Good day, and welcome to the Verona Pharma ATS 2023 Data Call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your telephone keypad. To withdraw your question, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to David Zaccardelli, Chief Executive Officer. Please go ahead. Good afternoon, everyone. Thank you for joining the call. With me today are Dr. Tara Rheault, our Head of Research and Development, Dr. Kathleen Rickard, our Chief Medical Officer, Chris Martin, Chief Commercial Officer, and Mark W. Hahn, our Chief Financial Officer. Before we begin, let me remind you that we may be making forward-looking statements and, as such, refer you to our Risks section in our recent SEC filings. It has been a very exciting and productive past few days at the ATS meeting in Washington, D.C. ensifentrine has been on full display with a comprehensive review of the phase III ENHANCE trial results. This has included a symposium presentation and 12 abstracts, including subset analyses and pooled analyses to ensifentrine in the ENHANCE program. As you can see on the slide, I'd remind you that ensifentrine is a novel molecule providing phosphodiesterase 3 and 4 inhibition and, as such, has very unique characteristics, including bronchodilation, primarily through PDE3, anti-inflammatory effects, primarily through PDE4, and also increases mucociliary clearance through CFTR activation. As you can imagine, that pharmacology has played out very well in the treatment of COPD. If we take a look at the pivotal phase III program, just to remind you, consists of two large phase III trials called ENHANCE-1 and ENHANCE-2, both enrolling approximately 800 patients, in which patients are randomized to receive either ensifentrine 3 mg BID or a placebo for 24 weeks, with ENHANCE-1 having an additional subset of patients going for an additional 24 weeks or a total of 48 weeks. As you recall, we've reported out top-line data on these trials in 2022. Just as a reminder of the patient population, they could have been receiving background therapy, either a LAMA or a LABA or not on background therapy, as well as up to 20% of the patient population was receiving a ICS in addition to a LAMA or a LABA. They were all symptomatic and all had compromised lung function. With that patient population enrolled, you can see on the next slide the actual demographics and baseline characteristics of both trials, ENHANCE-1 and ENHANCE-2. Please note, of course, that the balance between ensifentrine and placebo in both trials is incredibly well-balanced and very representative of typical COPD phase III trials. Note that background therapy in both trials exceeded 50%, with ENHANCE-2 approximately 55% and ENHANCE-1 greater than that, closer to So the ERS and the SGRQ showing symptomatic patients as well as smokers, which was approximately 50% of patients in the study. Very characteristic of phase III COPD trials. Just to summarize before we actually get into the specific data from the presentations here at ATS, remind you of the results from both ENHANCE-1 and ENHANCE-2, which were incredibly positive and compelling. As you remember, we did hit the primary endpoint average FEV1 AUC zero to 12 hours in both studies with approximately 900 mL improvement. Also, of course, in lung function peak FEV1, trough FEV1 were met as well as clinically and statistically meaningful results. ERS, SGRQ showed positive results in improving symptoms and quality of life in these patients. Absolutely noteworthy is the exacerbation rate reduction and time to first exacerbation in both trials with approximately a 40% reduction in exacerbation rate across the ENHANCE program. Of course remind you of the adverse events which we'll review in more detail today, but were very comparable to placebo between the ensifentrine and the placebo group with no AEs that were really differentiated between either ensifentrine or placebo and very few adverse experiences as we'll review today in the program. With that, I'm going to turn it over to Dr. Tara Rheault to walk us through the top-line data from the abstracts and give us a comprehensive review of the trials. Great. Thanks, Dave. Thanks for everyone for joining the call We'll start with a review of our expanded analyses of our lung function data. Here you see our primary endpoint, average FEV1, zero to 12 hours at week 12. We have conducted subgroup analyses across both trials and show very consistent results across all of the clinically relevant subgroups that we've assessed, including subjects with and without background medication, inhaled corticosteroid use, chronic bronchitis, yes or no, reversibility, and COPD severity. That was consistent, showing improvements with ensifentrine over placebo across both studies. In addition, we also did a similar analysis looking at peak FEV1, a similar look at subgroups, clinically relevant subgroups, showed a similar consistent effect across all subgroups assessed in both studies. Moving on to our analyses of exacerbation data and inflammatory biomarker data. Just briefly, remind everyone the definition of exacerbations that was used in the trials was the industry standard. Exacerbations were defined as a worsening of symptoms, at least