Verona Pharma plc (VRNA) Earnings Call Transcript & Summary

I'm David Zaccardelli, and thank you very much for joining us today for a commercial and launch readiness update for ensifentrine for the treatment of COPD. Today, we're going to review a number of items. First, I am going to start with just a very brief introduction and overview, just to level set today on ensifentrine, COPD. And then I'll turn over the meeting to Chris Martin and Dr. Rutland, which are going to walk through, from a clinician point of view, the impact of ensifentrine in the treatment of COPD. And then Chris will give a very comprehensive update on where we are for launch readiness for ensifentrine, followed by a Q&A with the Verona team, which is here today to answer your questions. So with that, I just want to remind everyone, of course, we'll be making forward-looking statements during today's presentation, and please refer to all our filings for risk factors related to these forward-looking statements. So Verona Pharma, as you know, has a very good history of execution in the past several years. This has included running the ensifentrine Phase 3 trials called the ENHANCE program, during which we all know was a pandemic and successfully executed a program from 2020 to 2022 and with extremely positive results, which I know all of you are aware of, and we'll review briefly. We then submitted an NDA in June of this year and subsequently, received an acceptance to file for the NDA from the FDA and with a PDUFA date of next year, June of 2024. And with that, we continue to expand, in our view, additional pipeline products, which over the coming several months, you'll be hearing more updates on where we are on our additional programs with ensifentrine. So as you know, COPD has been treated primarily with 3 different pharmacologic classes over the last several decades. This includes long-acting beta agonist, long-acting muscarinic antagonist as well as inhaled corticosteroids. And really, the field has had limited innovation outside packaging or delivering these 3 pharmacologic classes in different formats over that period of time. And while these medications have been effective in their own right, there has been limitations and today, patients continue to be symptomatic even with this treatment. And so ensifentrine, which is a novel mechanism as a PDE3, PDE4 inhibitor as you'll see today, has incredible promise and opportunity for the treatment of COPD. And ultimately, we believe will actually change the treatment paradigm for COPD. You all know that COPD is actually a progressive disease, which there is no cure. Patients continue to be symptomatic and progress through their disease. The characteristics of this disease is, of course, shortness of breath, cough and infections. And clearly, the hallmark of treatment is really to help alleviate these symptoms and make patients feel better, breathe easier and be able to function and also to prevent exacerbations, which is also something that in COPD, we try to avoid because that is ultimately where patients continue to lose lung function with additional exacerbations. And as you'll see, of course, ensifentrine has impacted across the board, both improvement of lung function, improvement of symptoms, quality of life and has also reduced the risk and rate of exacerbations. When you think about ensifentrine, one of the key things to keep in mind for the opportunity is its novel mechanism of action, which allows it to be used fairly broadly within COPD. As a PDE3, PDE4 inhibitor, it has features, as I've alluded to, of bronchodilation or lung function improvement, anti-inflammatory activity, which ultimately impacts exacerbation rate and also increases ciliary function, which ultimately can improve sputum and clearing the lungs. And so when you look at that pharmacology and apply it to the treatment of COPD, you can see how impactful ensifentrine can be. And when you think about the opportunity for ensifentrine, it's grounded in this novel mechanism of action. And of course, the data that goes along with it. Just as a reminder, the Phase 3 program called ENHANCE was 2 trials: ENHANCE-1, ENHANCE-2 each had approximately 800 patients. They were double-blind, placebo-controlled trials in which we enrolled patients with COPD, moderate to severe, either on background therapy, a LAMA, a LABA and some of them also an ICS in addition to their bronchodilator or not receiving any background therapy. They all had compromised lung function, as I mentioned, were symptomatic. And with that, they were randomized either to receive ensifentrine 3 milligrams twice daily or placebo. And everyone knows the data that was reported out late last year and incredibly positive results in meeting the primary endpoint was improvement of FEV1 at week 12 and improvement of lung function overall symptoms and reducing the exacerbation rate and risk. The data presented here in summary format really shows you the consistency of the data, not only on improvement of lung function, as I mentioned, the primary endpoint of improvement of around 90 milliliters, but also peak FEV1, trough FEV1, symptom improvement, exacerbation rate and risk reduction of around 40%, which we think and we know is quite dramatic in this disease. And then all of that with a safety profile that is very favorable and essentially, comparable to placebo. And so when you think about that efficacy, combined with that safety profile, you have an incredibly compelling benefit to risk, which again, is going to play a significant role in how ensifentrine is utilized broadly in the treatment of COPD. I already mentioned that the PDUFA date is next June, June 26, 2024, to be exact. And based on approval at that time or on that date, while we've been guiding that the launch would be in the second half of 2024, which is still the guidance, you can say, practically speaking, that would be in the third quarter of next year. So it is coming up very quickly. And with that, there's a lot of preparation and readiness to make sure that we deliver ensifentrine to physicians, patients and commercially becomes extremely successful because of its profile of efficacy and safety. Verona is also very well-funded, which, of course, is necessary in order to launch a product. As of the end of June, we had around $270 million in the bank. We have access to another $130 million in debt. So $400 million of excess, which keeps us extremely well-funded through the end of 2025 and through the launch. So we're quite pleased with that. And as you've seen in our history in which we've raised close to $0.5 billion, we'll continue to make sure that our balance sheet is structured in order to support the launch. So with that, I'm going to turn it over to Chris Martin, who heads up our commercial team as well as Dr. Rutland and they are going to walk you through, from a clinician point of view, the impact of ensifentrine in COPD.

With that color, I'd like to invite Dr. Rutland to the stage right now. And doctor -- we're privileged to have Dr. Rutland here. Dr. Rutland is a pulmonary critical care physician in California and most recently was actually the keynote speaker at CHEST. And so Dr. Rutland brings a nice perspective on what physicians are dealing with on a day-to-day basis when they see COPD patients in their practice. And so Dr. Rutland, it would be great if you could just give the audience a little bit of background on yourself, where you trained, a little bit of background on your practice and just so that they understand the context.

So I'd like to be called Jamie as my mom calls me. So please call me that. Again, I'm a pulmonary critical care physician in Southern California. I have my own practice. And in the other 1/2 of my time, I spend educating other physicians around the world about reactive airway disease, whether that reactive airway disease is asthmatic or whether that reactive airway disease is COPD or whether it's an interstitial lung disease, which is an autoimmune lung disease. And in the process of doing that and understanding the way that cells communicate with one another, the cells of your lung, and how that leads to systemic inflammation as well as lung inflammation, have been able to communicate that message to the public. And I've done that for, I don't know, almost a decade now in addition to running my own practice. I trained at the University of Iowa for medical school and residency and then I went to the University of Kansas for pulmonary and critical care fellowship, which is where I honed my skills in autoimmune lung disease. And then I've been practicing now in Orange County for about a decade. And that's pretty much my life.

That's great. And Dr. Rutland, you see a lot of patients in your practice today. Can you talk a little bit about how a COPD patient presents? And I know you have a few slides that you want to kind of cover, so can you walk the group through kind of what COPD is, how they present, and then we'll get to some of the questions that we have.

Yes. I think the most important thing about COPD is to understand that every single one of us takes a deep breath every single day and the way that our lungs work is there's a bunch of pipes that lead to a bunch of balloons that are stacked on top of one another. And what people don't think about is that when you are outside and you're in that environment, there are multiple molecules in the environment that you are snatching and introducing to the inside of your body, which is your lung cells. And when you have that genetic predisposition or if you're bombarded with molecules that activate that inflammatory response in the airway, it leads to cellular communication at least to the recruitment of white blood cells, which are trying to help, but also damaging your lung. And they do this through multiple different mechanisms and there's multiple different molecules that are involved that lead to this damage. And so some of these molecules are going to lead to this persistent inflammation and you have patients that present with chronic bronchitis. That is they are inflamed; they stimulate the cells that make mucus. You get a lot of mucus production in that airway and those patients are coughing all the time. And typically speaking, we describe those patients as blue bloaters, that's a COPD patient. Also a lot of the time, and I like to think about my mother-in-law, who's currently going through this, they can develop dead lung, which is emphysema. So like I said, your lungs are pipes and balloons. Inflammation of the pipes is that chronic bronchitis type of patient. Inflammation and then destruction of the balloon is that emphysema patient. That's dead lung. And so actually, what ends up happening is we used to say, and I would always have this discussion with my attendings, "Hey, listen, like does this patient have emphysema? Does this patient have chronic bronchitis?" Well, these patients actually have both. Not only do they have inflammation of the pipes that are carrying air to the balloons, but they also have damage and destruction of the balloons secondary to that inflammation or the molecules that they're constantly surrounded by where they live in a heavily polluted area, whether they're a smoker, whether they live -- whether they're a house cleaner and they're always spraying those chemicals. All of that exposure leads to these conditions that we see on a daily basis. And again, shortness of breath, mucus production, inability to exercise, inability to take that deep breath, inability to breathe air out, which is how we measure the severity of lung function through what we call that FEV1.

Let me ask you a little question on this. Like as you talk about -- as you see a patient that's dealing with that, what do they talk to you about? How does their life change and what goes on with them?

So there are 2 personal stories that I have. So the way that their life changes is that they can't do the things that they once loved to do. My grandfather had emphysema and chronic bronchitis really bad. And he was like a scratch golfer. He was so good. And one of the last events I got to spend with him was I got to take them on the golf course and we got to play a round of golf. I had to drive him to every single ball so he could swing the club, but he couldn't do -- he couldn't walk the course. And he continued to remind me of that, "I used to be able to walk this course. I can't do this anymore." He was very sad by that, not able to do the things that he loved. And my mother-in-law hasn't been able to come to California to see us because of her significant emphysema and chronic bronchitis. She just doesn't feel up to par to be able to walk to the plane, walk off the plane and be able to do the things that she once just took advantage of that we all do on a daily basis as we're walking the streets of New York. So I think that's the thing that really has a profound effect on us as physicians and on our practices is that patients have this inability to do the things that they never thought they wouldn't be able to do throughout their life.

Yes. That's really good perspective. I think one of the things you mentioned, too, is like this isn't going away either in these patients.

It's not going away. And again, the way that I like to explain and I do a lot of this for the American Lung Association is when you look at air pollution and you look at those -- if you look at the countries where you have a lot of COPD -- or not countries, the cities that have a lot of COPD patients, those are also the cities that have the highest air pollution. And that is an issue that is going to continue. And so as they're bombarded with the dirty air, they're going to develop inflammation, and it's important for us to educate these patients on inflammation and have therapies that can act in different ways to combat the inflammation that's constantly happening.

So I think there's a couple of other slides here. You talked a little bit about dyspnea, but you have a couple of images here, too.

Yes.

Walk us through those images.

