our patients. Yeah. Yas, just from a commercial perspective, one of the things that's really important to keep in mind about exacerbations is it's by definition a worsening of symptoms. When you look at the SGRQ data, you look at the exacerbation data, what you see is that ensifentrine is having an effect on the symptoms that these patients feel every single day. When we hear and talk to physicians like Dr. Anzueto, what they tell us is this idea that ensifentrine has the ability to provide an early benefit for these patients, which they're always struggling and hoping to feel better, be able to get to some of the activities that they do, reduce the risk of exacerbations, more importantly, that reduction is sustained over time, and you see that in the data across all measures. I think these are really important aspects as we get to commercialization that will encourage physicians to initially try ensifentrine, but more importantly, keep their patients on it and encourage future use as well. Thank you team, and congrats again. Thanks. The next question comes from Andreas Argyrides with Wedbush Securities. Please go ahead. Good morning. Thanks for taking our questions. Congrats on these fantastic results. These are two for Dr. Anzueto to start here. Thinking about the commercial opportunity, based on these results, where do you see ensifentrine being, you know, first used when available? Would you use this to treat exacerbations and include it in the insert? Then maybe just some of your comments on the safety profile at 48 weeks. Thanks. Sure. Thank you for your question. Let me address the later issue, the safety profile. Our safety profile is outstanding. Actually it's nothing that we have not seen before. It's very, there is no any issues that we saw with phosphodiesterase inhibitors on oral therapy. The safety profile is very, very clear. There's minimal side effects that the patients have. From the efficacy point of view, that is encouraging is this is a cohort that is not a exacerbation-rich cohort. This is a moderate COPD population that even in this population can impact the rate of their exacerbation. I think this is what makes it more exciting. Now, as a clinician, we're gonna be able to offer the patient both a bronchodilator and an anti-inflammatory. We need to look at further analysis in combination with other, concomitant medications, to understand exactly where they're gonna position. I can clearly see this medication to be as a first line of therapy in patients who are symptomatic, COPD. Okay, great. Thanks, Andreas. Yeah, just one quick follow-up. Just, in lung function improvements were consistent across both trials. Fantastic. What do you think contributed to the significance achieved on symptoms and quality of life, in this study versus the other one? Again, another fantastic result. Let me comment on the quality of life. In this one, if you see, at the end of the study and halfway through the study that St. George, improvement in lung function is a -6 point. It's well beyond that clinical significance. You also can see in the placebo it's close to 3 point something. In the prior study, it was probably the combination that the cohort that was enrolled, that there was a larger dropout and the patients who dropped out in the placebo group were the people who were sicker. The patients that actually stay were, quote-unquote, "healthier" in the 3 months period of the duration of the study. There was some signal there was an improvement in quality of life. Here you can see in the St. George that the improvements are much more dramatic than we have seen before. This is very comparable of the improvements in St. George's Respiratory Questionnaire that we have seen with dual fixed long-acting bronchodilators. Congrats again, guys. Thank you. Thanks, Andreas. The next question comes from Suji Jeong with Jefferies. Please go ahead. Hi. Good morning. Thanks for taking my question. Congratulations on the data again. From the ENHANCE-1 trial, just a quick question. What percentage of the patients came from Europe and also outside the U.S.? I noticed a bit of different patient characteristics between the two trials, ENHANCE-2, such as the higher number of moderate patients and a higher number of patients with chronic bronchitis, a higher percentage of patients on the background therapy. Are there any aspects of the patient demographics from two trials that differ from each other that make you concerned about the regulatory action? My third question is, on the exacerbation, was it mostly driven by the moderate exacerbation or severe exacerbation? Thank you. Great. Thanks, Suji. I think, Tara can speak to any demographic numerical differences. I would say that when running large phase III programs, we consider them incredibly comparable. You'll always find some numerical differences. The fact that we had slightly higher background therapy, I think, is only helpful in the sense that more patients were receiving background therapy and still, you know, had a benefit. I think, Tara, I don't know, on the percentage of patients that were from Europe versus... Oh. -US. Yeah. Yeah. In this trial, we did have more patients from Europe. I think it was around half of the subjects enrolled were from Europe. Here we had about 20% of subjects in the U.S., come, you know, and it was essentially more or less flipped in ENHANCE-2. In terms of moderate and severe COPD exacerbations, typically when you conduct these studies, you do see more moderate exacerbations than severe