two major symptoms, or one major and one minor symptom, requiring at least three days of treatment with oral or systemic corticosteroids and/or antibiotics for a moderate COPD exacerbation or hospitalization for a severe exacerbation. Any exacerbation events were verified in the analysis with the symptoms and treatment required. Here we're showing subgroup analyses of our exacerbation data, both across the ENHANCE-2 trial and also pooled with ENHANCE-2 and ENHANCE-1. On the left-hand side you'll see the forest plot looking at exacerbation rate reduction in the ENHANCE-2 trial. Here you can see a very consistent effect showing improvement with ensifentrine compared to placebo, in all clinically relevant subgroups favoring ensifentrine. These include subjects on any background medication, including inhaled corticosteroids, subjects with and without chronic bronchitis, and in subjects with either low baseline eosinophils less than or equal to 150 cells per microliter, or in patients with greater than 150 cells per microliter. Pooling the data, you see similar effects, consistent effects across all clinically relevant subgroups. The next slide shows the similar analysis, but this time on our second exacerbation endpoint, time to first moderate or severe COPD exacerbation. Here again, this analysis in the ENHANCE-2 population and also pooled across ENHANCE-2 and ENHANCE-1 continues to show consistent effects in all clinically relevant subgroups showing a longer time to first, in those patient groups that need important additional treatments for the reduction in exacerbations. In addition, we presented data this week on exacerbation rate and risk reduction over 48 weeks. You'll remember in the ENHANCE-1 trial, we have a 48-week subset where we collected exacerbation through the entire 48-week duration of the trial. Here we're showing effects that are consistent with those that were shown over 24 weeks, even slightly greater effects over 48 weeks, both on exacerbation rate reduction of 44% and also exacerbation risk reduction as measured by time to first of 52%. In ENHANCE-2, we also evaluated inflammatory biomarkers, circulating inflammatory biomarkers. Here we're showing a positive trend on decreasing circulating inflammatory biomarkers, both in terms of IL-6 reduction and reduction in IL-8. IL-6 is a pro-inflammatory cytokine implicated in systemic inflammation in patients with COPD, and IL-8 is a chemokine that induces neutrophil migration to the airways. These are important markers giving us a mechanistic basis for exacerbation reduction relating to the anti-inflammatory effects associated with PDE4 inhibition that Dave mentioned in our mechanism slide. Moving on to the symptom quality of life and healthcare resource utilization data. Here we've presented a responder analysis of our symptom and quality of life assessments in the ENHANCE-1 data. Here we're looking at ERS responder analysis, and that is ERS symptoms. The minimal clinically important difference here was -2 units, and this was looking at the proportion of patients meeting that threshold of -2 units as a change from baseline. Here you can see we show a substantial proportion of patients showing meeting the MCID in the study over week six, 12, and 24 that was statistically significant at week 12 and 24 compared to placebo. A similar analysis looking at SGRQ, with a -4 unit responder where the MCID is -4 units, is showing a very large proportion of responders, up to almost 60% of patients meeting the MCID at week 24 and statistically significant differences from placebo at all weeks. In addition, in ENHANCE-1, we did an extended analysis of ERS subdomains, and this includes not only the total score, which we've presented previously, but also the subdomain of breathlessness, cough and sputum, and chest symptoms, three of the major areas of concern for patients with COPD. Here, looking at these results comparing ensifentrine and placebo at week six, 12, and 24, we're showing improvements in all three domains at all weeks. Similar analysis of subdomains across the SGRQ. These include symptoms, activity, and impacts in ENHANCE 1 are showing, again, very large improvements in symptoms, as you would expect based on the ERS data at week six, 12, and 24. Also contributions in terms of improvements in activity and impacts in patients with COPD. Also very important features of ensifentrine and important properties that are drive patient utilization. Here at ATS, we've also presented data on our dyspnea, Transition Dyspnea Index, and rescue medication use. Here we're looking at the data from ENHANCE -1 and ENHANCE- 2 on the Transition Dyspnea Index. Dyspnea is the most debilitating symptom impacting patients with COPD and is often the symptom that are driving patients into the physician's office requesting a change in therapy. Here you can see we have very strong results with ensifentrine in the trial, in both studies showing statistically significant improvement versus placebo on dyspnea at all weeks in both trials. Rescue medication use shows a similar trend as the other symptom and quality-of-life endpoints, showing results favoring ensifentrine over placebo that were statistically significant