I really think it's important. This is -- these are histologic images. And so what these are is these are actually cross-sections of the lung. And if you look at the picture that's on top, what you have there is you have the pipe that's carrying air to the lung, the bronchial. And what you can see is you can see a lot of purple, which represents the inflammation that we're trying to combat. So you have a lot of inflammation in the muscle that's surrounding that pipe, the muscle's like pink right? And you see that inflammation, you get this infiltration of white blood cells that leads to bronco constriction. And you can see how narrow that hole is, right, that bronchial is. And that is the wheezing, right? You don't see mucus here. I didn't pick a picture that has mucus here, but that is bronchoconstriction; that's wheezing. So when I put my stethoscope on a patient's back when I'm listening to them, and I hear wheezing, in my mind, this is what I'm imagining, I'm seeing, I would see if I were to biopsy their lung. And on the picture below, that is emphysema. That is dead lung. You can see the big white spaces there. And again, you also have around the -- that's a bronchial there. You can also see purple around that bronchial. So you've got some inflammation and then you've got dead lung that surrounds that area. And that all leads to the symptoms that you're seeing there on your lefthand side, you're going to see patients with cough, wheezing, chest tightness, and they're going to have fatigue and weight loss. The reason they have this weight loss and anorexia is because they're spending so much energy trying to take a deep breath. They're using other muscles to try to take a deep breath. That's just burning their energy, and so they get weight loss and anorexia from that.

So as you see a patient that comes in, how does your maintenance treatment pathway change? How do you treat these patients today? And how often do these patients kind of cycle through therapies within the practice?

Yes. It's a great question. When patients initially present, right, now we have products that have all 3 of the medications that you mentioned, right, the inhaled corticosteroid, the long-acting muscarinic antagonist and the long-acting beta agonist. Again, I'm a mechanism guy. I'm a little bit of a mechanism nerd, I would say. And so understanding how these molecules work, right, the inhaled corticosteroids, which are genetically altering some of the expression of proteins that lead to inflammation, great. Long-acting muscarinic antagonist, you have these receptors on the smooth muscle. You also have receptors on white blood cells that inactivate the white blood cells and help with inflammation, but also dilate the bronchial. You have long-acting beta agonist which also dilates the bronchial. But we have to fully understand that there are so many different pathways to inflammation. And with phosphodiesterase, understanding that CAMP or C-A-M-P, which is the molecule that we're helping increase, these are second messengers. And what these second messengers actually do is they tell the immune system to calm down, right? They tell the cilia to beat faster, right? They activate some of the ion channels that lead to mucus becoming thinner. And so when you look at these pathways and you get a full understanding of how they complement one another, it really helps us look forward to medications that are going to add to the value of treating our patients that are on some of these therapies. Now most patients are just on a LABA and an ICS, right? But now we've been able to add the LAMAs, although it's not as many as you would think, which you're, I think, going to present in a moment. And so having visibility as well helps us combat the inflammation that is actually pretty common in this country.

So you mentioned a little bit about the PD mechanism. And if ensifentrine is approved, how do you see ensifentrine fitting in to how you manage these patients on a day-to-day basis? Like what do you see the -- how do you see it being used? How do you -- what are your thoughts there?

Yes. The wonderful thing about ensifentrine is that it's a nebulized product, right? Patients love their nebulizers for some reason, and I can't explain it. They love to have a machine that they feel like brings them relief, and they look forward to using this machine. So a lot of my patients ask me questions like, "Well, can my triple therapy -- can I get it in the nebulizer, right?" Like they want it in a nebulizer, they just want to have it. So knowing that you have a product that can be delivered through a nebulizer is key, right? So I see it fitting in as either being an add-on or being an initial product. And knowing that it's a bronchodilator, I can't help but think that physicians that take care of these patients acutely, urgent care, primary care physicians, even ER physicians wouldn't think of a product like this because it's nebulized and it's so easy to use and it's so familiar to the patients and familiar to physicians.

You mentioned a little bit here on the nebulizer side and patients' comfort with them. Is it common that patients have nebulizers even though they maybe don't have long-acting drugs in those -- in that delivery?

Another great question. That is a generational question. So if you look in my practice, right, the people who have a life experience of about 60, 65, all of those individuals pretty much have a nebulizer. The individuals who have a life experience that is 50, 40, they don't have a nebulizer as much because you can actually see that physicians, when that data came out that showed that the inhalers and the nebulizers were kind of the same in terms of FEV1 and things of that sort, they just started giving them the inhaler. But patients that had had experience with a nebulizer wanted the nebulizer, right? And so I think that having that experience has led to patients wanting it. And in fact, I had a patient -- actually 3 patients just last week asking me for a nebulizer. I've got no problem prescribing it. It's easy to prescribe. But I think you're going to see more and more patients wanting a nebulizer because as they use these inhalers and they feel like they're not getting enough, which you're going to talk about, too, they're going to ask for other delivery devices. And that's where I think the nebulizer comes into the fold and they start to ask, "Can I get this?" Because when patients present to the emergency department, what do they get? They get a nebulizer. It's [ mealy ] what they get. The respiratory therapists in the hospital, their primary job in the way that they're distributing their work is who is getting a neb on which floor and who gets it twice a day. So they're doing this every single day. So nebulizers are common in the hospital. Patients associate that -- if they go to the hospital, they associate it with a good outcome because they were in and now they're out of the hospital, so they ask for it.

So let me ask you this. You mentioned an interesting dynamic here of patients needing new therapies and nebulizer being common. Ensifentrine will be the first time that a drug is only available in a nebulizer. How does that dynamic maybe even enhance how nebulizers are -- how does innovation in a molecule actually enhance maybe the route of administration for you as a physician?

I think what it does for me as a physician is once you understand the mechanism of ensifentrine and you understand that product, knowing that it's only available via nebulizer, this opens your mind a little bit. And it's like, okay, wait a second, these nebulizers are very effective, especially for people that can't take a deep breath, people that can't generate the force necessary to get all of the drug from the inhaler into their lung. So a nebulizer is beneficial, right? And so I think it just opens up -- the younger generation of physicians, it opens up their mind a little bit to the nebulizer as a tool to enhance the therapy of individuals that are suffering from reactive airway disease.

Yes. You mentioned a little bit, too here on ensifentrine being either an early initiation or an add-on. Many patients remain symptomatic on all these drugs. At what point in time -- or how do you introduce the molecule to a patient in that situation? Like walk us through kind of how you would describe ensifentrine to a patient if you were going to prescribe it.

So I think the first thing to describe is the normal, how your body normally acts, how the lungs normally work. And then what you do is you go through the mechanism of inflammation, which leads to the patient symptoms. And as you're going through the mechanism of inflammation and you start to describe the strategies to combat that inflammation, that's where the opportunity to introduce this product serves itself, right? And so what you have to do is almost at least from a physician, nurse practitioner, PA standpoint, you have to educate them and remind them that a bread-and-butter disease like COPD does have a cellular pathophysiology that needs to be understood, right? And I think that we have to do that because COPD has become so bread and butter that most people don't think about the mechanism. And so primarily, at least my job has been to reinitiate that education, reteach that education so people can understand the cellular mechanism. And when you do that, then you can introduce the therapies and how they work, and that's where you can introduce ensifentrine. Now the obvious question is going to be, well, what's the best one? That's -- and the way that I always answer that question is it's not about the best. It's about how are we going to combat that inflammation in terms of cell receptors and response. And when you have a product like this that's not only a bronchodilator, but also an anti-inflammatory while enhancing those ion channels and cilia, you see that this product affects the airway in more ways than the other products do. And so that's what makes it effective. So for me, as an early adopter and in understanding the cell communication, the way I do, if I could -- and that all depends on how the product is approved, if I could, I would prescribe this product and recommend to prescribe this product when a patient comes in to see you with COPD. But that's me, and I understand how this product worked and how it has a positive effect on a very inflammatory environment in a patient's lung.

Yes. No, I appreciate that perspective. I think we'll show some market research a little bit later, where Dr. Rutland talks about how he'd use it. I think what we see from physicians out there today is a very similar trend of ensifentrine has broad applications across the treatment spectrum. So again, Dr. Rutland, Jamie, we appreciate you being here. Jamie will be here for additional questions. And if you want to talk to him afterwards also in the question and answer, you can ask him questions as well. But again, we appreciate you taking time from your busy practice and coming out here to join us. So thank you.

No problem. Thank you.