exacerbations. Severe exacerbations are fairly rare events where the subjects are hospitalized. The assessment of effect on moderate and severe exacerbations is typically best done in a pooled fashion across both of the studies. We don't have that data in hand yet. I think just to add, you know, our view is there, you know, there's no regulatory impact at all, based on the types of patients that were enrolled. We find them to be incredibly consistent, representative of past COPD trials. If anything, I think strengthens the submission based on the patients we enrolled. I see. Great. Just one last question. In 2023, seems like the focus will be prepping for the NDA submission as well as building out commercial capability. What are the strategies and activities you plan, you have it planned for the, for building commercial efforts, and what is your cash runway? Suji, this is Chris. I'll let Mark answer the cash runway question. From a commercial standpoint, we've always taken the approach of using milestones to drive our commercial activity. Of course, the first milestone that the organization reached was the ENHANCE-2 trial results. At that time, I strengthened my leadership team by bringing in our head of market access and trade, sales and marketing, and also operations, so that we could start to set the foundation for the commercial organization. With this data, we'll continue to build on that. Some specific examples in 2023 that we'll be working toward is on the market access and trade side, we'll be working within the Medicare Part B channel to establish our distribution pathway and our ability to make sure that patients can get this product very quickly when we're launched. I think that's a very defined pathway too. We know the steps which are required. We also know that in the Medicare Part B pathway, we believe we fall under an existing policy code. When ensifentrine is launched, there's access for physicians to write this. That's on the market access and trade side. On the sales and marketing side, we start to work on market shaping the environment for the first novel therapy in 20-plus years for physicians. Remember, the last 10 launches in COPD, 10-plus launches in COPD, have been the same product, either in combination or in different devices. There's some work that we can do to educate physicians on the need within COPD, the number of patients that remain symptomatic, and how new mechanisms are needed to help both bronchodilation and anti-inflammatory effects within these patients. That'll be work that we do this year. The last thing that we really need to do is set the foundation for our sales organization. That becomes refining our targeting and our deployment strategies, and that'll all be done during this year as well. Yeah. Suji, with respect to the runway, you know, we did a fairly substantial raise back in August, and we also put in place a $150 million credit facility with Oxford in October. When you pool our existing... I think at the end of September, we had about $230 million of cash. You pool that together with the proceeds from the loan facility, that provides us with enough cash to get through at least the end of 2025, including all the work that Chris just walked you through in terms of prepping the company and actually launching the drug. Okay, perfect. Thank you. Thanks, Suji. Congratulations again. Thank you. The next question comes from Edward Nash with Canaccord Genuity. Please go ahead. Hi, guys. Thanks for taking my call. Yeah, resounding congratulations on the data. Just wanted to know, in the subgroups, patients on ICS had a lower FEV1 improvement than those not on ICS. Just wanted to know if we could read anything from this with regards to future commercial positioning of the drug. Sure. You know, I think what you need to just take with a grain of salt on the subgroup analyses is that the confidence intervals here on these are very much overlapping, entirely overlapping, I would say. I wouldn't read too much into a numerical difference in the means here. I think those responses are essentially the same in the 2 groups. Okay. Could you just maybe just discuss a little bit maybe about how the, with regards to quality of life measures, how are these viewed, differently between the FDA and EMA? You know, I think, they are considered by both FDA and EMA. I think there's actually a lot of consistency between the two. I think we do expect SGRQ data certainly to be in the label. I think in EMA symptoms, including Transition Dyspnea Index, which we haven't shown yet, will also be included in the label. I think in the US, they are more inclined to stick with the SGRQ data. Got it. Great. Thanks again. Thanks, Edward. The next question comes from Joon Lee with Truist Securities. Please go ahead. Hi. Thanks for taking our questions, and congrats on the impressive data. Would a prospective EU or global partner who may want to develop ensifentrine as DPI or MDI formulation need to run a new phase III program? How much of ensifentrine's efficacy in COPD as a nebulizer do you think will be captured as MDI or P-DPI formulation? Also remind us if you have an Open-Label Extension ongoing, and if so, what% opted in for the OLE? I have a follow-up. Thank you. Thanks, Joon. To work backward, no, we do not have an Open-Label Extension study ongoing, there are no, you know, open COPD trials at this time. With regard to DPI, MDI, yes, we do think. That formulation would need to conduct, proper, you know, dose phase II and phase III trials. As you can