at all weeks in ENHANCE-1 and statistically significant at week six and 12 with a numerical improvement at week 24 in ENHANCE-2, supporting the improvement in symptoms, with reduction in rescue medication use in these patients. Here we've also, in the ENHANCE-2 study, taken a look at healthcare utilization over 24 weeks. What we're looking at here is overall healthcare utilization, which includes both COPD-related healthcare resource utilization and non-COPD-related healthcare utilization. In this group, we see a lower healthcare utilization in the ensifentrine-treated subjects compared to placebo-treated subjects, with 11.8% of subjects reporting healthcare utilization in the ensifentrine group and 15.1% in the placebo group. This difference is largely driven by unscheduled visits to physician's office, which were lower in the ensifentrine group, and unplanned hospital admissions, which were also lower in the ensifentrine group compared to placebo. Moving on to safety. We mentioned early on and you've seen the data supporting the safety profile with ensifentrine as similar to placebo. Here we've done an expanded analysis of the ENHANCE-2 data, looking specifically at cardiac adverse events and gastrointestinal adverse events. On the left-hand side, you see a full list of cardiovascular adverse events that were present in at least more than one subject. Here you can see we have numerically fewer subjects reporting cardiovascular adverse events in the ensifentrine group than the placebo group. Within the cardiovascular safety profile in ENHANCE-2, there were no clinically meaningful changes from baseline in either treatment group on ECG parameters, which includes heart rate and TQT, systolic blood pressure, diastolic blood pressure, or pulse rate. No subjects in the ENHANCE-2 study met the ECG withdrawal criteria. In terms of gastrointestinal adverse events, this is of interest, of course, because there are oral inhibitors of PDE4 that are marketed drugs, including for COPD, that do have substantial gastrointestinal side effects. These include rates of diarrhea, nausea, and vomiting up to including 10% of subjects. Here you can see the rates of gastrointestinal disorders in the ENHANCE-2 trial. Overall, similar in the ensifentrine and placebo arms, and very low rates in the ensifentrine and placebo arms in terms of diarrhea events, nausea, and vomiting. Regarding the few diarrhea events that occurred in this trial, we were looking at a potential temporal association with ensifentrine dosing. With other oral inhibitors of PDE4, you typically see these occur related to treatment quite early on within two weeks to four weeks. Here, seven out of eight events in the ensifentrine arm occurred after three months of therapy. We concluded that these were not temporally associated with ensifentrine treatment. The eighth event that occurred was due to atorvastatin and magnesium treatment. We had one additional treatment-emergent adverse event of vomiting in the ensifentrine group that was due to amphetamine withdrawal. In conclusion, we were able to present this week a broad analysis of the results across ENHANCE-1, ENHANCE-2, and even some pooled analyses that support the replicate effect in lung function across clinically relevant subgroups, both on peak FEV1 and also average FEV1 over 12 hours. We were able to show results supporting exacerbation reduction in clinically relevant subgroups that was substantiated over 48 weeks of treatment. We demonstrated improvement in symptoms, quality of life, and healthcare utilization, which included over 50% of subjects showing a clinically meaningful response on symptoms and quality of life in ENHANCE-1, and improvements in Transition Dyspnea Index and reductions in rescue medication use in both studies. Finally, showed an adverse event profile that continues to be consistent with placebo, including cardiovascular and gastrointestinal adverse events. This is not all of the study data yet from both studies. We do have additional data that we're presenting at the ERS conference in Milan later this year and at CHEST in October. Please do stay tuned for that additional data output. And with that, I believe we'll turn it back over to the operator for questions. Thank you. We will now begin the question-and-answer session. To ask a question, you may press star then one on your telephone keypad. 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. Our first question comes from Yasmeen Rahimi with Piper Sandler. Please go ahead. Team, thank you so much for sharing the fantastic results, and congrats on a very strong presentation at ATS. I would love to Given that a lot of clients who are listening to this call had not the opportunity to be at ATS, could you maybe comment on sort of the receptivity on this data from the community when the data was presented? What was the sort of audience participation? What were the commentaries? Could you maybe really maybe help us sort of capture, you know, the sentiment in response to this really outstanding results that you received from physicians who attended the session? More specifically, what were some attributes of this data that really resonated very well to them? Again, this is