So let's talk a little bit about where we're going. Dave talked about launch. It's not very often that you get to walk into an opportunity where you have a drug that Dr. Rutland, Jamie described, that looks like ensifentrine. We have a drug that has a novel differentiated profile. We have a market that has a significant unmet need, and we'll talk through this. We think about how are drugs successful and launches? How are launches successful in biotech? How are they successful for pharma? They have to have 3 things. They have to have unmet need. There has to be an unmet need in the market. They have to have a product that's differentiated and ultimately, we have to be able to get access to the product to physicians. And so we're going to talk through all 3 of these things as we think about the market opportunity. But the first thing I want to just ground everybody in is that COPD, as Jamie described, is not just 1 patient here, 1 patient there. It's 380 million patients worldwide. It's still the third leading cause of death and it's a substantial burden to the U.S. health care system and actually the world health care system. If we think about today, we've talked to a lot of you guys about various different regions. We've talked about Europe. We've talked about China before. But today, our focus is about the U.S. As Dave described, we have a PDUFA date of June 26. We're going to talk about how we're going to get ready and be prepared to launch this drug as successfully as possible. If you think about the market today, there's 8.6 million treated patients in the U.S. Those are chronically treated patients. There's about $10 billion in sales. It's a tremendous opportunity. But there are a lot of big markets with a lot of patients. The question is, is are these patients still dealing with symptoms, dealing with issues that new drugs can help? And what we know about COPD and what we know recently is that COPD patients are dealing with very persistent symptoms. And this burden is sometimes hit into the physician and these patients are very willing to try new drugs. So if you look at the screen right now, this is a published study from 2022 of 2,000 currently treated COPD patients, where we asked or where an outside vendor asked, "How are you feeling?" And what you see is almost 1/2 the patients are having symptoms for 24 to 30 days a month. As Jamie described, his grandfather or his mother-in-law, think about dealing with those symptoms every single day of the month. And so what that ends up happening to these patients is they have an unbelievable burden on their impact of their everyday life and their emotional health. So as we think about the times when we're supposed to be having fun, we're supposed to be enjoying time with our grandkids, we're supposed to be enjoying time, maybe in retirement, this disease is causing these patients to step away and become isolated. That's one study. Well, there's another study. Everybody says that when a patient gets on a dual and triple, we've maximally done what we can with these patients. This is a study looking at patients on dual and triple that have been maintained for at least 6 months. And what it shows is that -- and it shows that these patients are still dissatisfied. And it's not because these drugs aren't helping these patients. It's because we're dealing with a progressively declining lung -- we're dealing with progressively declining lung function and increasing symptoms. And you see that these patients have dyspnea, lack of energy, lack of sleep. Jamie described this perfectly as he was talking about what these patients deal with on a day-to-day basis. So what this tells us is that we do have -- there is a large market, but there's also a huge unmet need in the marketplace to provide new mechanisms, new therapies for physicians to be able to help the patient progress and maintain a lifestyle that they're hoping to live as they grow older. So how are patients treated today? And I think this comes to surprises for the physicians and also to investors in the room is everybody thinks patients are on triple LAMA/LABA, ICS. But in reality, of the 8.6 million patients treated in the United States, 60% of them are on either a single bronchodilator or LABA, ICS. That is the ENHANCE trial population. We know that about 1 million patients are on dual bronchodilators and then we know about 1.6 million patients are on triple. What we also know is it doesn't matter what they're on. At some point in time, they're going to deal with persistent symptoms that are going to cause them to seek for new therapies and hope to get treated by their physicians. And so what else do we know about these patients? Jamie talked about nebulizers. Recent data that we have shows that at least 50% have a nebulizer. I think we had a discussion last night that 50% seems like a low number. But based on experiences from physicians and what they're seeing in their practices, but at least 50% of these patients have nebulizers. We also know, as Jamie described, that physicians are very comfortable prescribing nebulizers. This isn't a new thing. It's not like the doctor's never seen a nebulizer before. And so what they say is that they believe that nebulizers provide a little bit faster onset of action. They help with the efficacy. They help the patient get the product to where it needs to be. It goes to the lung. They know it's working. And then from -- intrinsically because of the reimbursement pathway, they think nebulizers are much less expensive and have lower out-of-pocket costs. But when we see the actual WAC pricing, they're not. But because of the reimbursement channel, the doctors see that these drugs can be received by their patients at a low out-of-pocket cost. So again, what you not only see now is you see a significant number of patients treated, you see a high unmet need, but you also see the route of administration is common for many of these patients. So now when we sit here and say, well, how does ensifentrine fit into this whole world? We have a brand-new drug that's fitting into a large patient population, lots of patients symptomatic, how does it fit in? What you see here is recent market research where we showed physicians, like Dr. Rutland, profiles of ensifentrine. And you can see on the left or on the slide here, that these attributes are those that are important to physicians when they prescribe. So these are things they think about, tolerability, mechanism of action, reducing exacerbations, improvement in lung function. And regardless of the attribute, ensifentrine is on the righthand side of the scale, meaning the physicians see this as a highly differentiated product. This is something they haven't seen before. Remember, the last 10 product launches in COPD have been a LAMA, a LABA or an ICS in some form or fashion. They've not seen something that looks like this. And this excites them. What excites us is this next point. It's amazing to have a differentiated profile, but am I actually going to use this product? And what the research tells us is that when we survey physicians and show them what ensifentrine can do, 90% of them will use ensifentrine in the patients that they see in their practice within the first 12 months of launch. I've been around the industry for a long time. I think my team and the team here has seen a lot of different launches. The 90% number is unheard of. It's really high to see this type of adoption. And it speaks to 2 things. One, it speaks to what we need to be as successful. You need to have a product that's not a -- you need a differentiated product. This is a differentiated product. And then 2, it speaks to the significant unmet need that exists in the marketplace. Doctors wouldn't be willing to prescribe this, this quickly if your molecule wasn't differentiated and if they didn't see patients continually dealing with persistent symptoms. So this really gets us excited as we think about how we're going to prepare for launch. So now let's go back to the 8.6 million patients. And we're like, well, how does ensifentrine get used here? How do we -- how does ensifentrine potentially get used if it's approved? And what physicians tell us from a patient share perspective is if we take that largest group of patients, which is 60-plus percent of the patients out there, that ensifentrine could be potentially used between 15% and 20% of the time as an add-on to these patients. Why? The ENHANCE data, as Dave described, the next logical choice based on that data for these patients should be ensifentrine based on the data. And two, they're going to have continued symptoms. None of these drugs unfortunately stop the progression. They continue the progression. So they need another drug. So now let's talk about this other group of patients. These patients are on dual bronchodilators, LABA and triple. Well, the doctors think about using ensifentrine even more in those patients. You might ask, well, why is that happening? Well, and Jamie can talk about this. At any point in time, during that time when a patient comes in symptomatic, his choices are extraordinarily limited. And he wants to help and doctors want to help patients feel better. And so when they look at ensifentrine's profile, potential profile that shows bronchodilation, non-steroidal anti-inflammatory effects with limited or a very positive benefit/risk profile they say, "I can help these patients in a significant way potentially." So we see this higher share here. And what this tells us is we have a tremendous opportunity with ensifentrine to be able to reach a significant number of patients and potentially help a significant number of patients if approved. So the other question we always get, and we talk about as well, some patients have nebulizers, some patients don't have nebulizers. So we asked physicians, if a patient has a nebulizer, does your way you use this product change? And then actually, if they have some experience with a nebulizer, it's really easy for them to add ensifentrine to them. You see it here, it's up to 56% of the time they're adding ensifentrine. But what's interesting to us here is, as we talked about a little bit earlier, it doesn't matter if they have a nebulizer because in the patients that are "nebulizer inexperienced", physicians are willing to add ensifentrine up to 37% of the time depending on the severity. Again, for us, this goes back to one key point. When you bring a differentiated molecule to the market, the route of administration becomes secondary. If I'm talking about me-too products, and I'm talking about products that are the same products and different delivery then convenience and route of administration becomes important. But if I'm talking about a product that provides bronchodilation, non-steroidal anti-inflammatory effects in one molecule, route of administration becomes the way to get this product to the patient, and you see that the physicians see that very clearly. So this makes us very encouraged in how we think about how we're going to go to market and what that uptake could look like. So then the next part of a successful launch is you have to have access. We've all been in situations or you've all seen situations where a drug sounds great and then they launch it and the doctors can't get it. And I've been involved in that. I think my team has been involved in that and access can be challenging. Well, the dynamics for nebulizers in the U.S. is very favorable from an HCP and an access perspective. And the reason why is because nebulizers get reimbursed through the medical benefit or primarily through Medicare Part B. So what happens in Medicare Part B and Medicare Advantage, which has to act like Medicare Part B? Well, within those channels, they have --physicians and we have 100% access. Reimbursement is tied to nonspecific, product-specific J-Codes, local coverage determinations and this results in low out-of-pocket costs. We see this today where YUPELRI, which is close to $1,400 a month, 80% of their patients pay less than $10. It's because of the way the channel works that allows the physician to write the drug where they want to write it, and then the patient gets it for a low out-of-pocket cost. We do have to consider the other side, which is the pharmacy benefit side. And what we see with the discussions that the managed care team has had is that there's a high willingness to add ensifentrine. They understand the burden that exists within COPD. They understand that COPD places a tremendous burden on the health care system, and they see a new mechanism as something that they would want to add. We also have the benefit of the mechanism because our mechanism is not a substitutable mechanism. There's no other PDE3, PDE4 today. And so in the compendium, which is where managed care goes to look for like substitutions, ensifentrine, we believe would be listed as an N-of-1. This helps us from an access standpoint and puts us in a good position when it comes to ensuring that when a physician like Dr. Rutland wants to prescribe it, that they can actually get it to the patient. And that's what we ultimately need to do. And so let's see this in action. This played out 2 years ago, 3 years ago. So we have 2 products that, I would argue, are 2 undifferentiated assets. They're 2 LAMAs, both delivered through nebulizers. YUPELRI is different -- is delivered through standard jet nebulizer like ensifentrine, and Lonhala is in a proprietary device. Lonhala launched a little bit sooner. And because it's in a proprietary device and doesn't have Durable Medical Equipment designation, it goes through Medicare Part D. So what does that mean? It means that physicians write it, like Jamie will write it, and it gets rejected because Medicare Part D doesn't want to pay for that type of a product. But within a Medicare Part B pathway, you can see how a drug where physicians see utilization and see the ability to put it to help a patient because it actually gets the LAMA to the lungs, it continues to grow year over year over year. This is not a difference in product; it's a difference in channel. That's what this shows. And for us, what it shows, imagine what you -- what happens when you put a product that's a differentiated product in a channel like this. So let's talk about pricing. Let's talk about how these products are priced today. And so in the blue, what you see is how the current DPI or MDIs are priced. You can see that closer to the $300 range or what we consider single bronchodilators or dual bronchodilators, but you can also see as the value to the patient and the physician increases, the price goes up. TRELEGY is almost double the price of some of these other products out there. And then as you move to a different route of administration, a different delivery, you see the price moves again. And you can see the nebulizers somewhere clustered between the $1,100 and $1,300 price range today. And then what you can see is Dupixent, which has what I would -- has now data in COPD and is used potentially off-label in there as an endpoint of almost over -- almost close to $4,000 a month. So when we think about the dynamics and what the value of ensifentrine is to the marketplace and we compare it to what the other nebulizer products look like, the other nebulized products are single LAMAs or LABAs. They have bronchodilation effects. They don't have effects on exacerbations. They don't have nonsteroidal anti-inflammatory effects. Our value is different from where the current products are. So we believe there's flexibility in the way that we will be able to price ensifentrine in the future. If you think about how you might characterize this, the current nebulizers are the floor and Dupixent is probably your ceiling. But there's flexibility from us from a pricing standpoint because of the value that ensifentrine brings to the marketplace. So let's kind of bring this all together. I said at the beginning of this, that in order to have a successful launch, you have to have 3 things. You have to have a large market with significant unmet need. I hope that you guys see that there's a huge -- COPD is a huge market, but 50% of these patients are still symptomatic and there's a high dissatisfaction with it. I think you're here because ensifentrine's not -- differentiated. Our physicians see that it's differentiated. It's something that's not been seen in the market for a long time. So now we have the second run. So you have large market unmet need. Now you have differentiated product with high adoption and high utilization across background therapy, across nebulizer use. And now we just got to get it to the patient. We got to get it approved. And we have what we believe is a favorable access environment, because of Medicare Part B, and that gives us flexibility on the way we price. So this is how we view the market today, and we view the market as a place where ensifentrine can come in here and successfully compete. The question that all you guys probably have in the room is, well, how is Verona going to do this? And what is Verona going to do to get to that next point? And that's why we're here today. We're here to talk about how we're going to get ready and what we've been doing over the last 12 to 18 months. And what it does is it starts with people. We all work with really good people, but we build a company based on the people that we bring into an organization. And I think at Verona, we've been very lucky under Dave and Mark's leadership to bring in the right people. Between the organization and specifically on commercial, we have over 50 product launches. These products are some familiar products on the board here. They're billion-dollar products, they're multibillion-dollar products. They're in different therapeutic categories. Some of them are medical benefit drugs, some of them are pharmacy benefit drugs. The importance of this is it gives us different perspectives. It allows us to challenge the process and make sure that we're doing the right work necessary to launch a drug that looks like ensifentrine. And so how has this team come together? Well, Kavita Aggarwal who's here today, runs our Medical Science Liaisons team, our Medical Affairs team. And that team has been in place since the beginning of the year. They've been talking about -- to KOLs from a broad KOL engagement standpoint. They've built an extensive publication plan that includes not only abstracts, but publications that continue to talk about the potential of the disease and also ensifentrine. From an access and reimbursement standpoint, our payer team has been in place since the early part of this year as well. We've had payer conversations with all the major MAPD, Medicare Advantage plans. We finalized our hub and distribution model, and we'll talk about that a little bit today. And then from an overall infrastructure standpoint, the leadership team on the commercial side has actually been in place since the summer of 2022. And from a systems and an IT perspective, we've identified and actually implemented all the things necessary for us to launch successfully today. And so we are well -- we are 9 months from PDUFA, we are well ahead of schedule to be able to launch this drug appropriately. So let's talk a little bit about Medical Affairs. And what do they do? And what are they doing today? So their main job today is to engage HCPs. And during that time, they're engaging the HCPs, they get insights. Part of the discussion that we had here with Dr. Rutland, Jamie today is from the insights gathered between Kavita's team and the interactions they've had. From there, we have to look at it internally and analyze what we're going to do. And that involves a cross-functional team of medical, commercial, clinical to develop how are we going to give new evidence? And what are we going to do from an evidence generation standpoint? That leads to medical communication and education. You guys have seen this, this year. We had 12-plus posters at ATS. We had another 5 or 6 at CHEST. We had stuff at ERS. I know the team is also looking at places where we can encore-present this data as well because the data is phenomenal. So we take that data and then put it in different places. And the team has done a great job there. And then we go back to physicians like Dr. Rutland and we reengage them on what we put out there. This process doesn't end and has been going on for the last year. And so how does that lead to 2024? Well, the team will continue to engage with KOLs. They have a -- you will see in 2024, a significant publication and abstract plan, at both CHEST and ERS and ATS as well as conferences that are really important: a nurse practitioner conferences, physician assistant conferences, places where prescribers go, we will put information in front of them. Then we'll be at the places where physicians are. It's important for us to attend certain conferences. It's important for us to be at ATS. We were just at CHEST 1.5 weeks ago. It's important for us to be at the GOLD Conference. It's important for us to be at smaller conferences on the managed care side. And the team has been there and will be there in '24. And this ultimately will lead, once the product, if approved on the market, to real-world evidence generation and health care economics data that help support the brand's growth overall. So that's where Medical Affairs sits. Now what does -- if we think about, if we put commercial and we think about commercial as sales, marketing, training, market access and trade, what do we have to do to be ready? And we've thought about it as a team and really it comes down to 3 things and I'm a big fan of being simple. So the first thing is we have to educate on the burden of the disease. We've shown you a bunch of stuff on how patients are feeling and how physicians are feeling. So we have to do some work here. For the doctors, they've seen the same thing for the last 10 launches. So we can't just walk into the marketplace and say, "Here we are, we're a new mechanism." We've got to give them a little bit of work on what's going on in the marketplace and why new mechanisms are necessary. The second thing is we've got to make sure that we identify the right doctors to call on and the right patients for launch activation. And then the last thing is we've got to make sure the customer experience is good. And what I mean by customer experience is not just the physician, it's the patient. We want to make sure both customer experiences are good. And so we'll talk through each of these as we go through the next 20 or 30 minutes. So let's talk about the first thing. Discuss and educate on the burden of COPD. I've shown you some of these stats, but there's a lot of work that's happened since 2020. Verona as a company has invested a substantial number of time and effort to make sure we understand what's going on from an HCP and a patient perspective. We have over -- almost 1,000 HCP interactions through market research, and on the patient side, we've seen almost 3,000 patients through various methods. Well, this has taught us some stuff or it's led to some insights. And let's talk through that. What we see is that COPD is really -- the burden is a little bit unspoken in the marketplace. And the patients sometimes forget or are scared or are concerned to not talk about it. And from a physician perspective, they've done everything they can. Like doctors are not -- are giving patients what they have today, but they have limited mechanisms to treat these patients. So what's happening in the marketplace is this. When we ask physicians about triple therapy, they say they're 85% satisfied with the current triple therapy. But then when we ask patients, they say, "I'm about 50% satisfied. I don't feel good on these drugs, no matter what drug they are." And so we see a disconnect between what the patient and the physician feel. So then we go to, well, what do HCPs think about persistent symptoms? Well, they think about 20% to 40% of my patients are having persistent symptoms. We just saw earlier that it's at least 50% and there's a significant burden associated with those symptoms. So there's a disconnect here that's happening. And then this is the one that I think always surprises people, is physicians believe on the most of the time, their patient is being totally open, telling them everything that's going on in their lives, at least 1/2 the time, that's a good scenario. Well, the patient says, "I only do that about -- I don't do that ever. I do that 10% of the time. " So it's really important for the physician to ask questions and talk -- we've talked about this a ton. We have to spend time to understand the impact that's happening in the patient's lives. And it's understandable. Like doctors have a lot on their plates every day. There's a lot of work. There's a lot of patients they have to see and having this conversation may take a little bit more time. But it's important because if we don't, we don't see what's actually happening in the marketplace from a patient perspective. And so what are we doing about this? So we're going to talk about unspoken COPD. So what we know today is that the treaters, be it a doctor, a physician assistant, a nurse practitioner, believe they're doing the best they can and they are. They're doing what they have with the drugs they have today. But they're not sometimes fully aware of the chronic progressive nature and what the impact of that disease has on the patient. And it's natural. It's hard to remember this all the time. And so what we want to do with this is our unbranded campaign will highlight this persistent substantial burden that exists within the marketplace. And the goal is to just get them to think about and explore new ways to optimize care. We're not approved. This is about educating on the burden of disease at this point in time. And so what does that look like? So to truly understand what this burden looks like, we are asking physicians to put themselves in the patient's shoes. So what if every shower left you out of breath? So I think Jamie described his grandfather talking about trying to play golf. Just we all do this every day. Like just imagine doing that simple task leaves me out of breath. And what we hear from physicians is that this is a real struggle. This isn't something that we're making up. This is clear. It's a problem, and it's very common, and we forget about this sometimes. We go through our busy day and sometimes we forget that these little things are happening. What about this? We all walk our dogs. What if just walking the dog around the block left us gasping for air. This simple task is taken for granted by many of us in the room, but for a COPD patient, it's hard, and it's not easy for them to do