imagine, it is typical for the dose to be somewhat different for a DPI or an MDI versus the nebulized. The deposition characteristics, typically, you know, are different. Right now we would anticipate that it would require, you know, additional clinical studies in order for that formulation to be approved. I don't think we have done, you know, a deep analysis on any sort of capture or transition from nebulized to MDI or DPI. I think we firmly believe in the US that the nebulized approach is the best approach for ensifentrine for patients and the best strategy for us to make sure that patients have the access to the best treatment for ensifentrine as we've developed. Because it is a nebulized, we find that to be completely acceptable. I know Dr. Anzueto also can comment on that, but you know, we're very confident in that approach in the US. Any partner that would want to develop an MDI or DPI for either COPD or other indications, much like ourselves in the US, you know, asthma, for example, ILD and/or other respiratory conditions, clearly that would make some sense based on the types of patients have those diseases, et cetera. I'll sort of leave it at that. I don't know, Dr. Anzueto, if you wanna comment on the acceptability of a nebulized formulation for COPD patients? Sure. The, I think nebulized medication for COPD patients in the last five to eight years have had a tremendous revolution, mainly in the fact that more medications that are long-acting bronchodilators are becoming available. The nebulizer systems are highly efficient, portable, very easy to handle. I can tell you that I had at least 30% of my COPD patients in my practice that they are in nebulized therapy, and they love it. They really, they like the medications, they like the delivery system, and more important, they don't have to worry about do I get the medication? How I don't get the medication? 'Cause the certainly the nebulized systems are highly efficient for drug delivery. Great. Thank you. That is very helpful. Actually, I have a question for you, Doctor. You know, now that you have both phase III data, you know, would you now push the envelope a little further and say, you know, would you like to see data as an add-on to LAMA and LABA with or without ICS? Is that important to you? If not, why not? Sure. We have the standard of care today that are long-acting bronchodilators. If we look at the demographic data from the ENHANCE-1 study, we see that 1/3 of the patients are on LAMAs, and there is 18% on LABAs and another 20% of ICS LABA. I think it's gonna be very important to understand how do the medication works on in combination and without combination therapy and under which combination therapies have. How does it work? How much of the efficacy we see? The beauty now is we have both ENHANCE-1 and ENHANCE-2 studies, so we have much larger number of patients, more diverse baseline therapies that will further help us to understand this is an additional to the therapy that we're using, or they can be a standalone. Remember, like in ENHANCE-1, how close to 35% to44% of the patients were not on prior background medication. We're gonna have the whole spectrum to analyze, to understand how to use this medication. Great. Thank you, and congrats on the data again. Thanks so much. If you have a question, please press Star, then one. The next question comes from Raghuram Selvaraju with H.C. Wainwright. Please go ahead. Hi. Thanks for taking my questions. Congrats on the outstanding data. Just a few from us. Firstly, can you comment on your CMC capabilities? Yeah, CMC capabilities? Yeah. I think, as a company, we've had a very targeted strategic approach to CMC. We do manage it internally, but outsource the actual activities of API synthesis, and also drug product manufacturing. Both of those are either made in Europe or in the U.S., and we have a very strong relationship with those contractors. Both of them make a commercial product for the U.S. market, and have a very strong regulatory history. We're very comfortable with that. In addition, because of the development timeline, for ensifentrine, we have a incredibly strong handle on the CMC, from an API manufacturing synthesis perspective, and the ability to make, quantities, that, satisfy commercial amounts and, going through the validation of that. We also, you know, have incredible stability data already in hand. I think we're very comfortable, with our, CMC overall and our drug product. Great. Thanks for the color. This question may be for Dr. Anzueto. How does the ENHANCE-1 and ENHANCE-2 study results inform the future development of dual PDE3 and PDE4 inhibitors for COPD and other indications? These two studies are clearly show the benefits, both a lung function and reduction in exacerbation and in quality of life of this combination of medications. I think it's very exciting to have different mechanisms of action. This is, as it was mentioned at the beginning of the presentation, this is a novel medication. It's completely different mechanisms that we have had in the last 20, 25 years of a bronchodilator, and it's showing the benefit in lung function as well as the other endpoints that were mentioned. As well as the safety, I think, is the most important part because it's very well tolerated. Okay, great. One final question from me. This is for Chris. Chris, hypothetically speaking, if ensifentrine is a price premium over LABA or LAMA, do patients have to fail dual or triple therapy prior to receiving ensifentrine treatment? Based on our