quite important for a lot of clients of ours who are listening but were not able to be present at ATS. I'll jump back into the queue. Great. Thanks, Yas, for the question. It's been an absolute enthusiastic response. I can just characterize, you know, the presentation and the symposia was a very large room, very full. A lot of questions after the presentation by Dr. Anzueto. Very engaging. I think that the mood was very upbeat with enthusiasm around the consistency of the results, the magnitude of the results. I think for sure many people were just exposed to it with the depth at ATS that we had. I think the poster sessions, again, extremely well-attended, and involved with both, you know, physicians, and the healthcare community who were there. I think we're very pleased with the reception. Maybe I'll give, turn it over to Chris, and Tara to comment any more. Sure. I think, you know, one of the things we're hearing is excitement around utility across a broad COPD population. I think they're very interested to get, you know, hopefully an ensifentrine approval and be able to use this in their patients. I think we're understanding that there are a lot of different areas where they would find this type of treatment useful. The other data that I think, two pieces of data that I think they're really excited about is the exacerbation subgroup data showing that we really have not identified a subgroup where ensifentrine will not produce a benefit. I think that's exciting, you know, doesn't require assessment of blood markers or anything like that when they're making treatment decisions for their patients. I think for me, finally, the last thing I'm hearing is around the improvement in dyspnea. The results that we show on the TDI are really remarkable and unlike things that they've seen previously. That's a scale that's more physician-friendly. They understand it. It's been around for a long time and something that they can use in their practice as well. I think there's definitely some interest in that. Just to continue on what Tara's talking about on the Dyspnea Index. I think, you know, when we talk to physicians today, the dyspnea is the reason why they make treatment changes. The patients come in complaining about an inability to breathe. The ability to show this marked difference is something that allows them to really make a treatment decision or treatment change. That's an exciting aspect of the data. I think the other thing that it does is it continues to confirm across all the data endpoints that we have this early response, either through bronchodilation or through symptoms or through TDI, all the way to a sustained response where you see now exacerbation data that holds through to 48 weeks as well. It really plays to this totality of the story of an early response and this early and sustained response with the patient. Thank you, team, and I'm sorry, one logistical question. I know that you guys have worked also really hard on the publication. I know that those items take a while, but any update there on, you know, I think, in terms of the proximity of whether we may see a publication before NDA filing, around NDA filing or? Sure. It can be a little later. I know these things take a long time, so appreciate any color. Thank you. I'll jump back in the queue. Sure. I can't give any granularity around the timing of the publication regarding the NDA filing. That's, you know, out of our control. I can say, you know, we're in the late stages of manuscript finalization, and that should be out sooner rather than later. Okay. Thank you. Our next question comes from Andreas Argyrides with Wedbush Securities. Please go ahead. All right. Good afternoon, and thanks for taking our question. Also congrats on the presentations at ATS. Just to continuing from the point on exacerbations, maybe you can give us a bit of a sense of how that might play into the commercial strategy and how the medical community, you know, views it and how then they subsequently they prescribe it. Thank you. Thanks, Andreas, for the question. I think, you know, when we talk to physicians, not only here at ATS, but keep in mind, I think we're up to close to, I mean, somewhere between 700-1,000 physicians that we've talked to through market research on ensifentrine. What's remarkable to me is we have consistent results across ENHANCE-1 and ENHANCE-2, but when we get into the market research, our results when we do market research is as consistent as the data we see in our clinical trials. You know, the reasons why physicians are first intrigued by ensifentrine is the fact that you have a novel mechanism of action that provides bronchodilation and anti-inflammatory nonsteroidal anti-inflammatory effects. This MOA allows for conversation to be had and within that conversation becomes the totality of the data. You know, when they're dealing with patients every day that are symptomatic, they're looking to help these patients reduce the burden of the symptoms and be able to get back to some semblance of the quality of life that probably we all take for granted on the call or in the room here that we're in. You know, the other thing, they're trying to manage a risk of exacerbation. They need