these things. And so what we hear from the physician is , "It's what I hear in clinic. It's about the day-to-day activities when you have COPD." I want to keep this in mind because we all talk about exacerbations, that is amazing data. But the patients are thinking about day-to-day. They're thinking about how do I do a walk to a mailbox, how do I go play golf? How do I go to the grocery store? And so you can see that the doctors remember how debilitating this condition can be. And the last thing is what if just playing with a grandchild left you gasping for air? Again, the idea is it's not about FEV1 or lung function scores, it's about symptoms and how patients feel. And that's what we need doctors -- to remind physicians to think about. And so how this -- we believe is important is we believe it's important that Verona changes the conversation about COPD. The conversation about COPD has been about triple, dual, triple, we need to change how we're thinking about these patients and what we're talking to these patients about. And so at CHEST, 1.5 weeks ago, this unbranded campaign launched. It's in the early stages of the unbranded campaign. And at CHEST, there was targeted social engagement. There was a website. We data-captured people. We did search engine optimization and the unspoken COPD campaign launched at CHEST, 1.5 weeks ago. You might ask how many people visited? How many engaged with the site? We had over 2,000 interactions in a short 3-day period, 4-day period on this campaign. What that tells us is it resonates and that people are interested in learning more. What you see here is how the unbranded campaign will evolve over the course of the year. We're starting at CHEST today or last week, but as we move closer and closer to PDUFA, you'll see the unbranded campaign increase in its awareness and its visibility to HCPs. We'll also see more resources to be able to provide physicians the ability to talk and help their patients through this process. We think this is critical to ensure and set the stage for launch. We have to do this. We have to get people ready and understand what their patients are dealing with on a day-to-day basis. So if we think about this first pillar, this really is the foundation. It sets the stage for launch. If we're approved, this is the foundation setting that we need to do. We have to start with KOL engagements, which we've talked a ton about today. We have to put publications and scientific exchange out there. And then now you layer on the disease education campaign, which can launch -- which is launched and will now increase in omnichannel or digital promotion over the course of the next 6 to 9 months, we now have the foundation set for successfully moving into a launch of ensifentrine. So if we now move on to the second step is, okay, we have unbranded, we have the market shaping, how do we know who do we need to call on? How do we deploy reps? How many reps do we need? What does this look like? And the first thing we have to start with is what does the journey for a patient look like? Because we need to call on the doctors that are seeing the patients that are most likely to be using our drugs. So when a patient is initially diagnosed, they start in primary care. They get short-acting bronchodilators. As their lung function declines, their symptoms increase and they start to move from primary care to a pulmonologist. So when they are totally out of whack, they're primarily in a pulmonologist's office. And those persistent symptoms and future exacerbations lead to a referral to a specialist. And you say, well, in theory, this looks really good. Well, how does it work in real life? And we see this very clearly in the prescriber data today. This is recently pulled data. We're talking about what percentage of doctors write 70% of the volume of these products that have been recently launched? And what we know about this is these numbers here are primarily pulmonologists, nurse practitioners and PAs. And what we also know is that TRELEGY is over a $4 billion drug. And only 23,000 doctors write 70% of that volume. Think about that for a second. That's staggering to think that amount of volume comes from that small number of physicians. Then if we go to BREZTRI, which is between $800 million and $1 billion in revenue a year, it's about 11,000 doctors do 70% of that business. And then if we go to YUPELRI, which is a nebulized LAMA undifferentiated, you have a $320 million to $350 million run rate being generated by 1,500 doctors. These aren't big numbers of physicians that a company like Verona need to go to. This is very concentrated. So then we take this a step further because you know what? There's doctors that are in all these categories. And so in reality, when we look at this, if you combine all this business, there's 26,000 unique prescribers that we have -- that are really doing the majority of this business. And so when we dive in a little bit deeper, 77% of these doctors are pulmonologists, nurse practitioners or PA. Dr. Rutland can talk about how important the nurse practitioner and PA is in these offices. We believe that, that nurse practitioner and PA is a critical component to being successful at launch. They've become the physician extender, and they are the fastest-growing prescriber within COPD, and they are treating these patients on a regular basis and they spend more time, they dig in a little bit deeper. So we think this is critical. The other 23% are internal medicine, primary care and other specialties. But what you see here is a very tight concentration. So one of the questions we get all the time is it's a big market. You're going to need a lot of reps. Well, 26,000 doctors isn't a lot of doctors. If I told you how many doctors write 1 prescription, and we're going to talk about that, you're going to see that here. So if we break this down a little bit more. Verona is going to cover the busiest HCPs in COPD. So let's break this down. So we made this as simple as we could. There's a group of what we would call A physicians. There's 2,900 of them. They see about 153 patients a month. Then there's a drop off. It's not a short drop off. It's a steep drop-off. They see -- there's about 12,000 "B" physicians that see 45 each patients a month within COPD. Then there's another big drop off. And those are C physicians and those physicians, about 26,000 are seeing about 18 claims per month within COPD. And then this is where the big comes from, there's 370,000 physicians that write maybe 1 claim a month for COPD. So you look at this and say, well, where am I going to invest? Where am I going to spend my time? Well, from an organizational standpoint, we are going to set up our personal promotion or our reps in these A and B physicians. And then with virtual telesales engagements, we can start to talk to the C physicians. And that virtual telesales engagement has become standard practice. COVID has helped us because COVID now allows physicians to interact with reps in a variety of ways. Even our personal promotion to these A and B, we're set up to be virtual with these doctors because sometimes we need to meet the doctor where they want to be met. And we have set up the capabilities to do this. Layered on the bottom of this is omnichannel promotion. So that's a buzzword. Everybody talks about omnichannel promotion. So what does that actually mean? And we'll talk about that a little bit later, but we believe that we'll be in the offices of the busiest physicians and then we'll support that either through telesales or omnichannel promotion. So how does this really look? So if we go to these 15,000 doctors, they're writing all at least 1 -- let's just say, approximately 1 claim a day. There's about 400,000 that are way less than 1. So those 15,000 doctors live in 8,700 offices. So brick-and-mortar, they're in 8,700 offices, not a lot. And in those 8,700 offices, there's another 37,000 physicians. And so when we send a rep into a brick-and-mortar office to call on these 15,000, we're actually calling on almost 50,000 physicians because they're interacting in a broad sense. Jamie's practice, I think, has himself and nurse practitioner, 2 PAs, right? And so there's more than just 1 person in these practices. And so when we put a rep in a territory in a physical location, we actually get a much broader breadth of coverage. And so let's talk about that a little bit more. The doctors we'll physically be calling on that we say are our priority targets, see a substantial number of COPD patients. They see high numbers of dual, triple PDE4 and LABA/ICS patients. And then when we go to the 37,000, of course, that's going to drop, but you're seeing a wide breadth of physician coverage that we're able to get to. And so how do we do this? So we now have mapped how these physicians lay in the U.S. And we've completed mapping and we've started to deploy. Our Head of Sales, Marketing & Training is here today, but we also have an Area Executive Sales Director in the East and an Area Executive Sales Director in the West. So we've started to build this organization so that we can fit the market in the right place. We believe there's about 100 field-facing roles. Those can be respiratory specialists, virtual sales and field reimbursement managers. We also know that there's about 6 states that is 50% of the territories. And they're related back to the -- think about these, New York, Pennsylvania, Ohio, Florida, Texas, California, highest populations, they also have pollution. They are places where COPD has a higher prevalence as well. We've also, as an organization, made sure that we have the right partners to help us recruit. And I will say that we have never -- like from a recruitment standpoint and ability to get talent, people are excited about coming to Verona. And you can ask Matt and the rest of the team later on, the amount of interest we get for people being able to come here and be part of this organization is unbelievably high. So we've mapped and completed and started deployment. So what does the maps look like? I think everybody wants to see maps. So the top, very small, is the Respiratory Sales Specialist. There's about 100 territories in there. And you're like, there's a lot of white space. There's a lot of places in the West. Well, to be fair, there's not a lot of density of doctors and population. So we would not ever put a rep there. And so what these Respiratory Sales Reps look like is there's about 160 targets that they have at 70 unique offices, and there's about 75 pulmonologists in each territory. And then we layer on Virtual Sales Reps. Well, the Virtual Sales Reps cover and overlay the territories and the white space. And they can see a significant portion of more -- they're dialing for doctors. They're making phone calls. And it's a lot harder to call a doctor and get them on the phone than walking into an office, so we can give them more targets. And so they have 80 key doctors, but they actually have lists of almost over 3,000 doctors that they can continually call and try to interact with. And so we think this deployment not only supplements personal promotion, but also virtual and telesales promotion. I will say that this deployment is more than adequate to reach the opportunity. Where we're sitting from a territories perspective covers 90% of the patients that exist in the United States today or the COPD patients. And so that's an important aspect when we think about where we live. So the other side of this, and we've talked about deployment is, well, what do patients think? What do patients think about ensifentrine? And this is the first -- we just got this about a week ago. So over the last month, 2 months, we've done a significant amount of work on patients. And what we've seen is that the unmet need from a physician standpoint is even higher on the patient side. There's a lot on this chart, but I'm going to highlight that anything in pink, red is really good. And what you can see from patients, if they're moderate to severe to very severe, their likelihood on a scale of 1 to 5 to want to try ensifentrine is off the charts. And it doesn't -- again, doesn't matter about a nebulizer either. It's over 1/2. Like they don't care if it's a nebulizer. What they care about is how they feel and if they can get better. And so we think there's a tremendous opportunity to reach patients and activate patients as we move through the launch process. The patients are very willing and wanting new therapies. They want to be able to talk to their doctor about a drug that potentially could help them do a little bit more. And so we're very encouraged by this. And so how do we bring this all together? And the important thing here is we don't do this randomly. We don't say, "Oh, we have doctors, we have patients". We use data to drive all our decisions. And so we built our infrastructure through data management, through data warehouse, through our data acquisition to be able to hyperfocus on both HCPs and our patients. And we can do that through omnichannel marketing. So we can lever up or lever down our tactics and activities. The foundation is built, our data warehouse is there. We're actively bringing stuff into the data warehouse today. So what does that give us at launch? It gives us the ability for real-time feedback and adjustments. So we can make changes to programs, we can adjust, we can lever up messaging in real time. It makes us more efficient on our spend and our spend will be data driven. We're not just going to be picking and choosing different tactics. We're going to let data drive what our tactics and what tactics we should invest in more. And then lastly, we're going to -- we believe that this approach will actually increase the uptake of ensifentrine long term. So hopefully, if we think about Pillar 2, you come away with the idea that Verona, it's really a 15,000 HCP opportunity, and we've built the 100 territories that we're actively engaging with, and we're going to support that with not only virtual but telesales, but omnichannel promotion to get a broad swath of coverage when we go to launch. So the last thing we have to talk about is the customer experience. Sometimes this is the hardest thing that we have to think about. Access is not easy in today's environment. Patients struggle with co-pays and they struggle with getting drugs. So how does that look? So to start with, we have to lay the foundation of what we believe coverage and who pays for ensifentrine at launch. And we believe at launch that ensifentrine will be primarily 80% covered under medical benefit. So let me walk through this. Medicare Part B, as we talked about, works through coverage under Local Coverage Determination, Durable Medical Equipment and then J-Codes and nonspecific J-Codes. Well, Medicare Advantage also has a medical benefit component. They have to follow Medicare Part B. So if you're on Medicare Part B, you're covered under the medical benefit of Medicare Advantage. So within that 80% world, we have coverage. On the pharmacy benefit side, we've talked about the compendium. We've talked about how ensifentrine feels like it's going to be added. But we have to keep in mind that's a small proportion of the business. And the majority of the business, we're following under a medical benefit. And so what we see there is that a lot of patients will pay less than $10 on Medicare Part B and significantly low co-pays across the board. This is our anticipated what we believe, based on what we see in the market today. And so this sets a stage for a potential not only for the access for the physician to be able to match their demand, but also from a patient perspective, my willingness to stay on drug because my co-pays are hopefully in a range that I can afford. And so how do we get Medicare Part B reimbursement? We do this in a phased approach. So at launch, we launch with a nonspecific J-Code. So you see 2 J-Codes here. The first J-Code, J7699, is the J-Code that gets reimbursed at the DME MAX, which is the Durable Medical Equipment max. J3490 gets approved at the AB max. So we have to ensure and the physician needs to make sure they're putting the appropriate J-Codes for the appropriate adjudication. We'll talk through that process. But that's there. It's available at launch and physicians can run the product through the channel. Then we have to apply for a permanent J-Code and local coverage determinations. For everybody in the room today, we're not waiting until FDA approval to do this. We've already started the process of building those applications and getting those applications ready. There's a gating factor, though, you have to be approved because you have to attach the label. So we will be in a position, June 26 is PDUFA, to submit by July 1. And the reason why that's so important is they now review J-Code submissions on a quarterly basis. And so if we can get that within the first -- in those 3 days, we can get a J-Code as early as Q4 2024 or as late as Q1 of 2025, it slims down the process of using a nonspecific J-Code for the pharmacy at launch. So the team has done a great job in making sure that we're in the place to submit as quickly as possible. So then the other thing that we know about the market is optimizing the customer experience isn't just about co-pay, it isn't just about reimbursement; it's how the product actually gets to the patient at some point in time. So when we look at the current nebulizer products and how they're distributed to the patient, there are some hurdles that are challenging for physicians like Dr. Rutland and other physicians that we talk to. And we believe there's an ability to streamline this. So let me walk you through how the current process works. For everybody in the room, all your product typically goes to a third-party logistics company. These are like a Cardinal, a McKesson, one of those big ABC, these big companies. Your product sits there, and it can go down 2 pathways. It can go down a wholesaler distributor pathway where it gets to a retail pharmacy, and then ultimately, the patient. Well, there's a concern with this or there's a challenge with this. On this pathway, retail distribution has high distribution fees. So the wholesaler distributors take a portion of your sales. The other thing that happens within the Medicare Part B space is your local CVS, Walgreens, Duane Reade don't know how to adjudicate Medicare Part B scripts. They're not used to asking the government for reimbursement back on a script. They're used to asking -- getting it from the payer. So what happens down this channel is when a physician writes a script, like YUPELRI, BROVANA performance and send it to a CVS or Walgreens, it potentially gets sent back to the physician and it says not covered. When in reality, it's 100% access in that channel. But that's because the distribution network potentially has some challenges. So the other way the product gets distributed is through DME pharmacies, so Durable Medical Equipment pharmacies. These are like a Lincare or DirectRX. These are pharmacies that are used to distributing medical equipment. They don't usually do branded drugs. And so they have limited experience with branded drugs. They have limited experiences with Medicare Advantage. So sometimes the script goes down that path. And if it's a little bit outside of Medicare Part B, it causes consternation and issues. And so we believe there's even a simplicity that we can do here. So you can see that just getting the product to the patients sometime within the nebulizer world can be problematic. So how do we believe we've simplified this? So our proposed pathway is actually, we'll start the same place. We're going to start at a 3PL, but we're going to make a slight change. We're going to go to DME-accredited pharmacies. So remember, to get adjudication, you have to be DME accredited. You don't have to be a DME pharmacy, a pure DME pharmacy. So DME-accredited pharmacies are Lincare, DirectRX, but there's also CVS. There's also Humana. There's also Acaria. There's big pharmacies out there, specialty pharmacies that are DME accredited. So we believe by limiting the network to a DME pharmacy -- DME-accredited pharmacy, we can ultimately get that patient in a much more streamlined fashion. And so the reason why we believe this is important is because these pharmacies can handle the capacity and they cover the United States, and they also cover the majority of plans. We believe that it will streamline the process of getting the product to the patient and we also believe that potentially, it has the ability to help with adherence and overall approvals. So that's how we believe we can solve some of the problems that are occurring right now within the nebulizer space, by what we always do in marketing is try to limit choices. Sometimes we say choices are good, but when you have too many choices, you have no choice at all. And so we believe by limiting the choice in how the product flows, it actually enhances the experience to the customer. And this pathway is very similar for how physicians deal with other drugs today. Dupixent kind of flows through a similar channel, through a specialty pharmacy. You have other products for pulmonary hypertension that flow through the channel very similar to this. So this is not new to a pulmonologist, and it is a pathway that pulmonologists, I think, will like because we believe it will help that reimbursement pathway. So the other side of the patient story is that what happens with the patient when they go to the pharmacy is about 1/4 of the patients either abandon or walk away from their prescription at the pharmacy. And then if they get on product, they only stay on it for 5 to 7 months. So in order to help this, we believe there are 2 components that will assist in this process. We believe that a hub support system will help support the patient and the physician through this process. We believe it will help the patient navigate the reimbursement landscape, the HCP reimbursement landscape and it will overall support the adherence program. We hear from physicians that they would like to have these type of support programs in place because they deal with the reimbursement challenges all the time with COPD products. And then on the second component is we can support patients through patient support programs. That helps with adherence. It helps with ongoing education about why they're on drug. In the past, we've done this in very other similar conditions where patients struggle. And these are simple things that from an organization standpoint, we can set up the market to be able to hit these things in a very right way so that launch is appropriate. So we think these are critical. So if we think about this customer experience, we believe today that we have enhanced the distribution pathway. We understand the J-Code process. It's an established process, it's not new. We know how to navigate it. We're launching with a nonspecific J-Code, and then we'll supplement with patient services at launch to ensure that the patient can stay and maintain therapy. So now to bring this all together, the question we always get is what's the potential of ensifentrine? And how -- from a sales standpoint, what are we going to see with ensifentrine? And we believe that ensifentrine is a multibillion-dollar opportunity. And we believe this because, one, let's go back to the foundation. The foundation is unmet need, significant unmet need. We have a differentiated asset. And then we also have an access channel that allows the product to flow to the patient. So let's do some math here. So the market is about 8.6 million patients. If we just priced ensifentrine at $1,400, which we're not giving any guidance on price, and we had patients stay on drug for about 7 months, all of these are in the current dynamics of the marketplace. And then the gross to net was 25%, which is what Viatris' gross to net -- we believe Viatris' gross to net is on YUPELRI, you can see that for every 1% patient share that it's $600 million in net revenue. We showed you patient shares that were significantly higher than 1%. They're unadjusted. But you can see how very quickly you can get an asset with a differentiated profile to a very high potential peak revenue sales. So okay, so that's good data. Well, what do other products do today? So let's take a look at this. Daliresp, which is a PDE4 with significant side effect issues, is 1% of the market today. There's about 75,000 to 85,000 patients on Daliresp today. ANORO, a LAMA/LABA is about 5% of the patient share. TRELEGY is 12%. Symbicort is 21%. So imagine a little bit of penetration within this marketplace and what ensifentrine can do. We're not talking about a LAMA, a LABA, ICS project, we're talking about the first novel mechanism in 10 years. And so we believe from a drug standpoint, from a potential standpoint that we have all the dynamics in place to have a multibillion-dollar opportunity with this drug. So with that said, Verona is extraordinarily well positioned. I hope you guys have seen over the last -- I think we get questions when we go to investor events, what's commercial doing? What are we doing? I think -- I hope that you've seen over the last hour that the work that the team has done is substantial. And being 9 months from launch, we are in a very, very good place from a launch execution, a launch readiness standpoint. The PDUFA date's June 26. And as Dave said, we will be ready to launch this product as quickly as possible post PDUFA. Everything is in place to be able to do that. There's a large unmet need. Let's go back to the tenets. Large unmet need, millions of patients are symptomatic. It exists today. I'm going to go down instead because you go on large unmet need, but now you have a differentiated molecule that has a reimbursement pathway that's favorable. Now we have to support this. All our commercial preps are ongoing and in a very accelerated pace, and we believe 100 reps support this. And then lastly, you can't do this if we don't have the right people in the room, and we don't have the right financial resources. And we have the right financial resources to execute against everything within this plan to put us in the right position to reach the opportunity that we just talked about on the last slide. So that's my last slide. I know you guys are done with slides. So we're going to open it up to Q&A now. I know there's some other members of our team here, just so everybody knows. There are members from Market Access, Commercial Operations, IT, Clinical and Sales & Marketing as well. So I may defer to some of them, but it gives you an opportunity to meet the Verona team as well. So I think they have quite -- yes, or, David, do you want to go?