discussions with the payers, we have to keep in mind that ensifentrine will primarily be reimbursed through the Medicare Part B channel. Within the Medicare Part B channel, which we anticipate about 60% of the patients going through, that's an open access network where physicians have access to ensifentrine, and we don't anticipate any step-throughs there. I think the other thing that's really important is that we believe that ensifentrine has the potential based on the data to be priced at a premium versus the current nebulized products. I think the other thing that's really important here, despite the pricing, what we see in the nebulized market when you look at other branded products is that 80% of patients pay less than $10. That's a really key factor in this market. Because of the way Medicare Part B works, you actually can get these patients the drug at a very low cost, and that allows them to stay on the medicine, and get the benefits that we see in the trial. I think the other channels that we've talked to when we've talked to Medicare Part D, Medicare Advantage, what they've told us is that ensifentrine is an extraordinarily novel compound. They've not seen anything like this before in COPD. They're excited about that mechanism, they're excited about the data, and they anticipate putting ensifentrine on formulary and having access to ensifentrine within those channels as well. I will say that one area where it, there may be a step-through is if a patient is a newly diagnosed patient, most payers have said they would like a patient to at least try a generic LAMA or LABA before trying ensifentrine. But that's not a large step-through for many of these physicians. We believe that, you know, when we talk about the patient that will be on ensifentrine, like Dr. Anzueto said, which is the patient that's symptomatic, these symptomatic patients have already tried therapies, so going to ensifentrine will be a low burden within the payer community as well. Thanks for taking my questions. Thanks. Congrats on the outstanding data. Thanks so much. The next question comes from Tom Shrader with BTIG. Please go ahead. Good morning. Congratulations on the long, successful journey. It's nice to see. I have a little bit of a picky question for Dr. Anzueto or a detailed question. The way exacerbations are defined in the trial, is that what you care about, or do you care about keeping patients out of the hospital? Is this, is this the meaningful parameter that you and your colleagues think about? Sure. exacerbations are bad any way you look at it. We know that even exacerbations that are not reported, those mild in some extent are also bad for the patient, the lung function. Just I think it's important to put into context, this is not an exacerbation cohort. This is not an exacerbation study. This is a cohort of patients with moderate COPD. As we learn from the ECLIPSE trial in the New England Journal publication in 2010 with John Hurst, that patients doesn't have to have very severe lung function to develop exacerbations. Patients with moderate disease can develop exacerbations, and those can be significant. But the context of this study show you, yes, you can further reduce these exacerbations if you have the right mechanisms or the right medications on board. Certainly, we would like to have also reduction in hospitalization of very severe exacerbations. This is gonna be a completely different cohort because we know that the people who's gonna be hospitalized are people who was hospitalized in the past, who have comorbidities. This is not a patient who have moderate COPD. These are patients who have more severe COPD or significant comorbid conditions. In the context of this patient population, I believe that the data is very exciting because if you have the triple count, the triple win-win, you have the improvement in lung function, you have the reduction in exacerbations and improvement in quality of life, and it's safe. Do you see any reason why it wouldn't translate what we see today to these more serious patients? No, I don't see any reason at all. I think, I will say that if you go into a cohort of individuals who are more serious or an exacerbation cohort, you will see exactly this, and you will see a significant reduction in hospitalizations. Okay, maybe one quick one for the statisticians. I think the biggest difference between ENHANCE-1, ENHANCE-2 is the trough FEV. Is there anything you can ascribe that to? Is it driven by placebo or? To me, it's the biggest difference between the two trials. Can you make any sense out of it? Yeah. I think, you know, really a 14-milliliter difference in mean values, given the confidence intervals to us doesn't represent a real difference in effect, right? You know, both of these are statistically significant. We have confidence that there is an effect with ensifentrine over placebo. All right. That's good. Thank you. Thanks, Tom. This concludes our question and answer session. I would like to turn the conference back over to David Zaccardelli for any closing remarks. Thank you very much. We would like to thank you for your questions and thank the patients and healthcare professionals who participated in the ENHANCE program. Finally, I'd like to thank our shareholders for their continued support and the dedicated and talented team at Verona for their commitment. We look forward to discussing these highly positive results with many of you in the coming weeks and to keeping you posted on our progress. That concludes today's call.