to balance both things every day with these patients. When they look at the ensifentrine data, what they see is the ability to provide an acute bronchodilator, where they're getting lung function improvement at a very rapid rate, which provides the patients to breathe better, which you see in the Dyspnea Index score, that eventually translates into improvements in symptoms and quality of life, and then down the road, the improvement in exacerbations. For the research and the discussion, it really becomes a totality of the data, and there's not one single piece that maybe drives utilization. I think the other thing with the totality of the efficacy data is it's balanced by safety profile, as Tara described, that's similar to placebo. They can try this drug in a patient and see very quickly how a patient's going to respond with very low risk. That's a benefit risk profile that's very attractive to a physician who's looking for trying to help patients in a variety of different ways as they remain symptomatic. Okay, fantastic. Could you just remind, you know, us the size of that market, you know, given the totality of the data? Yes. Great question. What your estimate size, yeah? Within the U.S., there's about 8.5 million treated COPD patients. There's about 1.7 million of those patients are on a single bronchodilator, LAMA or LABA. There's about 4 million of those patients on LABA ICS. If you think about that, it's close to 6 million patients that are on what we would consider the ENHANCE patient population. If you look at the patients that have very limited treatment options, those on dual bronchodilators or triple therapy, that's about another like 2.8 million patients between the two of those. Across that group and that across that spectrum, we see patients being symptomatic between 40%-50% of the time. You know, the real thing here is how a new mechanism can be layered on top of these patients. Because in the past, what they've just continued to do is add the same drugs in a different delivery, different device to help these patients try to get a little better. In this reality, it's the first time they're really being able to add broadly a new mechanism that can provide benefit across a broad set of patients within their practice. Okay, great. Congrats, and I'll jump back in the queue. Our next question comes from Andrew Tsai with Jefferies. Please go ahead. Okay, thanks. Appreciate you guys sharing all these new analyses with us. Clearly you've generated a wealth of data across these Phase III studies. Looking ahead, how much of this information do you think can get into the eventual label? For instance, you know, the relatively fast exacerbation benefit over placebo. You have this nice force plot, for instance, your respective eosinophil count, and you're seeing equal benefits. The question is just, you know, how much do you think can get into the label? Yeah. I think, you know, where we're at in the COPD space, right? There is a lot of precedent, and there is a lot of drugs that are approved for the maintenance treatment of COPD, and you'll see a lot of consistency across the labeling there. I think I would go back to review, you know, recently approved drugs and see what's in there. I mean, we expect the lung function to be in there, quality of life, of course, and exacerbation data as informative for physicians who will be prescribing the drug. Makes sense. You know, moving ahead again, you do plan to file NDA soon. Do you plan to file for a priority review or standard review? Secondly, if we think about some of the more recent COPD drugs that have been approved, did they end up having an Adcom? I'm also curious if you're anticipating an Adcom for ensifentrine. Thank you. Yeah. Thanks, Andrew, for the question. You know, we think that ensifentrine and the results that you've seen, you know, here and previously, justify a priority review. We think we meet the standard as we understand it. Clearly, we'll make that case in the submission, and we'll see what the agency will provide their response to that. We expect that in that 60-day period, related to acceptance to understand whether they would give a priority review. You know, as you know, there are many products approved for COPD. That providing priority review may be a bit complicated with precedents, etc, for them, but we think we met the standard. Regardless, you know, if you can, you know, plan on a standard review, that's our base case, and I think priority review is upside to that. Your second question, sorry. Right. Thanks. Oh, Adcom. Mm-hmm. Yeah. Well, again, curious item. I mean, I think because it's new pharmacology mechanism of action, PDE3, PDE4 inhibition, new chemical entity and a first drug of that mechanism of, you know, for COPD, I think those are typical triggers for an Adcom. I balance that with, as we know it, and you've seen as well, the efficacy, the primary endpoint which has been used previously, the safety and overall benefit to risk being so compelling, I'm not sure what an Adcom would be reviewing at this time. Clearly we'll be prepared for one. Yeah, agreed. Makes sense. Thank you so much. Our next question comes from Joon Lee with Truist Securities. Please. Hey, congrats