Great. So my first question is for Dr. Rutland. How do you see ensifentrine being adopted in coming years relative to other forthcoming novel therapies? So if you could just sort of juxtapose this product and how it will be adopted in the event that products like Dupixent and TEZSPIRE and the IL-33s get approved in coming years as novel therapies for COPD?

So a very good question. And when you think about the -- let me repeat the question. How do you see ensifentrine versus newer molecules that have an upcoming release in the next 2 to 5 years? Right? Good question. I think when you understand the mechanism of those newer molecules after understanding the pathophysiology of COPD, inflammatory COPD, chronic bronchitis, you get to a point where all of these products support one another. They don't act in the same way, where you have dupilumab, which blocks interleukin-4 receptor and interleukin-33 is involved in some of the inflammatory cell recruitment into the airway as well. So blocking that is helpful, but they all work together like a symbiotic type of relationship, which I think is beneficial for patients. So I don't see those products as competitive products. I see those products as supporting products. Plus you also have that this product is delivered in a very familiar way. One of the issues that we've had with the adoption of the monoclonal antibodies, which is what you're referring to, is that most or a lot of physicians are uncomfortable with the use of monoclonal antibodies because of the mechanism and their worry about allergy and anaphylaxis and things of that sort, but they're just uncomfortable with it. So they are more inclined to adopt a nebulized product because of their comfort, and it's been in use for 50 years, right? And so I think that that's advantageous for this product as well. So that's how I would answer that question. I think that as a mechanism guy, and I know that I'm a zebra in the pulmonary space in terms of that. But I look forward to all of those products, because I think that using them together, understanding that there's not 1 cytokine that's going to dominate everything, I look forward to that, but I don't see it as a competition.