on the data, and thanks for taking our questions. You know, you have data as monotherapy and as add-on to LAMA or LABA. As you're talking to pulmonology, what proportion of COPD patients do you think ensifentrine would be used, you know, as monotherapy in frontline or as an add-on to either LAMA or LABA triple therapy? I have a follow-up question. Yes. Well, I think, Joon, I think, it's an interesting question. Actually, I think that the data patients, you know, frontline therapy, clearly those were included, you know, frontline in the sense that they were not on currently on background therapy included in the study, on top of because of the benefit to risk that exists with ensifentrine, I also think it, you know, makes sense to use it in symptomatic therapy they may be on. Those are patients that we studied as far as being symptomatic. You know, because of the ability to look at the effects fairly quick, dilation can occur after the first dose. Of course, the symptom improvement we've seen in that four - six-week timeframe, exacerbation, rate reduction has seemed to separate at that six-week period. you know, all of those lend itself to looking at ensifentrine and seeing if it can help patients who are symptomatic. In many ways, I think it's up to the physician to utilize it where they see fit, and I think there's a role for it across the spectrum of COPD patients. Right. You know, it was interesting to see roflumilast and anti microbials are added in the GOLD 2023 guideline, you know, algorithm. Do you think ensifentrine could be included in an algorithmic way to, in the treatment of COPD? I have one last follow-up. Yeah. absolutely. you know, once the drug is approved, assuming that it gets approved, it will certainly be assessed by those committees for where they think the appropriate use is. you know, guidelines are guidelines or strategy document, whatever, you're looking at. you know, I think physicians, especially in the U.S., are inclined to treat the patients the way they feel that they need to be treated. While those can be aspirational documents, you know, I think today what we understand is that most patients are still being treated by ICS/LABAs and LAMAs, and that's also who we had enrolled in our trials. All right. Last question. You know, after Dr. Anzueto's late breaker presentation, one of the audience member asked, maybe because he thought the exacerbation data was too good to be true if social distancing during the pandemic had anything to do with the exacerbation data. I couldn't really hear Dr. Anzueto's response, but what would be your response to that question? Sure. You know, we've looked at the exacerbation rates, both in our trial and that would be in the placebo arm, of course. Also other trials that did not enrich for patients with exacerbations. If you're looking across those rates, the rates we saw in our trial are very consistent with other trials that have not enriched for exacerbations and also are very aligned with general population rates in moderate and severe COPD patients, which show that you typically see a COPD exacerbation in 26 - 40 patients a year. That's right where we were in terms of exacerbation rate. I think, you know, in terms of background therapy used in the ENHANCE trials and also the exacerbation rates that we saw is very, very consistent with the broad COPD population and makes the results of the ENHANCE program very translatable to the real-world setting. All right. Thank you. Our next question comes from Swayampakula Ramakanth with H.C. Wainwright. Please go ahead. Hi. Congrats on the presentation. Thanks for taking our questions. Two from us. Maybe firstly, in slide 18, where you talk about your responder analysis of ERS and SGRQ. I'm just curious why there is a greater separation at week 12 versus, at week six and week 24. Just curious if there is any particular reason, because the delta appears to be fairly large versus, you know, the delta at week six or week 24. Sure. I don't think that's a signaling maybe a real increase at week 12 versus week 24, and there's you know, no statistical difference between those two numbers. You know, I think we would look at that and see essentially 50% of the subjects are responders, no matter what. I mean, you're seeing that consistency in response over time. All right. Maybe one more. There is this general consensus, at least, in multiple publications have suggested there's a link between PDE4 inhibition and incidence of adverse GI symptoms. Have this notion in any way changed in light of your ENHANCE study data? If not, why not? Sure. I think, you know, with oral, with oral drugs, obviously you get that GI direct exposure just from taking the drug, right? You get a much, much higher concentration of PDE4 inhibition locally, and it makes perfect sense actually that if you have PDE4 mediated gastrointestinal effects, that you're going to see them with oral drugs. Ensifentrine is delivered to the lungs, to the site of action for patients with COPD, and our systemic exposures are quite low by design, in order to avoid systemic effects, because it's really the local effects that we're looking for here. You know, I think that the data that we have