Great. And I don't think I mentioned my name, Dave Risinger from Leerink Partners. So -- and with respect to ensifentrine, could you just comment a little bit on how you see it being adopted relative to the currently approved therapies today? What it will displace? What it will be added on to? So how you see prescribing it, assuming it's approved next summer?

How do I see ensifentrine being adopted with the current landscape of the inhaled respiratory products? Okay. So I see it as an add-on to all of the products. So everybody who is on a product, and you see that most patients are on just a dual, you can add this product on very easily. And I think it's going to be adopted relatively quickly. My barometer for that is I have a partner in my practice who is 56 years old, trained at Harvard, like one of the smartest men that I know, and he reads literature probably more than I do, and he's been in practice for longer than I have, and he's a pulmonologist, but he is 95% primary care. He is excited about this product. And he is very much into making sure that the patients aren't paying as much, making sure that the patients are well taken care of with generic products that don't cost a lot out of their own pocket. So seeing his excitement helped me a lot in terms of the average primary care provider and pulmonologists across the country. And when you go on and you educate other physicians about COPD, I see it adopted really, really early. We had an ad board last week in Hawaii. And those physicians will adopt it really early. And they are community-based physicians who practice in the average community away from the academic centers because it's such a familiar delivery device. So I see it as an add-on to all the current products out there.

Great. One final question. So just thinking about YUPELRI since that's an approved, branded, promoted nebulized product. Could you talk about ensifentrine relative to YUPELRI? Maybe start with YUPELRI's sort of adoption ramp, what its positives are, what its challenges are. And clearly, ensifentrine has a completely different profile and a much more transformational profile, but just sort of setting the stage to help us better understand your view on YUPELRI. And then adding on your comments about how ensifentrine's adoption is going to be much steeper would be helpful.

Yes, no problem. So how is YUPELRI's adoption compared to ensifentrine's adoption with the current landscape? Another great question. YUPELRI is a long-acting muscarinic antagonist, right? And it's also an nebulized product. One of the -- I want to say, I don't want to be too mean to YUPELRI's team, but one of their mistakes was they did not spend as much time on education as they should have in terms of educating physicians on COPD because they thought that it's such a bread-and-butter medicine topic that they didn't have to do that. But when you look at the mechanism of action of a muscarinic antagonist, it not only inhibits some of the receptors in the smooth muscle that lead to bronchoconstriction, so you get bronchodilation, but it also inhibits the activation of some of the white blood cells in the airway. And I think that with that type of education, could the product launch have been a little bit better? Yes. But when you look at the science of the phosphodiesterase 3 and 4 inhibitors, of which ensifentrine is, the physiologic impact on the lung pathophysiology of COPD is greater mechanistically, right, in terms of what avenues that it affects from anti-inflammatory capabilities, bronchodilation capabilities and improving the mechanics of the airway, enhancing the CFTR ion channel as well as increasing that cilia beat frequency and also understanding that due to its effects, it's being investigated in cystic fibrosis and other -- and bronchiectasis and other lung illnesses that would benefit from those mechanisms. So I think that ensifentrine has a more profound impact mechanistically, scientifically and physiologically on the lung than does only a long-acting muscarinic antagonist.

David, just to add to that, too. If you think about the launch of YUPELRI, it's a replacement launch. So they have to take someone off LAMA to put them on YUPELRI. And as Dr. Rutland talked about, ensifentrine, he's describing is an add-on. So you can layer it. You don't have to replace anything. Again, we don't -- we're not saying there's -- we're not saying any -- we don't have to compete with anything. What we know is we need to help patients. We need to help patients who are still symptomatic and this gives doctors like Dr. Rutland, a chance to add another drug to these patients and hopefully, get them back to some of the normal activities they face. I think Yas, you had a question.

To start off with saying superb job, like really, this presentation and this detail that you provided us is really thoughtful and kind of gives us really a glimpse how you're thinking about the launch across every aspect of it. So I just really wanted to say congratulations on that. Questions for Dr. Rutland first. One of the things that we get as an analyst covering Verona will be clients saying to us, "I understand ensifentrine's product profile looks really good, but the studies were done on top of mono and dual treatment. There is no data on triples. Docs aren't going to use it because there's no data existing." They also recognize that it's in the right reimbursement channel being in B. So question posed to you is like, you, a very thoughtful physician, as well as your colleagues, like are you going to be like there's no data. So therefore, I'm not going to put it on triple. If you could highlight that, that would be great. And then I have questions for Chris, a few of them.

So what about adding on to triple therapy and doctors kind of saying that, "Well, there's no data on triple therapy" and this being a product that you add on. Well, at the time of the studies and recruitment of the studies, when you look at the GOLD guidelines, the GOLD guidelines did not say patients need to be on triple and then you're adding on from there. The GOLD guidelines said dual bronchodilators, right, or single bronchodilators, period. So they followed what the guidelines were at that particular time. Now have we had and have I come into contact with physicians who say, "Well, it's not added on to triple, so I don't know if I'm going to use the product." So then what I think is a very, very powerful piece of information is the slide in this deck that showed that what 80% of patients are on dual therapies across this country. And so that's what we're talking about. We're talking about adding a product onto a therapy strategy that includes 80% of the patients now. So I think that would be my conversation with most of those physicians. I do think that, yes, you want to discuss that, but when you look at the exacerbation data and the delay to first exacerbation and you understand the capability of this product, I think as we saw in the ad board, that question went by the wayside at about 45 minutes into it after the physicians were shown that exacerbation data. It was something that I have never seen in the billions of ad boards that I have been to or led or whatever. I think that I've never seen a room turn after that exacerbation data was shown like that. And so I just felt like, wow, this is really, really interesting and powerful. The other thing I will say, and this is something that a lot of people don't discuss, and I think it needs to be discussed, inhaled corticosteroids, not only do they lead or can they lead to increasing pneumonias in these patients, but they also cause dysphagia, you get this voice hoarseness. And so a lot of these patients, I have to take off of the inhaled corticosteroid. What a privilege it would be to have a steroid-sparing nebulized inhaled product that I could use that has some of the same effects of steroids and additional effects. And I think being able to market to that and articulate that is extremely beneficial for these products as well.