definitely supports, you know, our premise for the development of ensifentrine as an inhaled drug to avoid seeing such effects. Okay. Thanks again. Our next question comes from David Risinger with SVB Securities. Please go ahead. Hey, this is David Tarjan on for Dave. Thanks for taking our question, and congrats on the data. We'd like to ask about the speed of uptake across the spectrum of patient severity. In the past, you've talked about physicians telling you they want to use ensifentrine first as an add-on in their symptomatic patients kind of maxed out on double and triple therapy, and then moving to patients on single therapy later. Can you give us some more color on how quickly you expect prescribers to get comfortable with using ensifentrine in the later lines and then perhaps to the earlier lines, or if that's the wrong way to think about it? What have you heard at the conference on this topic? Thank you. Yeah, I think, you know, David, as we think about, like, speed of uptake, I think the thing that we have to ground everybody in is, you know, no matter what drug they're on today, we know that there are a significant number of patients that are symptomatic within the physician's office. Those symptomatic patients today are looking for new therapies. They're being transitioned to new therapies when they have increased symptoms like dyspnea or when they have a risk of exacerbation. That allows ensifentrine to really insert itself many times and very quickly into a treatment conversation with a physician. I think when we look at our market research and our discussions with the physicians, their excitement of being able to do something different in COPD and adding a new novel mechanism is an extremely compelling thing for them as they think about these patients that come into their practice, which allows the physician to potentially use that drug very soon, and allowing them to see the benefit within these patients. I think the important thing is when a physician does try ensifentrine, we believe that what they're going to see is in many of these patients are gonna see a marked improvement in lung function and symptoms. As Tara talked about, 50% of these patients respond to at least an MCID level within both ERS, the symptoms, and the quality of life scale. In that situation, the physician's gonna be able to see very quickly with very minimal risk, how these patients are doing, which further encourages use in other patient populations as they get that experience. I think that feedback loop and that mechanism of seeing patients do well, trying ensifentrine, seeing patients do well only enhances how quickly a physician will eventually uptake the product in their practice. Got it. That's super helpful. Maybe one more, if I may. On the exacerbation rate, it looked like the 48 week data were consistent with the 24 week data, if I saw that right. Just kind of a point to annualize event rate reduction across the arms. Correct me if I'm wrong on that. How have physicians kind of been reacting to that kind of effect size? You know, where does that figure into the prescribing decision? I think a lot of what we've heard today is more about kind of the dyspnea and the symptomatic improvements. I get that. You know, where does the exacerbation rate reduction come in for the prescribing decision, or is this kind of more important in the payer conversation? Thanks for that. This is Chris again. From a prescriber situation, exacerbation is just another piece of the equation. Remember, you know, the symptoms and dyspnea are stuff they deal with every day. Even in an exacerbation-enriched trial, you're talking about a patient having maybe one exacerbation a year. You know, you're preventing one or two events with exacerbation. It's a balance of helping that patient feel better while reducing that long-term risk of exacerbations. I think we believe the data from ensifentrine is very compelling in being able to give the physician the opportunity to do both with a novel mechanism of action. Your conversation around the payer is an important one because exacerbations lead to direct healthcare utilization costs. As you saw in the data, there is a trend and a sign that ensifentrine has reduced healthcare utilization. As we think about plans outside of Medicare Part B, as in boy, remember, ensifentrine is primarily reimbursed for Medicare Part B. That exacerbation data further enhances the overall value that ensifentrine brings to a payer. It also helps us as we think about how we're going to price ensifentrine in the future, because exacerbations do have a value to the overall cost of the healthcare system that are important for us to consider. That's very helpful. Thank you very much. That's all for me. This concludes our question and answer session. I would like to turn the call back over to David Zaccardelli for any closing remarks. Great. Thank you, operator. Thank you, everybody, for your questions. It was great to review all the data with you today, we look forward to keeping you updated on our progress, which we would expect next up is our NDA filing. Look forward to speaking with you all in the future. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.