Got it. Sorry, you alluded to exacerbation rates being really exciting. Another question we get from our clients always is, "Well, what happens if it doesn't end up on the label, right? And instead, we end up with a publication?" So do you, as a physician care that it's not an actual label language rather than a publication? Like the data is clear, but what we don't know is whether that will end up in the label or not? Like how is that going to impact usage?

Great question. My job -- or how is it going to impact usage in terms of what the label is? My job as a physician is to make certain that my patients are feeling better. Once a product is available, it is my job to figure out how I can get the product to the patient. So once I deem that the product is safe, if I believe that the product is going to help my patient, I don't care what the label says. I will flip around the diagnosis, I will do whatever it takes to make certain that my patient can receive this product. I'll give you an example of that. So with -- and I'm just going to say dupilumab, right? So in patients that have significant type 2 inflammation due to their -- whatever is going on in their environment, I will find a way to find an indication for Dupixent, so I can get the patient on dupilumab if I feel that it's beneficial. What I think you're going to see is a lot of patients that have asthma, which is also a chronic obstructive pulmonary disease, you might see that these older adults with asthma that are 65, 66 years old, physicians may end up switching their diagnosis or putting on COPD as an additional diagnosis so that this product is available for their use as nebulization, which is something that's really fascinating as well, just thinking about this product over the last several months.

Great. Very helpful. And then, Chris, for you, how many DME-accredited facilities exist here in the U.S.? What percentage of them have been ready, like will be ready to go or ready now, will be ready by launch? And then the J-Code thing is like what if you miss July 1, like and you resubmit and then you get -- how soon do you get the answer? And I'll pass it on.

Yes. So I'm going to actually -- I'm going to let Matt Rysavy answer the question on DME-accredited pharmacies. Matt is our VP of Market Access & Trade. And then, Matt, I'll cover the DMEs, the J-Code, if you want, or you can cover the J-Code as well. Yes.

So yes, thanks for the questions. Can you hear me?

Yes.

Thanks for your question, Yas. So there is a lot of DME-accredited pharmacies. I think when we were looking at the pharmacy network, there was really 2 things that we looked at with Chris. Number one, having DME accreditations; and number two, having the capacity to actually carry the volume of [indiscernible]. I must just be loud. So based on that, what we did was we narrowed it down to pharmacies that have those criteria. So we came up with a limited distribution network that can handle that. So in order with -- or excuse me, in regard to the J-Code, what we're going to do is we'll use a temporary J-Code for inhalation devices, which is the J7699 that we'll use initially, and then we'll submit for a permanent J-Code at the PDUFA date. That, to Chris' point earlier, will take about 3 to 6 months to get that, but that should be in the normal process of any kind of product that flows through Medicare Part B.

Yes. And if we were to miss, which we're, let me be that clear. If we -- you can submit quarterly. So it moves at a quarter. Unlike the past, which was biannually, there now are quarterly submissions under the J-Code. Thanks, Matt. Tom? Tom and then Boobalan.

Tom Shrader from BTIG. A couple of questions for Dr. Rutland. What's your definition of a well-controlled patient? When are you happy? And a follow-up. For a patient on either a LABA or a LAMA, what's the chance that the next drug for you is ensifentrine, rather than to add the other existing drug?

So what's the definition of a well-controlled COPD patient? I would say my definition of a well-controlled COPD patient is a patient who is not on therapy and has no symptoms whatsoever, right? If you want me to be like perfect. But a patient that is on therapy that's having no symptoms, right, so the MMRC score is low, their CAT score is low, those are the patients that are well controlled, they're well controlled that have COPD in my mind. And the second question was?

If they're on just a LABA or a LAMA what's the chance that in your practice, ensifentrine is the next drug?

So my practice, right? So my practice is very particular. I get kind of the most severe patients in my area. My patients are not on just the LABA or LAMA. Most of my patients are on either a LABA/LAMA combination because they couldn't handle the inhaled corticosteroid because of the hoarseness it caused or my patients are on a LABA/ICS or they're on triple therapy. So in my practice, again, and I know that I operate probably a little bit differently than the average pulmonologist, understanding the mechanism of action, I just feel like being able to hit another molecule, right, and enhancing the patho or enhancing the physiology of the airway, allowing it to work better and lead to less inflammation, more bronchodilation and enhancing those ion channels and such. I'm an early adopter. So I would use it early because it's so familiar. It's a nebulized product. And I know that the physicians in my area, who I would be talking to and educating, would probably begin to use it earlier as well because I'm using it earlier. That's me in my practice in my region.

And then a quick one for Chris. As you think about price, who do you negotiate against? Is it just the commercial piece that takes the tiny piece and everyone else takes that price? Or as you think about price, who argues the other side?

Well, I mean, I think it's -- we price drugs based on the value they provide the HCP and the system. So it then becomes do you have to discount to your payer, the payer that you're looking through. So the way we look at price is we believe the value that ensifentrine provides these patients is very high. We talked about novel mechanism action, bronchodilation, anti-inflammatory effects. We talked about lung function improvement, symptom improvement, exacerbation improvement. That's a very different profile than what exists on the marketplace today from a LAMA. So we can -- it's an internal discussion on how we price based on what the value we believe ensifentrine provides. And then the question is to gain access, like say, on a commercial standpoint, do we have to discount and provide a discount to get access within that channel? We believe, if you look at how ensifentrine is reimbursed and you look at how the gross to nets are with YUPELRI, that like discounting is limited within the primary channel. And to be fair, commercial is such a small percentage of COPD patients. Like, the majority of patients that are on chronic long-term therapy are Medicare, Medicaid. Medicare patients, like it's 70-plus percent of even the inhaler business that's out there right now. So that commercial business is very small, and we don't believe we would have to do anything special to gain access within that. And the other side is we have ways to help the patient in that channel. Unlike Medicare, where you can't provide co-pay assistance, we can provide co-pay assistance to commercial payers -- patients. So like we may not have to negotiate, but we may have to provide a co-pay card that you see for TRELEGY and BREZTRI to those patients. But those are all things that we've thought about and are planned to do. Boobalan?

Boobalan from H.C. Wainwright. So a couple of questions. So firstly, to Dr. Jamie. So assuming ensifentrine is approved, I wanted to know -- I wanted to get your thoughts on how it would impact or even reduce health care-related burdens such as emergency visits or hospitalization. So maybe if you can quantify, that would be really helpful. And then from a patient perspective, are they going to be on ensifentrine forever, assuming if it's approved? Or would there be like ensifentrine holidays? And I have a question for Chris later.

Great question. So ensifentrine holiday and basically its impact on health care utilization, so the economic burden I think is what you're getting at. Great question. I think there's no economic burden study. So I can't specifically refer to numbers. But what I can say is when you look at delay to first exacerbation and you look at exacerbation reduction, that's what leads to patients presenting in the emergency room, right? And when you had that 44% reduction in exacerbations, that's significant, right? So you're halving their exacerbations. So I think from my standpoint, it's going to have a significant impact on those hospital visits, those urgent care visits, those visits to the clinic. So I think it's going to have a profound impact on that, profound. I think it's going to be something that I think is excellent because a lot of these patients go to the hospital, get admitted to the hospital. And we also have to remember, if you have patients that are not on an inhaled corticosteroid and they're on ensifentrine as well, you're going to reduce the pneumonias that patients present with as well. So you have to look at it that way as well. So I think that thinking about all those things is going to have a profound impact. Your second question was -- I forgot, I'm sorry. Oh, ensifentrine holidays. I get this question about all the products, right? Here's the way that I always answer this question. I'm consistent with my answer. A patient lives in a certain environment. What people don't think about is that the environment impacts the amount of lung inflammation the patient may have, whether they're around smokers, whether they're around air pollution. If their environment has not changed, the inflammation within their airway is not going to change that much. So if they're in the same environment, when I prescribed the product, you're on the product. Your genetics have demonstrated that your body is going to respond in this manner. That's not going to change, right? Yes, these products are disease modifying, which is a popular topic these days in all our leadership meetings at these conferences. But it doesn't mean that the disease stops, right? COPD is chronic obstructive pulmonary disease. In other words, it is a chronic issue. So I fully expect that this inflammatory process, even though we take quick snapshots at every visit, the inflammatory process continues. That's why I like to think histologically and cellularly what's happening inside the body, because that process continues, even though I just saw that patient on Tuesday. It doesn't mean it's stopped because I'm not going to see them for another 6 months on a Tuesday. So that's how I think about that.

Okay. Chris, so you presented a lot of market research studies, and they are very insightful and very detailed. So in one of the slides, you talked about patient motivation. So I'm curious whether there is any correlation between patients' age and motivation to use ensifentrine?

As far as -- let me just -- so the question here is about patients' motivation to use ensifentrine. Yes. If it goes back, if you look at how we classified that slide, it's based on patient types. So you have moderate patients, you have severe, very severe patients that have either not experienced an exacerbation or experienced an exacerbation. I think the important thing when you look at that is it doesn't really matter what their experience has been from a patient standpoint. What we know is, as Jamie just described, we're dealing with a chronic obstructive pulmonary disease where the patient is always going to have some sort of symptom burden, and they're looking for new drugs to potentially help them. And that's, I think, what the data shows very clearly, is that patients are motivated to try something that's very different, and that has the potential to help them very quickly within their COPD landscape.

Can I add to that?

Go for it.

Yes. What I learned when he presented that data and when you see that disconnect between physicians and patients, where it was a 90% of patients say, "I don't tell my physician everything," 50% of physicians were like, "Oh, no, my patient tells me everything." What I saw right there was when I looked at that, I learned something and what I learned was patients want to please their physician if they like their physician. So if they feel like their physician is doing everything for them, they're going to say that they're telling them everything. But 40% of the time, they're not telling them everything because there's probably nothing else -- they realize that there's nothing else the physician can do. What I see there is a motivated patient who wants to do something more if something becomes available. So that's where I think if patients understand that this is available, what you're going to see is that gap kind of close in terms of that disconnect, which is another profound effect that this product may have on the market. So that's just something that I picked up and learned from looking at that data.

Okay, right here. A.J.?

[ A.J. ] for Andrew Tsai, Jefferies. My first question is for Dr. Jamie. So would it be fair to say that pulmonologists ultimately want to move away from steroid usage? And if so, what does that mean for ensifentrine in terms of displacing that in the marketplace?

Great question. Would it be fair to say that pulmonologists want to move away from steroid usage? Yes, we would like to move away from steroid usage. When you look at some of the products, and again, I'll use Dupixent as an example here, oral corticosteroid-sparing agent, because of the profound impact that steroids have on morbidity, increasing your blood sugar levels, weight gain, increasing cardiovascular disease, increasing cerebral vascular disease, cataracts, thin skin, easy bruising, All of these side effects secondary to oral corticosteroid use are bad, right? They're not good for our patients. We don't like it. When you look at inhaled corticosteroids, pneumonias, most of the time, we try to ignore that because we know that they're significantly beneficial. But when you have a steroid-sparing product, that -- whose mechanism can operate in a similar way -- or a similar result, not in a similar way, a similar result, which leads to less inflammation, that opens up our eyes to man, we can get our patients, maybe we can get our patients off of steroids, maybe have the same outcomes or better outcomes overall. And that is something that we look at as positive. Again, it's a lot of education and there's going to be a lot of explaining to these physicians and educating these physicians, which they have a plan for, but also educating nurse practitioners and PAs and even late-grade medical students and such, so that they have an understanding of this. So I do see potential for possible displacement of inhaled corticosteroids. And I would bet that you're going to see that study where you're going to see LABA/LAMA/ensifentrine, right, and see if those outcomes are the same as the LABA/LABA, ICS. So yes, I think that whenever you can eliminate the use of steroids, it helps. I'm an autoimmune lung disease guy. That's all my clinic is, is autoimmune lung disease. So I use a lot of steroids, and I do understand their benefit, but I also understand the significant morbidity as well. And I would like not to use them and try not to use them.

Got it. And then my next question is for Chris. So how should The Street be thinking about the launch cadence here in terms of the first few quarters in terms of patients treated and gross to net over time? And do you intend to disclose those KPI?

Yes. I think -- and Mark can jump in here a little bit as well. We have not disclosed a forecast at this point in time or revenue guidance. I think we will, as Yas said earlier, we're transparent. We tell you guys what's going on, how we're preparing. We will have key performance measures that we will report out on a quarterly basis to ensure that you understand how the product's being uptake. I think one of the things that's important in that aspect is when we think about the channel, you guys, the access to data is going to be confined to the limited network. So we have to be able to report out what patients are on drug, what patients aren't on drug. We're still working through kind of what those KPIs will be. But I think as you've seen from our experience over the last 2 years that have interacted with us, we will be very open in how the drug is performing and what's going on. From an uptake standpoint, internally, what we usually do is we look at the YUPELRI launch curve. And because what the YUPELRI launch curve does is it shows the Medicare Part B dynamic. They launched with a nonspecific J-Code, then they transitioned to a product-specific J-Code. There are some dynamics that are different there than us. We're a novel mechanism. So that changes that curve slightly. We're also -- the J-Code reimbursement has changed since YUPELRI launched. YUPELRI launched in 2018, and you had to submit J-Codes on a biannual basis. So your lag to permanent J-Code was longer. So that change probably helps accelerate some of that conversion as well. So we use YUPELRI as the base and then modify based on the profile of the drug and also some of the payer dynamics that exist in the marketplace as well.

Vamil Divan from Guggenheim. Just two questions, actually. One, you talked a lot about the physician side and getting them educated. What about the patient side, especially in terms of this disconnect around getting the patients and physicians online with the opportunity?

Yes. I'm going to let Matt Casbon answer this about -- and, Matt, the question is really from a marketing side, how do we educate patients and what are we doing to kind of educate patients? I think we can talk about advocacy and some of the other work that we're doing.

Yes. I think we're at the beginning of understanding the patient. Chris showed you some early headline data of their willingness to learn more. That's always a starting point. I think we're digging in pretty deeply on some segmentation work. Obviously, we have to get physicians writing the prescription and understanding how it's going to perform in the real world. And I think maybe early on, we would have thought we would have had to wait longer to go directly to patients, but I think this is showing that there's, as you pointed out, a significant unmet need that these patients might get activated a little bit sooner to go in and ask for some more help. I think they need a little bit more help. And what's different about this drug and this launch is we can get added to what they're currently on. They don't have to go in and say stop using this, use this. It's a big difference for this launch. It's pretty exciting.

And then one other one just on the manufacturing side. I don't know what's the latest you've sort of shared there in terms of any updates around inspections? And...

Yes. And Dave, I don't know if you want to provide a comment on the manufacturing side and...

Yes, sure. So with regard to drug product and that whole supply chain, clearly, we have been progressing substantially over the past several months. I'm very confident in where we stand both in API because of the history of ensifentrine, it's very well characterized. We've already scaled it up. We already know how to make it at the commercial scale and have [ created ] there an employee for our API to support the launch and even beyond that, as we prepare for a number of years after that. That supplier is in Europe and a supplier that provides other APIs to commercially available products not only in Europe but also in United States. We believe it has very good regulatory history, that's our view and our [indiscernible] systems and their inspection history. The drug product is made in United States. It is a [indiscernible] product that has already been scaled up and very well characterized, long expiration dating, 3 years plus. So I think we're in very good shape. Again, a supplier that provides a commercial product to the United States and other geographies, very good inspection history. But of course, we're always diligent because what I just said is true today. It is a dynamic process, as you well know. But we're very confident in our CMC.

I think before [ Matt ] and then [ Rakesh ].

Asim Rana for Joon Lee's team at Truist. Just a question for Chris. You mentioned 90% of HCPs would consider adopting ensifentrine within 12 months of launch. Have the other 10% cited any reasons as to why they might be hesitant? And then just as a follow-up, what are the time lines on hiring the 100% sales force?

Yes. Okay. Let me take both of these. So the first question is about physician adoption. The second question is time line for hiring. So from the first standpoint, I want to just be -- 90% adopting ensifentrine within 12 months is unbelievably high. And the other 10% adopting ensifentrine, it just takes them a little bit longer. It's within the first 2 years, within a period of time. It's not that they're not adopting ensifentrine, they're just not doing it as rapidly as the majority of other physicians that we talked to. And I think that's something to keep in mind is that we've not heard doctors that say in any of the market research or ad boards that this product doesn't have utility in my practice. It's a question of how quickly and how much. And so no matter what the doctor is, we believe that every pulmonologist is seeing patients that are appropriate for ensifentrine today, and will always see patients that are appropriate for ensifentrine. So I think that's the key takeaway. And I would -- if you walk away with something, like walk away with the 90% is really unheard of from an adoption standpoint. We do market research all the time. We've done this for 15, 20 years, Matt and I. And not often we see a number that looks like that. And again, it goes back to unmet need differentiated product for us. The second question was on hiring. Matt, I'll just cover -- I'll do this quickly. From a hiring standpoint, we've done everything gated at this point from a commercial organization actually as an organization, we've used milestones to gate our hires and approvals. So Matt, Mark and Matt, who -- Market Access, Commercial Operations and Sales & Marketing came in when the ENHANCE 2 trial data read out. And then we've slowly built the organization based on other milestones. We have -- everybody here looks at LinkedIn posts, I think, and looks at our websites when we have job openings. We get that feedback. We have posted the Regional Sales Director jobs, which is our Regional Sales Directors across the U.S. We would anticipate bringing those people in sometime in the first quarter of 2024. You do that because they have to work their territories to get the candidates and make sure they have the right candidates for their territories that they're going to be managing. So that's our first step. The reps would be hired around PDUFA or at PDUFA. We can hire reps contingent on approval and we bring them and hold them for about a 3- to 4-week period. And our plan is to do -- to have everybody kind of locked and loaded and have their offers convert on approval. And I've done this. Matt and Matt have done this in the past with other organizations. It's a very successful way of being able to hire a large group of people in a very short period of time. And to be fair, we're not going to have problems finding people because the interest in Verona is extraordinary. I know Kavita, from a Medical Affairs standpoint, is getting tremendous interest from Medical Science Liaison, I think from our Regional Sales Director roles that we just posted, we're getting inundated. I think that tells you that the industry and the people in this industry understand what the opportunity is that ensifentrine has. Like I've been lucky in my career to have very good products to be able to launch, but this is a unique situation where you have a product that looks like this, with a market that has got a tremendous unmet need and you have access that has the potential to be very favorable. And so that's attractive to a lot of people from a recruitment standpoint.

And then just a quick question for Dr. Rutland. In your practice, are there any patients that you think might not be suitable for ensifentrine?

Are there any COPD patients who are not suitable for ensifentrine?

Yes.

No.

All right.

So apologies if someone already asked this question. But earlier, there was a slide that identified HCPs ranked basically from like A to D based on the scripts that they wrote. And you had mentioned that you were very kind of data-driven in terms of specifically identifying who those were. Do you actually have like a list of names of who's in the A so that you can specifically like target those?

Yes. I'm going to let my data guru answer that one. So Mark Zappia runs all our commercial analytics and did all the work on identifying targets. So Mark, if you want to give a feedback on kind of what we have and how we identify these people?

Yes, sure. Thanks. I appreciate the question. So yes, we do and we actually are going a step further than that. We've taken these AB -- really the A and B and are validating where these physicians practice. And so we are mainly curating that list to validate where are they primarily practicing. But as important, who else is associated with that practice? And so our mission is upon the regional managers being here, they're going to be given a list of core physicians, core accounts, core addresses. And we're going to be working with those managers to develop business plans to really set up the reps to say not only do we have your launch year ready to go as far as your call planning, but we also are going to identify who you should be speaking to in those offices and what we think you could be saying and then let them do what they do best, which is sell. So our mission here is really every minute, every hour matters for the rep and especially for physicians. So let's take some of the administrative burden off of their hands, so they're ready to go.

I apologize for this question as I know it's a commercial specific event but for Mark or David, in terms of a partnering opportunity, is that still something that's under consideration? Or kind of what are your thoughts around that, if you could provide some that would be great.

Yes, sure. So with regard to partnering opportunities, our strategy remains the same. We are looking to partner ensifentrine outside the United States, which, as you know, we've done already in Greater China. And so we'll continue to do that. We don't intend to start operations outside the U.S. At the same point, I want to emphasize that the biggest opportunity for Verona Pharma is in the U.S. And so our other partnering opportunities are incremental to that. They're positive, but they're not transformational. And so we are also very patient. We're also looking for partners that can bring additional characteristics, for example, secondary manufacturing as we look to provide the worldwide supply. And so a lot of partners in other geographies, we're looking to have them contribute that element of it. So it's a certain partner type. Also, IP around delivery devices. DPIs or MDIs or experience in development and manufacturing of products and devices is also another attribute. So we're getting very specific and targeted, but we'll continue to advance that strategy. And of course, you can expect that some of those partners also have a broad view and a worldwide footprint. And so that's also part of our discussions and seeing how that goes. But nothing is going to slow us or stop us in the sense, as you've seen here today, to make sure we're prepared to control what we control and that is being ready to launch ensifentrine in the U.S.

And what about within the U.S., partnering or potentially selling the assets? Is that something that was still under consideration or...

Well, I think as you've seen today, we feel very confident that we can launch it ourselves. And so we do not, at this time, see any advantage without -- in a broad view of some co-promote or other types of partnering to give us an additional benefit. That, of course, could change. But I think if you've seen today, the size of the market, the targeted HCP, the way that the access channel works, the reimbursement, all of that is in our favor for Verona, and so we don't see the need.

That might have been the last question. So again, I know everybody gave up their mornings this morning to come listen to us today. We appreciate the time. The management team will be here to answer questions afterwards as will Dr. Rutland. But again, as you walk away here, realize that Verona is well positioned to launch this product. The 3 things that are necessary for a launch, unmet need, a differentiated access and favorable market conditions are set for us. So we believe we're in a really good place. Again, we're here afterwards. Thanks again for the time, and we look forward to talking to you in the future.